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COVID-19 outbreak had a major impact on the organization of care in Italy, and a survey to evaluate provision of for arrhythmia during COVID-19 outbreak (March-April 2020) was launched.,A total of 104 physicians from 84 Italian arrhythmia centres took part in the survey.,The vast majority of participating centres (95.2%) reported a significant reduction in the number of elective pacemaker implantations during the outbreak period compared to the corresponding two months of year 2019 (50.0% of centres reported a reduction of > 50%).,Similarly, 92.9% of participating centres reported a significant reduction in the number of implantable cardioverter-defibrillator (ICD) implantations for primary prevention, and 72.6% a significant reduction of ICD implantations for secondary prevention (> 50% in 65.5 and 44.0% of the centres, respectively).,The majority of participating centres (77.4%) reported a significant reduction in the number of elective ablations (> 50% in 65.5% of the centres).,Also the interventional procedures performed in an emergency setting, as well as acute management of atrial fibrillation had a marked reduction, thus leading to the conclusion that the impact of COVID-19 was disrupting the entire organization of health care, with a massive impact on the activities and procedures related to arrhythmia management in Italy.,The online version of this article (10.1007/s11739-020-02487-w) contains supplementary material, which is available to authorized users.

An increase in out-of-hospital cardiac arrest (OHCA) incidence has been reported in the very early phase of the COVID-19 epidemic, but a clear demonstration of a correlation between the increased incidence of OHCA and COVID-19 is missing so far.,We aimed to verify whether there is an association between the OHCA difference compared with 2019 and the COVID-19 epidemic curve.,We included all the consecutive OHCAs which occurred in the Provinces of Lodi, Cremona, Pavia, and Mantova in the 2 months following the first documented case of COVID-19 in the Lombardia Region and compared them with those which occurred in the same time frame in 2019.,The cumulative incidence of COVID-19 from 21 February to 20 April 2020 in the study territory was 956 COVID-19/100 000 inhabitants and the cumulative incidence of OHCA was 21 cases/100 000 inhabitants, with a 52% increase as compared with 2019 (490 OHCAs in 2020 vs. 321 in 2019).,A strong and statistically significant correlation was found between the difference in cumulative incidence of OHCA between 2020 and 2019 per 100 000 inhabitants and the COVID-19 cumulative incidence per 100 000 inhabitants both for the overall territory (ρ 0.87, P < 0.001) and for each province separately (Lodi: ρ 0.98, P < 0.001; Cremona: ρ 0.98, P < 0.001; Pavia: ρ 0.87, P < 0.001; Mantova: ρ 0.81, P < 0.001).,The increase in OHCAs in 2020 is significantly correlated to the COVID-19 pandemic and is coupled with a reduction in short-term outcome.,Government and local health authorities should seriously consider our results when planning healthcare strategies to face the epidemic, especially considering the expected recurrent outbreaks.,Graphical Abstract

Severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019 (COVID-19)-induced infection can be associated with a coagulopathy, findings consistent with infection-induced inflammatory changes as observed in patients with disseminated intravascular coagulopathy (DIC).,The lack of prior immunity to COVID-19 has resulted in large numbers of infected patients across the globe and uncertainty regarding management of the complications that arise in the course of this viral illness.,The lungs are the target organ for COVID-19; patients develop acute lung injury that can progress to respiratory failure, although multiorgan failure can also occur.,The initial coagulopathy of COVID-19 presents with prominent elevation of D-dimer and fibrin/fibrinogen-degradation products, whereas abnormalities in prothrombin time, partial thromboplastin time, and platelet counts are relatively uncommon in initial presentations.,Coagulation test screening, including the measurement of D-dimer and fibrinogen levels, is suggested.,COVID-19-associated coagulopathy should be managed as it would be for any critically ill patient, following the established practice of using thromboembolic prophylaxis for critically ill hospitalized patients, and standard supportive care measures for those with sepsis-induced coagulopathy or DIC.,Although D-dimer, sepsis physiology, and consumptive coagulopathy are indicators of mortality, current data do not suggest the use of full-intensity anticoagulation doses unless otherwise clinically indicated.,Even though there is an associated coagulopathy with COVID-19, bleeding manifestations, even in those with DIC, have not been reported.,If bleeding does occur, standard guidelines for the management of DIC and bleeding should be followed.

We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals.,In answering questions raised regarding our study, we updated our database and repeated all analyses.,We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first.,We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%).,The median follow-up duration increased from 7 to 14 days.,All patients received pharmacological thromboprophylaxis.,The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41-57%).,The majority of thrombotic events were PE (65/75; 87%).,In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091-0.92).,Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4-12).,Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35-1.8).,In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia.

Coronavirus disease 2019 (COVID-19) is a rapidly expanding global pandemic caused by severe acute respiratory syndrome coronavirus 2, resulting in significant morbidity and mortality.,A substantial minority of patients hospitalized develop an acute COVID-19 cardiovascular syndrome, which can manifest with a variety of clinical presentations but often presents as an acute cardiac injury with cardiomyopathy, ventricular arrhythmias, and hemodynamic instability in the absence of obstructive coronary artery disease.,The cause of this injury is uncertain but is suspected to be related to myocarditis, microvascular injury, systemic cytokine-mediated injury, or stress-related cardiomyopathy.,Although histologically unproven, severe acute respiratory syndrome coronavirus 2 has the potential to directly replicate within cardiomyocytes and pericytes, leading to viral myocarditis.,Systemically elevated cytokines are also known to be cardiotoxic and have the potential to result in profound myocardial injury.,Prior experience with severe acute respiratory syndrome coronavirus 1 has helped expedite the evaluation of several promising therapies, including antiviral agents, interleukin-6 inhibitors, and convalescent serum.,Management of acute COVID-19 cardiovascular syndrome should involve a multidisciplinary team including intensive care specialists, infectious disease specialists, and cardiologists.,Priorities for managing acute COVID-19 cardiovascular syndrome include balancing the goals of minimizing healthcare staff exposure for testing that will not change clinical management with early recognition of the syndrome at a time point at which intervention may be most effective.,This article aims to review the best available data on acute COVID-19 cardiovascular syndrome epidemiology, pathogenesis, diagnosis, and treatment.,From these data, we propose a surveillance, diagnostic, and management strategy that balances potential patient risks and healthcare staff exposure with improvement in meaningful clinical outcomes.

Severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019 (COVID-19)-induced infection can be associated with a coagulopathy, findings consistent with infection-induced inflammatory changes as observed in patients with disseminated intravascular coagulopathy (DIC).,The lack of prior immunity to COVID-19 has resulted in large numbers of infected patients across the globe and uncertainty regarding management of the complications that arise in the course of this viral illness.,The lungs are the target organ for COVID-19; patients develop acute lung injury that can progress to respiratory failure, although multiorgan failure can also occur.,The initial coagulopathy of COVID-19 presents with prominent elevation of D-dimer and fibrin/fibrinogen-degradation products, whereas abnormalities in prothrombin time, partial thromboplastin time, and platelet counts are relatively uncommon in initial presentations.,Coagulation test screening, including the measurement of D-dimer and fibrinogen levels, is suggested.,COVID-19-associated coagulopathy should be managed as it would be for any critically ill patient, following the established practice of using thromboembolic prophylaxis for critically ill hospitalized patients, and standard supportive care measures for those with sepsis-induced coagulopathy or DIC.,Although D-dimer, sepsis physiology, and consumptive coagulopathy are indicators of mortality, current data do not suggest the use of full-intensity anticoagulation doses unless otherwise clinically indicated.,Even though there is an associated coagulopathy with COVID-19, bleeding manifestations, even in those with DIC, have not been reported.,If bleeding does occur, standard guidelines for the management of DIC and bleeding should be followed.

Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been associated with cardiovascular features of myocardial involvement including elevated serum troponin levels and acute heart failure with reduced ejection fraction.,The cardiac pathological changes in these patients with COVID-19 have yet to be well described.,In an international multicentre study, cardiac tissue from the autopsies of 21 consecutive COVID-19 patients was assessed by cardiovascular pathologists.,The presence of myocarditis, as defined by the presence of multiple foci of inflammation with associated myocyte injury, was determined, and the inflammatory cell composition analysed by immunohistochemistry.,Other forms of acute myocyte injury and inflammation were also described, as well as coronary artery, endocardium, and pericardium involvement.,Lymphocytic myocarditis was present in 3 (14%) of the cases.,In two of these cases, the T lymphocytes were CD4 predominant and in one case the T lymphocytes were CD8 predominant.,Increased interstitial macrophage infiltration was present in 18 (86%) of the cases.,A mild pericarditis was present in four cases.,Acute myocyte injury in the right ventricle, most probably due to strain/overload, was present in four cases.,There was a non-significant trend toward higher serum troponin levels in the patients with myocarditis compared with those without myocarditis.,Disrupted coronary artery plaques, coronary artery aneurysms, and large pulmonary emboli were not identified.,In SARS-CoV-2 there are increased interstitial macrophages in a majority of the cases and multifocal lymphocytic myocarditis in a small fraction of the cases.,Other forms of myocardial injury are also present in these patients.,The macrophage infiltration may reflect underlying diseases rather than COVID-19.

To compare demographic characteristics, clinical presentation, and outcomes of patients with and without concomitant cardiac disease, hospitalized for COVID-19 in Brescia, Lombardy, Italy.,The study population includes 99 consecutive patients with COVID-19 pneumonia admitted to our hospital between 4 March and 25 March 2020.,Fifty-three patients with a history of cardiac disease were compared with 46 without cardiac disease.,Among cardiac patients, 40% had a history of heart failure, 36% had atrial fibrillation, and 30% had coronary artery disease.,Mean age was 67 ± 12 years, and 80 (81%) patients were males.,No differences were found between cardiac and non-cardiac patients except for higher values of serum creatinine, N-terminal probrain natriuretic peptide, and high sensitivity troponin T in cardiac patients.,During hospitalization, 26% patients died, 15% developed thrombo-embolic events, 19% had acute respiratory distress syndrome, and 6% had septic shock.,Mortality was higher in patients with cardiac disease compared with the others (36% vs. 15%, log-rank P = 0.019; relative risk 2.35; 95% confidence interval 1.08-5.09).,The rate of thrombo-embolic events and septic shock during the hospitalization was also higher in cardiac patients (23% vs. 6% and 11% vs. 0%, respectively).,Hospitalized patients with concomitant cardiac disease and COVID-19 have an extremely poor prognosis compared with subjects without a history of cardiac disease, with higher mortality, thrombo-embolic events, and septic shock rates.

The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades.,We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies.,While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system.,Risk of severe infection and mortality increase with advancing age and male sex.,Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer.,The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC).,Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes.,This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI).,While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis.,Hence, patients should not discontinue their use.,Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19.,Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19.,Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications.,Preventive measures (social distancing and social isolation) also increase cardiovascular risk.,Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.

Coronavirus Disease 2019 (COVID-19) has quickly progressed to a global health emergency.,Respiratory illness is the major cause of morbidity and mortality in these patients with the disease spectrum ranging from asymptomatic subclinical infection, to severe pneumonia progressing to acute respiratory distress syndrome.,There is growing evidence describing pathophysiological resemblance of SARS-CoV-2 infection with other coronavirus infections such as Severe Acute Respiratory Syndrome coronavirus and Middle East Respiratory Syndrome coronavirus (MERS-CoV).,Angiotensin Converting Enzyme-2 receptors play a pivotal role in the pathogenesis of the virus.,Disruption of this receptor leads to cardiomyopathy, cardiac dysfunction, and heart failure.,Patients with cardiovascular disease are more likely to be infected with SARS-CoV-2 and they are more likely to develop severe symptoms.,Hypertension, arrhythmia, cardiomyopathy and coronary heart disease are amongst major cardiovascular disease comorbidities seen in severe cases of COVID-19.,There is growing literature exploring cardiac involvement in SARS-CoV-2.,Myocardial injury is one of the important pathogenic features of COVID-19.,As a surrogate for myocardial injury, multiple studies have shown increased cardiac biomarkers mainly cardiac troponins I and T in the infected patients especially those with severe disease.,Myocarditis is depicted as another cause of morbidity amongst COVID-19 patients.,The exact mechanisms of how SARS-CoV-2 can cause myocardial injury are not clearly understood.,The proposed mechanisms of myocardial injury are direct damage to the cardiomyocytes, systemic inflammation, myocardial interstitial fibrosis, interferon mediated immune response, exaggerated cytokine response by Type 1 and 2 helper T cells, in addition to coronary plaque destabilization, and hypoxia.,Unlabelled Image

To assess the prognostic utility of quantitative 2D‐echocardiography, including strain, in patients with COVID‐19 disease.,COVID‐19‐infected patients admitted to the San Paolo University Hospital of Milan that underwent a clinically indicated echocardiographic examination were included in the study.,To limit contamination, all measurements were performed offline.,Quantitative measurements were obtained by an operator blinded to the clinical data.,Among the 49 patients, nonsurvivors (33%) had worse respiratory parameters, index of multiorgan failure, and worse markers of lung involvement.,Right ventricular (RV) dysfunction (as assessed by conventional and 2‐dimensional speckle tracking) was a common finding and a powerful independent predictor of mortality.,At the ROC curve analyses, RV free wall longitudinal strain (LS) showed an AUC 0.77 ± 0.08 in predicting death, P = .008, and global RV LS (RV‐GLS) showed an AUC 0.79 ± 0.04, P = .004.,This association remained significant after correction for age (OR = 1.16, 95%CI 1.01-1.34, P = .029 for RV free wall LS and OR = 1.20, 95%CI 1.01-1.42, P = .033 for RV‐GLS), for oxygen partial pressure at arterial gas analysis/fraction of inspired oxygen (OR = 1.28, 95%CI 1.04-1.57, P = .021 for RV free wall‐LS and OR = 1.30, 95%CI 1.04-1.62, P = .020 for RV‐GLS) and for the severity of pulmonary involvement measured by a computed tomography lung score (OR = 1.27, 95%CI 1.02-1.19, P = .034 for RV free wall LS and OR = 1.30, 95%CI 1.04-1.63, P = .022 for RV‐GLS).,In patients hospitalized with COVID‐19, offline quantitative 2D‐echocardiographic assessment of cardiac function is feasible.,Parameters of RV function are frequently abnormal and have an independent prognostic value over markers of lung involvement.

Cardiovascular complications related to coronavirus disease 2019 (COVID‐19) have led to the need for echocardiographic services during the pandemic.,The present study aimed to identify the echocardiographic findings in hospitalized COVID‐19 patients and their utility in disease management.,We included patients who were diagnosed with COVID‐19 using polymerase chain reaction and those who underwent echocardiographic examination during their hospitalization.,Altogether, 45 patients were evaluated.,The mean age was 61.4 ± 12.2 years.,Hypertension (n = 29, 64%) and diabetes mellitus (n = 25, 55%) were the most common comorbidities followed by congestive heart failure (n = 11, 24%), coronary artery disease (n = 9, 20%), and valvular heart disease (n = 3, 7%).,Eight patients (18%) showed evidence of myocardial injury, as suggested by elevated troponin levels.,Brain natriuretic peptide was elevated in 14 patients (36%), and 14 patients had left ventricular dysfunction in the form of reduced ejection fraction (31%).,Right ventricular (RV) dilatation was observed in six patients, and five patients had reduced RV ejection fraction.,RV pressure and volume overload were observed in three patients.,RV thrombus was observed in one patient.,Pulmonary pressure was elevated in 10 patients (24%).,Two‐dimensional echocardiography can be an important bedside tool for the assessment of cardiovascular abnormalities and hemodynamic status of COVID‐19 patients.

Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Coronavirus disease 2019 (COVID-19) has been demonstrated to be the cause of pneumonia.,Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis.,A 63-year-old male was admitted with pneumonia and cardiac symptoms.,He was genetically confirmed as having COVID-19 according to sputum testing on the day of admission.,He also had elevated troponin I (Trop I) level (up to 11.37 g/L) and diffuse myocardial dyskinesia along with a decreased left ventricular ejection fraction (LVEF) on echocardiography.,The highest level of interleukin-6 was 272.40 pg/ml.,Bedside chest radiographs showed typical ground-glass changes indicative of viral pneumonia.,Laboratory test results for viruses that cause myocarditis were all negative.,The patient conformed to the diagnostic criteria of the Chinese expert consensus statement for fulminant myocarditis.,After receiving antiviral therapy and mechanical life support, Trop I was reduced to 0.10 g/L, and interleukin-6 was reduced to 7.63 pg/mL.,Moreover, the LVEF of the patient gradually recovered to 68%.,The patient died of aggravation of secondary infection on the 33rd day of hospitalization.,COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure.,This is the first report of COVID-19 complicated with fulminant myocarditis.,The mechanism of cardiac pathology caused by COVID-19 needs further study.

Left ventricular (LV) hypertrophy, a key process in human cardiac disease, results from cellular (hypertrophy) and extracellular matrix expansion (interstitial fibrosis).,This study sought to investigate whether human myocardial interstitial fibrosis in aortic stenosis (AS) is plastic and can regress.,Patients with symptomatic, severe AS (n = 181; aortic valve area index 0.4 ± 0.1 cm2/m2) were assessed pre-aortic valve replacement (AVR) by echocardiography (AS severity, diastology), cardiovascular magnetic resonance (CMR) (for volumes, function, and focal or diffuse fibrosis), biomarkers (N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T), and the 6-min walk test.,CMR was used to measure the extracellular volume fraction (ECV), thereby deriving matrix volume (LV mass × ECV) and cell volume (LV mass × [1 − ECV]).,Biopsy excluded occult bystander disease.,Assessment was repeated at 1 year post-AVR.,At 1 year post-AVR in 116 pacemaker-free survivors (age 70 ± 10 years; 54% male), mean valve gradient had improved (48 ± 16 mm Hg to 12 ± 6 mm Hg; p < 0.001), and indexed LV mass had regressed by 19% (88 ± 26 g/m2 to 71 ± 19 g/m2; p < 0.001).,Focal fibrosis by CMR late gadolinium enhancement did not change, but ECV increased (28.2 ± 2.9% to 29.9 ± 4.0%; p < 0.001): this was the result of a 16% reduction in matrix volume (25 ± 9 ml/m2 to 21 ± 7 ml/m2; p < 0.001) but a proportionally greater 22% reduction in cell volume (64 ± 18 ml/m2 to 50 ± 13 ml/m2; p < 0.001).,These changes were accompanied by improvement in diastolic function, N-terminal pro-B-type natriuretic peptide, 6-min walk test results, and New York Heart Association functional class.,Post-AVR, focal fibrosis does not resolve, but diffuse fibrosis and myocardial cellular hypertrophy regress.,Regression is accompanied by structural and functional improvements suggesting that human diffuse fibrosis is plastic, measurable by CMR and a potential therapeutic target.,(Regression of Myocardial Fibrosis After Aortic Valve Replacement; NCT02174471)

Patients with type 2 diabetes mellitus and elevated urinary albumin:creatinine ratio (ACR) have increased risk of heart failure.,We hypothesized this was because of cardiac tissue changes rather than silent coronary artery disease.,In a case‐controlled observational study 130 subjects including 50 ACR+ve diabetes mellitus patients with persistent microalbuminuria (ACR >2.5 mg/mol in males and >3.5 mg/mol in females, ≥2 measurements, no previous renin-angiotensin-aldosterone therapy, 50 ACR−ve diabetes mellitus patients and 30 controls underwent cardiovascular magnetic resonance for investigation of myocardial fibrosis, ischemia and infarction, and echocardiography.,Thirty ACR+ve patients underwent further testing after 1‐year treatment with renin-angiotensin-aldosterone blockade.,Cardiac extracellular volume fraction, a measure of diffuse fibrosis, was higher in diabetes mellitus patients than controls (26.1±3.4% and 23.3±3.0% P=0.0002) and in ACR+ve than ACR−ve diabetes mellitus patients (27.2±4.1% versus 25.1±2.9%, P=0.004).,ACR+ve patients also had lower E′ measured by echocardiography (8.2±1.9 cm/s versus 8.9±1.9 cm/s, P=0.04) and elevated high‐sensitivity cardiac troponin T 18% versus 4% ≥14 ng/L (P=0.05).,Rate of silent myocardial ischemia or infarction were not influenced by ACR status.,Renin-angiotensin-aldosterone blockade was associated with increased left ventricular ejection fraction (59.3±7.8 to 61.5±8.7%, P=0.03) and decreased extracellular volume fraction (26.5±3.6 to 25.2±3.1, P=0.01) but no changes in diastolic function or high‐sensitivity cardiac troponin T levels.,Asymptomatic diabetes mellitus patients with persistent microalbuminuria have markers of diffuse cardiac fibrosis including elevated extracellular volume fraction, high‐sensitivity cardiac troponin T, and diastolic dysfunction, which may in part be reversible by renin-angiotensin-aldosterone blockade.,Increased risk in these patients may be mediated by subclinical changes in tissue structure and function.,URL: http://www.clinicaltrials.gov.,Unique identifier: NCT01970319.

Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers.,We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM).,This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM.,Lymphodepletion was performed using cyclophosphamide 300 mg/m2.,LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 106 cells/kg [range, 0.07 to 2.1 × 106]) were infused in 3 separate infusions.,The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group.,At data cutoff, 57 patients had received LCAR-B38M CAR T cells.,All patients experienced ≥ 1 adverse events (AEs).,Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%).,Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases.,One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity.,The overall response rate was 88% (95% confidence interval [CI], 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response.,Minimal residual disease was negative for 36/57 (63%) patients.,The median time to response was 1 month (range, 0.4 to 3.5).,At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable).,Median overall survival for all patients was not reached.,LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM.,ClinicalTrials.gov, NCT03090659; Registered on March 27, 2017, retrospectively registered,The online version of this article (10.1186/s13045-018-0681-6) contains supplementary material, which is available to authorized users.

Despite major improvements in the treatment landscape, most multiple myeloma (MM) patients eventually succumb to the underlying malignancy.,Immunotherapy represents an attractive strategy to achieve durable remissions due to its specificity and capacity for long term memory.,Activation of immune cells is controlled by a balance of agonistic and inhibitory signals via surface and intracellular receptors.,Blockade of such inhibitory immune receptors (termed as “immune checkpoints”) including PD-1/PD-L1 has led to impressive tumor regressions in several cancers.,Preclinical studies suggest that these immune checkpoints may also play a role in regulating tumor immunity in MM.,Indeed, myeloma was among the first tumors wherein therapeutic efficacy of blockade of PD-1 axis was demonstrated in preclinical models.,Expression of PD-L1 on tumor and immune cells also correlates with the risk of malignant transformation.,However, early clinical studies of single agent PD-1 blockade have not led to meaningful tumor regressions.,Immune modulatory drugs (IMiDs) are now the mainstay of most MM therapies.,Interestingly, the mechanism of immune activation by IMiDs also involves release of inhibitory checkpoints, such as Ikaros-mediated suppression of IL-2.,Combination of PD-1 targeted agents with IMiDs led to promising clinical activity, including objective responses in some patients refractory to IMiD therapy.,However, some of these studies were transiently halted in 2017 due to concern for a possible safety signal with IMiD-PD1 combination.,The capacity of the immune system to control MM has been further reinforced by recent success of adoptive cell therapies, such as T cells redirected by chimeric-antigen receptors (CAR-Ts).,There remains an unmet need to better understand the immunologic effects of checkpoint blockade, delineate mechanisms of resistance to these therapies and identify optimal combination of agonistic signaling, checkpoint inhibitors as well as other therapies including CAR-Ts, to realize the potential of the immune system to control and prevent MM.

Endoglin (ENG) forms a receptor complex with ALK1 in endothelial cells (ECs) to promote BMP9/10 signalling.,Loss of function mutations in either ENG or ALK1 genes lead to the inherited vascular disorder hereditary haemorrhagic telangiectasia (HHT), characterised by arteriovenous malformations (AVMs).,However, the vessel-specific role of ENG and ALK1 proteins in protecting against AVMs is unclear.,For example, AVMs have been described to initiate in arterioles, whereas ENG is predominantly expressed in venous ECs.,To investigate whether ENG has any arterial involvement in protecting against AVM formation, we specifically depleted the Eng gene in venous and capillary endothelium whilst maintaining arterial expression, and investigated how this affected the incidence and location of AVMs in comparison with pan-endothelial Eng knockdown.,Using the mouse neonatal retinal model of angiogenesis, we first established the earliest time point at which Apj-Cre-ERT2 activity was present in venous and capillary ECs but absent from arterial ECs.,We then compared the incidence of AVMs following pan-endothelial or venous/capillary-specific ENG knockout.,Activation of Apj-Cre-ERT2 with tamoxifen from postnatal day (P) 5 ensured preservation of arterial ENG protein expression.,Specific loss of ENG expression in ECs of veins and capillaries led to retinal AVMs at a similar frequency to pan-endothelial loss of ENG.,AVMs occurred in the proximal as well as the distal part of the retina consistent with a defect in vascular remodelling during maturation of the vasculature.,Expression of ENG is not required in arterial ECs to protect against AVM formation.,The online version of this article (10.1007/s10456-020-09731-z) contains supplementary material, which is available to authorized users.

Cardiac disease is associated with deleterious emission of mitochondrial reactive oxygen species (mito-ROS), as well as enhanced oxidation and activity of the sarcoplasmic reticulum (SR) Ca2+ release channel, the ryanodine receptor (RyR2).,The transfer of Ca2+ from the SR via RyR2 to mitochondria is thought to play a key role in matching increased metabolic demand during stress.,In this study, we investigated whether augmented RyR2 activity results in self-imposed exacerbation of SR Ca2+ leak, via altered SR-mitochondrial Ca2+ transfer and elevated mito-ROS emission.,Fluorescent indicators and spatially restricted genetic ROS probes revealed that both pharmacologically and genetically enhanced RyR2 activity, in ventricular myocytes from rats and catecholaminergic polymorphic ventricular tachycardia (CPVT) mice, respectively, resulted in increased ROS emission under β-adrenergic stimulation.,Expression of mitochondrial Ca2+ probe mtRCamp1h revealed diminished net mitochondrial [Ca2+] with enhanced SR Ca2+ leak, accompanied by depolarization of the mitochondrial matrix.,While this may serve as a protective mechanism to prevent mitochondrial Ca2+ overload, protection is not complete and enhanced mito-ROS emission resulted in oxidation of RyR2, further amplifying proarrhythmic SR Ca2+ release.,Importantly, the effects of augmented RyR2 activity could be attenuated by mitochondrial ROS scavenging, and experiments with dominant-negative paralogs of the mitochondrial Ca2+ uniporter (MCU) supported the hypothesis that SR-mitochondria Ca2+ transfer is essential for the increase in mito-ROS.,We conclude that in a process whereby leak begets leak, augmented RyR2 activity modulates mitochondrial Ca2+ handling, promoting mito-ROS emission and driving further channel activity in a proarrhythmic feedback cycle in the diseased heart.

Critically ill COVID-19 patients have a clear pattern of inflammation and hypercoagulable state.,The main aim of the study was to evaluate the outcome of severe COVID-19 patients basing on prothrombotic risk factors (i.e.,D-dimer).,We also evaluated the impact of different doses of low molecular weight heparin (LMWH) on the incidence of bleedings.,The data of forty-two patients admitted to the Intensive Care Unit (ICU) were retrospectively analyzed.,On ICU admission, patients with D-dimer < 3000 ng/mL (Group 1) received enoxaparin 4000 UI (6000 UI, if body mass index >35) subcutaneously b.i.d. and patients with D-dimer ≥ 3000 ng/mL (Group 2) received enoxaparin 100 UI/kg every 12 h.,Aspirin was administered to all patients once a day.,Both groups presented a high incidence of perivascular thrombosis (40.9% in Group 1 and 30% in Group 2).,Patients of Group 2 suffered a higher incidence of venous thromboembolism (VTE) than Group 1 (65% vs 13.6%, p = 0.001).,One patient (4.5%) of Group 1 and three patients (15%) of Group 2 suffered from minor bleeding; no patient had major bleeding.,Group 2 had a longer ICU and hospital stay than Group 1 (11.5 ± 5.6 vs 9.0 ± 4.8 and 30 ± 4.9 vs 21 ± 2.3, p < 0.05, respectively) as well as increased ICU mortality (25% vs 9.1%).,More severe critically ill COVID-19 patients have a high incidence of VTE and worse outcome, despite the use of heparin at the therapeutic dose.,However, the use of heparin did not increase the incidence of bleeding complications.,•Risk stratification based on D-dimer values is fundamental in critically ill patients with COVID-19 pneumonia.,•High-risk patients have a higher incidence of thromboembolic events and worse outcome compared with low risk ones.,•The use of heparin in therapeutic doses did not lead to an increase of bleeding risk.,Risk stratification based on D-dimer values is fundamental in critically ill patients with COVID-19 pneumonia.,High-risk patients have a higher incidence of thromboembolic events and worse outcome compared with low risk ones.,The use of heparin in therapeutic doses did not lead to an increase of bleeding risk.

Critically ill patients with COVID-19 pneumonia suffered both high thrombotic and bleeding risk.,The effect of SARS-CoV-2 on coagulation and fibrinolysis is not well known.,We conducted a retrospective study of critically ill patients admitted to an intensive care unit (ICU) a cause of severe COVID-19 pneumonia and we evaluated coagulation function using rotational thromboelastometry (ROTEM) on day of admission (T0) and 5 (T5) and 10 (T10) days after admission to ICU.,Coagulation standard parameters were also evaluated.,Forty patients were enrolled into the study.,The ICU and the hospital mortality were 10% and 12.5%, respectively.,On ICU admission, prothrombin time was slightly reduced and it increased significantly at T10 (T0 = 65.1 ± 9.8 vs T10 = 85.7 ± 1.5, p = 0.002), while activated partial thromboplastin time and fibrinogen values were higher at T0 than T10 (32.2 ± 2.9 vs 27.2 ± 2.1, p = 0.017 and 895.1 ± 110 vs 332.5 ± 50, p = 0.002, respectively); moreover, whole blood thromboelastometry profiles were consistent with hypercoagulability characterized by an acceleration of the propagation phase of blood clot formation [i.e., CFT below the lower limit in INTEM 16/40 patients (40%) and EXTEM 20/40 patients (50%)] and significant higher clot strength [MCF above the upper limit in INTEM 20/40 patients (50%), in EXTEM 28/40 patients (70%) and in FIBTEM 29/40 patients (72.5%)]; however, this hypercoagulable state persists in the first five days, but it decreases ten day after, without returning to normal values.,No sign of secondary hyperfibrinolysis or sepsis induced coagulopathy (SIC) were found during the study period.,In six patients (15%) a deep vein thrombosis and in 2 patients (5%) a thromboembolic event, were found; 12 patients (30%) had a catheter-related thrombosis.,ROTEM analysis confirms that patients with severe COVID-19 pneumonia had a hypercoagulation state that persisted over time.

Risk factors for pulmonary embolism in patients with coronavirus disease 2019 include obesity, an elevated d-dimer value, elevated C-reactive protein level, and a rising d-dimer value over time.

To evaluate the prevalence of acute pulmonary embolism (APE) in non-hospitalized COVID-19 patients referred to CT pulmonary angiography (CTPA) by the emergency department.,From March 14 to April 6, 2020, 72 non-hospitalized patients referred by the emergency department to CTPA for COVID-19 pneumonia were retrospectively identified.,Relevant clinical and laboratory data and CT scan findings were collected for each patient.,CTPA scans were reviewed by two radiologists to determinate the presence or absence of APE.,Clinical classification, lung involvement of COVID-19 pneumonia, and CT total severity score were compared between APE group and non-APE group.,APE was identified in 13 (18%) CTPA scans.,The mean age and D-dimer of patients from the APE group were higher in comparison with those from the non-APE group (74.4 vs.,59.6 years, p = 0.008, and 7.29 vs.,3.29 μg/ml, p = 0.011).,There was no significant difference between APE and non-APE groups concerning clinical type, COVID-19 pneumonia lung lesions (ground-glass opacity: 85% vs. 97%; consolidation: 69% vs. 68%; crazy paving: 38% vs. 37%; linear reticulation: 69% vs.,78%), CT severity score (6.3 vs.,7.1, p = 0.365), quality of CTPA (1.8 vs.,2.0, p = 0.518), and pleural effusion (38% vs. 19%, p = 0.146).,Non-hospitalized patients with COVID-19 pneumonia referred to CT scan by the emergency departments are at risk of APE.,The presence of APE was not limited to severe or critical clinical type of COVID-19 pneumonia.,• Acute pulmonary embolism was found in 18% of non-hospitalized COVID-19 patients referred by the emergency department to CTPA.,Two (15%) patients had main, four (30%) lobar, and seven (55%) segmental acute pulmonary embolism.,• Five of 13 (38%) patients with acute pulmonary embolism had a moderate clinical type.,• Severity and radiological features of COVID-19 pneumonia showed no significant difference between patients with or without acute pulmonary embolism.

Hyperacute assessment and management of patients with stroke, termed code stroke, is a time-sensitive and high-stakes clinical scenario.,In the context of the current coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 virus, the ability to deliver timely and efficacious care must be balanced with the risk of infectious exposure to the clinical team.,Furthermore, rapid and effective stroke care remains paramount to achieve maximal functional recovery for those needing admission and to triage care appropriately for those who may be presenting with neurological symptoms but have an alternative diagnosis.,Available resources, COVID-19-specific infection prevention and control recommendations, and expert consensus were used to identify clinical screening criteria for patients and provide the required nuanced considerations for the healthcare team, thereby modifying the conventional code stroke processes to achieve a protected designation.,A protected code stroke algorithm was developed.,Features specific to prenotification and clinical status of the patient were used to define precode screening.,These include primary infectious symptoms, clinical, and examination features.,A focused framework was then developed with regard to a protected code stroke.,We outline the specifics of personal protective equipment use and considerations thereof including aspects of crisis resource management impacting team role designation and human performance factors during a protected code stroke.,We introduce the concept of a protected code stroke during a pandemic, as in the case of COVID-19, and provide a framework for key considerations including screening, personal protective equipment, and crisis resource management.,These considerations and suggested algorithms can be utilized and adapted for local practice.

This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury.

Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has rapidly evolved into a sweeping pandemic.,Its major manifestation is in the respiratory tract, and the general extent of organ involvement and the microscopic changes in the lungs remain insufficiently characterised.,Autopsies are essential to elucidate COVID‐19‐associated organ alterations.,This article reports the autopsy findings of 21 COVID‐19 patients hospitalised at the University Hospital Basel and at the Cantonal Hospital Baselland, Switzerland.,An in‐corpore technique was performed to ensure optimal staff safety.,The primary cause of death was respiratory failure with exudative diffuse alveolar damage and massive capillary congestion, often accompanied by microthrombi despite anticoagulation.,Ten cases showed superimposed bronchopneumonia.,Further findings included pulmonary embolism (n = 4), alveolar haemorrhage (n = 3), and vasculitis (n = 1).,Pathologies in other organ systems were predominantly attributable to shock; three patients showed signs of generalised and five of pulmonary thrombotic microangiopathy.,Six patients were diagnosed with senile cardiac amyloidosis upon autopsy.,Most patients suffered from one or more comorbidities (hypertension, obesity, cardiovascular diseases, and diabetes mellitus).,Additionally, there was an overall predominance of males and individuals with blood group A (81% and 65%, respectively).,All relevant histological slides are linked as open‐source scans in supplementary files.,This study provides an overview of postmortem findings in COVID‐19 cases, implying that hypertensive, elderly, obese, male individuals with severe cardiovascular comorbidities as well as those with blood group A may have a lower threshold of tolerance for COVID‐19.,This provides a pathophysiological explanation for higher mortality rates among these patients.

Three months ago, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) broke out in Wuhan, China, and spread rapidly around the world.,Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned.,To determine the incidence of VTE in patients with severe NCP.,In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled.,The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed.,The incidence of VTE in these patients was 25% (20/81), of which 8 patients with VTE events died.,The VTE group was different from the non‐VTE group in age, lymphocyte counts, activated partial thromboplastin time (APTT), D‐dimer, etc.,If 1.5 µg/mL was used as the D‐dimer cut‐off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value (NPV) was 94.7%.,The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis.,The significant increase of D‐dimer in severe NCP patients is a good index for identifying high‐risk groups of VTE.

We tested the hypothesis that dapagliflozin may regress left ventricular hypertrophy (LVH) in people with type 2 diabetes (T2D).,We randomly assigned 66 people (mean age 67 ± 7 years, 38 males) with T2D, LVH, and controlled blood pressure (BP) to receive dapagliflozin 10 mg once daily or placebo for 12 months.,Primary endpoint was change in absolute left ventricular mass (LVM), assessed by cardiac magnetic resonance imaging.,In the intention-to-treat analysis, dapagliflozin significantly reduced LVM compared with placebo with an absolute mean change of −2.82g [95% confidence interval (CI): −5.13 to −0.51, P = 0.018].,Additional sensitivity analysis adjusting for baseline LVM, baseline BP, weight, and systolic BP change showed the LVM change to remain statistically significant (mean change −2.92g; 95% CI: −5.45 to −0.38, P = 0.025).,Dapagliflozin significantly reduced pre-specified secondary endpoints including ambulatory 24-h systolic BP (P = 0.012), nocturnal systolic BP (P = 0.017), body weight (P < 0.001), visceral adipose tissue (VAT) (P < 0.001), subcutaneous adipose tissue (SCAT) (P = 0.001), insulin resistance, Homeostatic Model Assessment of Insulin Resistance (P = 0.017), and high-sensitivity C-reactive protein (hsCRP) (P = 0.049).,Dapagliflozin treatment significantly reduced LVM in people with T2D and LVH.,This reduction in LVM was accompanied by reductions in systolic BP, body weight, visceral and SCAT, insulin resistance, and hsCRP.,The regression of LVM suggests dapagliflozin can initiate reverse remodelling and changes in left ventricular structure that may partly contribute to the cardio-protective effects of dapagliflozin.,NCT02956811

Diabetes is associated closely with an increased risk of cardiovascular events, including diastolic dysfunction and heart failure that leads to a shortening of life expectancy.,It is therefore extremely valuable to evaluate the impact of antidiabetic agents on cardiac function.,However, the influence of dipeptidyl peptidase 4 inhibitors on cardiac function is controversial and a major matter of clinical concern.,We therefore evaluated the effect of sitagliptin on echocardiographic parameters of diastolic function in patients with type 2 diabetes as a sub-analysis of the PROLOGUE study.,Patients in the PROLOGUE study were assigned randomly to either add-on sitagliptin treatment or conventional antidiabetic treatment.,Of the 463 patients in the overall study, 115 patients (55 in the sitagliptin group and 60 in the conventional group) who had complete echocardiographic data of the ratio of peak early diastolic transmitral flow velocity (E) to peak early diastolic mitral annular velocity (e′) at baseline and after 12 and 24 months were included in this study.,The primary endpoint of this post hoc sub-analysis was a comparison of the changes in the ratio of E to e′ (E/e′) between the two groups from baseline to 24 months.,The baseline-adjusted change in E/e′ during 24 months was significantly lower in the sitagliptin group than in the conventional group (−0.18 ± 0.55 vs.,1.91 ± 0.53, p = 0.008), irrespective of a higher E/e′ value at baseline in the sitagliptin group.,In analysis of covariance, sitagliptin treatment was significantly associated with change in E/e′ over 24 months (β = −9.959, p = 0.001), independent of other clinical variables at baseline such as blood pressure, HbA1c, and medications for diabetes.,Changes in other clinical variables including blood pressure and glycemic parameters, and echocardiographic parameters, such as cardiac structure and systolic function, were comparable between the two groups.,There was also no significant difference in the serum levels of N-terminal-pro brain natriuretic peptide and high-sensitive C-reactive protein between the two groups during the study period.,Adding sitagliptin to conventional antidiabetic regimens in patients with T2DM for 24 months attenuated the annual exacerbation in the echocardiographic parameter of diastolic dysfunction (E/e′) independent of other clinical variables such as blood pressure and glycemic control.,Trial registration UMIN000004490 (University Hospital Medical Information Network Clinical Trials). https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?,recptno=R000005356; registered November 1, 2010,The online version of this article (doi:10.1186/s12933-017-0546-2) contains supplementary material, which is available to authorized users.

Supplemental Digital Content is available in the text.,After initially hypothesizing a positive relationship between use of renin-angiotensin-aldosterone system inhibitors and risk of coronavirus disease 2019 (COVID-19), more recent evidence suggests negative associations.,We examined whether COVID-19 risk differs according to antihypertensive drug class in patients treated by ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers (ARBs) compared with calcium channel blockers (CCBs).,Three exclusive cohorts of prevalent ACE inhibitors, ARB and CCB users, aged 18 to 80 years, from the French National Health Insurance databases were followed from February 15, 2020 to June 7, 2020.,We excluded patients with a history of diabetes, known cardiovascular disease, chronic renal failure, or chronic respiratory disease during the previous 5 years, to only consider patients treated for uncomplicated hypertension and to limit indication bias.,The primary end point was time to hospitalization for COVID-19.,The secondary end point was time to intubation/death during a hospital stay for COVID-19.,In a population of almost 2 million hypertensive patients (ACE inhibitors: 566 023; ARB: 958 227; CCB: 358 306) followed for 16 weeks, 2338 were hospitalized and 526 died or were intubated for COVID-19.,ACE inhibitors and ARBs were associated with a lower risk of COVID-19 hospitalization compared with CCBs (hazard ratio, 0.74 [95% CI, 0.65-0.83] and 0.84 [0.76-0.93], respectively) and a lower risk of intubation/death.,Risks were slightly lower for ACE inhibitor users than for ARB users.,This large observational study may suggest a lower COVID-19 risk in hypertensive patients treated over a long period with ACE inhibitors or ARBs compared with CCBs.,These results, if confirmed, tend to contradict previous hypotheses and raise new hypotheses.

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase the risk of coronavirus disease 2019 (COVID-19) infection or affect disease severity.,Prior studies have not examined risks by medication dose.,This retrospective cohort study included people aged ≥18 years enrolled in a US integrated healthcare system for at least 4 months as of 2/29/2020.,Current ACEI and ARB use was identified from pharmacy data, and the estimated daily dose was calculated and standardized across medications.,COVID-19 infections and hospitalizations were identified through 6/14/2020 from laboratory and hospitalization data.,We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for race/ethnicity, obesity, and other covariates.,Among 322,044 individuals, 826 developed COVID-19 infection.,Among people using ACEI/ARBs, 204/56,105 developed COVID-19 (3.6 per 1,000 individuals) compared with 622/265,939 without ACEI/ARB use (2.3 per 1,000), yielding an adjusted OR of 0.91 (95% CI 0.74-1.12).,For use of <1 defined daily dose (DDD) vs. nonuse, the adjusted OR for infection was 0.92 (95% CI 0.66-1.28); for 1 to <2 DDDs, 0.89 (95% CI 0.66-1.19); and for ≥2 DDDs, 0.92 (95% CI 0.72-1.18).,The OR was similar for ACEIs and ARBs and in subgroups by age and sex. 26% of people with COVID-19 infection were hospitalized; the adjusted OR for hospitalization in relation to ACEI/ARB use was 0.98 (95% CI 0.63-1.54), and there was no association with dose.,These findings support current recommendations that individuals on these medications continue their use.

Coronavirus disease 2019 (COVID-19)-related critical illness and acute illness are associated with a risk of venous thromboembolism (VTE).,These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis for patients with COVID-19-related critical illness and acute illness who do not have confirmed or suspected VTE.,ASH formed a multidisciplinary guideline panel and applied strict management strategies to minimize potential bias from conflicts of interest.,The panel included 3 patient representatives.,The McMaster University GRADE Centre supported the guideline-development process, including performing systematic evidence reviews (up to 19 August 2020).,The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients.,The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment.,The panel agreed on 2 recommendations.,The panel issued conditional recommendations in favor of prophylactic-intensity anticoagulation over intermediate-intensity or therapeutic-intensity anticoagulation for patients with COVID-19-related critical illness or acute illness who do not have confirmed or suspected VTE.,These recommendations were based on very low certainty in the evidence, underscoring the need for high-quality, randomized controlled trials comparing different intensities of anticoagulation.,They will be updated using a living recommendation approach as new evidence becomes available.

A compelling body of evidence points to pulmonary thrombosis and thromboembolism as a key feature of COVID-19.,As the pandemic spread across the globe over the past few months, a timely call to arms was issued by a team of clinicians to consider the prospect of long-lasting pulmonary fibrotic damage and plan for structured follow-up.,However, the component of post-thrombotic sequelae has been less widely considered.,Although the long-term outcomes of COVID-19 are not known, should pulmonary vascular sequelae prove to be clinically significant, these have the potential to become a public health problem.,In this Personal View, we propose a proactive follow-up strategy to evaluate residual clot burden, small vessel injury, and potential haemodynamic sequelae.,A nuanced and physiological approach to follow-up imaging that looks beyond the clot, at the state of perfusion of lung tissue, is proposed as a key triage tool, with the potential to inform therapeutic strategies.

Patients with coronavirus disease 2019 (COVID-19) have elevated D-dimer levels.,Early reports describe high venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) rates, but data are limited.,This multicenter retrospective study describes the rate and severity of hemostatic and thrombotic complications of 400 hospital-admitted COVID-19 patients (144 critically ill) primarily receiving standard-dose prophylactic anticoagulation.,Coagulation and inflammatory parameters were compared between patients with and without coagulation-associated complications.,Multivariable logistic models examined the utility of these markers in predicting coagulation-associated complications, critical illness, and death.,The radiographically confirmed VTE rate was 4.8% (95% confidence interval [CI], 2.9-7.3), and the overall thrombotic complication rate was 9.5% (95% CI, 6.8-12.8).,The overall and major bleeding rates were 4.8% (95% CI, 2.9-7.3) and 2.3% (95% CI, 1.0-4.2), respectively.,In the critically ill, radiographically confirmed VTE and major bleeding rates were 7.6% (95% CI, 3.9-13.3) and 5.6% (95% CI, 2.4-10.7), respectively.,Elevated D-dimer at initial presentation was predictive of coagulation-associated complications during hospitalization (D-dimer >2500 ng/mL, adjusted odds ratio [OR] for thrombosis, 6.79 [95% CI, 2.39-19.30]; adjusted OR for bleeding, 3.56 [95% CI, 1.01-12.66]), critical illness, and death.,Additional markers at initial presentation predictive of thrombosis during hospitalization included platelet count >450 × 109/L (adjusted OR, 3.56 [95% CI, 1.27-9.97]), C-reactive protein (CRP) >100 mg/L (adjusted OR, 2.71 [95% CI, 1.26-5.86]), and erythrocyte sedimentation rate (ESR) >40 mm/h (adjusted OR, 2.64 [95% CI, 1.07-6.51]).,ESR, CRP, fibrinogen, ferritin, and procalcitonin were higher in patients with thrombotic complications than in those without.,DIC, clinically relevant thrombocytopenia, and reduced fibrinogen were rare and were associated with significant bleeding manifestations.,Given the observed bleeding rates, randomized trials are needed to determine any potential benefit of intensified anticoagulant prophylaxis in COVID-19 patients.,•In addition to thrombotic complications, bleeding is a significant cause of morbidity in patients with COVID-19.,•D-dimer elevation at admission was predictive of bleeding, thrombosis, critical illness, and death in patients with COVID-19.,In addition to thrombotic complications, bleeding is a significant cause of morbidity in patients with COVID-19.,D-dimer elevation at admission was predictive of bleeding, thrombosis, critical illness, and death in patients with COVID-19.

The Coronavirus Disease 2019 (COVID-19) is now a global pandemic with millions affected and millions more at risk for contracting the infection.,The COVID-19 virus, SARS-CoV-2, affects multiple organ systems, especially the lungs and heart.,Elevation of cardiac biomarkers, particularly high-sensitivity troponin and/or creatine kinase MB, is common in patients with COVID-19 infection.,In our review of clinical analyses, we found that in 26 studies including 11,685 patients, the weighted pooled prevalence of acute myocardial injury was 20% (ranged from 5% to 38% depending on the criteria used).,The plausible mechanisms of myocardial injury include, 1) hyperinflammation and cytokine storm mediated through pathologic T-cells and monocytes leading to myocarditis, 2) respiratory failure and hypoxemia resulting in damage to cardiac myocytes, 3) down regulation of ACE2 expression and subsequent protective signaling pathways in cardiac myocytes, 4) hypercoagulability and development of coronary microvascular thrombosis, 5) diffuse endothelial injury and ‘endotheliitis’ in several organs including the heart, and, 6) inflammation and/or stress causing coronary plaque rupture or supply-demand mismatch leading to myocardial ischemia/infarction.,Cardiac biomarkers can be used to aid in diagnosis as well as risk stratification.,In patients with elevated hs-troponin, clinical context is important and myocarditis as well as stress induced cardiomyopathy should be considered in the differential, along with type I and type II myocardial infarction.,Irrespective of etiology, patients with acute myocardial injury should be prioritized for treatment.,Clinical decisions including interventions should be individualized and carefully tailored after thorough review of risks/benefits.,Given the complex interplay of SARS-CoV-2 with the cardiovascular system, further investigation into potential mechanisms is needed to guide effective therapies.,Randomized trials are urgently needed to investigate treatment modalities to reduce the incidence and mortality associated with COVID-19 related acute myocardial injury.

Acute ischemic stroke may occur in patients with coronavirus disease 2019 (COVID-19), but risk factors, in-hospital events, and outcomes are not well studied in large cohorts.,We identified risk factors, comorbidities, and outcomes in patients with COVID-19 with or without acute ischemic stroke and compared with patients without COVID-19 and acute ischemic stroke.,We analyzed the data from 54 health care facilities using the Cerner deidentified COVID-19 dataset.,The dataset included patients with an emergency department or inpatient encounter with discharge diagnoses codes that could be associated to suspicion of or exposure to COVID-19 or confirmed COVID-19.,A total of 103 (1.3%) patients developed acute ischemic stroke among 8163 patients with COVID-19.,Among all patients with COVID-19, the proportion of patients with hypertension, diabetes, hyperlipidemia, atrial fibrillation, and congestive heart failure was significantly higher among those with acute ischemic stroke.,Acute ischemic stroke was associated with discharge to destination other than home or death (relative risk, 2.1 [95% CI, 1.6-2.4]; P<0.0001) after adjusting for potential confounders.,A total of 199 (1.0%) patients developed acute ischemic stroke among 19 513 patients without COVID-19.,Among all ischemic stroke patients, COVID-19 was associated with discharge to destination other than home or death (relative risk, 1.2 [95% CI, 1.0-1.3]; P=0.03) after adjusting for potential confounders.,Acute ischemic stroke was infrequent in patients with COVID-19 and usually occurs in the presence of other cardiovascular risk factors.,The risk of discharge to destination other than home or death increased 2-fold with occurrence of acute ischemic stroke in patients with COVID-19.

In order to cope with the exponentially increasing number of patients infected with SARS‐CoV‐2, European countries made enormous efforts to reorganize medical assistance and several diseases, including stroke, were particularly impacted.,We report the experience of stroke neurologists from three European countries (Italy, France and Germany) that faced the pandemic at diverse time points and with different approaches, depending on their resources and healthcare system organization.,Pre‐hospital and in‐hospital acute stroke pathways were reorganized to prioritize COVID‐19 management and, in severely affected regions of Italy and France, stroke care was centralized to a limited number of centers, whereas the remaining stroke units were dedicated to patients with COVID‐19.,Access to acute stroke diagnostics and time‐dependent therapies was limited or delayed because of reduced capacities of emergency services due to the burden of patients with COVID‐19.,A marked reduction in the number of patients presenting with transient ischaemic attack and stroke was noted in the emergency departments of all three countries.,Although we only have preliminary data, these conditions may have affected stroke outcome.,These indirect effects of the COVID‐19 pandemic could negate the efforts of stroke neurologists over the last few years to improve outcome and reduce mortality of stroke patients.,Although the SARS‐CoV‐2 infection rate is slowing down in Europe, the effects of ending lockdown in the next months are unpredictable.,It is important for the European and world stroke community to share what has been learned so far to be plan strategies to ensure stroke care in the future and upcoming challenging times.

Coronavirus disease 2019 (COVID‐19) can lead to systemic coagulation activation and thrombotic complications.,To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID‐19.,Single‐center cohort study of 198 hospitalized patients with COVID‐19.,Seventy‐five patients (38%) were admitted to the intensive care unit (ICU).,At time of data collection, 16 (8%) were still hospitalized and 19% had died.,During a median follow‐up of 7 days (IQR, 3‐13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis.,The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10‐22), 33% (95% CI, 23‐43) and 42% (95% CI 30‐54) respectively.,For symptomatic VTE, these were 10% (95% CI, 5.8‐16), 21% (95% CI, 14‐30) and 25% (95% CI 16‐36).,VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02‐5.5).,The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17‐37), 47% (95% CI, 34‐58), and 59% (95% CI, 42‐72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4‐15), 9.2% (95% CI, 2.6‐21), and 9.2% (2.6‐21) at 7, 14, and 21 days).,The observed risk for VTE in COVID‐19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE.,Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival.

SARS-CoV-2 viruses are positive single-stranded RNA viruses, whose infection can be asymptomatic or lead to the coronavirus disease 2019 (Covid-19).,Covid-19 is a respiratory infection with a significant impact on the hematopoietic system and hemostasis leading to several cardiovascular complications.,Hematologic consequences of this new infection allowed medical community to start new treatment approaches concerning infection going from targeted anti-inflammatory drugs to anticoagulation or stem cell therapies.,A better understanding of Covid-19 pathophysiology, in particular hematological disorders, will help to choose appropriate treatment strategies.

A new type of pneumonia caused by a novel coronavirus SARS-CoV-2 outbreaks recently in China and spreads into many other countries.,This disease, named as COVID-19, is similar to patients infected by SARS-CoV and MERS-CoV, and nearly 20% of patients developed severe condition.,Cardiac injury is a prevalent complication of severe patients, exacerbating the disease severity in coronavirus disease 2019 (COVID-19) patients.,Angiotensin-converting enzyme 2 (ACE2), the key host cellular receptor of SARS-CoV-2, has been identified in multiple organs, but its cellular distribution in human heart is not illuminated clearly.,This study performed the first state-of-art single cell atlas of adult human heart, and revealed that pericytes with high expression of ACE2 might act as the target cardiac cell of SARS-CoV-2.,The pericytes injury due to virus infection may result in capillary endothelial cells dysfunction, inducing microvascular dysfunction.,And patients with basic heart failure disease showed increased ACE2 expression at both mRNA and protein levels, meaning that if infected by the virus these patients may have higher risk of heart attack and critically ill condition.,The finding of this study explains the high rate of severe cases among COVID-19 patients with basic cardiovascular disease; and these results also perhaps provide important reference to clinical treatment of cardiac injury among severe patients infected by SARS-CoV-2.

This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury.

The novel coronavirus infection (COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as adult respiratory syndrome, sepsis, coagulopathy, and death in a proportion of patients.,Among other factors and direct viral effects, the increase in the vasoconstrictor angiotensin II, the decrease in the vasodilator angiotensin, and the sepsis-induced release of cytokines can trigger a coagulopathy in COVID-19.,A coagulopathy has been reported in up to 50% of patients with severe COVID-19 manifestations.,An increase in d-dimer is the most significant change in coagulation parameters in severe COVID-19 patients, and progressively increasing values can be used as a prognostic parameter indicating a worse outcome.,Limited data suggest a high incidence of deep vein thrombosis and pulmonary embolism in up to 40% of patients, despite the use of a standard dose of low-molecular-weight heparin (LMWH) in most cases.,In addition, pulmonary microvascular thrombosis has been reported and may play a role in progressive lung failure.,Prophylactic LMWH has been recommended by the International Society on Thrombosis and Haemostasis (ISTH) and the American Society of Hematology (ASH), but the best effective dosage is uncertain.,Adapted to the individual risk of thrombosis and the d-dimer value, higher doses can be considered, especially since bleeding events in COVID-19 are rare.,Besides the anticoagulant effect of LMWH, nonanticoagulant properties such as the reduction in interleukin 6 release have been shown to improve the complex picture of coagulopathy in patients with COVID-19.

The 2019 coronavirus disease (COVID-19) presents with a large variety of clinical manifestations ranging from asymptomatic carrier state to severe respiratory distress, multiple organ dysfunction and death.,While it was initially considered primarily a respiratory illness, rapidly accumulating data suggests that COVID-19 results in a unique, profoundly prothrombotic milieu leading to both arterial and venous thrombosis.,Consistently, elevated D-dimer level has emerged as an independent risk factor for poor outcomes, including death.,Several other laboratory markers and blood counts have also been associated with poor prognosis, possibly due to their connection to thrombosis.,At present, the pathophysiology underlying the hypercoagulable state is poorly understood.,However, a growing body of data suggests that the initial events occur in the lung.,A severe inflammatory response, originating in the alveoli, triggers a dysfunctional cascade of inflammatory thrombosis in the pulmonary vasculature, leading to a state of local coagulopathy.,This is followed, in patients with more severe disease, by a generalized hypercoagulable state that results in macro- and microvascular thrombosis.,Of concern, is the observation that anticoagulation may be inadequate in many circumstances, highlighting the need for alternative or additional therapies.,Numerous ongoing studies investigating the pathophysiology of the COVID-19 associated coagulopathy may provide mechanistic insights that can direct appropriate interventional strategies.,•COVID-19 generates a significantly increased risk for thrombosis•Pulmonary inflammation and localized vasculopathy are central to the hypercoagulable state•Immune dysregulation is notable in severe illness•Rising D-dimer levels correlate with worse outcomes•Anticoagulant guidelines are rapidly evolving as we gather further insights,COVID-19 generates a significantly increased risk for thrombosis,Pulmonary inflammation and localized vasculopathy are central to the hypercoagulable state,Immune dysregulation is notable in severe illness,Rising D-dimer levels correlate with worse outcomes,Anticoagulant guidelines are rapidly evolving as we gather further insights

COVID-19 infections are associated with a high prevalence of venous thromboembolism, particularly pulmonary embolism (PE).,It is suggested that COVID-19 associated PE represents in situ immunothrombosis rather than venous thromboembolism, although the origin of thrombotic lesions in COVID-19 patients remains largely unknown.,In this study, we assessed the clinical and computed tomography (CT) characteristics of PE in 23 consecutive patients with COVID-19 pneumonia and compared these to those of 100 consecutive control patients diagnosed with acute PE before the COVID-19 outbreak.,Specifically, RV/LV diameter ratio, pulmonary artery trunk diameter and total thrombus load (according to Qanadli score) were measured and compared.,We observed that all thrombotic lesions in COVID-19 patients were found to be in lung parenchyma affected by COVID-19.,Also, the thrombus load was lower in COVID-19 patients (Qanadli score −8%, 95% confidence interval [95%CI] −16 to −0.36%) as was the prevalence of the most proximal PE in the main/lobar pulmonary artery (17% versus 47%; −30%, 95%CI −44% to −8.2).,Moreover, the mean RV/LV ratio (mean difference −0.23, 95%CI −0.39 to −0.07) and the prevalence of RV/LV ratio >1.0 (prevalence difference −23%, 95%CI −41 to −0.86%) were lower in the COVID-19 patients.,Our findings therefore suggest that the phenotype of COVID-19 associated PE indeed differs from PE in patients without COVID-19, fuelling the discussion on its pathophysiology.,•COVID-19 pneumonia is associated with high incidence of pulmonary embolism (PE).,•The origin of COVID-19 associated PE is debated.,•We compared radiological PE parameters in COVID-19 patients with control patients.,•In COVID-19 patients, thrombus load and prevalence of RV dysfunction was lower.,•Our findings support the concept of in situ immunothrombosis in COVID-19 patients,COVID-19 pneumonia is associated with high incidence of pulmonary embolism (PE).,The origin of COVID-19 associated PE is debated.,We compared radiological PE parameters in COVID-19 patients with control patients.,In COVID-19 patients, thrombus load and prevalence of RV dysfunction was lower.,Our findings support the concept of in situ immunothrombosis in COVID-19 patients

An increased risk of venous thromboembolism (VTE) in patients with COVID-19 pneumonia admitted to intensive care unit (ICU) has been reported.,Whether COVID-19 increases the risk of VTE in non-ICU wards remains unknown.,We aimed to evaluate the burden of asymptomatic deep vein thrombosis (DVT) in COVID-19 patients with elevated D-dimer levels.,In this prospective study consecutive patients hospitalized in non-intensive care units with diagnosis of COVID-19 pneumonia and D-dimer > 1000 ng/ml were screened for asymptomatic DVT with complete compression doppler ultrasound (CCUS).,The study was approved by the Institutional Ethics Committee.,The study comprised 156 patients (65.4% male).,All but three patients received standard doses of thromboprophylaxis.,Median days of hospitalization until CCUS was 9 (IQR 5-17).,CCUS was positive for DVT in 23 patients (14.7%), of whom only one was proximal DVT.,Seven patients (4.5%) had bilateral distal DVT.,Patients with DVT had higher median D-dimer levels: 4527 (IQR 1925-9144) ng/ml vs 2050 (IQR 1428-3235) ng/ml; p < 0.001.,D-dimer levels > 1570 ng/ml were associated with asymptomatic DVT (OR 9.1; CI 95% 1.1-70.1).,D-dimer showed an acceptable discriminative capacity (area under the ROC curve 0.72, 95% CI 0.61-0.84).,In patients admitted with COVID-19 pneumonia and elevated D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series.,Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients.,•An increased risk of VTE in patients with COVID-19 pneumonia admitted to intensive care unit has been reported.,•The most consistent hemostatic abnormalities with COVID-19 include mild thrombocytopenia and increased D-dimer levels.,•In COVID-19 patients with high D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series.,•Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients.,An increased risk of VTE in patients with COVID-19 pneumonia admitted to intensive care unit has been reported.,The most consistent hemostatic abnormalities with COVID-19 include mild thrombocytopenia and increased D-dimer levels.,In COVID-19 patients with high D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series.,Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients.

Current understanding of the impact of coronavirus disease-2019 (COVID-19) on arrhythmias continues to evolve as new data emerge.,Cardiac arrhythmias are more common in critically ill COVID-19 patients.,The potential mechanisms that could result in arrhythmogenesis among COVID-19 patients include hypoxia caused by direct viral tissue involvement of lungs, myocarditis, abnormal host immune response, myocardial ischemia, myocardial strain, electrolyte derangements, intravascular volume imbalances, and drug sides effects.,To manage these arrhythmias, it is imperative to increase the awareness of potential drug-drug interactions, to monitor QTc prolongation while receiving COVID therapy and provide special considerations for patients with inherited arrhythmia syndromes.,It is also crucial to minimize exposure to COVID-19 infection by stratifying the need for intervention and using telemedicine.,As COVID-19 infection continues to prevail with a potential for future surges, more data are required to better understand pathophysiology and to validate management strategies.,•Cardiac arrhythmias are more common in critically ill COVID-19 patients.,•Arrhythmias occur not only as a result of direct viral effect, but also due to systemic illness and drug interactions.,•Management strategies to minimize the impact on arrhythmias and exposure to COVID-19 infection are imperative.,•More data are required to better understand the pathophysiology and to validate management strategies.,Cardiac arrhythmias are more common in critically ill COVID-19 patients.,Arrhythmias occur not only as a result of direct viral effect, but also due to systemic illness and drug interactions.,Management strategies to minimize the impact on arrhythmias and exposure to COVID-19 infection are imperative.,More data are required to better understand the pathophysiology and to validate management strategies.

The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur.,This brief report evaluates cardiovascular complications in the setting of COVID-19 infection.,The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death.,The virus binds and enters through angiotensin-converting enzyme 2 (ACE2).,COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness.,The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events.,Current therapies for COVID-19 may interact with cardiovascular medications.,Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.

The COVID-19 pandemic is associated with neurological symptoms and complications including stroke.,There is hypercoagulability associated with COVID-19 that is likely a “sepsis-induced coagulopathy” and may predispose to stroke.,The SARS-CoV-2 virus binds to angiotensin-converting enzyme 2 (ACE2) present on brain endothelial and smooth muscle cells.,ACE2 is a key part of the renin angiotensin system (RAS) and a counterbalance to angiotensin-converting enzyme 1 (ACE1) and angiotensin II.,Angiotensin II is proinflammatory, is vasoconstrictive, and promotes organ damage.,Depletion of ACE2 by SARS-CoV-2 may tip the balance in favor of the “harmful” ACE1/angiotensin II axis and promote tissue injury including stroke.,There is a rationale to continue to treat with tissue plasminogen activator for COVID-19-related stroke and low molecular weight heparinoids may reduce thrombosis and mortality in sepsis-induced coagulopathy.

•Coronoviruses not only affect the respiratory system, but also have deleterious effects on the central nervous system.,•Most neurological diseases could be caused by coronoviruses invasion.,•Coronoviruses cause nerve damage via diverse pathways.,Coronoviruses not only affect the respiratory system, but also have deleterious effects on the central nervous system.,Most neurological diseases could be caused by coronoviruses invasion.,Coronoviruses cause nerve damage via diverse pathways.,Viral infections have detrimental impacts on neurological functions, and even to cause severe neurological damage.,Very recently, coronaviruses (CoV), especially severe acute respiratory syndrome CoV 2 (SARS-CoV-2), exhibit neurotropic properties and may also cause neurological diseases.,It is reported that CoV can be found in the brain or cerebrospinal fluid.,The pathobiology of these neuroinvasive viruses is still incompletely known, and it is therefore important to explore the impact of CoV infections on the nervous system.,Here, we review the research into neurological complications in CoV infections and the possible mechanisms of damage to the nervous system.

The COVID-19 pandemic has disrupted life throughout the world.,Newly developed vaccines promise relief to people who live in high-income countries, although vaccines and expensive new treatments are unlikely to arrive in time to help people who live in low-and middle-income countries.,The pathogenesis of COVID-19 is characterized by endothelial dysfunction.,Several widely available drugs like statins, ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have immunometabolic activities that (among other things) maintain or restore endothelial cell function.,For this reason, we undertook an observational study in four Belgian hospitals to determine whether in-hospital treatment with these drugs could improve survival in 959 COVID-19 patients.,We found that treatment with statins and ACEIs/ARBs reduced 28-day mortality in hospitalized COVID-19 patients.,Moreover, combination treatment with these drugs resulted in a 3-fold reduction in the odds of hospital mortality (OR = 0.33; 95% CI 0.17-0.69).,These findings were in general agreement with other published studies.,Additional observational studies and clinical trials are needed to convincingly show that in-hospital treatment with statins, ACEIs/ARBs, and especially their combination saves lives.

The effects of cardiometabolic drugs on the prognosis of diabetic patients with COVID-19, especially very old patients, are not well-known.,This work aims to analyze the association between preadmission cardiometabolic therapy (antidiabetic, antiaggregant, antihypertensive, and lipid-lowering drugs) and in-hospital mortality among patients ≥80 years with type 2 diabetes mellitus hospitalized for COVID-19.,We conducted a nationwide, multicenter, observational study in patients ≥80 years with type 2 diabetes mellitus hospitalized for COVID-19 between March 1 and May 29, 2020.,The primary outcome measure was in-hospital mortality.,A multivariate logistic regression analysis were performed to assess the association between preadmission cardiometabolic therapy and in-hospital mortality.,Of the 2,763 patients ≥80 years old hospitalized due to COVID-19, 790 (28.6%) had T2DM.,Of these patients, 385 (48.7%) died during admission.,On the multivariate analysis, the use of dipeptidyl peptidase-4 inhibitors (AOR 0.502, 95%CI 0.309-0.815, p=0.005) and angiotensin receptor blockers (AOR 0.454, 95%CI 0.274-0.759, p=0.003) were independent protectors against in-hospital mortality whereas the use of acetylsalicylic acid was associated with higher in-hospital mortality (AOR 1.761, 95%CI 1.092-2.842, p=0.020).,Other antidiabetic drugs, angiotensin-converting enzyme inhibitors and statins showed neutral association with in-hospital mortality.,We found important differences between cardiometabolic drugs and in-hospital mortality in older patients with type 2 diabetes mellitus hospitalized for COVID-19.,Preadmission treatment with dipeptidyl peptidase-4 inhibitors and angiotensin receptor blockers could reduce in-hospital mortality; other antidiabetic drugs, angiotensin-converting enzyme inhibitors and statins seem to have a neutral effect; and acetylsalicylic acid could be associated with excess mortality.

Emerging evidence shows that severe coronavirus disease 2019 (COVID‐19) can be complicated with coagulopathy, namely disseminated intravascular coagulation, which has a rather prothrombotic character with high risk of venous thromboembolism.,The incidence of venous thromboembolism among COVID‐19 patients in intensive care units appears to be somewhat higher compared to that reported in other studies including such patients with other disease conditions.,D‐dimer might help in early recognition of these high‐risk patients and also predict outcome.,Preliminary data show that in patients with severe COVID‐19, anticoagulant therapy appears to be associated with lower mortality in the subpopulation meeting sepsis‐induced coagulopathy criteria or with markedly elevated d‐dimer.,Recent recommendations suggest that all hospitalized COVID‐19 patients should receive thromboprophylaxis, or full therapeutic‐intensity anticoagulation if such an indication is present.

Higher aspirin doses may be inferior in ticagrelor-treated acute coronary syndrome (ACS) patients and reducing bleeding risk whilst maintaining antithrombotic benefits could improve outcomes.,We characterized the pharmacodynamics of a novel dual-antiplatelet-therapy regimen consisting of very-low-dose twice-daily (BD) aspirin with standard-dose ticagrelor.,A total of 20 ticagrelor-treated ACS patients entered a randomized crossover to take aspirin 20 mg BD (12-hourly) during one 14-day period and 75 mg once-daily (OD) in the other.,After 14 days of treatment, serum thromboxane (TX)B2 and light-transmittance aggregometry were assessed pre- and 2 h post-morning-dose, bleeding time was measured post-dose, and TXA2 and prostacyclin stable metabolites were measured in urine collected 2 h post-morning-dose.,Data are expressed as mean ± SD.,After 14 days treatment, serum TXB2 levels were significantly greater 2 h post-dosing with aspirin 20 mg BD vs. 75 mg OD (3.0 ± 3.6 ng/mL vs.,0.8 ± 1.9 ng/mL; p = 0.018) whereas pre-dosing levels were not significantly different (3.5 ± 4.1 ng/mL vs.,2.5 ± 3.1 ng/mL, p = 0.23). 1-mmol/L arachidonic acid-induced platelet aggregation was similarly inhibited by both regimens pre-dose (8.5 ± 14.3% vs.,5.1 ± 3.6%, p = 0.24) and post-dose (8.7 ± 14.2% vs.,6.6 ± 5.3%; p = 0.41).,Post-dose bleeding time was shorter with 20 mg BD (680 ± 306 s vs. 834 ± 386 s, p = 0.02).,Urinary prostacyclin and TX metabolite excretion were not significantly different.,In conclusion, compared to aspirin 75 mg OD, aspirin 20 mg BD provided consistent inhibition of platelet TXA2 release and aggregation, and improved post-dose hemostasis, in ticagrelor-treated ACS patients.,Further studies are warranted to assess whether this regimen improves the balance of clinical efficacy and safety.

A limited number of publications have assessed the prevalence of hypertension (HTN) in polycystic ovary syndrome (PCOS) patients with inconclusive results.,Since in general populations the occurrence of hypertension is related to age per se, we investigated the prevalence (P) / relative risk (RR) of HTN in pooled patients with PCOS, vs control population among reproductive age women with PCOS, compared to menopause/aging patients.,PubMed, Scopus, ScienceDirect, web of science, and Google scholar were systematically searched for retrieving observational studies published from inception to April 2019 investigating the HTN in patients with PCOS.,The primary outcome of interest was pooled P and RR of HTN in reproductive and menopausal/aging women with PCOS compared to control population.,The pooled prevalence of HTN in reproductive and menopausal/aging women with PCOS was higher than in the control population [(Pooled P: 0.15, 95% CI: 0.12-0.18 vs.,Pooled P: 0.09, 95% CI: 0.08-0.10) and (Pooled P: 0.49, 95% CI: 0.28-0.70 vs.,Pooled P: 0.40, 95% CI: 0.22-0.57), respectively].,Compared to the control population, pooled relative risk (RR) of HTN patients was increased only in reproductive age PCOS (1.70-fold, 95% CI: 1.43-2.07) but not in menopausal/aging patients who had PCOS during their reproductive years.,The same results were obtained for subgroups of population-based studies.,Meta-regression analysis of population-based studies showed that the RR of HTN in reproductive age PCOS patients was 1.76-fold than menopausal/aging PCOS patients (P = 0.262).,This meta-analysis confirms a greater risk of HTN in PCOS patients but demonstrates that this risk is increased only in reproductive age women with PCOS, indicating that after menopause, having a history of PCOS may not be as an important predisposing factor for developing HTN.

Polycystic ovary syndrome (PCOS) is associated with obesity and low grade inflammation and the risk for cardiovascular disease (CVD) could be increased in PCOS.,National register-based study including women with PCOS and no previous diagnosis of CVD, hypertension, or dyslipidemia.,PCOS Denmark (N = 18,112) included women with PCOS in the Danish National Patient Register.,PCOS Odense University Hospital (OUH, N = 1165) was an embedded cohort including premenopausal women with PCOS and clinical and biochemical examination.,Three age-matched controls were included per patient in PCOS Denmark (N = 52,769).,The main study outcome was CVD events including hypertension and dyslipidemia defined according to nationwide in- and outpatient hospital contact diagnosis codes and/or inferred from filled medicine prescriptions.,The age at inclusion was median (quartiles) 29 (23-35) years and follow up was 11.1 (6.9-16.0) years.,The Hazard ratio (95% CI) for development of CVD in PCOS Denmark was 1.7 (1.7; 1.8) (P < 0.001) and the total event rate of CVD was 22.6 per 1000 patient years in PCOS Denmark vs.,13.2 per 1000 patient years in controls (P < 0.001).,The median age at diagnosis of CVD was 35 (28-42) years in PCOS Denmark vs. 36 (30-43) years in controls (P < 0.001).,Obesity, diabetes, and infertility, and previous use of oral contraceptives were associated with increased risk of development of CVD in PCOS Denmark (P < 0.001).,Women in PCOS OUH resembled women in PCOS Denmark regarding risk of CVD.,Age, BMI, blood pressure, lipid status, and glycemic status predicted development of CVD in PCOS OUH.,The event rate of CVD including hypertension and dyslipidemia was higher in PCOS compared to controls.,The risk of developing CVD must be considered even in young women with PCOS.,The online version of this article (10.1186/s12933-018-0680-5) contains supplementary material, which is available to authorized users.

Cardiac disease is associated with deleterious emission of mitochondrial reactive oxygen species (mito-ROS), as well as enhanced oxidation and activity of the sarcoplasmic reticulum (SR) Ca2+ release channel, the ryanodine receptor (RyR2).,The transfer of Ca2+ from the SR via RyR2 to mitochondria is thought to play a key role in matching increased metabolic demand during stress.,In this study, we investigated whether augmented RyR2 activity results in self-imposed exacerbation of SR Ca2+ leak, via altered SR-mitochondrial Ca2+ transfer and elevated mito-ROS emission.,Fluorescent indicators and spatially restricted genetic ROS probes revealed that both pharmacologically and genetically enhanced RyR2 activity, in ventricular myocytes from rats and catecholaminergic polymorphic ventricular tachycardia (CPVT) mice, respectively, resulted in increased ROS emission under β-adrenergic stimulation.,Expression of mitochondrial Ca2+ probe mtRCamp1h revealed diminished net mitochondrial [Ca2+] with enhanced SR Ca2+ leak, accompanied by depolarization of the mitochondrial matrix.,While this may serve as a protective mechanism to prevent mitochondrial Ca2+ overload, protection is not complete and enhanced mito-ROS emission resulted in oxidation of RyR2, further amplifying proarrhythmic SR Ca2+ release.,Importantly, the effects of augmented RyR2 activity could be attenuated by mitochondrial ROS scavenging, and experiments with dominant-negative paralogs of the mitochondrial Ca2+ uniporter (MCU) supported the hypothesis that SR-mitochondria Ca2+ transfer is essential for the increase in mito-ROS.,We conclude that in a process whereby leak begets leak, augmented RyR2 activity modulates mitochondrial Ca2+ handling, promoting mito-ROS emission and driving further channel activity in a proarrhythmic feedback cycle in the diseased heart.

Comorbidities of ischemic heart disease, including diabetes mellitus (DM), hypercholesterolemia (HC) and chronic kidney disease (CKD), are associated with coronary microvascular dysfunction (CMD).,Increasing evidence suggests that CMD may contribute to myocardial ‘Ischemia and No Obstructive Coronary Artery disease’ (INOCA).,In the present study, we tested the hypothesis that CMD results in perturbations in myocardial perfusion and oxygen delivery using a novel swine model with multiple comorbidities.,DM (streptozotocin), HC (high-fat diet) and CKD (renal embolization) were induced in 10 female swine (DM + HC + CKD), while 12 healthy female swine on a normal diet served as controls (Normal).,After 5 months, at a time when coronary atherosclerosis was still negligible, myocardial perfusion, metabolism, and function were studied at rest and during treadmill exercise.,DM + HC + CKD animals showed hyperglycemia, hypercholesterolemia, and impaired kidney function.,During exercise, DM + HC + CKD swine demonstrated perturbations in myocardial blood flow and oxygen delivery, necessitating a higher myocardial oxygen extraction-achieved despite reduced capillary density-resulting in lower coronary venous oxygen levels.,Moreover, myocardial efficiency was lower, requiring higher oxygen consumption for a given level of myocardial work.,These perturbations in myocardial oxygen balance were associated with lower myocardial lactate consumption, stroke volume, and LVdP/dtmax, suggestive of myocardial ischemia and dysfunction.,Further analyses showed a reduction in adenosine-recruitable coronary flow reserve, but this was exclusively the result of an increase in basal coronary blood flow, while maximal coronary flow per gram of myocardium was maintained; the latter was consistent with the unchanged arteriolar wall/lumen ratio, arteriolar density and peri-arteriolar collagen content.,However, isolated small arteries displayed selective blunting of endothelium-dependent vasodilation in response to bradykinin in DM + HC + CKD swine, suggesting that changes in coronary microvascular function rather than in structure contributed to the perturbations in myocardial oxygen delivery.,In conclusion, common comorbidities in swine result in CMD, in the absence of appreciable atherosclerosis, which is severe enough to produce perturbations in myocardial oxygen balance, particularly during exercise, resembling key features of INOCA.,The online version of this article (10.1007/s00395-020-0778-2) contains supplementary material, which is available to authorized users.

The degree of myocardial injury, as reflected by troponin elevation, and associated outcomes among U.S. hospitalized patients with coronavirus disease-2019 (COVID-19) are unknown.,The purpose of this study was to describe the degree of myocardial injury and associated outcomes in a large hospitalized cohort with laboratory-confirmed COVID-19.,Patients with COVID-19 admitted to 1 of 5 Mount Sinai Health System hospitals in New York City between February 27, 2020, and April 12, 2020, with troponin-I (normal value <0.03 ng/ml) measured within 24 h of admission were included (n = 2,736).,Demographics, medical histories, admission laboratory results, and outcomes were captured from the hospitals’ electronic health records.,The median age was 66.4 years, with 59.6% men.,Cardiovascular disease (CVD), including coronary artery disease, atrial fibrillation, and heart failure, was more prevalent in patients with higher troponin concentrations, as were hypertension and diabetes.,A total of 506 (18.5%) patients died during hospitalization.,In all, 985 (36%) patients had elevated troponin concentrations.,After adjusting for disease severity and relevant clinical factors, even small amounts of myocardial injury (e.g., troponin I >0.03 to 0.09 ng/ml; n = 455; 16.6%) were significantly associated with death (adjusted hazard ratio: 1.75; 95% CI: 1.37 to 2.24; p < 0.001) while greater amounts (e.g., troponin I >0.09 ng/dl; n = 530; 19.4%) were significantly associated with higher risk (adjusted HR: 3.03; 95% CI: 2.42 to 3.80; p < 0.001).,Myocardial injury is prevalent among patients hospitalized with COVID-19; however, troponin concentrations were generally present at low levels.,Patients with CVD are more likely to have myocardial injury than patients without CVD.,Troponin elevation among patients hospitalized with COVID-19 is associated with higher risk of mortality.

Supplemental Digital Content is available in the text.,Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension.,To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19.,This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57-69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020.,In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19-0.92]; P=0.03).,In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15-0.89]; P=0.03).,Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12-0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension.,Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers.,While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.

Supplemental Digital Content is available in the text.,Patients with coronavirus disease 2019 (COVID-19) who develop cardiac injury are reported to experience higher rates of malignant cardiac arrhythmias.,However, little is known about these arrhythmias-their frequency, the underlying mechanisms, and their impact on mortality.,We extracted data from a registry (NCT04358029) regarding consecutive inpatients with confirmed COVID-19 who were receiving continuous telemetric ECG monitoring and had a definitive disposition of hospital discharge or death.,Between patients who died versus discharged, we compared a primary composite end point of cardiac arrest from ventricular tachycardia/fibrillation or bradyarrhythmias such as atrioventricular block.,Among 800 patients with COVID-19 at Mount Sinai Hospital with definitive dispositions, 140 patients had telemetric monitoring, and either died (52) or were discharged (88).,The median (interquartile range) age was 61 years (48-74); 73% men; and ethnicity was White in 34%.,Comorbidities included hypertension in 61%, coronary artery disease in 25%, ventricular arrhythmia history in 1.4%, and no significant comorbidities in 16%.,Compared with discharged patients, those who died had elevated peak troponin I levels (0.27 versus 0.02 ng/mL) and more primary end point events (17% versus 4%, P=0.01)-a difference driven by tachyarrhythmias.,Fatal tachyarrhythmias invariably occurred in the presence of severe metabolic imbalance, while atrioventricular block was largely an independent primary event.,Hospitalized patients with COVID-19 who die experience malignant cardiac arrhythmias more often than those surviving to discharge.,However, these events represent a minority of cardiovascular deaths, and ventricular tachyarrhythmias are mainly associated with severe metabolic derangement.,URL: https://www.clinicaltrials.gov; Unique identifier: NCT04358029.

The coronavirus disease 2019 (COVID-19) outbreak, along with implementation of lockdown and strict public movement restrictions, in Greece has affected hospital visits and admissions.,We aimed to investigate trends of cardiac disease admissions during the outbreak of the pandemic and possible associations with the applied restrictive measures.,This is a retrospective observational study.,Data for 4970 patients admitted via the cardiology emergency department (ED) across 3 large-volume urban hospitals in Athens and 2 regional/rural hospitals from February 3, 2020, up to April 12 were recorded.,Data from the equivalent (for the COVID-19 outbreak) time period of 2019 and from the postlockdown time period were also collected.,A falling trend of cardiology ED visits and hospital admissions was observed starting from the week when the restrictive measures due to COVID-19 were implemented.,Compared with the pre-COVID-19 outbreak time period, acute coronary syndrome (ACS) [145 (29/week) vs. 60 (12/week), −59%, P < 0.001], ST elevation myocardial infarction [46 (9.2/week) vs.,21 (4.2/week), −54%, P = 0.002], and non-ST elevation ACS [99 cases (19.8/week) vs.,39 (7.8/week), −60% P < 0.001] were reduced at the COVID-19 outbreak time period.,Reductions were also noted for heart failure worsening and arrhythmias.,The ED visits in the postlockdown period were significantly higher than in the COVID-19 outbreak time period (1511 vs 660; P < 0.05).,Our data show significant drops in cardiology visits and admissions during the COVID-19 outbreak time period.,Whether this results from restrictive measures or depicts a true reduction of cardiac disease cases warrants further investigation.,•The coronavirus disease 2019 (COVID-19) outbreak has led to an unprecedented health system overload.,•The restrictive measures in Greece resulted in a low number of COVID-19 cases.,•Hospital visits and cardiovascular events have diminished after implementation of restrictive measures.,•Acute coronary syndromes reduced by approximately 55%, despite limited incidence of COVID-19.,•The multifactorial etiology of this finding should be thoroughly investigated.,The coronavirus disease 2019 (COVID-19) outbreak has led to an unprecedented health system overload.,The restrictive measures in Greece resulted in a low number of COVID-19 cases.,Hospital visits and cardiovascular events have diminished after implementation of restrictive measures.,Acute coronary syndromes reduced by approximately 55%, despite limited incidence of COVID-19.,The multifactorial etiology of this finding should be thoroughly investigated.

Three months ago, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) broke out in Wuhan, China, and spread rapidly around the world.,Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned.,To determine the incidence of VTE in patients with severe NCP.,In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled.,The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed.,The incidence of VTE in these patients was 25% (20/81), of which 8 patients with VTE events died.,The VTE group was different from the non‐VTE group in age, lymphocyte counts, activated partial thromboplastin time (APTT), D‐dimer, etc.,If 1.5 µg/mL was used as the D‐dimer cut‐off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value (NPV) was 94.7%.,The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis.,The significant increase of D‐dimer in severe NCP patients is a good index for identifying high‐risk groups of VTE.

This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury.

Coronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease.,In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis.,Although these therapies may have direct antithrombotic effects, other mechanisms of action, including anti-inflammatory or antiviral effects, have been postulated.,Based on survey results from this group of authors, we suggest research priorities for specific agents and subgroups of patients with COVID-19.,Further, we review other agents, including immunomodulators, that may have antithrombotic properties.,It is our hope that the present document will encourage and stimulate future prospective studies and randomized trials to study the safety, efficacy, and optimal use of these agents for prevention or management of thrombosis in COVID-19.

COVID-19 affects millions of patients worldwide, with clinical presentation ranging from isolated thrombosis to acute respiratory distress syndrome (ARDS) requiring ventilator support.,Neutrophil extracellular traps (NETs) originate from decondensed chromatin released to immobilize pathogens, and they can trigger immunothrombosis.,We studied the connection between NETs and COVID-19 severity and progression.,We conducted a prospective cohort study of COVID-19 patients (n = 33) and age- and sex-matched controls (n = 17).,We measured plasma myeloperoxidase (MPO)-DNA complexes (NETs), platelet factor 4, RANTES, and selected cytokines.,Three COVID-19 lung autopsies were examined for NETs and platelet involvement.,We assessed NET formation ex vivo in COVID-19 neutrophils and in healthy neutrophils incubated with COVID-19 plasma.,We also tested the ability of neonatal NET-inhibitory factor (nNIF) to block NET formation induced by COVID-19 plasma.,Plasma MPO-DNA complexes increased in COVID-19, with intubation (P < .0001) and death (P < .0005) as outcome.,Illness severity correlated directly with plasma MPO-DNA complexes (P = .0360), whereas Pao2/fraction of inspired oxygen correlated inversely (P = .0340).,Soluble and cellular factors triggering NETs were significantly increased in COVID-19, and pulmonary autopsies confirmed NET-containing microthrombi with neutrophil-platelet infiltration.,Finally, COVID-19 neutrophils ex vivo displayed excessive NETs at baseline, and COVID-19 plasma triggered NET formation, which was blocked by nNIF.,Thus, NETs triggering immunothrombosis may, in part, explain the prothrombotic clinical presentations in COVID-19, and NETs may represent targets for therapeutic intervention.,•NETs contribute to microthrombi through platelet-neutrophil interactions in COVID-19 ARDS.•nNIF blocks NETs induced by COVID-19 plasma and represents a potential therapeutic intervention in COVID-19.,NETs contribute to microthrombi through platelet-neutrophil interactions in COVID-19 ARDS.,nNIF blocks NETs induced by COVID-19 plasma and represents a potential therapeutic intervention in COVID-19.

Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19).,We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.,In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis.,The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge.,This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level.,The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met.,Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58).,The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2).,The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort.,Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis.,In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis.,(ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT04359277, and NCT02735707.)

COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation.,Reports on the incidence of thrombotic complications are however not available.,We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.,We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020.,All patients received at least standard doses thromboprophylaxis.,The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%).,PE was the most frequent thrombotic complication (n = 25, 81%).,Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.,The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high.,Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.

Early studies suggest that coronavirus disease 2019 (COVID-19) is associated with a high incidence of cardiac arrhythmias.,Severe acute respiratory syndrome coronavirus 2 infection may cause injury to cardiac myocytes and increase arrhythmia risk.,The purpose of this study was to evaluate the risk of cardiac arrest and arrhythmias including incident atrial fibrillation (AF), bradyarrhythmias, and nonsustained ventricular tachycardia (NSVT) in a large urban population hospitalized for COVID-19.,We also evaluated correlations between the presence of these arrhythmias and mortality.,We reviewed the characteristics of all patients with COVID-19 admitted to our center over a 9-week period.,Throughout hospitalization, we evaluated the incidence of cardiac arrests, arrhythmias, and inpatient mortality.,We also used logistic regression to evaluate age, sex, race, body mass index, prevalent cardiovascular disease, diabetes, hypertension, chronic kidney disease, and intensive care unit (ICU) status as potential risk factors for each arrhythmia.,Among 700 patients (mean age 50 ± 18 years; 45% men; 71% African American; 11% received ICU care), there were 9 cardiac arrests, 25 incident AF events, 9 clinically significant bradyarrhythmias, and 10 NSVTs.,All cardiac arrests occurred in patients admitted to the ICU.,In addition, admission to the ICU was associated with incident AF (odds ratio [OR] 4.68; 95% confidence interval [CI] 1.66-13.18) and NSVT (OR 8.92; 95% CI 1.73-46.06) after multivariable adjustment.,Also, age and incident AF (OR 1.05; 95% CI 1.02-1.09) and prevalent heart failure and bradyarrhythmias (OR 9.75; 95% CI 1.95-48.65) were independently associated.,Only cardiac arrests were associated with acute in-hospital mortality.,Cardiac arrests and arrhythmias are likely the consequence of systemic illness and not solely the direct effects of COVID-19 infection.

The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades.,We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies.,While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system.,Risk of severe infection and mortality increase with advancing age and male sex.,Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer.,The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC).,Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes.,This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI).,While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis.,Hence, patients should not discontinue their use.,Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19.,Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19.,Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications.,Preventive measures (social distancing and social isolation) also increase cardiovascular risk.,Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.

Maternal exposure to endocrine disrupting chemicals (EDCs) and a high-fat intake may induce the developmental programming of hypertension in adult offspring.,Bisphenol A (BPA) is one of the most commonly environmental EDCs.,As the nitric oxide (NO) and aryl hydrocarbon receptor (AHR) signaling pathways both contribute to the pathogenesis of hypertension, we evaluated whether resveratrol, an antioxidant and an AHR antagonist, can prevent hypertension programmed by a maternal BPA and HF diet.,Sixteen-week-old male rat offspring were assigned to six groups (n = 8 per group): Control, HF (D12331, Research Diets), BPA (50 μg/kg/day), HF + BPA, BPA + R (resveratrol 50mg/L in drinking water throughout pregnancy and lactation), and HF + BPA + R.,Maternal BPA exposure exacerbated hypertension programmed by HF consumption in adult male offspring, which was protected by maternal resveratrol therapy.,The BPA and HF diet synergistically induced oxidative stress in offspring kidneys, which resveratrol treatment prevented.,We observed that HF + BPA-induced programmed hypertension was associated with a decreased NO bioavailability, increased oxidative stress, and an activated AHR signaling pathway.,The beneficial effects of resveratrol are relevant to restoring NO bioavailability, reducing oxidative stress, and antagonizing the AHR signaling pathway.,Our results cast a new light on resveratrol as a reprogramming strategy to protect against hypertension programmed by combined BPA and HF exposure, but this strategy has yet to be translated into clinical applications.

Development of the kidney can be altered in response to adverse environments leading to renal programming and increased vulnerability to the development of hypertension and kidney disease in adulthood.,By contrast, reprogramming is a strategy shifting therapeutic intervention from adulthood to early life to reverse the programming processes.,Nitric oxide (NO) is a key mediator of renal physiology and blood pressure regulation.,NO deficiency is a common mechanism underlying renal programming, while early-life NO-targeting interventions may serve as reprogramming strategies to prevent the development of hypertension and kidney disease.,This review will first summarize the regulation of NO in the kidney.,We also address human and animal data supporting the link between NO system and developmental programming of hypertension and kidney disease.,This will be followed by the links between NO deficiency and the common mechanisms of renal programming, including the oxidative stress, renin-angiotensin system, nutrient-sensing signals, and sex differences.,Recent data from animal studies have suggested that interventions targeting the NO pathway could be reprogramming strategies to prevent the development of hypertension and kidney disease.,Further clinical studies are required to bridge the gap between animal models and clinical trials in order to develop ideal NO-targeting reprogramming strategies and to be able to have a lifelong impact, with profound savings in the global burden of hypertension and kidney disease.

The impact of COVID-19 on pre-hospital and hospital services and hence on the prevalence and outcomes of out-of-hospital cardiac arrests (OHCA) remain unclear.,The review aimed to evaluate the influence of the COVID-19 pandemic on the incidence, process, and outcomes of OHCA.,A systematic review of PubMed, EMBASE, and pre-print websites was performed.,Studies reporting comparative data on OHCA within the same jurisdiction, before and during the COVID-19 pandemic were included.,Study quality was assessed based on the Newcastle-Ottawa Scale.,Ten studies reporting data from 35,379 OHCA events were included.,There was a 120% increase in OHCA events since the pandemic.,Time from OHCA to ambulance arrival was longer during the pandemic (p = 0.036).,While mortality (OR = 0.67, 95%-CI 0.49−0.91) and supraglottic airway use (OR = 0.36, 95%-CI 0.27−0.46) was higher during the pandemic, automated external defibrillator use (OR = 1.78 95%-CI 1.06-2.98), return of spontaneous circulation (OR = 1.63, 95%CI 1.18-2.26) and intubation (OR = 1.87, 95%-CI 1.12--3.13) was more common before the pandemic.,More patients survived to hospital admission (OR = 1.75, 95%-CI 1.42-2.17) and discharge (OR = 1.65, 95%-CI 1.28-2.12) before the pandemic.,Bystander CPR (OR = 1.18, 95%-CI 0.95-1.46), unwitnessed OHCA (OR = 0.84, 95%-CI 0.66-1.07), paramedic-resuscitation attempts (OR = 1.19 95%-CI 1.00-1.42) and mechanical CPR device use (OR = 1.57 95%-CI 0.55-4.55) did not defer significantly.,The incidence and mortality following OHCA was higher during the COVID-19 pandemic.,There were significant variations in resuscitation practices during the pandemic.,Research to define optimal processes of pre-hospital care during a pandemic is urgently required.,PROSPERO (CRD42020203371).

The COVID-19 pandemic resulted in prioritisation of National Health Service (NHS) resources to cope with the surge in infected patients.,However, there have been no studies in the UK looking at the effect of the COVID-19 work pattern on the provision of cardiology services.,We aimed to assess the impact of the pandemic on cardiology services and clinical activity.,We analysed key performance indicators in cardiology services in a single centre in the UK in the periods prior to and during lockdown to assess reduction or changes in service provision.,There has been a greater than 50% drop in the number of patients presenting to cardiology and those diagnosed with myocardial infarction.,All areas of cardiology service provision sustained significant reductions, which included outpatient clinics, investigations, procedures and cardiology community services such as heart failure and cardiac rehabilitation.,As ischaemic heart disease continues to be the leading cause of death nationally and globally, cardiology services need to prepare for a significant increase in workload in the recovery phase and develop new pathways to urgently help those adversely affected by the changes in service provision.

Mutations in LMNA, which encodes the nuclear proteins Lamin A/C, can cause cardiomyopathy and conduction disorders.,Here, we employ induced pluripotent stem cells (iPSCs) generated from human cells carrying heterozygous K219T mutation on LMNA to develop a disease model.,Cardiomyocytes differentiated from these iPSCs, and which thus carry K219T-LMNA, have altered action potential, reduced peak sodium current and diminished conduction velocity.,Moreover, they have significantly downregulated Nav1.5 channel expression and increased binding of Lamin A/C to the promoter of SCN5A, the channel’s gene.,Coherently, binding of the Polycomb Repressive Complex 2 (PRC2) protein SUZ12 and deposition of the repressive histone mark H3K27me3 are increased at SCN5A.,CRISPR/Cas9-mediated correction of the mutation re-establishes sodium current density and SCN5A expression.,Thus, K219T-LMNA cooperates with PRC2 in downregulating SCN5A, leading to decreased sodium current density and slower conduction velocity.,This mechanism may underlie the conduction abnormalities associated with LMNA-cardiomyopathy.,Mutation of LMNA, encoding Lamin A/C nuclear proteins, cause dilated cardiomyopathy and conduction disorders.,Here, the authors show that patient-specific iPSC-derived CMs carrying the K219T LMNA mutation have downregulated Nav1.5 channels due to dynamic cooperation of Lamin A/C and Polycomb repressor complex 2 at the SCN5A promoter.

Dilated cardiomyopathy (DCM), a myocardial disorder that can result in progressive heart failure and arrhythmias, is defined by ventricular chamber enlargement and dilatation, and systolic dysfunction.,Despite extensive research, the pathological mechanisms of DCM are unclear mainly due to numerous mutations in different gene families resulting in the same outcome-decreased ventricular function.,Titin (TTN)-a giant protein, expressed in cardiac and skeletal muscles, is an important part of the sarcomere, and thus TTN mutations are the most common cause of adult DCM.,To decipher the basis for the cardiac pathology in titin-mutated patients, we investigated the hypothesis that induced Pluripotent Stem Cell (iPSC)-derived cardiomyocytes (iPSC-CM) generated from patients, recapitulate the disease phenotype.,The hypothesis was tested by 3 Aims: (1) Investigate key features of the excitation-contraction-coupling machinery; (2) Investigate the responsiveness to positive inotropic interventions; (3) Investigate the proteome profile of the AuP cardiomyocytes using mass-spectrometry (MS).,iPSC were generated from the patients' skin fibroblasts.,The major findings were: (1) Sarcomeric organization analysis in mutated iPSC-CM showed defects in assembly and maintenance of sarcomeric structure.,(2) Mutated iPSC-CM exhibited diminished inotropic and lusitropic responses to β-adrenergic stimulation with isoproterenol, increased [Ca2+]out and angiotensin-II.,Additionally, mutated iPSC-CM displayed prolonged recovery in response to caffeine.,These findings may result from defective or lack of interactions of the sarcomeric components with titin through its kinase domain which is absent in the mutated cells.,These findings show that the mutated cardiomyocytes from DCM patients recapitulate abnormalities of the inherited cardiomyopathies, expressed as blunted inotropic response.

Coagulopathy represents one of the most important determinants of morbidity and mortality in coronavirus disease-19 (COVID-19).,Whether standard thromboprophylaxis is sufficient or higher doses are needed, especially in severe patients, is unknown.,To evaluate the safety of intermediate dose regimens of low-weight molecular heparin (LWMH) in COVID-19 patients with pneumonia, particularly in older patients.,We retrospectively evaluated 105 hospitalized patients (61 M, 44 F; mean age 73.7 years) treated with subcutaneous enoxaparin: 80 mg/day in normal weight and mild-to-moderate impair or normal renal function; 40 mg/day in severe chronic renal failure or low bodyweight (< 45 kg); 100 mg/day if bodyweight was higher than 100 kg.,All the patients had radiologically confirmed pneumonia and 63.8% had severe COVID-19.,None of the patients had fatal haemorrhage; two (1.9%) patients had a major bleeding event (one spontaneous hematoma and one gastrointestinal bleeding).,Only 6.7% of patients needed transfusions of red blood cells.,One thrombotic event (pulmonary embolism) was observed.,When compared to younger patients, patients older than 85 years had a higher mortality (40% vs 13.3%), but not an increased risk of bleeding or need for blood transfusion.,The use of an intermediate dose of LWMH appears to be feasible and data suggest safety in COVID-19 patients, although further studies are needed.

We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals.,In answering questions raised regarding our study, we updated our database and repeated all analyses.,We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first.,We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%).,The median follow-up duration increased from 7 to 14 days.,All patients received pharmacological thromboprophylaxis.,The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41-57%).,The majority of thrombotic events were PE (65/75; 87%).,In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091-0.92).,Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4-12).,Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35-1.8).,In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia.

Critically ill patients diagnosed with COVID-19 may develop a pro-thrombotic state that places them at a dramatically increased lethal risk.,Although platelet activation is critical for thrombosis and is responsible for the thrombotic events and cardiovascular complications, the role of platelets in the pathogenesis of COVID-19 remains unclear.,Using platelets from healthy volunteers, non-COVID-19 and COVID-19 patients, as well as wild-type and hACE2 transgenic mice, we evaluated the changes in platelet and coagulation parameters in COVID-19 patients.,We investigated ACE2 expression and direct effect of SARS-CoV-2 virus on platelets by RT-PCR, flow cytometry, Western blot, immunofluorescence, and platelet functional studies in vitro, FeCl3-induced thrombus formation in vivo, and thrombus formation under flow conditions ex vivo.,We demonstrated that COVID-19 patients present with increased mean platelet volume (MPV) and platelet hyperactivity, which correlated with a decrease in overall platelet count.,Detectable SARS-CoV-2 RNA in the blood stream was associated with platelet hyperactivity in critically ill patients.,Platelets expressed ACE2, a host cell receptor for SARS-CoV-2, and TMPRSS2, a serine protease for Spike protein priming.,SARS-CoV-2 and its Spike protein directly enhanced platelet activation such as platelet aggregation, PAC-1 binding, CD62P expression, α granule secretion, dense granule release, platelet spreading, and clot retraction in vitro, and thereby Spike protein enhanced thrombosis formation in wild-type mice transfused with hACE2 transgenic platelets, but this was not observed in animals transfused with wild-type platelets in vivo.,Further, we provided evidence suggesting that the MAPK pathway, downstream of ACE2, mediates the potentiating role of SARS-CoV-2 on platelet activation, and that platelet ACE2 expression decreases following SARS-COV-2 stimulation.,SARS-CoV-2 and its Spike protein directly stimulated platelets to facilitate the release of coagulation factors, the secretion of inflammatory factors, and the formation of leukocyte-platelet aggregates.,Recombinant human ACE2 protein and anti-Spike monoclonal antibody could inhibit SARS-CoV-2 Spike protein-induced platelet activation.,Our findings uncovered a novel function of SARS-CoV-2 on platelet activation via binding of Spike to ACE2.,SARS-CoV-2-induced platelet activation may participate in thrombus formation and inflammatory responses in COVID-19 patients.

This study evaluated cardiac involvement in patients recovered from coronavirus disease-2019 (COVID-19) using cardiac magnetic resonance (CMR).,Myocardial injury caused by COVID-19 was previously reported in hospitalized patients.,It is unknown if there is sustained cardiac involvement after patients’ recovery from COVID-19.,Twenty-six patients recovered from COVID-19 who reported cardiac symptoms and underwent CMR examinations were retrospectively included.,CMR protocols consisted of conventional sequences (cine, T2-weighted imaging, and late gadolinium enhancement [LGE]) and quantitative mapping sequences (T1, T2, and extracellular volume [ECV] mapping).,Edema ratio and LGE were assessed in post-COVID-19 patients.,Cardiac function, native T1/T2, and ECV were quantitatively evaluated and compared with controls.,Fifteen patients (58%) had abnormal CMR findings on conventional CMR sequences: myocardial edema was found in 14 (54%) patients and LGE was found in 8 (31%) patients.,Decreased right ventricle functional parameters including ejection fraction, cardiac index, and stroke volume/body surface area were found in patients with positive conventional CMR findings.,Using quantitative mapping, global native T1, T2, and ECV were all found to be significantly elevated in patients with positive conventional CMR findings, compared with patients without positive findings and controls (median [interquartile range]: native T1 1,271 ms [1,243 to 1,298 ms] vs. 1,237 ms [1,216 to 1,262 ms] vs. 1,224 ms [1,217 to 1,245 ms]; mean ± SD: T2 42.7 ± 3.1 ms vs.,38.1 ms ± 2.4 vs.,39.1 ms ± 3.1; median [interquartile range]: 28.2% [24.8% to 36.2%] vs.,24.8% [23.1% to 25.4%] vs.,23.7% [22.2% to 25.2%]; p = 0.002; p < 0.001, and p = 0.002, respectively).,Cardiac involvement was found in a proportion of patients recovered from COVID-19.,CMR manifestation included myocardial edema, fibrosis, and impaired right ventricle function.,Attention should be paid to the possible myocardial involvement in patients recovered from COVID-19 with cardiac symptoms.

The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular care of patients.,First, those with COVID-19 and pre-existing cardiovascular disease have an increased risk of severe disease and death.,Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism.,Third, therapies under investigation for COVID-19 may have cardiovascular side effects.,Fourth, the response to COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular conditions.,Finally, the provision of cardiovascular care may place health care workers in a position of vulnerability as they become hosts or vectors of virus transmission.,We hereby review the peer-reviewed and pre-print reports pertaining to cardiovascular considerations related to COVID-19 and highlight gaps in knowledge that require further study pertinent to patients, health care workers, and health systems.,•Patients with pre-existing CVD appear to have worse outcomes with COVID-19.,•CV complications include biomarker elevations, myocarditis, heart failure, and venous thromboembolism, which may be exacerbated by delays in care.,•Therapies under investigation for COVID-19 may have significant drug-drug interactions with CV medications.,•Health care workers and health systems should take measures to ensure safety while providing high-quality care for COVID-19 patients.,Patients with pre-existing CVD appear to have worse outcomes with COVID-19.,CV complications include biomarker elevations, myocarditis, heart failure, and venous thromboembolism, which may be exacerbated by delays in care.,Therapies under investigation for COVID-19 may have significant drug-drug interactions with CV medications.,Health care workers and health systems should take measures to ensure safety while providing high-quality care for COVID-19 patients.

Studies have reminded that cardiovascular metabolic comorbidities made patients more susceptible to suffer 2019 novel corona virus (2019-nCoV) disease (COVID-19), and exacerbated the infection.,The aim of this analysis is to determine the association of cardiovascular metabolic diseases with the development of COVID-19.,A meta-analysis of eligible studies that summarized the prevalence of cardiovascular metabolic diseases in COVID-19 and compared the incidences of the comorbidities in ICU/severe and non-ICU/severe patients was performed.,Embase and PubMed were searched for relevant studies.,A total of six studies with 1527 patients were included in this analysis.,The proportions of hypertension, cardia-cerebrovascular disease and diabetes in patients with COVID-19 were 17.1%, 16.4% and 9.7%, respectively.,The incidences of hypertension, cardia-cerebrovascular diseases and diabetes were about twofolds, threefolds and twofolds, respectively, higher in ICU/severe cases than in their non-ICU/severe counterparts.,At least 8.0% patients with COVID-19 suffered the acute cardiac injury.,The incidence of acute cardiac injury was about 13 folds higher in ICU/severe patients compared with the non-ICU/severe patients.,Patients with previous cardiovascular metabolic diseases may face a greater risk of developing into the severe condition and the comorbidities can also greatly affect the prognosis of the COVID-19.,On the other hand, COVID-19 can, in turn, aggravate the damage to the heart.

This is an observational cohort study comparing 156 patients evaluated for acute stroke between March 30 and May 31, 2020 at a comprehensive stroke center with 138 patients evaluated during the corresponding time period in 2019.,During the pandemic, the proportion of COVID-19 positive patients was low (3%), the time from symptom onset to hospital presentation was significantly longer, and a smaller proportion of patients underwent reperfusion therapy.,Among patients directly evaluated at our institution, door-to-needle and door-to-recanalization metrics were significantly longer.,Our findings support concerns that the current pandemic may have a negative impact on the management of acute stroke.

The Coronavirus disease 2019 (COVID-19) pandemic is rapidly evolving and affecting healthcare systems across the world.,Singapore has escalated its alert level to Disease Outbreak Response System Condition (DORSCON) Orange, signifying severe disease with community spread.,We aimed to study the overall volume of AIS cases and the delivery of hyperacute stroke services during DORSCON Orange.,This was a single-centre, observational cohort study performed at a comprehensive stroke centre responsible for AIS cases in the western region of Singapore, as well as providing care for COVID-19 patients.,All AIS patients reviewed as an acute stroke activation in the Emergency Department (ED) from November 2019 to April 2020 were included.,System processes timings, treatment and clinical outcome variables were collected.,We studied 350 AIS activation patients admitted through the ED, 206 (58.9%) pre- and 144 during DORSCON Orange.,Across the study period, number of stroke activations showed significant decline (p = 0.004, 95% CI 6.513 to − 2.287), as the number of COVID-19 cases increased exponentially, whilst proportion of activations receiving acute recanalization therapy remained stable (p = 0.519, 95% CI − 1.605 to 2.702).,Amongst AIS patients that received acute recanalization therapy, early neurological outcomes in terms of change in median NIHSS at 24 h (-4 versus -4, p = 0.685) were largely similar between the pre- and during DORSCON orange periods.,The number of stroke activations decreased while the proportion receiving acute recanalization therapy remained stable in the current COVID-19 pandemic in Singapore.,The online version of this article (10.1007/s11239-020-02225-1) contains supplementary material, which is available to authorized users.

Little is still known about the prognostic impact of incident arrhythmias in hospitalized patients with COVID‐19.,The aim of this study was to evaluate the incidence and predictors of sustained tachyarrhythmias in hospitalized patients with COVID‐19, and their potential association with disease severity and in‐hospital mortality.,This was a retrospective multicenter observation study including consecutive patients with laboratory confirmed COVID‐19 admitted to emergency department of ten Italian Hospitals from 15 February to 15 March 2020.,The prevalence and the type of incident sustained arrhythmias have been collected.,The correlation between the most prevalent arrhythmias and both baseline characteristics and the development of ARDS and in‐hospital mortality has been evaluated.,414 hospitalized patients with COVID‐19 (66.9 ± 15.0 years, 61.1% male) were included in the present study.,During a median follow‐up of 28 days (IQR: 12‐45), the most frequent incident sustained arrhythmia was AF (N: 71; 17.1%), of which 50 (12.1%) were new‐onset and 21 (5.1%) were recurrent, followed by VT (N: 14, 3.4%) and supraventricular arrhythmias (N: 5, 1.2%).,Incident AF, both new‐onset and recurrent, did not affect the risk of severe adverse events including ARDS and death during hospitalization; in contrast, incident VT significantly increased the risk of in‐hospital mortality (RR: 2.55; P: .003).,AF is the more frequent incident tachyarrhythmia; however, it not seems associated to ARDS development and death.,On the other hand, incident VT is a not frequent but independent predictor of in‐hospital mortality among hospitalized COVID‐19 patients.

To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died.,Retrospective case series.,Tongji Hospital in Wuhan, China.,Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed.,Data were collected until 28 February 2020.,Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms.,The median age of deceased patients (68 years) was significantly older than recovered patients (51 years).,Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%).,Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)).,Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)).,The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days.,Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively.,Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients.,Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%).,Patients with cardiovascular comorbidity were more likely to develop cardiac complications.,Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients.,Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk.,Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

Supplemental Digital Content is available in the text.,Shelter-in-place (SIP) orders implemented to mitigate severe acute respiratory syndrome coronavirus 2 spread may inadvertently discourage patient care-seeking behavior for critical conditions like acute ischemic stroke.,We aimed to compare temporal trends in volume of acute stroke alerts, patient characteristics, telestroke care, and short-term outcomes pre- and post-SIP orders.,We conducted a cohort study in 21 stroke centers of an integrated healthcare system serving 4.4+ million members across Northern California.,We included adult patients who presented with suspected acute stroke and were evaluated by telestroke between January 1, 2019, and May 9, 2020.,SIP orders announced the week of March 15, 2020, created pre (January 1, 2019, to March 14, 2020) and post (March 15, 2020, to May 9, 2020) cohort for comparison.,Main outcomes were stroke alert volumes and inpatient mortality for stroke.,Stroke alert weekly volume post-SIP (mean, 98 [95% CI, 92-104]) decreased significantly compared with pre-SIP (mean, 132 [95% CI, 130-136]; P<0.001).,Stroke discharges also dropped, in concordance with acute stroke alerts decrease.,In total, 9120 patients were included: 8337 in pre- and 783 in post-SIP cohorts.,There were no differences in patient demographics.,Compared with pre-SIP, post-SIP patients had higher National Institutes of Health Stroke Scale scores (P=0.003), lower comorbidity score (P<0.001), and arrived more often by ambulance (P<0.001).,Post-SIP, more patients had large vessel occlusions (P=0.03), and there were fewer stroke mimics (P=0.001).,Discharge outcomes were similar for post-SIP and pre-SIP cohorts.,In this cohort study, regional stroke alert and ischemic stroke discharge volumes decreased significantly in the early COVID-19 pandemic.,Compared with pre-SIP, the post-SIP population showed no significant demographic differences but had lower comorbidity scores, more severe strokes, and more large vessel occlusions.,The inpatient mortality was similar in both cohorts.,Further studies are needed to understand the causes and implications of care avoidance to patients and healthcare systems.

The 2019 novel coronavirus outbreak and its associated disease (coronavirus disease 2019 [COVID-19]) have created a worldwide pandemic.,Early data suggest higher rate of ischemic stroke in severe COVID-19 infection.,We evaluated whether a relationship exists between emergent large vessel occlusion (ELVO) and the ongoing COVID-19 outbreak.,This is a retrospective, observational case series.,Data were collected from all patients who presented with ELVO to the Mount Sinai Health System Hospitals across New York City during the peak 3 weeks of hospitalization and death from COVID-19.,Patients’ demographic, comorbid conditions, cardiovascular risk factors, COVID-19 disease status, and clinical presentation were extracted from the electronic medical record.,Comparison was made between COVID-19 positive and negative cohorts.,The incidence of ELVO stroke was compared with the pre-COVID period.,Forty-five consecutive ELVO patients presented during the observation period.,Fifty-three percent of patients tested positive for COVID-19.,Total patients’ mean (±SD) age was 66 (±17).,Patients with COVID-19 were significantly younger than patients without COVID-19, 59±13 versus 74±17 (odds ratio [95% CI], 0.94 [0.81-0.98]; P=0.004).,Seventy-five percent of patients with COVID-19 were male compared with 43% of patients without COVID-19 (odds ratio [95% CI], 3.99 [1.12-14.17]; P=0.032).,Patients with COVID-19 were less likely to be White (8% versus 38% [odds ratio (95% CI), 0.15 (0.04-0.81); P=0.027]).,In comparison to a similar time duration before the COVID-19 outbreak, a 2-fold increase in the total number of ELVO was observed (estimate: 0.78 [95% CI, 0.47-1.08], P≤0.0001).,More than half of the ELVO stroke patients during the peak time of the New York City’s COVID-19 outbreak were COVID-19 positive, and those patients with COVID-19 were younger, more likely to be male, and less likely to be White.,Our findings also suggest an increase in the incidence of ELVO stroke during the peak of the COVID-19 outbreak.

Coronavirus disease 2019 (COVID‐19) can lead to systemic coagulation activation and thrombotic complications.,To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID‐19.,Single‐center cohort study of 198 hospitalized patients with COVID‐19.,Seventy‐five patients (38%) were admitted to the intensive care unit (ICU).,At time of data collection, 16 (8%) were still hospitalized and 19% had died.,During a median follow‐up of 7 days (IQR, 3‐13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis.,The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10‐22), 33% (95% CI, 23‐43) and 42% (95% CI 30‐54) respectively.,For symptomatic VTE, these were 10% (95% CI, 5.8‐16), 21% (95% CI, 14‐30) and 25% (95% CI 16‐36).,VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02‐5.5).,The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17‐37), 47% (95% CI, 34‐58), and 59% (95% CI, 42‐72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4‐15), 9.2% (95% CI, 2.6‐21), and 9.2% (2.6‐21) at 7, 14, and 21 days).,The observed risk for VTE in COVID‐19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE.,Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival.

•COVID-19 in critically ill patients causes death not only from pneumonia but also from multiple organ injuries.,•In critically ill COVID-19 patients with pneumonia, pulmonary thromboembolism may be considered.,•In critically ill COVID-19 patients, contrast-enhanced computed tomography of the chest is mandatory to assess parenchymal patterns and to diagnose pulmonary thromboembolism.,COVID-19 in critically ill patients causes death not only from pneumonia but also from multiple organ injuries.,In critically ill COVID-19 patients with pneumonia, pulmonary thromboembolism may be considered.,In critically ill COVID-19 patients, contrast-enhanced computed tomography of the chest is mandatory to assess parenchymal patterns and to diagnose pulmonary thromboembolism.

Elevated plasma levels of direct low‐density lipoprotein cholesterol (LDL‐C), small dense LDL‐C (sdLDL‐C), low‐density lipoprotein (LDL) triglycerides, triglycerides, triglyceride‐rich lipoprotein cholesterol, remnant lipoprotein particle cholesterol, and lipoprotein(a) have all been associated with incident atherosclerotic cardiovascular disease (ASCVD).,Our goal was to assess which parameters were most strongly associated with ASCVD risk.,Plasma total cholesterol, triglycerides, high‐density lipoprotein cholesterol, direct LDL‐C, sdLDL‐C, LDL triglycerides, remnant lipoprotein particle cholesterol, triglyceride‐rich lipoprotein cholesterol, and lipoprotein(a) were measured using standardized automated analysis (coefficients of variation, <5.0%) in samples from 3094 fasting subjects free of ASCVD.,Of these subjects, 20.2% developed ASCVD over 16 years.,On univariate analysis, all ASCVD risk factors were significantly associated with incident ASCVD, as well as the following specialized lipoprotein parameters: sdLDL‐C, LDL triglycerides, triglycerides, triglyceride‐rich lipoprotein cholesterol, remnant lipoprotein particle cholesterol, and direct LDL‐C.,Only sdLDL‐C, direct LDL‐C, and lipoprotein(a) were significant on multivariate analysis and net reclassification after adjustment for standard risk factors (age, sex, hypertension, diabetes mellitus, smoking, total cholesterol, and high‐density lipoprotein cholesterol).,Using the pooled cohort equation, many specialized lipoprotein parameters individually added significant information, but no parameter added significant information once sdLDL‐C (hazard ratio, 1.42; P<0.0001) was in the model.,These results for sdLDL‐C were confirmed by adjusted discordance analysis versus calculated non-high‐density lipoprotein cholesterol, in contrast to LDL triglycerides.,sdLDL‐C, direct LDL‐C, and lipoprotein(a) all contributed significantly to ASCVD risk on multivariate analysis, but no parameter added significant risk information to the pooled cohort equation once sdLDL‐C was in the model.,Our data indicate that small dense LDL is the most atherogenic lipoprotein parameter.

Aims: This study aims to investigate the association between serum small dense low-density lipoprotein (sdLDL) cholesterol level and the development of coronary heart disease (CHD) in a Japanese community.,Methods: A total of 3,080 participants without prior cardiovascular disease, aged 40 years or older, were followed up for 8 years.,The participants were divided into the quartiles of serum sdLDL cholesterol levels.,The risk estimates were computed using a Cox proportional hazards model.,Results: During the follow-up period, 79 subjects developed CHD.,Subjects in the highest quartile had a 5.41-fold (95% confidence interval, 2.12-13.82) higher risk of CHD than those in the lowest quartile after controlling for confounders.,In the analysis classifying the participants into four groups according to the levels of serum sdLDL cholesterol and serum low-density lipoprotein (LDL) cholesterol levels, the risk of CHD almost doubled in subjects with sdLDL cholesterol of ≥ 32.9 mg/dL (median), regardless of serum LDL cholesterol levels, as compared with subjects with serum sdLDL cholesterol of < 32.9 mg/dL and serum LDL cholesterol of < 120.1 mg/dL (median).,When serum sdLDL cholesterol levels were incorporated into a model with known cardiovascular risk factors, c-statistics was significantly increased (from 0.77 to 0.79; p = 0.02), and the net reclassification improvement was also significant (0.40; p < 0.001).,Conclusions: The present findings suggest that the serum sdLDL cholesterol level is a relevant biomarker for the future development of CHD that offers benefit beyond the serum LDL cholesterol level and a possible therapeutic target to reduce the burden of CHD in a Japanese community.

The coronavirus disease (COVID-19) pandemic has changed routine clinical practice worldwide with major impacts on the provision of care and treatment for stroke patients.,This retrospective observational study included all patients admitted to the Royal Stoke University Hospital in Stoke-on-Trent, UK, with a stroke or transient ischaemic attack between March 15th and April 14th, 2020 (COVID).,Patient demographics, characteristics of the stroke, treatment details and logistics were compared with patients admitted in the corresponding weeks in the year before (2019).,There was a 39.5% (n = 101 vs n = 167) reduction in admissions in the COVID cohort compared with 2019 with more severe strokes (median National Institutes of Health Stroke Scale (NIHSS) 7 vs 4, p = 0.02), and fewer strokes with no visible acute pathology (21.8 vs 37.1%, p = 0.01) on computed tomography.,There was no statistically significant difference in the rates of thrombolysis (10.9 vs 13.2%, p = 0.72) and/or thrombectomy (5.9 vs 4.8%, p = 0.90) and no statistically significant difference in time from stroke onset to arrival at hospital (734 vs 576 min, p = 0.34), door-to-needle time for thrombolysis (54 vs 64 min, p = 0.43) and door-to-thrombectomy time (181 vs 445 min, p = 0.72).,Thirty-day mortality was not significantly higher in the COVID year (10.9 vs 8.9%, p = 0.77).,None of the 7 stroke patients infected with COVID-19 died.,During the COVID-19 pandemic, the number of stroke admissions fell, and stroke severity increased.,There was no statistically significant change in the delivery of thrombolysis and mechanical thrombectomy and no increase in mortality.

The purpose of the study is to analyze how the coronavirus disease 2019 (COVID-19) pandemic affected acute stroke care in a Comprehensive Stroke Center.,On February 28, 2020, contingency plans were implemented at Hospital Clinic of Barcelona to contain the COVID-19 pandemic.,Among them, the decision to refrain from reallocating the Stroke Team and Stroke Unit to the care of patients with COVID-19.,From March 1 to March 31, 2020, we measured the number of emergency calls to the Emergency Medical System in Catalonia (7.5 million inhabitants), and the Stroke Codes dispatched to Hospital Clinic of Barcelona.,We recorded all stroke admissions, and the adequacy of acute care measures, including the number of thrombectomies, workflow metrics, angiographic results, and clinical outcomes.,Data were compared with March 2019 using parametric or nonparametric methods as appropriate.,At Hospital Clinic of Barcelona, 1232 patients with COVID-19 were admitted in March 2020, demanding 60% of the hospital bed capacity.,Relative to March 2019, the Emergency Medical System had a 330% mean increment in the number of calls (158 005 versus 679 569), but fewer Stroke Code activations (517 versus 426).,Stroke admissions (108 versus 83) and the number of thrombectomies (21 versus 16) declined at Hospital Clinic of Barcelona, particularly after lockdown of the population.,Younger age was found in stroke admissions during the pandemic (median [interquartile range] 69 [64-73] versus 75 [73-80] years, P=0.009).,In-hospital, there were no differences in workflow metrics, angiographic results, complications, or outcomes at discharge.,The COVID-19 pandemic reduced by a quarter the stroke admissions and thrombectomies performed at a Comprehensive Stroke Center but did not affect the quality of care metrics.,During the lockdown, there was an overload of emergency calls but fewer Stroke Code activations, particularly in elderly patients.,Hospital contingency plans, patient transport systems, and population-targeted alerts must act concertedly to better protect the chain of stroke care in times of pandemic.

Despite a lack of clinical evidence, hydroxychloroquine and azithromycin are being administered widely to patients with verified or suspected coronavirus disease 2019 (COVID‐19).,Both drugs may increase risk of lethal arrhythmias associated with QT interval prolongation.,We analyzed a case series of COVID‐19-positive/suspected patients admitted between February 1, 2020, and April 4, 2020, who were treated with azithromycin, hydroxychloroquine, or a combination of both drugs.,We evaluated baseline and postmedication QT interval (corrected QT interval [QTc]; Bazett) using 12‐lead ECGs.,Critical QTc prolongation was defined as follows: (1) maximum QTc ≥500 ms (if QRS <120 ms) or QTc ≥550 ms (if QRS ≥120 ms) and (2) QTc increase of ≥60 ms.,Tisdale score and Elixhauser comorbidity index were calculated.,Of 490 COVID‐19-positive/suspected patients, 314 (64%) received either/both drugs and 98 (73 COVID‐19 positive and 25 suspected) met study criteria (age, 62±17 years; 61% men).,Azithromycin was prescribed in 28%, hydroxychloroquine in 10%, and both in 62%.,Baseline mean QTc was 448±29 ms and increased to 459±36 ms (P=0.005) with medications.,Significant prolongation was observed only in men (18±43 ms versus −0.2±28 ms in women; P=0.02).,A total of 12% of patients reached critical QTc prolongation.,Changes in QTc were highest with the combination compared with either drug, with much greater prolongation with combination versus azithromycin (17±39 ms versus 0.5±40 ms; P=0.07).,No patients manifested torsades de pointes.,Overall, 12% of patients manifested critical QTc prolongation, and the combination caused greater prolongation than either drug alone.,The balance between uncertain benefit and potential risk when treating COVID‐19 patients should be carefully assessed.

Most of the drugs associations that have been used to treat patients with SARS-CoV-2 infection increase the risk of prolongation of the corrected QT interval (QTc).,To evaluate the effects of an association therapy of hydroxychloroquine (HY) plus ritonavir/darunavir (RD) or azithromycin (AZ) on QTc intervals.,At the beginning of COVID-19 pandemic patients admitted to our hospital were treated with the empiric association of HY/RD; one week later the therapeutic protocol was modified with the combination of HY/AZ.,Patients underwent an ECG at baseline, then 3 and 7 days after starting therapy.,We prospectively enrolled 113 patients (61 in the HY/RD group-52 in the HY/AZ group).,A significant increase in median QTc was reported after seven days of therapy in both groups: from 438 to 452 ms in HY/RD patients; from 433 to 440 ms in HY/AZ patients (p = 0.001 for both). 23 patients (21.2%) had a QTc > 500 ms at 7 days.,The risk of developing a QTc > 500 ms was greater in patients with prolonged baseline QTc values (≥ 440 ms for female and ≥ 460 ms for male patients) (OR 7.10 (95% IC 1.88-26.81); p = 0.004) and in patients with an increase in the QTc > 40 ms 3 days after onset of treatment (OR 30.15 (95% IC 6.96-130.55); p = 0.001).,One patient per group suffered a malignant ventricular arrhythmia.,Hydroxychloroquine with both ritonavir/darunavir or azithromycin therapy significantly increased the QTc-interval at 7 days.,The risk of developing malignant arrhythmias remained relatively low when these drugs were administered for a limited period of time.

The triglyceride glucose (TyG) index has been suggested as a simple surrogate marker of insulin resistance.,However, there are limited data regarding the association between the TyG index and arterial stiffness in adults.,Therefore, we evaluated the relationship between the TyG index and arterial stiffness as measured based on brachial ankle pulse wave velocity (baPWV) in Korean adults.,A total of 3587 subjects were enrolled in this study.,Anthropometric and cardiovascular risk factors were measured.,The TyG index was calculated as ln[fasting triglycerides(mg/dl) × fasting glucose(mg/dl)/2], and the insulin resistance index of homeostasis model assessment (HOMA-IR) was estimated.,Arterial stiffness was determined by measuring baPWV.,The subjects were stratified into four groups based on the TyG index.,There were significant differences in cardiovascular parameters among the groups; the mean baPWV increased significantly with increasing TyG index.,According to the logistic regression analysis after adjusting for multiple risk factors, the odds ratio (95% CI) for increased baPWV (> 75th percentile) for the highest and lowest quartiles of the TyG index was 2.92 (1.92-4.44) in men and 1.84 (1.15-2.96) in women, and the odds ratio for increased baPWV for the highest and lowest quartiles of the HOMA-IR was 1.80 (1.17-2.78) in men and 1.46 (1.06-2.47) in women, respectively.,The TyG index is more independently associated with increased arterial stiffness than HOMA-IR in Korean adults.

The triglyceride glucose (TyG) index has been considered a simple surrogate marker of insulin resistance.,However, few studies have investigated the relationship between the TyG index and coronary artery calcification (CAC).,Thus, we investigated the relationship between the TyG index and CAC in healthy Korean adults.,In total, 4319 participants who underwent cardiac computed tomography (CT) in a health promotion center were enrolled.,Anthropometric profiles and multiple cardiovascular risk factors were measured.,The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2], and the insulin resistance index of homeostasis model assessment (HOMA-IR) was estimated.,The CAC was measured using multidetector CT, and CAC presence was defined as an Agatston score of >0.,All subjects were stratified into four groups based on their TyG indices.,Significant differences were observed in cardiovascular parameters among the groups, and the prevalence of CAC significantly increased with increasing TyG index.,In the logistic regression analysis after adjustment for multiple risk factors, the odds ratio for the prevalence of CAC, when comparing the highest and lowest quartiles of the TyG index was 1.95 (95% CI 1.23-3.11; P for trend = 0.01); the odds ratio for the prevalence of CAC, when comparing the highest and lowest quartiles of HOMA-IR was 1.64 (95% CI 1.12-2.40; P for trend = 0.04).,In the receiver operating characteristics analysis, the TyG index was superior to HOMA-IR in predicting CAC.,The TyG index is more independently associated with the presence of coronary artery atherosclerosis than is HOMA-IR in healthy Korean adults.,The online version of this article (doi:10.1186/s12933-017-0589-4) contains supplementary material, which is available to authorized users.

In inflammatory bowel disease (IBD), the impact of established cardiovascular risk factors and disease-related factors on the risk of acute arterial events is still unclear.,We aimed to identify risk factors of acute arterial events in patients with IBD.,All consecutive patients followed at Saint-Antoine Hospital between 1996 and 2015 with subsequent occurrence of acute arterial events (acute coronary syndrome or ischemic stroke) were identified.,Traditional cardiovascular risk factors, treatment exposure, systemic inflammation (mean serum CRP level greater than or equal to 5 mg/L) and IBD clinical activity were assessed.,A nested case-control study was performed including cases and controls without arterial ischemic event, matched on age, gender, and disease extent.,A total of 30 patients (median age at acute vascular event occurrence: 42 years (interquartile range: 25-59)) developed acute coronary syndrome (n = 22) or ischemic stroke (n = 8).,In univariate analysis, clinical disease activity and the persistence of systemic inflammation, diabetes, dyslipidemia and hypertension were significantly associated with an increased risk of acute arterial events.,Neither protective nor aggravating effects associated with treatment exposure were identified.,In multivariate analysis, the presence of diabetes (Odds ratio (OR): 14.5, 95% confidence interval (CI): 1.1-184.7) and clinical disease activity (OR: 10.4, 95% CI: 2.1-49.9) remained significantly associated with the risk of acute arterial event.,Disease activity may have an independent impact on the risk of acute arterial events in patients with IBD.,These findings may highlight new potential benefits of optimizing anti-inflammatory treatment in patients with persisting clinical activity.

Several immune‐mediated diseases have been shown to be associated with an increased risk of cardiovascular disease.,However, studies evaluating the association between inflammatory bowel disease and risk of cardiovascular disease reported inconsistent results.,We assessed the association between inflammatory bowel disease and risk of ischemic heart disease in a meta‐analysis of cohort studies.,We conducted a literature search of PubMed and Embase up to October 2016 to identify relevant studies.,The summary relative risks were calculated using the random‐effects models.,To explore the source of heterogeneity, we performed subgroup and sensitivity analysis.,We included 10 cohort studies that satisfied our inclusion criteria.,Patients with inflammatory bowel disease were associated with an increased risk of ischemic heart disease (relative risk: 1.244; 95% CI, 1.142-1.355).,Considerable heterogeneity was observed.,Crohn's disease showed a significantly increased risk of ischemic heart disease (relative risk=1.243; 95% CI, 1.042-1.482) and a positive association was also observed in ulcerative colitis (relative risk=1.206; 95% CI, 1.170-1.242).,Based on meta‐analysis of cohort studies, we found an increased risk of ischemic heart disease in patients with inflammatory bowel disease.,Large long‐term prospective studies are warranted to confirm our results.

In 2007, we reported a summary of data comparing diabetic foot complications to cancer.,The purpose of this brief report was to refresh this with the best available data as they currently exist.,Since that time, more reports have emerged both on cancer mortality and mortality associated with diabetic foot ulcer (DFU), Charcot arthropathy, and diabetes-associated lower extremity amputation.,We collected data reporting 5-year mortality from studies published following 2007 and calculated a pooled mean.,We evaluated data from DFU, Charcot arthropathy and lower extremity amputation.,We dichotomized high and low amputation as proximal and distal to the ankle, respectively.,This was compared with cancer mortality as reported by the American Cancer Society and the National Cancer Institute.,Five year mortality for Charcot, DFU, minor and major amputations were 29.0, 30.5, 46.2 and 56.6%, respectively.,This is compared to 9.0% for breast cancer and 80.0% for lung cancer. 5 year pooled mortality for all reported cancer was 31.0%.,Direct costs of care for diabetes in general was $237 billion in 2017.,This is compared to $80 billion for cancer in 2015.,As up to one-third of the direct costs of care for diabetes may be attributed to the lower extremity, these are also readily comparable.,Diabetic lower extremity complications remain enormously burdensome.,Most notably, DFU and LEA appear to be more than just a marker of poor health.,They are independent risk factors associated with premature death.,While advances continue to improve outcomes of care for people with DFU and amputation, efforts should be directed at primary prevention as well as those for patients in diabetic foot ulcer remission to maximize ulcer-free, hospital-free and activity-rich days.

To assess the risk of diabetic foot ulcer (DFU) and find out its associated factors among subjects with type 2 diabetes (T2D) of Bangladesh.,This cross-sectional study recruited 1200 subjects with T2D who visited 16 centres of Health Care Development Project run by Diabetic Association of Bangladesh.,Risk of DFU was assessed using a modified version of International Working Group on the Diabetic Foot (IWGDF) Risk Classification System.,The modified system was based on five parameters, namely peripheral neuropathy (PN), peripheral arterial diseases (PAD), deformity, ulcer history and amputation.,The risks were categorised as group 0 (no PN, no PAD), group 1 (PN, no PAD and no deformity), group 2A (PN and deformity, no PAD), group 2B (PAD), group 3A (ulcer history) and group 3B (amputation).,The associated factors of DFU risk were determined using multinomial logistic regression for each risk category separately.,Overall, 44.5% of the subjects were found ‘at risk’ of DFU.,This risk was higher among men (45.6%) than women and among those who lived in rural areas (45.5%) as compared with the urban population.,According to IWGDF categories, the risk was distributed as 55.5%, 4.2%, 11.6%, 0.3%, 20.6% and 7.9% for group 0, group 1, group 2A, group 2B, group 3A and group 3B, respectively.,The associated factors of DFU (OR >1) were age ≥50 years, rural area, low economic status, insulin use, history of trauma, diabetic retinopathy and diabetic nephropathy.,A significant number of the subjects with T2D under study were at risk of DFU, which demands an effective screening programme to reduce DFU-related morbidity and mortality.

Supplemental Digital Content is available in the text.,In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction.,We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo.,We examined the effects of study treatment in the following subgroups: no diuretic and diuretic dose equivalent to furosemide <40, 40, and >40 mg daily at baseline.,We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms.,Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on <40 mg, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were taking >40 mg.,Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: hazard ratios were 0.57 (95% CI, 0.36-0.92), 0.83 (95% CI, 0.63-1.10), 0.77 (95% CI, 0.60-0.99), and 0.78 (95% CI, 0.63-0.97), respectively (P for interaction=0.61).,The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68-0.90).,Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups.,Diuretic dose did not change in most patients during follow-up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization.,The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF.,URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.

Supplemental Digital Content is available in the text.,Canagliflozin is a sodium glucose cotransporter 2 inhibitor that reduces the risk of cardiovascular events.,We report the effects on heart failure (HF) and cardiovascular death overall, in those with and without a baseline history of HF, and in other participant subgroups.,The CANVAS Program (Canagliflozin Cardiovascular Assessment Study) enrolled 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk.,Participants were randomly assigned to canagliflozin or placebo and followed for a mean of 188 weeks.,The primary end point for these analyses was adjudicated cardiovascular death or hospitalized HF.,Participants with a history of HF at baseline (14.4%) were more frequently women, white, and hypertensive and had a history of prior cardiovascular disease (all P<0.001).,Greater proportions of these patients were using therapies such as blockers of the renin angiotensin aldosterone system, diuretics, and β-blockers at baseline (all P<0.001).,Overall, cardiovascular death or hospitalized HF was reduced in those treated with canagliflozin compared with placebo (16.3 versus 20.8 per 1000 patient-years; hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.67-0.91), as was fatal or hospitalized HF (HR, 0.70; 95% CI, 0.55-0.89) and hospitalized HF alone (HR, 0.67; 95% CI, 0.52-0.87).,The benefit on cardiovascular death or hospitalized HF may be greater in patients with a prior history of HF (HR, 0.61; 95% CI, 0.46-0.80) compared with those without HF at baseline (HR, 0.87; 95% CI, 0.72-1.06; P interaction =0.021).,The effects of canagliflozin compared with placebo on other cardiovascular outcomes and key safety outcomes were similar in participants with and without HF at baseline (all interaction P values >0.130), except for a possibly reduced absolute rate of events attributable to osmotic diuresis among those with a prior history of HF (P=0.03).,In patients with type 2 diabetes mellitus and an elevated risk of cardiovascular disease, canagliflozin reduced the risk of cardiovascular death or hospitalized HF across a broad range of different patient subgroups.,Benefits may be greater in those with a history of HF at baseline.,URL: https://www.clinicaltrials.gov.,Unique identifiers: NCT01032629 and NCT01989754.

We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals.,In answering questions raised regarding our study, we updated our database and repeated all analyses.,We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first.,We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%).,The median follow-up duration increased from 7 to 14 days.,All patients received pharmacological thromboprophylaxis.,The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41-57%).,The majority of thrombotic events were PE (65/75; 87%).,In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091-0.92).,Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4-12).,Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35-1.8).,In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia.

Angiotensin converting enzyme-2 (ACE2) receptors mediate the entry into the cell of three strains of coronavirus: SARS-CoV, NL63 and SARS-CoV-2.,ACE2 receptors are ubiquitous and widely expressed in the heart, vessels, gut, lung (particularly in type 2 pneumocytes and macrophages), kidney, testis and brain.,ACE2 is mostly bound to cell membranes and only scarcely present in the circulation in a soluble form.,An important salutary function of membrane-bound and soluble ACE2 is the degradation of angiotensin II to angiotensin1-7.,Consequently, ACE2 receptors limit several detrimental effects resulting from binding of angiotensin II to AT1 receptors, which include vasoconstriction, enhanced inflammation and thrombosis.,The increased generation of angiotensin1-7 also triggers counter-regulatory protective effects through binding to G-protein coupled Mas receptors.,Unfortunately, the entry of SARS-CoV2 into the cells through membrane fusion markedly down-regulates ACE2 receptors, with loss of the catalytic effect of these receptors at the external site of the membrane.,Increased pulmonary inflammation and coagulation have been reported as unwanted effects of enhanced and unopposed angiotensin II effects via the ACE→Angiotensin II→AT1 receptor axis.,Clinical reports of patients infected with SARS-CoV-2 show that several features associated with infection and severity of the disease (i.e., older age, hypertension, diabetes, cardiovascular disease) share a variable degree of ACE2 deficiency.,We suggest that ACE2 down-regulation induced by viral invasion may be especially detrimental in people with baseline ACE2 deficiency associated with the above conditions.,The additional ACE2 deficiency after viral invasion might amplify the dysregulation between the ‘adverse’ ACE→Angiotensin II→AT1 receptor axis and the ‘protective’ ACE2→Angiotensin1-7→Mas receptor axis.,In the lungs, such dysregulation would favor the progression of inflammatory and thrombotic processes triggered by local angiotensin II hyperactivity unopposed by angiotensin1-7.,In this setting, recombinant ACE2, angiotensin1-7 and angiotensin II type 1 receptor blockers could be promising therapeutic approaches in patients with SARS-CoV-2 infection.

To estimate the incidence, risk factors, and outcomes associated with in-hospital cardiac arrest and cardiopulmonary resuscitation in critically ill adults with coronavirus disease 2019 (covid-19).,Multicenter cohort study.,Intensive care units at 68 geographically diverse hospitals across the United States.,Critically ill adults (age ≥18 years) with laboratory confirmed covid-19.,In-hospital cardiac arrest within 14 days of admission to an intensive care unit and in-hospital mortality.,Among 5019 critically ill patients with covid-19, 14.0% (701/5019) had in-hospital cardiac arrest, 57.1% (400/701) of whom received cardiopulmonary resuscitation.,Patients who had in-hospital cardiac arrest were older (mean age 63 (standard deviation 14) v 60 (15) years), had more comorbidities, and were more likely to be admitted to a hospital with a smaller number of intensive care unit beds compared with those who did not have in-hospital cardiac arrest.,Patients who received cardiopulmonary resuscitation were younger than those who did not (mean age 61 (standard deviation 14) v 67 (14) years).,The most common rhythms at the time of cardiopulmonary resuscitation were pulseless electrical activity (49.8%, 199/400) and asystole (23.8%, 95/400). 48 of the 400 patients (12.0%) who received cardiopulmonary resuscitation survived to hospital discharge, and only 7.0% (28/400) survived to hospital discharge with normal or mildly impaired neurological status.,Survival to hospital discharge differed by age, with 21.2% (11/52) of patients younger than 45 years surviving compared with 2.9% (1/34) of those aged 80 or older.,Cardiac arrest is common in critically ill patients with covid-19 and is associated with poor survival, particularly among older patients.

To evaluate the impact of the COVID-19 pandemic on patient admissions to Italian cardiac care units (CCUs).,We conducted a multicentre, observational, nationwide survey to collect data on admissions for acute myocardial infarction (AMI) at Italian CCUs throughout a 1 week period during the COVID-19 outbreak, compared with the equivalent week in 2019.,We observed a 48.4% reduction in admissions for AMI compared with the equivalent week in 2019 (P < 0.001).,The reduction was significant for both ST-segment elevation myocardial infarction [STEMI; 26.5%, 95% confidence interval (CI) 21.7-32.3; P = 0.009] and non-STEMI (NSTEMI; 65.1%, 95% CI 60.3-70.3; P < 0.001).,Among STEMIs, the reduction was higher for women (41.2%; P = 0.011) than men (17.8%; P = 0.191).,A similar reduction in AMI admissions was registered in North Italy (52.1%), Central Italy (59.3%), and South Italy (52.1%).,The STEMI case fatality rate during the pandemic was substantially increased compared with 2019 [risk ratio (RR) = 3.3, 95% CI 1.7-6.6; P < 0.001].,A parallel increase in complications was also registered (RR = 1.8, 95% CI 1.1-2.8; P = 0.009).,Admissions for AMI were significantly reduced during the COVID-19 pandemic across Italy, with a parallel increase in fatality and complication rates.,This constitutes a serious social issue, demanding attention by the scientific and healthcare communities and public regulatory agencies.

Although the direct toll of COVID-19 in the United States has been substantial, concerns have also arisen about the indirect effects of the pandemic.,Hospitalizations for acute cardiovascular conditions have declined, raising concern that patients may be avoiding hospitals because of fear of contracting severe acute respiratory syndrome- coronavirus-2 (SARS-CoV-2).,Other factors, including strain on health care systems, may also have had an indirect toll.,This investigation aimed to evaluate whether population-level deaths due to cardiovascular causes increased during the COVID-19 pandemic.,The authors conducted an observational cohort study using data from the National Center for Health Statistics to evaluate the rate of deaths due to cardiovascular causes after the onset of the pandemic in the United States, from March 18, 2020, to June 2, 2020, relative to the period immediately preceding the pandemic (January 1, 2020 to March 17, 2020).,Changes in deaths were compared with the same periods in the previous year.,There were 397,042 cardiovascular deaths from January 1, 2020, to June 2, 2020.,Deaths caused by ischemic heart disease increased nationally after the onset of the pandemic in 2020, compared with changes over the same period in 2019 (ratio of the relative change in deaths per 100,000 in 2020 vs.,2019: 1.11, 95% confidence interval: 1.04 to 1.18).,An increase was also observed for deaths caused by hypertensive disease (1.17, 95% confidence interval: 1.09 to 1.26), but not for heart failure, cerebrovascular disease, or other diseases of the circulatory system.,New York City experienced a large relative increase in deaths caused by ischemic heart disease (2.39, 95% confidence interval: 1.39 to 4.09) and hypertensive diseases (2.64, 95% confidence interval: 1.52 to 4.56) during the pandemic.,More modest increases in deaths caused by these conditions occurred in the remainder of New York State, New Jersey, Michigan, and Illinois but not in Massachusetts or Louisiana.,There was an increase in deaths caused by ischemic heart disease and hypertensive diseases in some regions of the United States during the initial phase of the COVID-19 pandemic.,These findings suggest that the pandemic may have had an indirect toll on patients with cardiovascular disease.

This cross-sectional study describes the characteristics associated with outpatient cardiac arrests and death during the coronavirus disease 2019 pandemic in New York City.,What characteristics are associated with out-of-hospital cardiac arrests and death during the COVID-19 pandemic in New York City?,In this population-based cross-sectional study of 5325 patients with out-of-hospital cardiac arrests, the number undergoing resuscitation was 3-fold higher during the 2020 COVID-19 period compared with during the comparison period in 2019.,Patients with out-of-hospital cardiac arrest during 2020 were older, less likely to be white, and more likely to have specific comorbidities and substantial reductions in return and sustained return of spontaneous circulation.,Identifying patients at risk for out-of-hospital cardiac arrest and death during the COVID-19 pandemic should lead to interventions in the outpatient setting to help reduce out-of-hospital deaths.,Risk factors for out-of-hospital death due to novel coronavirus disease 2019 (COVID-19) are poorly defined.,From March 1 to April 25, 2020, New York City, New York (NYC), reported 17 118 COVID-19-related deaths.,On April 6, 2020, out-of-hospital cardiac arrests peaked at 305 cases, nearly a 10-fold increase from the prior year.,To describe the characteristics (race/ethnicity, comorbidities, and emergency medical services [EMS] response) associated with outpatient cardiac arrests and death during the COVID-19 pandemic in NYC.,This population-based, cross-sectional study compared patients with out-of-hospital cardiac arrest receiving resuscitation by the NYC 911 EMS system from March 1 to April 25, 2020, compared with March 1 to April 25, 2019.,The NYC 911 EMS system serves more than 8.4 million people.,The COVID-19 pandemic.,Characteristics associated with out-of-hospital arrests and the outcomes of out-of-hospital cardiac arrests.,A total of 5325 patients were included in the main analysis (2935 men [56.2%]; mean [SD] age, 71 [18] years), 3989 in the COVID-19 period and 1336 in the comparison period.,The incidence of nontraumatic out-of-hospital cardiac arrests in those who underwent EMS resuscitation in 2020 was 3 times the incidence in 2019 (47.5/100 000 vs 15.9/100 000).,Patients with out-of-hospital cardiac arrest during 2020 were older (mean [SD] age, 72 [18] vs 68 [19] years), less likely to be white (611 of 2992 [20.4%] vs 382 of 1161 [32.9%]), and more likely to have hypertension (2134 of 3989 [53.5%] vs 611 of 1336 [45.7%]), diabetes (1424 of 3989 [35.7%] vs 348 of 1336 [26.0%]), and physical limitations (2259 of 3989 [56.6%] vs 634 of 1336 [47.5%]).,Compared with 2019, the odds of asystole increased in the COVID-19 period (odds ratio [OR], 3.50; 95% CI, 2.53-4.84; P < .001), as did the odds of pulseless electrical activity (OR, 1.99; 95% CI, 1.31-3.02; P = .001).,Compared with 2019, the COVID-19 period had substantial reductions in return of spontaneous circulation (ROSC) (727 of 3989 patients [18.2%] vs 463 of 1336 patients [34.7%], P < .001) and sustained ROSC (423 of 3989 patients [10.6%] vs 337 of 1336 patients [25.2%], P < .001), with fatality rates exceeding 90%.,These associations remained statistically significant after adjustment for potential confounders (OR for ROSC, 0.59 [95% CI, 0.50-0.70; P < .001]; OR for sustained ROSC, 0.53 [95% CI, 0.43-0.64; P < .001]).,In this population-based, cross-sectional study, out-of-hospital cardiac arrests and deaths during the COVID-19 pandemic significantly increased compared with the same period the previous year and were associated with older age, nonwhite race/ethnicity, hypertension, diabetes, physical limitations, and nonshockable presenting rhythms.,Identifying patients with the greatest risk for out-of-hospital cardiac arrest and death during the COVID-19 pandemic should allow for early, targeted interventions in the outpatient setting that could lead to reductions in out-of-hospital deaths.

Patients with cardiovascular disease and, namely, heart failure are more susceptible to coronavirus disease 2019 (COVID‐19) and have a more severe clinical course once infected.,Heart failure and myocardial damage, shown by increased troponin plasma levels, occur in at least 10% of patients hospitalized for COVID‐19 with higher percentages, 25% to 35% or more, when patients critically ill or with concomitant cardiac disease are considered.,Myocardial injury may be elicited by multiple mechanisms, including those occurring with all severe infections, such as fever, tachycardia, adrenergic stimulation, as well as those caused by an exaggerated inflammatory response, endotheliitis and, in some cases, myocarditis that have been shown in patients with COVID‐19.,A key role may be that of the renin-angiotensin-aldosterone system.,Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infects human cells binding to angiotensin‐converting enzyme 2 (ACE2), an enzyme responsible for the cleavage of angiotensin II into angiotensin 1-7, which has vasodilating and anti‐inflammatory effects.,Virus‐mediated down‐regulation of ACE2 may increase angiotensin II stimulation and contribute to the deleterious hyper‐inflammatory reaction of COVID‐19.,On the other hand, ACE2 may be up‐regulated in patients with cardiac disease and treated with ACE inhibitors or angiotensin receptor blockers.,ACE2 up‐regulation may increase the susceptibility to COVID‐19 but may be also protective vs. angiotensin II‐mediated vasoconstriction and inflammatory activation.,Recent data show the lack of untoward effects of ACE inhibitors or angiotensin receptor blockers for COVID‐19 infection and severity.,Prospective trials are needed to ascertain whether these drugs may have protective effects.

COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation.,Reports on the incidence of thrombotic complications are however not available.,We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.,We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020.,All patients received at least standard doses thromboprophylaxis.,The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%).,PE was the most frequent thrombotic complication (n = 25, 81%).,Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.,The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high.,Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.

Obesity is an emerging independent risk factor for susceptibility to and severity of coronavirus disease 2019 (COVID‐19) caused by the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2).,Previous viral pandemics have shown that obesity, particularly severe obesity (BMI > 40 kg/m2), is associated with increased risk of hospitalization, critical care admission and fatalities.,In this narrative review, we examine emerging evidence of the influence of obesity on COVID‐19, the challenges to clinical management from pulmonary, endocrine and immune dysfunctions in individuals with obesity and identify potential areas for further research.,We recommend that people with severe obesity be deemed a vulnerable group for COVID‐19; clinical trials of pharmacotherapeutics, immunotherapies and vaccination should prioritize inclusion of people with obesity.

The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur.,This brief report evaluates cardiovascular complications in the setting of COVID-19 infection.,The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death.,The virus binds and enters through angiotensin-converting enzyme 2 (ACE2).,COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness.,The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events.,Current therapies for COVID-19 may interact with cardiovascular medications.,Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.

Tumor necrosis factor-alpha (TNF-α) plays an important pathogenic role in cardiac hypertrophy and heart failure (HF); however, anti-TNF is paradoxically negative in clinical trials and even worsens HF, indicating a possible protective role of TNF-α in HF.,TNF-α exists in transmembrane (tmTNF-α) and soluble (sTNF-α) forms.,Herein, we found that TNF receptor 1 (TNFR1) knockout (KO) or knockdown (KD) by short hairpin RNA or small interfering RNA (siRNA) significantly alleviated cardiac hypertrophy, heart dysfunction, fibrosis, and inflammation with increased tmTNF-α expression, whereas TNFR2 KO or KD exacerbated the pathological phenomena with increased sTNF-α secretion in transverse aortic constriction (TAC)- and isoproterenol (ISO)-induced cardiac hypertrophy in vivo and in vitro, respectively, indicating the beneficial effects of TNFR2 associated with tmTNF-α.,Suppressing TNF-α converting enzyme by TNF-α Protease Inhibitor-1 (TAPI-1) to increase endogenous tmTNF-α expression significantly alleviated TAC-induced cardiac hypertrophy.,Importantly, direct addition of exogenous tmTNF-α into cardiomyocytes in vitro significantly reduced ISO-induced cardiac hypertrophy and transcription of the pro-inflammatory cytokines and induced proliferation.,The beneficial effects of tmTNF-α were completely blocked by TNFR2 KD in H9C2 cells and TNFR2 KO in primary myocardial cells.,Furthermore, we demonstrated that tmTNF-α displayed antihypertrophic and anti-inflammatory effects by activating the AKT pathway and inhibiting the nuclear factor (NF)-κB pathway via TNFR2.,Our data suggest that tmTNF-α exerts cardioprotective effects via TNFR2.,Specific targeting of tmTNF-α processing, rather than anti-TNF therapy, may be more useful for the treatment of hypertrophy and HF.,In contrast to detrimental effects of soluble tumor necrosis factor-alpha (TNF-α) via TNFR1, this study shows that transmembrane TNF-α protects the heart by suppressing pressure overload-induced cardiac hypertrophy and inflammation via TNFR2.,Targeting tmTNF-α processing may be more useful than TNF-antagonist for treatment of hypertrophy and heart failure.

We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)‐α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease.,CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) is a randomized clinical trial comparing clarithromycin with placebo in patients with stable coronary heart disease.,The primary outcome was a composite of nonfatal acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all‐cause mortality.,Patients were followed up for 10 years; discovery sample, those assigned placebo (1204 events in n=1998); and replication sample, those assigned clarithromycin (1220 events in n=1979).,We used Cox regression adjusted for C‐reactive protein level, established cardiovascular risk factors, kidney function, and cardiovascular drugs.,After adjustments, higher serum levels of TNFR1 and TNFR2 were associated with the composite outcome in the discovery sample (hazard ratio per SD increase, 1.13; 95% confidence interval, 1.05-1.22; P=0.001 for TNFR1; hazard ratio, 1.16; 95% confidence interval, 1.08-1.24; P<0.001 for TNFR2).,The associations were similar in the replication sample.,The associations with the composite outcome were mainly driven by acute myocardial infarction, cardiovascular mortality, and noncardiovascular mortality.,The addition of TNFR1 and TNFR2 to established cardiovascular risk factors improved prediction only modestly (<1%).,Increased concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease.,Yet, the utility of measuring TNFR1 and TNFR2 to improve risk prediction in these patients appears limited.,URL: https://www.clinicaltrials.gov.,Unique identifier: NCT00121550.

Although COVID-19 has been reported to be associated with high rates of venous thromboembolism (VTE), the risk of VTE and bleeding after hospitalization for COVID-19 remains unclear, and the optimal hospital VTE prevention strategy is not known.,We collected retrospective observational data on thrombosis and bleeding in 303 consecutive adult patients admitted to the hospital for at least 24 hours for COVID-19.,Patients presenting with VTE on admission were excluded.,Data were collected until 90 days after admission or known death by using medical records and an established national VTE network.,Maximal level of care was ward based in 78% of patients, with 22% requiring higher dependency care (12% noninvasive ventilation, 10% invasive ventilation).,Almost all patients (97.0%) received standard thromboprophylaxis or were already receiving therapeutic anticoagulation (17.5%).,Symptomatic image-confirmed VTE occurred in 5.9% of patients during index hospitalization, and in 7.2% at 90 days after admission (23.9% in patients requiring higher dependency care); half the events were isolated segmental or subsegmental defects on lung imaging.,Bleeding occurred in 13 patients (4.3%) during index hospitalization (1.3% had major bleeding).,The majority of bleeds occurred in patients on the general ward, and 6 patients were receiving treatment-dose anticoagulation, highlighting the need for caution in intensifying standard thromboprophylaxis strategies.,Of 152 patients discharged from the hospital without an indication for anticoagulation, 97% did not receive thromboprophylaxis after discharge, and 3% received 7 days of treatment with low molecular weight heparin after discharge.,The rate of symptomatic VTE in this group at 42 days after discharge was 2.6%, highlighting the need for large prospective randomized controlled trials of extended thromboprophylaxis after discharge in COVID-19.,•The rate of symptomatic VTE in patients after hospitalization for COVID-19 was 2.6% at 42 days after discharge.,•Bleeding is a significant cause of morbidity in addition to thrombosis in patients admitted with COVID-19.,The rate of symptomatic VTE in patients after hospitalization for COVID-19 was 2.6% at 42 days after discharge.,Bleeding is a significant cause of morbidity in addition to thrombosis in patients admitted with COVID-19.

The degree of myocardial injury, as reflected by troponin elevation, and associated outcomes among U.S. hospitalized patients with coronavirus disease-2019 (COVID-19) are unknown.,The purpose of this study was to describe the degree of myocardial injury and associated outcomes in a large hospitalized cohort with laboratory-confirmed COVID-19.,Patients with COVID-19 admitted to 1 of 5 Mount Sinai Health System hospitals in New York City between February 27, 2020, and April 12, 2020, with troponin-I (normal value <0.03 ng/ml) measured within 24 h of admission were included (n = 2,736).,Demographics, medical histories, admission laboratory results, and outcomes were captured from the hospitals’ electronic health records.,The median age was 66.4 years, with 59.6% men.,Cardiovascular disease (CVD), including coronary artery disease, atrial fibrillation, and heart failure, was more prevalent in patients with higher troponin concentrations, as were hypertension and diabetes.,A total of 506 (18.5%) patients died during hospitalization.,In all, 985 (36%) patients had elevated troponin concentrations.,After adjusting for disease severity and relevant clinical factors, even small amounts of myocardial injury (e.g., troponin I >0.03 to 0.09 ng/ml; n = 455; 16.6%) were significantly associated with death (adjusted hazard ratio: 1.75; 95% CI: 1.37 to 2.24; p < 0.001) while greater amounts (e.g., troponin I >0.09 ng/dl; n = 530; 19.4%) were significantly associated with higher risk (adjusted HR: 3.03; 95% CI: 2.42 to 3.80; p < 0.001).,Myocardial injury is prevalent among patients hospitalized with COVID-19; however, troponin concentrations were generally present at low levels.,Patients with CVD are more likely to have myocardial injury than patients without CVD.,Troponin elevation among patients hospitalized with COVID-19 is associated with higher risk of mortality.

Coagulopathy is a common abnormality in patients with COVID‐19.,However, the exact incidence of venous thromboembolic event is unknown in anticoagulated, severe COVID‐19 patients.,Systematic assessment of venous thromboembolism (VTE) using complete duplex ultrasound (CDU) in anticoagulated COVID‐19 patients.,We performed a retrospective study in 2 French intensive care units (ICU) where CDU is performed as a standard of care.,A CDU from thigh to ankle at selected sites with Doppler waveforms and images was performed early during ICU stay in patients admitted with COVID‐19.,Anticoagulation dose was left to the discretion of the treating physician based on the individual risk of thrombosis.,Patients were classified as treated with prophylactic anticoagulation or therapeutic anticoagulation.,Pulmonary embolism was systematically searched in patients with persistent hypoxemia or secondary deterioration.,From March 19 to April 11, 2020, 26 consecutive patients with severe COVID‐19 were screened for VTE.,Eight patients (31%) were treated with prophylactic anticoagulation, whereas 18 patients (69%) were treated with therapeutic anticoagulation.,The overall rate of VTE in patients was 69%.,The proportion of VTE was significantly higher in patients treated with prophylactic anticoagulation when compared with the other group (100% vs 56%, respectively, P = .03).,Surprisingly, we found a high rate of thromboembolic events in COVID‐19 patients treated with therapeutic anticoagulation, with 56% of VTE and 6 pulmonary embolisms.,Our results suggest considering both systematic screening of VTE and early therapeutic anticoagulation in severe ICU COVID‐19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system.,Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19.

The orf8b protein of the coronavirus SARS-CoV, analogous to SARS-CoV-2, triggers the NLRP3 inflammasome in macrophages in vitro.,Deregulated inflammasome-mediated release of interleukin-1 family cytokines is important in hyper-inflammatory syndromes, like happens in SARS-CoV-2-mediated cytokine release syndrome.,We propose that an intense inflammasome formation characterizes the lungs of patients with fatal COVID-19 disease due to pneumonia and acute respiratory distress syndrome (ARDS).,Samples from four patients with confirmed COVID-19 pneumonia who had been hospitalized at the Hospital of the University of Trieste (Italy) and died of ARDS and four lung samples from a historical repository from subjects who had died of cardiopulmonary arrest and had not been placed on mechanical ventilation and without evidence of pulmonary infection at postmortem examination were collected.,Pathology samples had been fixed in formalin 10% at time of collection and subsequently embedded in paraffin.,We conducted staining for ASC (Apoptosis-associated Speck-like protein containing a Caspase recruitment domain), NLRP3 (NACHT, LRR, and PYD domains-containing protein 3), and cleaved caspase-1.,Intense expression of the inflammasome was detected, mainly in leukocytes, within the lungs of all patients with fatal COVID-19 in the areas of lung injury.,The number of ASC inflammasome specks per high power fields was significantly higher in the lungs of patients with fatal COVID-19 as compared with the lungs of control subjects (52 ± 22 vs 6 ± 3, P = 0.0064).,These findings identify the presence of NLRP3 inflammasome aggregates in the lungs of fatal COVID-19 pneumonia thus providing the potential molecular link between viral infection and cytokine release syndrome.,The online version of this article (10.1007/s00011-020-01413-2) contains supplementary material, which is available to authorized users.

COVID-19 affects millions of patients worldwide, with clinical presentation ranging from isolated thrombosis to acute respiratory distress syndrome (ARDS) requiring ventilator support.,Neutrophil extracellular traps (NETs) originate from decondensed chromatin released to immobilize pathogens, and they can trigger immunothrombosis.,We studied the connection between NETs and COVID-19 severity and progression.,We conducted a prospective cohort study of COVID-19 patients (n = 33) and age- and sex-matched controls (n = 17).,We measured plasma myeloperoxidase (MPO)-DNA complexes (NETs), platelet factor 4, RANTES, and selected cytokines.,Three COVID-19 lung autopsies were examined for NETs and platelet involvement.,We assessed NET formation ex vivo in COVID-19 neutrophils and in healthy neutrophils incubated with COVID-19 plasma.,We also tested the ability of neonatal NET-inhibitory factor (nNIF) to block NET formation induced by COVID-19 plasma.,Plasma MPO-DNA complexes increased in COVID-19, with intubation (P < .0001) and death (P < .0005) as outcome.,Illness severity correlated directly with plasma MPO-DNA complexes (P = .0360), whereas Pao2/fraction of inspired oxygen correlated inversely (P = .0340).,Soluble and cellular factors triggering NETs were significantly increased in COVID-19, and pulmonary autopsies confirmed NET-containing microthrombi with neutrophil-platelet infiltration.,Finally, COVID-19 neutrophils ex vivo displayed excessive NETs at baseline, and COVID-19 plasma triggered NET formation, which was blocked by nNIF.,Thus, NETs triggering immunothrombosis may, in part, explain the prothrombotic clinical presentations in COVID-19, and NETs may represent targets for therapeutic intervention.,•NETs contribute to microthrombi through platelet-neutrophil interactions in COVID-19 ARDS.•nNIF blocks NETs induced by COVID-19 plasma and represents a potential therapeutic intervention in COVID-19.,NETs contribute to microthrombi through platelet-neutrophil interactions in COVID-19 ARDS.,nNIF blocks NETs induced by COVID-19 plasma and represents a potential therapeutic intervention in COVID-19.

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.

To raise awareness for possible benefits of examining known COVID-19 patients presenting sudden clinical worsening with CT pulmonary angiography instead of standard non-contrast chest CT.,•Patients having COVID-19 pneumonia are at risk of coagulopathy and pulmonary embolism•In the absence of contraindications, patients admitted for COVID-19 should receive prophylactic low molecular weight heparin•Elevated D-dimer levels on admission or sudden clinical deterioration should raise suspicion of pulmonary embolism•Selected patients may benefit from CT pulmonary angiography to confirm pulmonary embolism and initiate appropriate therapy,Patients having COVID-19 pneumonia are at risk of coagulopathy and pulmonary embolism,In the absence of contraindications, patients admitted for COVID-19 should receive prophylactic low molecular weight heparin,Elevated D-dimer levels on admission or sudden clinical deterioration should raise suspicion of pulmonary embolism,Selected patients may benefit from CT pulmonary angiography to confirm pulmonary embolism and initiate appropriate therapy

Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality.,To evaluate the pathologic changes of organ systems and the clinicopathologic basis for severe and fatal outcomes.,Prospective autopsy study.,Single pathology department.,11 deceased patients with COVID-19 (10 of whom were selected at random for autopsy).,Systematic macroscopic, histopathologic, and viral analysis (SARS-CoV-2 on real-time polymerase chain reaction assay), with correlation of pathologic and clinical features, including comorbidities, comedication, and laboratory values.,Patients' age ranged from 66 to 91 years (mean, 80.5 years; 8 men, 3 women).,Ten of the 11 patients received prophylactic anticoagulant therapy; venous thromboembolism was not clinically suspected antemortem in any of the patients.,Both lungs showed various stages of diffuse alveolar damage (DAD), including edema, hyaline membranes, and proliferation of pneumocytes and fibroblasts.,Thrombosis of small and mid-sized pulmonary arteries was found in various degrees in all 11 patients and was associated with infarction in 8 patients and bronchopneumonia in 6 patients.,Kupffer cell proliferation was seen in all patients, and chronic hepatic congestion in 8 patients.,Other changes in the liver included hepatic steatosis, portal fibrosis, lymphocytic infiltrates and ductular proliferation, lobular cholestasis, and acute liver cell necrosis, together with central vein thrombosis.,Additional frequent findings included renal proximal tubular injury, focal pancreatitis, adrenocortical hyperplasia, and lymphocyte depletion of spleen and lymph nodes.,Viral RNA was detectable in pharyngeal, bronchial, and colonic mucosa but not bile.,The sample was small.,COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency.,Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation.,Studies are needed to further understand the thrombotic complications of COVID-19, together with the roles for strict thrombosis prophylaxis, laboratory, and imaging studies and early anticoagulant therapy for suspected pulmonary arterial thrombosis or thromboembolism.,None.,The clinicopathological basis for morbidity and mortality with SARS-CoV-2 infection is not well understood.,This study reports the clinical and autopsy findings of patients who died of COVID-19.

It remains uncertain whether the hypertension (HT) medications angiotensin‐converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) mitigate or exacerbate SARS‐CoV‐2 infection.,We evaluated the association of ACEi and ARB with severe coronavirus disease 19 (COVID‐19) as defined by hospitalization or mortality among individuals diagnosed with COVID‐19.,We investigated whether these associations were modified by age, the simultaneous use of the diuretic thiazide, and the health conditions associated with medication use.,In an observational study utilizing data from a Massachusetts group medical practice, we identified 1449 patients with a COVID‐19 diagnosis.,In our study, pre‐infection comorbidities including HT, cardiovascular disease, and diabetes were associated with increased risk of severe COVID‐19.,Risk was further elevated in patients under age 65 with these comorbidities or cancer.,Twenty percent of those with severe COVID‐19 compared to 9% with less severe COVID‐19 used ACEi, 8% and 4%, respectively, used ARB.,In propensity score‐matched analyses, use of neither ACEi (OR = 1.30, 95% CI 0.93 to 1.81) nor ARB (OR = 0.94, 95% CI 0.57 to 1.55) was associated with increased risk of severe COVID‐19.,Thiazide use did not modify this relationship.,Beta blockers, calcium channel blockers, and anticoagulant medications were not associated with COVID‐19 severity.,In conclusion, cardiovascular‐related comorbidities were associated with severe COVID‐19 outcomes, especially among patients under age 65.,We found no substantial increased risk of severe COVID‐19 among patients taking antihypertensive medications.,Our findings support recommendations against discontinuing use of renin-angiotensin system (RAS) inhibitors to prevent severe COVID‐19.

Association of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) use with coronavirus disease 2019 (COVID-19) remains controversial.,We aimed to investigate the impact of ACEI/ARB use on all-cause mortality in severe COVID-19 patients with hypertension.,We enrolled 650 COVID-19 patients from Changsha and Wuhan city between 17 January 2020 and 8 March 2020.,Demographic, clinical characteristics, and outcomes were collected.,Multivariable analysis and propensity-score matching were performed to assess the impact of ACEI/ARB therapy on mortality.,Among the 650 patients, 126 who had severe COVID-19 concomitant with hypertension were analyzed.,The average age was 66 years and 56 (44.4%) were men.,There were 37 ACEI/ARB users and 21 in-hospital deaths (mortality rate, 16.7%).,Male sex (odds ratio [OR], 5.13; 95% confidence interval [CI], 1.75 to 17.8), but not ACEI/ARB use (OR, 1.09; 95%CI, 0.31 to 3.43), was an independent risk factor for mortality in severe COVID-19 patients with hypertension.,After propensity-score matching, 60 severe COVID-19 patients were included and no significant correlation between use of ACEI/ARB and mortality was observed.,There was no significant association of ACEI/ARB use with mortality in severe COVID-19 patients with hypertension.,These findings support the continuation of ACEI/ARB therapy for such patients.

Metabolic pathways integrate to support tissue homeostasis and to prompt changes in cell phenotype.,In particular, the heart consumes relatively large amounts of substrate not only to regenerate ATP for contraction but also to sustain biosynthetic reactions for replacement of cellular building blocks.,Metabolic pathways also control intracellular redox state, and metabolic intermediates and end products provide signals that prompt changes in enzymatic activity and gene expression.,Mounting evidence suggests that the changes in cardiac metabolism that occur during development, exercise, and pregnancy as well as with pathological stress (eg, myocardial infarction, pressure overload) are causative in cardiac remodeling.,Metabolism-mediated changes in gene expression, metabolite signaling, and the channeling of glucose-derived carbon toward anabolic pathways seem critical for physiological growth of the heart, and metabolic inefficiency and loss of coordinated anabolic activity are emerging as proximal causes of pathological remodeling.,This review integrates knowledge of different forms of cardiac remodeling to develop general models of how relationships between catabolic and anabolic glucose metabolism may fortify cardiac health or promote (mal)adaptive myocardial remodeling.,Adoption of conceptual frameworks based in relational biology may enable further understanding of how metabolism regulates cardiac structure and function.

The metabolism of the failing heart is characterized by an increase in glucose uptake with reduced fatty acid (FA) oxidation.,We previously found that the genetic deletion of FA-binding protein-4 and -5 [double knockout (DKO)] induces an increased myocardial reliance on glucose with decreased FA uptake in mice.,However, whether this fuel switch confers functional benefit during the hypertrophic response remains open to debate.,To address this question, we investigated the contractile function and metabolic profile of DKO hearts subjected to pressure overload.,Transverse aortic constriction (TAC) significantly reduced cardiac contraction in DKO mice (DKO-TAC), although an increase in cardiac mass and interstitial fibrosis was comparable with wild-type TAC (WT-TAC).,DKO-TAC hearts exhibited enhanced glucose uptake by 8-fold compared with WT-TAC.,Metabolic profiling and isotopomer analysis revealed that the pool size in the TCA cycle and the level of phosphocreatine were significantly reduced in DKO-TAC hearts, despite a marked increase in glycolytic flux.,The ingestion of a diet enriched in medium-chain FAs restored cardiac contractile dysfunction in DKO-TAC hearts.,The de novo synthesis of amino acids as well as FA from glycolytic flux was unlikely to be suppressed, despite a reduction in each precursor.,The pentose phosphate pathway was also facilitated, which led to the increased production of a coenzyme for lipogenesis and a precursor for nucleotide synthesis.,These findings suggest that reduced FA utilization is not sufficiently compensated by a robust increase in glucose uptake when the energy demand is elevated.,Glucose utilization for sustained biomass synthesis further enhances diminishment of the pool size in the TCA cycle.,Our data suggest that glucose is preferentially utilized for biomass synthesis rather than ATP production during pressure-overload-induced cardiac hypertrophy and that the efficient supplementation of energy substrates may restore cardiac dysfunction caused by energy insufficiency.

Supplemental Digital Content is available in the text.,The severe acute respiratory syndrome coronavirus 2 (SARs-CoV-2) has resulted in a global pandemic.,Hydroxychloroquine±azithromycin have been widely used to treat coronavirus disease 2019 (COVID-19) despite a paucity of evidence regarding efficacy.,The incidence of torsade de pointes remains unknown.,Widespread use of these medications forced overwhelmed health care systems to search for ways to effectively monitor these patients while simultaneously trying to minimize health care provider exposure and use of personal protective equipment.,Patients with COVID-19 positive who received hydroxychloroquine±azithromycin across 13 hospitals between March 1 and April 15 were included in this study.,A comprehensive search of the electronic medical records was performed using a proprietary python script to identify any mention of QT prolongation, ventricular tachy-arrhythmias and cardiac arrest.,The primary outcome of torsade de pointes was observed in 1 (0.015%) out of 6476 hospitalized patients with COVID-19 receiving hydroxychloroquine±azithromycin.,Sixty-seven (1.03%) had hydroxychloroquine±azithromycin held or discontinued due to an average QT prolongation of 60.5±40.5 ms from a baseline QTc of 473.7±35.9 ms to a peak QTc of 532.6±31.6 ms.,Of these patients, hydroxychloroquine±azithromycin were discontinued in 58 patients (86.6%), while one or more doses of therapy were held in the remaining nine (13.4%).,A simplified approach to monitoring for QT prolongation and arrythmia was implemented on April 5.,There were no deaths related to the medications with the simplified monitoring approach and health care provider exposure was reduced.,The risk of torsade de pointes is low in hospitalized patients with COVID-19 receiving hydroxychloroquine±azithromycin therapy.

Thromboembolic disease is common in coronavirus disease-2019 (COVID-19).,There is limited evidence on the association of in-hospital anticoagulation (AC) with outcomes and postmortem findings.,The purpose of this study was to examine association of AC with in-hospital outcomes and describe thromboembolic findings on autopsies.,This retrospective analysis examined the association of AC with mortality, intubation, and major bleeding.,Subanalyses were also conducted on the association of therapeutic versus prophylactic AC initiated ≤48 h from admission.,Thromboembolic disease was contextualized by premortem AC among consecutive autopsies.,Among 4,389 patients, median age was 65 years with 44% women.,Compared with no AC (n = 1,530; 34.9%), therapeutic AC (n = 900; 20.5%) and prophylactic AC (n = 1,959; 44.6%) were associated with lower in-hospital mortality (adjusted hazard ratio [aHR]: 0.53; 95% confidence interval [CI]: 0.45 to 0.62 and aHR: 0.50; 95% CI: 0.45 to 0.57, respectively), and intubation (aHR: 0.69; 95% CI: 0.51 to 0.94 and aHR: 0.72; 95% CI: 0.58 to 0.89, respectively).,When initiated ≤48 h from admission, there was no statistically significant difference between therapeutic (n = 766) versus prophylactic AC (n = 1,860) (aHR: 0.86; 95% CI: 0.73 to 1.02; p = 0.08).,Overall, 89 patients (2%) had major bleeding adjudicated by clinician review, with 27 of 900 (3.0%) on therapeutic, 33 of 1,959 (1.7%) on prophylactic, and 29 of 1,530 (1.9%) on no AC.,Of 26 autopsies, 11 (42%) had thromboembolic disease not clinically suspected and 3 of 11 (27%) were on therapeutic AC.,AC was associated with lower mortality and intubation among hospitalized COVID-19 patients.,Compared with prophylactic AC, therapeutic AC was associated with lower mortality, although not statistically significant.,Autopsies revealed frequent thromboembolic disease.,These data may inform trials to determine optimal AC regimens.

Since the appearance of the first case of coronavirus disease 2019 (COVID-19) a pandemic has emerged affecting millions of people worldwide.,Although the main clinical manifestations are respiratory, an increase in neurological conditions, specifically acute cerebrovascular disease, has been detected.,We present cerebrovascular disease case incidence in hospitalized patients with SARS-CoV-2 infection.,Patients were confirmed by microbiological/serological testing, or on chest CT semiology.,Available data on comorbidity, laboratory parameters, treatment administered, neuroimaging, neuropathological studies and clinical evolution during hospitalization, measured by the modified Rankin scale, were analysed.,A bivariate study was also designed to identify differences between ischaemic and haemorrhagic subtypes.,A statistical model of binary logistic regression and sensitivity analysis was designed to study the influence of independent variables over prognosis.,In our centre, there were 1683 admissions of patients with COVID-19 over 50 days, of which 23 (1.4%) developed cerebrovascular disease.,Within this group of patients, cerebral and chest CT scans were performed in all cases, and MRI in six (26.1%).,Histological samples were obtained in 6/23 cases (two brain biopsies, and four arterial thrombi).,Seventeen patients were classified as cerebral ischaemia (73.9%, with two arterial dissections), five as intracerebral haemorrhage (21.7%), and one leukoencephalopathy of posterior reversible encephalopathy type.,Haemorrhagic patients had higher ferritin levels at the time of stroke (1554.3 versus 519.2, P = 0.004).,Ischaemic strokes were unexpectedly frequent in the vertebrobasilar territory (6/17, 35.3%).,In the haemorrhagic group, a characteristic radiological pattern was identified showing subarachnoid haemorrhage, parieto-occipital leukoencephalopathy, microbleeds and single or multiple focal haematomas.,Brain biopsies performed showed signs of thrombotic microangiopathy and endothelial injury, with no evidence of vasculitis or necrotizing encephalitis.,The functional prognosis during the hospital period was unfavourable in 73.9% (17/23 modified Rankin scale 4-6), and age was the main predictive variable (odds ratio = 1.5; 95% confidence interval 1.012-2.225; P = 0.043).,Our series shows cerebrovascular disease incidence of 1.4% in patients with COVID-19 with high morbidity and mortality.,We describe pathological and radiological data consistent with thrombotic microangiopathy caused by endotheliopathy with a haemorrhagic predisposition.

Supplemental Digital Content is available in the text.,We conducted this study to investigate the prevalence and distribution of cerebral microbleeds and leukoencephalopathy in hospitalized patients with coronavirus disease 2019 (COVID-19) and correlate with clinical, laboratory, and functional outcomes.,We performed a retrospective chart review of 4131 COVID-19 positive adult patients who were admitted to 3 tertiary care hospitals of an academic medical center at the epicenter of the COVID-19 pandemic in New York City from March 1, 2020, to May 10, 2020, to identify patients who had magnetic resonance imaging (MRI) of the brain.,We evaluated the MRIs in detail, and identified a subset of patients with leukoencephalopathy and/or cerebral microbleeds.,We compared clinical, laboratory, and functional outcomes for these patients to patients who had a brain MRI that did not show these findings.,Of 115 patients who had an MRI of the brain performed, 35 (30.4%) patients had leukoencephalopathy and/or cerebral microbleeds.,Patients with leukoencephalopathy and/or cerebral microbleeds had neuroimaging performed later during the hospitalization course (27 versus 10.6 days; P<0.001), were clinically sicker at the time of brain MRI (median GCS 6 versus 14; P<0.001), and had higher peak D-dimer levels (8018±6677 versus 3183±3482; P<0.001), lower nadir platelet count (116.9±62.2 versus 158.3±76.2; P=0.03), higher peak international normalized ratio (2.2 versus 1.57; P<0.001) values when compared with patients who had a brain MRI that did not show these findings.,They required longer ventilator support (34.6 versus 9.1 days; P<0.001) and were more likely to have moderate and severe acute respiratory distress syndrome score (88.6% versus 23.8%, P<0.001).,These patients had longer hospitalizations (42.1 versus 20.9 days; P<0.001), overall worse functional status on discharge (mRS 5 versus 4; P=0.001), and higher mortality (20% versus 9%; P=0.144).,The presence of leukoencephalopathy and/or cerebral microbleeds is associated with a critical illness, increased mortality, and worse functional outcome in patients with COVID-19.

To determine the incidence, patient characteristics, and related events associated with new-onset atrial fibrillation (AF) during a national COVID-19 lockdown.,Using nationwide Danish registries, we included all patients, aged 18-90 years, receiving a new-onset AF diagnosis during the first 3 months of 2019 and 2020.,The main comparison was between patients diagnosed during lockdown (12 March 12-1 April 2020) and patients diagnosed in the corresponding period 1 year previously.,We found a lower incidence of new-onset AF during the 3 weeks of lockdown compared with the corresponding weeks in 2019 [incidence rate ratios with 95% confidence intervals (CIs) for the 3 weeks: 0.66 (0.56-0.78), 0.53 (0.45-0.64), and 0.41 (0.34-0.50)].,There was a 47% drop in total numbers (562 vs.,1053).,Patients diagnosed during lockdown were younger and with a lower CHA2DS2-VASc score, while history of cancer, heart failure, and vascular disease were more prevalent.,During lockdown, 30 (5.3%) patients with new-onset AF suffered an ischaemic stroke and 15 (2.7%) died, compared with 45 (4.3%) and 14 (1.3%) patients during the corresponding 2019 period, respectively.,The adjusted odds ratio of a related event (ischaemic stroke or all-cause death) during lock-down compared with the corresponding weeks was 1.41 (95% CI 0.93-2.12).,Following a national lockdown in Denmark, a 47% drop in registered new-onset AF cases was observed.,In the event of prolonged or subsequent lockdowns, the risk of undiagnosed AF patients developing complications could potentially translate into poorer outcomes in patients with AF during the COVID-19 pandemic.,Graphical Abstract

To evaluate the impact of the COVID-19 pandemic on patient admissions to Italian cardiac care units (CCUs).,We conducted a multicentre, observational, nationwide survey to collect data on admissions for acute myocardial infarction (AMI) at Italian CCUs throughout a 1 week period during the COVID-19 outbreak, compared with the equivalent week in 2019.,We observed a 48.4% reduction in admissions for AMI compared with the equivalent week in 2019 (P < 0.001).,The reduction was significant for both ST-segment elevation myocardial infarction [STEMI; 26.5%, 95% confidence interval (CI) 21.7-32.3; P = 0.009] and non-STEMI (NSTEMI; 65.1%, 95% CI 60.3-70.3; P < 0.001).,Among STEMIs, the reduction was higher for women (41.2%; P = 0.011) than men (17.8%; P = 0.191).,A similar reduction in AMI admissions was registered in North Italy (52.1%), Central Italy (59.3%), and South Italy (52.1%).,The STEMI case fatality rate during the pandemic was substantially increased compared with 2019 [risk ratio (RR) = 3.3, 95% CI 1.7-6.6; P < 0.001].,A parallel increase in complications was also registered (RR = 1.8, 95% CI 1.1-2.8; P = 0.009).,Admissions for AMI were significantly reduced during the COVID-19 pandemic across Italy, with a parallel increase in fatality and complication rates.,This constitutes a serious social issue, demanding attention by the scientific and healthcare communities and public regulatory agencies.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has infected more than 42.5 million people globally resulting in the death of over 1.15 million subjects.,It has inflicted severe public health and economic hardships across the world.,In addition to acute respiratory distress syndrome, respiratory failure, sepsis, and acute kidney injury, COVID-19 also causes heart failure (HF).,COVID-19-induced HF is manifested via different mechanisms, including, but not limited to, (1) virus-induced infiltration of inflammatory cells, which could impair the function of the heart; (2) pro-inflammatory cytokines (monocyte chemoattractant protein-1, interleukin-1β; interleukin-6; tumor necrosis factor-α) that could cause necrosis and death of the myocardium; (3) endothelial injury coupled with micro-thrombosis which could damage the endocardium; and (4) acute respiratory distress syndrome and respiratory failure that could lead to heart failure due to severe hypoxia.,It is concluded that the etiology of COVID-19-induced HF is multifactorial and mitigation of the development of HF in patients with COVID-19 will require different approaches such as social distancing, drug therapy, and the urgent development of a vaccine to eradicate the disease.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has emerged as a global pandemic.,SARS-CoV-2 infection can lead to elevated markers of cardiac injury associated with higher risk of mortality.,It is unclear whether cardiac injury is caused by direct infection of cardiomyocytes or is mainly secondary to lung injury and inflammation.,Here, we investigate whether cardiomyocytes are permissive for SARS-CoV-2 infection.,Two strains of SARS-CoV-2 infected human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) as demonstrated by detection of intracellular double-stranded viral RNA and viral spike glycoprotein expression.,Increasing concentrations of viral RNA are detected in supernatants of infected cardiomyocytes, which induced infections in Caco-2 cell lines, documenting productive infections.,SARS-COV-2 infection and induced cytotoxic and proapoptotic effects associated with it abolished cardiomyocyte beating.,RNA sequencing confirmed a transcriptional response to viral infection as demonstrated by the up-regulation of genes associated with pathways related to viral response and interferon signalling, apoptosis, and reactive oxygen stress.,SARS-CoV-2 infection and cardiotoxicity was confirmed in a 3D cardiosphere tissue model.,Importantly, viral spike protein and viral particles were detected in living human heart slices after infection with SARS-CoV-2.,Coronavirus particles were further observed in cardiomyocytes of a patient with COVID-19.,Infection of iPS-CMs was dependent on cathepsins and angiotensin-converting enzyme 2 (ACE2), and was blocked by remdesivir.,This study demonstrates that SARS-CoV-2 infects cardiomyocytes in vitro in an ACE2- and cathepsin-dependent manner.,SARS-CoV-2 infection of cardiomyocytes is inhibited by the antiviral drug remdesivir.,Although this study cannot address whether cardiac injury and dysfunction in COVID-19 patients is caused by direct infection of cardiomyocytes, the demonstration of direct cardiotoxicity in cardiomyocytes, organ mimics, human heart slices and human hearts warrants the further monitoring of cardiotoxic effects in COVID-19 patients.,Graphical Abstract

Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has rapidly evolved into a sweeping pandemic.,Its major manifestation is in the respiratory tract, and the general extent of organ involvement and the microscopic changes in the lungs remain insufficiently characterised.,Autopsies are essential to elucidate COVID‐19‐associated organ alterations.,This article reports the autopsy findings of 21 COVID‐19 patients hospitalised at the University Hospital Basel and at the Cantonal Hospital Baselland, Switzerland.,An in‐corpore technique was performed to ensure optimal staff safety.,The primary cause of death was respiratory failure with exudative diffuse alveolar damage and massive capillary congestion, often accompanied by microthrombi despite anticoagulation.,Ten cases showed superimposed bronchopneumonia.,Further findings included pulmonary embolism (n = 4), alveolar haemorrhage (n = 3), and vasculitis (n = 1).,Pathologies in other organ systems were predominantly attributable to shock; three patients showed signs of generalised and five of pulmonary thrombotic microangiopathy.,Six patients were diagnosed with senile cardiac amyloidosis upon autopsy.,Most patients suffered from one or more comorbidities (hypertension, obesity, cardiovascular diseases, and diabetes mellitus).,Additionally, there was an overall predominance of males and individuals with blood group A (81% and 65%, respectively).,All relevant histological slides are linked as open‐source scans in supplementary files.,This study provides an overview of postmortem findings in COVID‐19 cases, implying that hypertensive, elderly, obese, male individuals with severe cardiovascular comorbidities as well as those with blood group A may have a lower threshold of tolerance for COVID‐19.,This provides a pathophysiological explanation for higher mortality rates among these patients.

Patients with cardiovascular disease and, namely, heart failure are more susceptible to coronavirus disease 2019 (COVID‐19) and have a more severe clinical course once infected.,Heart failure and myocardial damage, shown by increased troponin plasma levels, occur in at least 10% of patients hospitalized for COVID‐19 with higher percentages, 25% to 35% or more, when patients critically ill or with concomitant cardiac disease are considered.,Myocardial injury may be elicited by multiple mechanisms, including those occurring with all severe infections, such as fever, tachycardia, adrenergic stimulation, as well as those caused by an exaggerated inflammatory response, endotheliitis and, in some cases, myocarditis that have been shown in patients with COVID‐19.,A key role may be that of the renin-angiotensin-aldosterone system.,Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infects human cells binding to angiotensin‐converting enzyme 2 (ACE2), an enzyme responsible for the cleavage of angiotensin II into angiotensin 1-7, which has vasodilating and anti‐inflammatory effects.,Virus‐mediated down‐regulation of ACE2 may increase angiotensin II stimulation and contribute to the deleterious hyper‐inflammatory reaction of COVID‐19.,On the other hand, ACE2 may be up‐regulated in patients with cardiac disease and treated with ACE inhibitors or angiotensin receptor blockers.,ACE2 up‐regulation may increase the susceptibility to COVID‐19 but may be also protective vs. angiotensin II‐mediated vasoconstriction and inflammatory activation.,Recent data show the lack of untoward effects of ACE inhibitors or angiotensin receptor blockers for COVID‐19 infection and severity.,Prospective trials are needed to ascertain whether these drugs may have protective effects.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic in just a few months, causing millions infected.,Nearly 20% of COVID-19 patients present severe coagulation abnormalities, which may occur in almost all of the severe and critical ill COVID-19 cases.,Concomitant venous thromboembolism (VTE), a potential cause of unexplained deaths, has been frequently reported in COVID-19 cases, but its management is still challenging due to the complexity between antithrombotic therapy and coagulation disorders.,Based on frontline practical experience and comprehensive literature review, here a panel of experts and physicians from China and Europe developed an evidence and opinion-based consensus on the prophylaxis and management of VTE associated with COVID-19.,This statement aims for clinicians treating COVID-19 and provides practical recommendations in detailed situations, for example, how to choose thromboprophylactic measures for patients with diverse severity of disease and bleeding risk, or which kind of anticoagulant should be prescribed.,With limited experience on COVID19-associated VTE, this expert consensus statement should be helpful for clinicians worldwide with specific suggestions.

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.

Ever since the first case was reported at the end of 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated coronavirus disease 2019 (COVID-19) has become a serious threat to public health globally in short time.,At this point in time, there is no proven effective therapy.,The interactions with concomitant disease are largely unknown, and that may be particularly pertinent to inherited arrhythmia syndrome.,An arrhythmogenic effect of COVID-19 can be expected, potentially contributing to disease outcome.,This may be of importance for patients with an increased risk of cardiac arrhythmias, either secondary to acquired conditions or comorbidities or consequent to inherited syndromes.,Management of patients with inherited arrhythmia syndromes such as long QT syndrome, Brugada syndrome, short QT syndrome, and catecholaminergic polymorphic ventricular tachycardia in the setting of the COVID-19 pandemic may prove particularly challenging.,Depending on the inherited defect involved, these patients may be susceptible to proarrhythmic effects of COVID-19-related issues such as fever, stress, electrolyte disturbances, and use of antiviral drugs.,Here, we describe the potential COVID-19-associated risks and therapeutic considerations for patients with distinct inherited arrhythmia syndromes and provide recommendations, pending local possibilities, for their monitoring and management during this pandemic.

COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation.,Reports on the incidence of thrombotic complications are however not available.,We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.,We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020.,All patients received at least standard doses thromboprophylaxis.,The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%).,PE was the most frequent thrombotic complication (n = 25, 81%).,Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.,The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high.,Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.

COVID-19 is also manifested with hypercoagulability, pulmonary intravascular coagulation, microangiopathy, and venous thromboembolism (VTE) or arterial thrombosis.,Predisposing risk factors to severe COVID-19 are male sex, underlying cardiovascular disease, or cardiovascular risk factors including noncontrolled diabetes mellitus or arterial hypertension, obesity, and advanced age.,The VAS-European Independent Foundation in Angiology/Vascular Medicine draws attention to patients with vascular disease (VD) and presents an integral strategy for the management of patients with VD or cardiovascular risk factors (VD-CVR) and COVID-19.,VAS recommends (1) a COVID-19-oriented primary health care network for patients with VD-CVR for identification of patients with VD-CVR in the community and patients' education for disease symptoms, use of eHealth technology, adherence to the antithrombotic and vascular regulating treatments, and (2) close medical follow-up for efficacious control of VD progression and prompt application of physical and social distancing measures in case of new epidemic waves.,For patients with VD-CVR who receive home treatment for COVID-19, VAS recommends assessment for (1) disease worsening risk and prioritized hospitalization of those at high risk and (2) VTE risk assessment and thromboprophylaxis with rivaroxaban, betrixaban, or low-molecular-weight heparin (LMWH) for those at high risk.,For hospitalized patients with VD-CVR and COVID-19, VAS recommends (1) routine thromboprophylaxis with weight-adjusted intermediate doses of LMWH (unless contraindication); (2) LMWH as the drug of choice over unfractionated heparin or direct oral anticoagulants for the treatment of VTE or hypercoagulability; (3) careful evaluation of the risk for disease worsening and prompt application of targeted antiviral or convalescence treatments; (4) monitoring of D-dimer for optimization of the antithrombotic treatment; and (5) evaluation of the risk of VTE before hospital discharge using the IMPROVE-D-dimer score and prolonged post-discharge thromboprophylaxis with rivaroxaban, betrixaban, or LMWH.

Coronavirus disease 2019 (COVID-19) is associated with coagulation activation and high incidence of venous thromboembolism (VTE) in severe patients despite routine thromboprophylaxis.,Conflicting results exist regarding the epidemiology of VTE for unselected anticoagulated COVID-19 patients hospitalized in general wards.,The aim of this study was to evaluate the prevalence of asymptomatic deep venous thrombosis (DVT) in unselected patients with COVID-19 recently hospitalized in general wards.,We performed a systematic complete doppler ultrasound (CDU) at a median 4 days after admission in 42 consecutive COVID-19 patients hospitalized in general wards of our university hospital, irrespective of D-Dimer level, and retrospectively collected clinical, biological and outcome data from electronic charts.,Thromboprophylaxis was systematically applied following a French national proposal.,In our population, the prevalence of asymptomatic DVT was 19% (8/42 patients), with distal thrombosis in 7/8 cases and bilateral DVT in 4/8 cases.,Symptomatic pulmonary embolism was detected in 4 (9.5%) patients, associated to DVT in one case.,Compared to patients without DVT, patients with DVT were older and experienced poorer outcomes.,In conclusion, prevalence of asymptomatic DVT is high in the first days of hospitalization of unselected COVID-19 patients in general wards and may be related to poor prognosis.,Individualized assessment of thromboprophylaxis and early systematic screening for DVT is warranted in this context.,The online version of this article (10.1007/s11239-020-02246-w) contains supplementary material, which is available to authorized users.

Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19).,We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.,In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis.,The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge.,This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level.,The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met.,Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58).,The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2).,The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort.,Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis.,In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis.,(ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT04359277, and NCT02735707.)

COVID-19 affects millions of patients worldwide, with clinical presentation ranging from isolated thrombosis to acute respiratory distress syndrome (ARDS) requiring ventilator support.,Neutrophil extracellular traps (NETs) originate from decondensed chromatin released to immobilize pathogens, and they can trigger immunothrombosis.,We studied the connection between NETs and COVID-19 severity and progression.,We conducted a prospective cohort study of COVID-19 patients (n = 33) and age- and sex-matched controls (n = 17).,We measured plasma myeloperoxidase (MPO)-DNA complexes (NETs), platelet factor 4, RANTES, and selected cytokines.,Three COVID-19 lung autopsies were examined for NETs and platelet involvement.,We assessed NET formation ex vivo in COVID-19 neutrophils and in healthy neutrophils incubated with COVID-19 plasma.,We also tested the ability of neonatal NET-inhibitory factor (nNIF) to block NET formation induced by COVID-19 plasma.,Plasma MPO-DNA complexes increased in COVID-19, with intubation (P < .0001) and death (P < .0005) as outcome.,Illness severity correlated directly with plasma MPO-DNA complexes (P = .0360), whereas Pao2/fraction of inspired oxygen correlated inversely (P = .0340).,Soluble and cellular factors triggering NETs were significantly increased in COVID-19, and pulmonary autopsies confirmed NET-containing microthrombi with neutrophil-platelet infiltration.,Finally, COVID-19 neutrophils ex vivo displayed excessive NETs at baseline, and COVID-19 plasma triggered NET formation, which was blocked by nNIF.,Thus, NETs triggering immunothrombosis may, in part, explain the prothrombotic clinical presentations in COVID-19, and NETs may represent targets for therapeutic intervention.,•NETs contribute to microthrombi through platelet-neutrophil interactions in COVID-19 ARDS.•nNIF blocks NETs induced by COVID-19 plasma and represents a potential therapeutic intervention in COVID-19.,NETs contribute to microthrombi through platelet-neutrophil interactions in COVID-19 ARDS.,nNIF blocks NETs induced by COVID-19 plasma and represents a potential therapeutic intervention in COVID-19.

Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

The current COVID-19 pandemic started several months ago and is still exponentially growing in most parts of the world - this is the most recent and alarming update.,COVID-19 requires the collaboration of nearly 200 countries to curb the spread of SARS-CoV-2 while gaining time to explore and improve treatment options especially for cardiovascular disease (CVD) and immunocompromised patients, who appear to be at high-risk to die from cardiopulmonary failure.,Currently unanswered questions are why elderly people, particularly those with pre-existing comorbidities seem to exhibit higher mortality rates after SARS-CoV-2 infection and whether intensive care becomes indispensable for these patients to prevent multi-organ failure and sudden death.,To face these challenges, we here summarize the molecular insights into viral infection mechanisms and implications for cardiovascular disease.,Since the infection starts in the upper respiratory system, first flu-like symptoms develop that spread throughout the body.,The wide range of affected organs is presumably based on the common expression of the major SARS-CoV-2 entry-receptor angiotensin-converting enzyme 2 (ACE2).,Physiologically, ACE2 degrades angiotensin II, the master regulator of the renin-angiotensin-aldosterone system (RAAS), thereby converting it into vasodilatory molecules, which have well-documented cardio-protective effects.,Thus, RAAS inhibitors, which may increase the expression levels of ACE2, are commonly used for the treatment of hypertension and CVD.,This, and the fact that SARS-CoV-2 hijacks ACE2 for cell-entry, have spurred controversial discussions on the role of ACE2 in COVID-19 patients.,In this review, we highlight the state-of-the-art knowledge on SARS-CoV-2-dependent mechanisms and the potential interaction with ACE2 expression and cell surface localization.,We aim to provide a list of potential treatment options and a better understanding of why CVD is a high risk factor for COVID-19 susceptibility and further discuss the acute as well as long-term cardiac consequences.,Unlabelled Image,•COVID-19 patients with underlying CVD have drastically increased risks of mortality.,•SARS-CoV2 uses ACE2 as cell entry receptor.,•Current and novel COVID-19 drugs may act on the SARS-CoV-2 receptor ACE2.,•ACE-I and ARB may interfere with COVID-19 susceptibility and effects on the heart.,COVID-19 patients with underlying CVD have drastically increased risks of mortality.,SARS-CoV2 uses ACE2 as cell entry receptor.,Current and novel COVID-19 drugs may act on the SARS-CoV-2 receptor ACE2.,ACE-I and ARB may interfere with COVID-19 susceptibility and effects on the heart.

Supplemental Digital Content is available in the text.,Myocarditis has been recognized as a rare complication of coronavirus disease 2019 (COVID-19) mRNA vaccinations, especially in young adult and adolescent males.,According to the US Centers for Disease Control and Prevention, myocarditis/pericarditis rates are ≈12.6 cases per million doses of second-dose mRNA vaccine among individuals 12 to 39 years of age.,In reported cases, patients with myocarditis invariably presented with chest pain, usually 2 to 3 days after a second dose of mRNA vaccination, and had elevated cardiac troponin levels.,ECG was abnormal with ST elevations in most, and cardiac MRI was suggestive of myocarditis in all tested patients.,There was no evidence of acute COVID-19 or other viral infections.,In 1 case, a cardiomyopathy gene panel was negative, but autoantibody levels against certain self-antigens and frequency of natural killer cells were increased.,Although the mechanisms for development of myocarditis are not clear, molecular mimicry between the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and self-antigens, trigger of preexisting dysregulated immune pathways in certain individuals, immune response to mRNA, and activation of immunologic pathways, and dysregulated cytokine expression have been proposed.,The reasons for male predominance in myocarditis cases are unknown, but possible explanations relate to sex hormone differences in immune response and myocarditis, and also underdiagnosis of cardiac disease in women.,Almost all patients had resolution of symptoms and signs and improvement in diagnostic markers and imaging with or without treatment.,Despite rare cases of myocarditis, the benefit-risk assessment for COVID-19 vaccination shows a favorable balance for all age and sex groups; therefore, COVID-19 vaccination is recommended for everyone ≥12 years of age.

Vaccination plays an important role in the fight against SARS-CoV-2 to minimie the spread of coronavirus disease 2019 (COVID-19) and its life-threatening complications.,Myocarditis has been reported as a possible and rare adverse consequence of different vaccines, and its clinical presentation can range from influenza-like symptoms to acute heart failure.,We report a case of a 30-year-old man who presented progressive dyspnea and constrictive retrosternal pain after receiving SARS-CoV-2 vaccine.,Cardiac magnetic resonance and laboratory data revealed typical findings of acute myopericarditis.

Nearly 20% novel coronavirus disease 2019 (COVID-19) patients have abnormal coagulation function.,Padua prediction score (PPS) is a validated tools for venous thromboembolism (VTE) risk assessment.,However, its clinical value in COVID-19 patients evaluation was unclear.,We prospectively evaluated the VTE risk of COVID-19 patients using PPS.,Demographic and clinical data were collected.,Association of PPS with 28-days mortality was analyzed by multivariate logistic regression and Kaplan-Meier analysis.,274 continuous patients were enrolled, with total mortality of 17.2%.,Patients in high PPS group, with significantly abnormal coagulation, have a higher levels of interleukin 6 (25.27 pg/ml vs.2.55 pg/ml, P < 0.001), prophylactic anticoagulation rate (60.7% vs.,6.5%, P<0.001) and mortality (40.5% vs.,5.9%, P<0.001) as compared with that in low PPS group.,Critical patients showed higher PPS (6 score vs. 2 score, P<0.001) than that in severe patients.,Multivariate logistic regression revealed the independent risk factors of in-hospital mortality included high PPS (OR: 7.35, 95%CI: 3.08 - 16.01), increased interleukin-6 (OR: 11.79, 95%CI: 5.45 - 26.20) and elevated d-dimer (OR: 4.65, 95%CI: 1.15 - 12.15).,Kaplan-Meier analysis indicated patients with higher PPS had a significant survival disadvantage.,Prophylactic anticoagulation in higher PPS patients show a mild advantage of mortality but without statistical significance (37.1% vs.,45.7%, P=0.42).,Higher PPS associated with in-hospital poor prognosis in COVID-19 patients.,Prophylactic anticoagulation showed a mild advantage of mortality in COVID-19 patients with higher PPS, but it remain need further investigation.

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.

Is the receipt of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) associated with worse clinical outcomes among patients with COVID-19?,In this systematic review and meta-analysis of 52 studies that evaluated clinical outcomes among 101 949 total patients with COVID-19 who did and did not receive ACEIs or ARBs, a significantly lower risk of multivariable-adjusted mortality and severe adverse events was found among patients who received ACEIs or ARBs compared with patients who did not.,A subgroup analysis of patients with hypertension indicated significant decreases in mortality and severe adverse events among patients receiving ACEIs or ARBs in both unadjusted and adjusted analyses.,The study’s findings suggest that ACEIs and ARBs may be associated with protective benefits for patients with COVID-19 and that patients may continue receiving ACEIs and ARBs for the treatment of any condition without an increased risk of worse outcomes unless specifically advised to avoid them by treating clinicians.,The chronic receipt of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) has been assumed to exacerbate complications associated with COVID-19 and produce worse clinical outcomes.,To conduct an updated and comprehensive systematic review and meta-analysis comparing mortality and severe adverse events (AEs) associated with receipt vs nonreceipt of ACEIs or ARBs among patients with COVID-19.,PubMed and Embase databases were systematically searched from December 31, 2019, until September 1, 2020.,The meta-analysis included any study design, with the exception of narrative reviews or opinion-based articles, in which COVID-19 was diagnosed through laboratory or radiological test results and in which clinical outcomes (unadjusted or adjusted) associated with COVID-19 were assessed among adult patients (≥18 years) receiving ACEIs or ARBs.,Three authors independently extracted data on mortality and severe AEs associated with COVID-19.,Severe AEs were defined as intensive care unit admission or the need for assisted ventilation.,For each outcome, a random-effects model was used to compare the odds ratio (OR) between patients receiving ACEIs or ARBs vs those not receiving ACEIs or ARBs.,Unadjusted and adjusted ORs for mortality and severe AEs associated with COVID-19.,A total of 1788 records from the PubMed and Embase databases were identified; after removal of duplicates, 1664 records were screened, and 71 articles underwent full-text evaluation.,Clinical data were pooled from 52 eligible studies (40 cohort studies, 6 case series, 4 case-control studies, 1 randomized clinical trial, and 1 cross-sectional study) enrolling 101 949 total patients, of whom 26 545 (26.0%) were receiving ACEIs or ARBs.,When adjusted for covariates, significant reductions in the risk of death (adjusted OR [aOR], 0.57; 95% CI, 0.43-0.76; P < .001) and severe AEs (aOR, 0.68; 95% CI, 0.53-0.88; P < .001) were found.,Unadjusted and adjusted analyses of a subgroup of patients with hypertension indicated decreases in the risk of death (unadjusted OR, 0.66 [95% CI, 0.49-0.91]; P = .01; aOR, 0.51 [95% CI, 0.32-0.84]; P = .008) and severe AEs (unadjusted OR, 0.70 [95% CI, 0.54-0.91]; P = .007; aOR, 0.55 [95% CI, 0.36-0.85]; P = .007).,In this systematic review and meta-analysis, receipt of ACEIs or ARBs was not associated with a higher risk of multivariable-adjusted mortality and severe AEs among patients with COVID-19 who had either hypertension or multiple comorbidities, supporting the recommendations of medical societies.,On the contrary, ACEIs and ARBs may be associated with protective benefits, particularly among patients with hypertension.,Future randomized clinical trials are warranted to establish causality.,This systematic review and meta-analysis examines the association between the receipt of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and clinical outcomes among adult patients with coronavirus disease 2019.

Coronavirus disease 2019 (COVID-19), caused by a strain of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic that has affected the lives of billions of individuals.,Extensive studies have revealed that SARS-CoV-2 shares many biological features with SARS-CoV, the zoonotic virus that caused the 2002 outbreak of severe acute respiratory syndrome, including the system of cell entry, which is triggered by binding of the viral spike protein to angiotensin-converting enzyme 2.,Clinical studies have also reported an association between COVID-19 and cardiovascular disease.,Pre-existing cardiovascular disease seems to be linked with worse outcomes and increased risk of death in patients with COVID-19, whereas COVID-19 itself can also induce myocardial injury, arrhythmia, acute coronary syndrome and venous thromboembolism.,Potential drug-disease interactions affecting patients with COVID-19 and comorbid cardiovascular diseases are also becoming a serious concern.,In this Review, we summarize the current understanding of COVID-19 from basic mechanisms to clinical perspectives, focusing on the interaction between COVID-19 and the cardiovascular system.,By combining our knowledge of the biological features of the virus with clinical findings, we can improve our understanding of the potential mechanisms underlying COVID-19, paving the way towards the development of preventative and therapeutic solutions.,The presence of cardiovascular comorbidities is linked with worse outcomes in patients with coronavirus disease 2019 (COVID-19), and COVID-19 can induce cardiovascular damage.,In this Review, Wu and colleagues summarize the latest mechanistic and clinical studies that contribute to our current understanding of COVID-19-related cardiovascular disease.,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), shares many biological features with SARS-CoV, the virus that causes severe acute respiratory syndrome, owing to 80% genomic sequence identity.The interaction between the viral spike (S) protein and angiotensin-converting enzyme 2, which triggers entry of the virus into host cells, is likely to be involved in the cardiovascular manifestations of COVID-19.,The presence of underlying cardiovascular comorbidities in patients with COVID-19 is associated with high mortality.COVID-19 can cause cardiovascular disorders, including myocardial injury, arrhythmias, acute coronary syndrome and venous thromboembolism.Several medications used for the treatment of COVID-19 have uncertain safety and efficacy profiles.,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), shares many biological features with SARS-CoV, the virus that causes severe acute respiratory syndrome, owing to 80% genomic sequence identity.,The interaction between the viral spike (S) protein and angiotensin-converting enzyme 2, which triggers entry of the virus into host cells, is likely to be involved in the cardiovascular manifestations of COVID-19.,The presence of underlying cardiovascular comorbidities in patients with COVID-19 is associated with high mortality.,COVID-19 can cause cardiovascular disorders, including myocardial injury, arrhythmias, acute coronary syndrome and venous thromboembolism.,Several medications used for the treatment of COVID-19 have uncertain safety and efficacy profiles.

The triglyceride-glucose (TyG) index is a marker of insulin resistance (IR) and has been associated with various metabolic syndromes, cardiovascular diseases, and cerebrovascular diseases.,However, limited information is available regarding its association with subclinical cerebral small vessel disease (cSVD).,In this study, we evaluated the relationship between the TyG index and cSVD, including silent brain infarcts (SBIs) and white matter hyperintensity (WMH).,We assessed health check-up participants aged 40-79 years from 2006 to 2013.,The TyG index was calculated using the log scale of fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2.,The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was also calculated.,This was compared with two insulin surrogates and cSVD as another IR indicator and compared the association between two insulin surrogates and cSVD.,SBI was measured for both prevalence and burden.,The WMH volume was quantitatively rated using a computer-assisted semi-automated technique.,A total of 2615 participants were evaluated (median age: 56 years, male sex: 53%).,In the multivariable logistic regression analysis, the TyG index was seen to be associated with SBI prevalence (adjusted odds ratio: 1.39; 95% confidence interval [CI] = 1.06-1.81).,Further quantitative analyses showed a positive dose-response relationship between the TyG index and SBI burden (P for trend = 0.006).,In multivariable linear regression analysis, the TyG index was also found to be related to the volume of WMH (β = 0.084; 95% CI = 0.013 to 0.154).,Additionally, the TyG index showed a similar or slightly stronger association with the prevalence of SBI and the volume of WMH than did HOMA-IR.,A high TyG index was associated with a higher prevalence and burden of cSVD in a neurologically healthy population.,This marker of IR could be a convenient and useful predictor of cSVD.

Hypertension and the triglyceride and glucose index both have been associated with insulin resistance; however, the longitudinal association remains unclear.,This study was designed to investigate the longitudinal association between the triglyceride and glucose index and incident hypertension among the Chinese population.,We studied 4686 subjects (3177 males and 1509 females) and followed up for 9 years.,The subjects were divided into four groups based on the triglyceride and glucose index.,Univariate and multivariate Cox regression models were used to analyse the risk factors of hypertension.,After 9 years of follow-up, 2047 subjects developed hypertension.,The overall 9-year cumulative incidence of hypertension was 43.7%, ranging from 28.5% in quartile 1 to 36.9% in quartile 2, 49.2% in quartile 3 and 59.8% in quartile 4 (p for trend < 0.001).,Cox regression analyses indicated that higher triglyceride and glucose index was associated with an increased risk of subsequent incident hypertension.,The triglyceride and glucose index can predict the incident hypertension among the Chinese population.

COVID-19 outbreak had a major impact on the organization of care in Italy, and a survey to evaluate provision of for arrhythmia during COVID-19 outbreak (March-April 2020) was launched.,A total of 104 physicians from 84 Italian arrhythmia centres took part in the survey.,The vast majority of participating centres (95.2%) reported a significant reduction in the number of elective pacemaker implantations during the outbreak period compared to the corresponding two months of year 2019 (50.0% of centres reported a reduction of > 50%).,Similarly, 92.9% of participating centres reported a significant reduction in the number of implantable cardioverter-defibrillator (ICD) implantations for primary prevention, and 72.6% a significant reduction of ICD implantations for secondary prevention (> 50% in 65.5 and 44.0% of the centres, respectively).,The majority of participating centres (77.4%) reported a significant reduction in the number of elective ablations (> 50% in 65.5% of the centres).,Also the interventional procedures performed in an emergency setting, as well as acute management of atrial fibrillation had a marked reduction, thus leading to the conclusion that the impact of COVID-19 was disrupting the entire organization of health care, with a massive impact on the activities and procedures related to arrhythmia management in Italy.,The online version of this article (10.1007/s11739-020-02487-w) contains supplementary material, which is available to authorized users.

Early studies suggest that coronavirus disease 2019 (COVID-19) is associated with a high incidence of cardiac arrhythmias.,Severe acute respiratory syndrome coronavirus 2 infection may cause injury to cardiac myocytes and increase arrhythmia risk.,The purpose of this study was to evaluate the risk of cardiac arrest and arrhythmias including incident atrial fibrillation (AF), bradyarrhythmias, and nonsustained ventricular tachycardia (NSVT) in a large urban population hospitalized for COVID-19.,We also evaluated correlations between the presence of these arrhythmias and mortality.,We reviewed the characteristics of all patients with COVID-19 admitted to our center over a 9-week period.,Throughout hospitalization, we evaluated the incidence of cardiac arrests, arrhythmias, and inpatient mortality.,We also used logistic regression to evaluate age, sex, race, body mass index, prevalent cardiovascular disease, diabetes, hypertension, chronic kidney disease, and intensive care unit (ICU) status as potential risk factors for each arrhythmia.,Among 700 patients (mean age 50 ± 18 years; 45% men; 71% African American; 11% received ICU care), there were 9 cardiac arrests, 25 incident AF events, 9 clinically significant bradyarrhythmias, and 10 NSVTs.,All cardiac arrests occurred in patients admitted to the ICU.,In addition, admission to the ICU was associated with incident AF (odds ratio [OR] 4.68; 95% confidence interval [CI] 1.66-13.18) and NSVT (OR 8.92; 95% CI 1.73-46.06) after multivariable adjustment.,Also, age and incident AF (OR 1.05; 95% CI 1.02-1.09) and prevalent heart failure and bradyarrhythmias (OR 9.75; 95% CI 1.95-48.65) were independently associated.,Only cardiac arrests were associated with acute in-hospital mortality.,Cardiac arrests and arrhythmias are likely the consequence of systemic illness and not solely the direct effects of COVID-19 infection.

Coronavirus induced disease 2019 (COVID-19) can be complicated by severe organ damage leading to dysfunction of the lungs and other organs.,The processes that trigger organ damage in COVID-19 are incompletely understood.,Samples were donated from hospitalized patients.,Sera, plasma, and autopsy-derived tissue sections were examined employing flow cytometry, enzyme-linked immunosorbent assays, and immunohistochemistry.,Here, we show that severe COVID-19 is characterized by a highly pronounced formation of neutrophil extracellular traps (NETs) inside the micro-vessels.,Intravascular aggregation of NETs leads to rapid occlusion of the affected vessels, disturbed microcirculation, and organ damage.,In severe COVID-19, neutrophil granulocytes are strongly activated and adopt a so-called low-density phenotype, prone to spontaneously form NETs.,In accordance, markers indicating NET turnover are consistently increased in COVID-19 and linked to disease severity.,Histopathology of the lungs and other organs from COVID-19 patients showed congestions of numerous micro-vessels by aggregated NETs associated with endothelial damage.,These data suggest that organ dysfunction in severe COVID-19 is associated with excessive NET formation and vascular damage.,Deutsche Forschungsgemeinschaft (DFG), EU, Volkswagen-Stiftung

We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals.,In answering questions raised regarding our study, we updated our database and repeated all analyses.,We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first.,We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%).,The median follow-up duration increased from 7 to 14 days.,All patients received pharmacological thromboprophylaxis.,The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41-57%).,The majority of thrombotic events were PE (65/75; 87%).,In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091-0.92).,Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4-12).,Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35-1.8).,In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia.

•Cerebrovascular disease was associated with mortality and severity of COVID-19 (borderline).,•Cardiovascular disease was associated with mortality and severity of COVID-19.,•Gender, age, hypertension, diabetes, and respiratory comorbidities did not influence the associations•The association between cerebrovascular disease and poor outcome in COVID-19 was not affected by cardiovascular diseases and vice versa .,Cerebrovascular disease was associated with mortality and severity of COVID-19 (borderline).,Cardiovascular disease was associated with mortality and severity of COVID-19.,Gender, age, hypertension, diabetes, and respiratory comorbidities did not influence the associations,The association between cerebrovascular disease and poor outcome in COVID-19 was not affected by cardiovascular diseases and vice versa .,We conducted a systematic review and meta-analysis to evaluate the latest evidence on the association between cerebrovascular, and cardiovascular diseases and poor outcome in patients with Coronavirus Disease 2019 (COVID-19) pneumonia.,A comprehensive systematic literature search was performed using PubMed, SCOPUS, EuropePMC, and Cochrane Central Database.,The outcome of interest was composite poor outcome that comprised of mortality and severe COVID-19.,A total of 4448 patients were obtained from 16 studies.,Cerebrovascular disease was associated with an increased composite poor outcome (RR 2.04 [1.43,2.91], p<0.001; I2: 77%).,Subgroup analysis revealed that cerebrovascular disease was associated with mortality (RR 2.38 [1.92,2.96], p<0.001; I2: 0%) and showed borderline significance for severe COVID-19 (RR 1.88 [1.00,3.51], p = 0.05; I2: 87%).,Cardiovascular disease was associated with increased composite poor outcome (RR 2.23 [1.71,2.91], p<0.001; I2: 60%), mortality (RR 2.25 [1.53,3.29], p<0.001; I2: 33%) and severe COVID-19 (RR 2.25 [1.51,3.36], p<0.001; I2: 76%).,Meta-regression demonstrate that the association was not influenced by gender, age, hypertension, diabetes, and respiratory comorbidities.,Furthermore, the association between cerebrovascular disease and poor outcome was not affected by cardiovascular diseases and vice versa.,Cerebrovascular and cardiovascular diseases were associated with an increased risk for poor outcome in patients with COVID-19.

To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died.,Retrospective case series.,Tongji Hospital in Wuhan, China.,Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed.,Data were collected until 28 February 2020.,Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms.,The median age of deceased patients (68 years) was significantly older than recovered patients (51 years).,Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%).,Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)).,Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)).,The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days.,Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively.,Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients.,Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%).,Patients with cardiovascular comorbidity were more likely to develop cardiac complications.,Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients.,Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk.,Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

Myocardial injury, diagnosed by troponin elevation, is common in COVID-19 patients, but cardiac involvement with clinical manifestations occurs less frequently.,We analyzed the literature on COVID-19 (2020) and systematically reviewed the cases where individual patient data were presented.,We searched PubMed and Google Scholar for “COVID,” “COVID-19,” and “coronavirus” in combination with “myocarditis,” “heart failure,” “takotsubo,” “cardiomyopathy,” and “cardiogenic shock.”,We identified 90 cases of COVID-19 with myocardial involvement, mean age 52.9 ± 18.3 years, 54.5% males.,Of them, 55 survived (61.1%), 20 died (22.2%), and in 15 (16.7%) the outcome was unknown at the time of publication.,Among patients with known outcome, mortality was 26%.,The nadir LVEF was 31.7 ± 13.1% and recovered to 50.1 ± 16.0%.,Pericardial effusion was a common finding, reported in 21 (23.3%) of patients, including moderate size effusion in 8.9% and large in 7.8%.,The effusion caused tamponade in 11 (12.2%) of patients.,Out of 83 patients who experienced a decrease in LVEF, 30 could be classified as takotsubo syndrome.,The takotsubo patients were older than those with myocarditis, and with relatively high proportion of males.,About one third of the cases was complicated by cardiogenic shock.,Myocardial involvement in COVID-19 patients most often presents as a new, rapid decrease in LVEF, although normal LVEF or takotsubo-like wall motion pattern does not rule out myocarditis.,Moderate and large pericardial effusion is common, and cardiac tamponade occurs in 12.2% of patients.,Cardiogenic shock develops in one third of the patients.,Mortality appears to be high at 26%.

Since its recognition in December 2019, covid-19 has rapidly spread globally causing a pandemic.,Pre-existing comorbidities such as hypertension, diabetes, and cardiovascular disease are associated with a greater severity and higher fatality rate of covid-19.,Furthermore, COVID-19 contributes to cardiovascular complications, including acute myocardial injury as a result of acute coronary syndrome, myocarditis, stress-cardiomyopathy, arrhythmias, cardiogenic shock, and cardiac arrest.,The cardiovascular interactions of COVID-19 have similarities to that of severe acute respiratory syndrome, Middle East respiratory syndrome and influenza.,Specific cardiovascular considerations are also necessary in supportive treatment with anticoagulation, the continued use of renin-angiotensin-aldosterone system inhibitors, arrhythmia monitoring, immunosuppression or modulation, and mechanical circulatory support.

Italy is one of the most affected countries by the coronavirus disease 2019 (COVID-19).,The responsible pathogen is named severe acute respiratory syndrome coronavirus (SARS-CoV-2).,The clinical spectrum ranges from asymptomatic infection to severe pneumonia, leading to intensive care unit admission.,Evidence of cerebrovascular complications associated with SARS-CoV-2 is limited.,We herein report six patients who developed acute stroke during COVID-19 infection.,A retrospective case series of patients diagnosed with COVID-19 using reverse-transcriptase polymerase chain reaction (RT-PCR) on nasopharyngeal swabs, who developed clinical and neuroimaging evidence of acute stroke during SARS-CoV-2 infection.,Six patients were identified (5 men); median age was 69 years (range 57-82).,Stroke subtypes were ischemic (4, 67%) and hemorrhagic (2, 33%).,All patients but one had pre-existing vascular risk factors.,One patient developed encephalopathy prior to stroke, characterized by focal seizures and behavioral abnormalities.,COVID-19-related pneumonia was severe (i.e., requiring critical care support) in 5/6 cases (83%).,Liver enzyme alteration and lactate dehydrogenase (LDH) elevation were registered in all cases.,Four patients (67%) manifested acute kidney failure prior to stroke.,Four patients (67%) had abnormal coagulation tests.,The outcome was poor in the majority of the patients: five died (83%) and the remaining one (17%) remained severely neurologically affected (mRS: 4).,Both ischemic and hemorrhagic stroke can complicate the course of COVI-19 infection.,In our series, stroke developed mostly in patients with severe pneumonia and multiorgan failure, liver enzymes and LDH were markedly increased in all cases, and the outcome was poor.

•COVID-19 pneumonia could be associated with an increased risk of venous thrombosis.,•Antiphospholipid antibodies might be involved in thrombosis in COVID-19 patients.,•Prevalence of antiphospholipid antibodies in COVID-19 and venous thrombosis was low.,COVID-19 pneumonia could be associated with an increased risk of venous thrombosis.,Antiphospholipid antibodies might be involved in thrombosis in COVID-19 patients.,Prevalence of antiphospholipid antibodies in COVID-19 and venous thrombosis was low.

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability.,This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019.,GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019.,Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019.,The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period.,The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019.,The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019.,Cardiovascular diseases remain the leading cause of disease burden in the world.,CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries.,There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases.,•The burden of CVD, in number of DALYs and deaths, continues to increase globally.,•CVD burden attributable to modifiable risk factors continues to increase globally.,•Countries should invest in existing cost-effective public health programs and clinical interventions to target modifiable risks, promote healthy aging across the lifespan, and reduce disability and premature death due to CVD.,The burden of CVD, in number of DALYs and deaths, continues to increase globally.,CVD burden attributable to modifiable risk factors continues to increase globally.,Countries should invest in existing cost-effective public health programs and clinical interventions to target modifiable risks, promote healthy aging across the lifespan, and reduce disability and premature death due to CVD.

Background and Objective: There is a lack of reliable epidemiological data on the long-term survival after acute myocardial infarction (AMI) in the Lithuanian population.,The aim of the study was to evaluate the long-term (36 months) survival after AMI among persons aged 25-64 years, who had experienced AMI in four time-periods 1996, 2003-2004, 2008, and 2012.,Material and Methods: The source of the data was Kaunas population-based Ischemic heart disease (IHD) register.,Long-term survival after AMI (36 months) was evaluated using the Kaplan-Meier method.,The survival curves significantly differed when p < 0.05.,Hazard ratio for all-cause mortality and their 95% CIs, adjusted for baseline characteristics, were estimated with the Cox proportional hazards regression model.,Results: The analysis of data on 36 months long-term survival among Kaunas population by sex and age groups showed that the survival rates among men and women were 83.4% and 87.6%, respectively (p < 0.05) and among 25-54 years-old and 55-64 years-old persons, 89.2% and 81.7%, respectively (p < 0.05).,The rates of long-term survival of post-AMI Kaunas population were better in past periods than in first period.,According to the data of the Kaplan-Meier survival analysis, long-term survival of 25 to 64-year-old post-AMI Kaunas population was without significantly difference in 1996, 2003-2004, 2008 and 2012 (Log-rank = 6.736, p = 0.081).,The adjusted risk of all-cause mortality during 36 months among men and 25 to 54-year-old patients was on the average by 35% and 60% lower in 2012 than in 1996, respectively.,Conclusion: It was found that 36 months survival post MI among women and younger (25-54 years) persons was significant better compared to men and older (55-64 years) persons.,Long-term survival among 55 to 64-year-old post-AMI Kaunas population had a tendency to decrease during last period, while among 25-54 years old persons long-term survival was without significant changes.,The results highlight the fact that AMI survivors, especially in youngest age, remain a high-risk group and reinforce the importance of primary and secondary prevention for the improvement of long-term prognosis of AMI patients.

Supplemental Digital Content is available in the text.,Myocarditis has been recognized as a rare complication of coronavirus disease 2019 (COVID-19) mRNA vaccinations, especially in young adult and adolescent males.,According to the US Centers for Disease Control and Prevention, myocarditis/pericarditis rates are ≈12.6 cases per million doses of second-dose mRNA vaccine among individuals 12 to 39 years of age.,In reported cases, patients with myocarditis invariably presented with chest pain, usually 2 to 3 days after a second dose of mRNA vaccination, and had elevated cardiac troponin levels.,ECG was abnormal with ST elevations in most, and cardiac MRI was suggestive of myocarditis in all tested patients.,There was no evidence of acute COVID-19 or other viral infections.,In 1 case, a cardiomyopathy gene panel was negative, but autoantibody levels against certain self-antigens and frequency of natural killer cells were increased.,Although the mechanisms for development of myocarditis are not clear, molecular mimicry between the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and self-antigens, trigger of preexisting dysregulated immune pathways in certain individuals, immune response to mRNA, and activation of immunologic pathways, and dysregulated cytokine expression have been proposed.,The reasons for male predominance in myocarditis cases are unknown, but possible explanations relate to sex hormone differences in immune response and myocarditis, and also underdiagnosis of cardiac disease in women.,Almost all patients had resolution of symptoms and signs and improvement in diagnostic markers and imaging with or without treatment.,Despite rare cases of myocarditis, the benefit-risk assessment for COVID-19 vaccination shows a favorable balance for all age and sex groups; therefore, COVID-19 vaccination is recommended for everyone ≥12 years of age.

The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur.,This brief report evaluates cardiovascular complications in the setting of COVID-19 infection.,The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death.,The virus binds and enters through angiotensin-converting enzyme 2 (ACE2).,COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness.,The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events.,Current therapies for COVID-19 may interact with cardiovascular medications.,Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.

Cardiometabolic disease, comprising cardiovascular diseases, type 2 diabetes, and their associated risk factors including metabolic syndrome and obesity, is the leading cause of death worldwide.,Plant foods are rich sources of different groups of bioactive compounds, which might not be essential throughout life but promote health and well-being by reducing the risk of age-related chronic diseases.,However, heterogeneity in the responsiveness to bioactive compounds can obscure associations between their intakes and health outcomes, resulting in the hiding of health benefits for specific population groups and thereby limiting our knowledge of the exact role of the different bioactive compounds for health.,The heterogeneity in response suggests that some individuals may benefit more than others from the health effects of these bioactive compounds.,However, to date, this interindividual variation after habitual intake of plant bioactive compounds has been little explored.,The aim of this review is to provide an overview of the existing research that has revealed interindividual variability in the responsiveness to plant-food bioactive compound consumption regarding cardiometabolic outcomes, focusing on polyphenols, caffeine and plant sterols, and the identified potential determinants involved.

Several epidemiological studies have linked flavonols with decreased risk of cardiovascular disease (CVD).,However, some heterogeneity in the individual physiological responses to the consumption of these compounds has been identified.,This meta-analysis aimed to study the effect of flavonol supplementation on biomarkers of CVD risk such as, blood lipids, blood pressure and plasma glucose, as well as factors affecting their inter-individual variability.,Data from 18 human randomized controlled trials were pooled and the effect was estimated using fixed or random effects meta-analysis model and reported as difference in means (DM).,Variability in the response of blood lipids to supplementation with flavonols was assessed by stratifying various population subgroups: age, sex, country, and health status.,Results showed significant reductions in total cholesterol (DM = −0.10 mmol/L; 95% CI: −0.20, −0.01), LDL cholesterol (DM = −0.14 mmol/L; 95% CI: −0.21, 0.07), and triacylglycerol (DM = −0.10 mmol/L; 95% CI: −0.18, 0.03), and a significant increase in HDL cholesterol (DM = 0.05 mmol/L; 95% CI: 0.02, 0.07).,A significant reduction was also observed in fasting plasma glucose (DM = −0.18 mmol/L; 95% CI: −0.29, −0.08), and in blood pressure (SBP: DM = −4.84 mmHg; 95% CI: −5.64, −4.04; DBP: DM = −3.32 mmHg; 95% CI: −4.09, −2.55).,Subgroup analysis showed a more pronounced effect of flavonol intake in participants from Asian countries and in participants with diagnosed disease or dyslipidemia, compared to healthy and normal baseline values.,In conclusion, flavonol consumption improved biomarkers of CVD risk, however, country of origin and health status may influence the effect of flavonol intake on blood lipid levels.

Lamin A/C (LMNA) is one of the most frequently mutated genes in dilated cardiomyopathy (DCM).,LMNA-related DCM is a common inherited cardiomyopathy associated with systolic dysfunction and high prevalence arrhythmias.,Here we modeled the LMNA-DCM in vitro using patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs).,Electrophysiological studies showed that the mutant iPSC-CMs displayed aberrant calcium homeostasis leading to arrhythmias at the single-cell level.,Mechanistically, we uncovered that the platelet-derived growth factor (PDGF) signaling pathway was activated in mutant iPSC-CMs when compared to isogenic controls.,Conversely, pharmacological and molecular inhibition of the PDGF signaling pathway ameliorated the arrhythmia phenotypes of mutant iPSC-CMs in vitro.,Taken together, our findings suggest that the activation of the PDGF pathway contributes to the pathogenesis of the LMNA-DCM and point to PDGF receptor beta (PDGFRB) as a potential therapeutic target.

Accurately predicting cardioactive effects of new molecular entities for therapeutics remains a daunting challenge.,Immense research effort has been focused toward creating new screening platforms that utilize human pluripotent stem cell (hPSC)-derived cardiomyocytes and three-dimensional engineered cardiac tissue constructs to better recapitulate human heart function and drug responses.,As these new platforms become increasingly sophisticated and high throughput, the drug screens result in larger multidimensional datasets.,Improved automated analysis methods must therefore be developed in parallel to fully comprehend the cellular response across a multidimensional parameter space.,Here, we describe the use of machine learning to comprehensively analyze 17 functional parameters derived from force readouts of hPSC-derived ventricular cardiac tissue strips (hvCTS) electrically paced at a range of frequencies and exposed to a library of compounds.,A generated metric is effective for then determining the cardioactivity of a given drug.,Furthermore, we demonstrate a classification model that can automatically predict the mechanistic action of an unknown cardioactive drug.,•Machine learning on multidimensional drug-response data to determine cardioactivity•Classify unknown drugs based on mechanistic action,Machine learning on multidimensional drug-response data to determine cardioactivity,Classify unknown drugs based on mechanistic action,Analysis methods must be improved in parallel with advancements in drug screening platforms.,Machine learning principles are used here to analyze multidimensional datasets to determine cardioactivity of unknown drugs.,Furthermore, this study describes the use of multiclassification algorithms to classify unknown drugs based on their mechanistic action and compare their potency with related drugs.

The COVID-19 pandemic has led to extensive morbidity and mortality throughout the world.,Clinical features that drive SARS-CoV-2 pathogenesis in humans include inflammation and thrombosis, but the mechanistic details underlying these processes remain to be determined.,In this study, we demonstrate endothelial disruption and vascular thrombosis in histopathologic sections of lungs from both humans and rhesus macaques infected with SARS-CoV-2.,To define key molecular pathways associated with SARS-CoV-2 pathogenesis in macaques, we performed transcriptomic analyses of bronchoalveolar lavage and peripheral blood and proteomic analyses of serum.,We observed macrophage infiltrates in lung and upregulation of macrophage, complement, platelet activation, thrombosis, and proinflammatory markers, including C-reactive protein, MX1, IL-6, IL-1, IL-8, TNFα, and NF-κB.,These results suggest a model in which critical interactions between inflammatory and thrombosis pathways lead to SARS-CoV-2-induced vascular disease.,Our findings suggest potential therapeutic targets for COVID-19.,Aid et al. show that SARS-CoV-2 causes endothelial disruption and vascular thrombosis in both human and rhesus macaques lungs by inducing an upregulation of proinflammatory cytokines.,Using an approach that combines histopathology and multiomics in macaques, they show the progression to vascular disease over time, which involves complement, macrophage, cytokine, and thrombosis cascades.

Little evidence of increased thrombotic risk is available in COVID-19 patients.,Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.,All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included.,Medical history, symptoms, biological data and imaging were prospectively collected.,Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.,150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points).,Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting.,Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO.,Most patients (> 95%) had elevated D-dimer and fibrinogen.,No patient developed disseminated intravascular coagulation.,Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant.,Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs.,2.1%, p < 0.008).,Coagulation parameters significantly differed between the two groups.,Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications.,Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.,The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users.

To investigate sex differences in acute myocardial infarction (AMI) guideline-indicated care as defined by the European Society of Cardiology (ESC) Acute Cardiovascular Care Association (ACCA) quality indicators.,Nationwide cohort study comprising 691 290 AMI hospitalisations in England and Wales (n=233 hospitals) from the Myocardial Ischaemia National Audit Project between 1 January 2003 and 30 June 2013.,There were 34.5% (n=238 489) women (median age 76.7 (IQR 66.3-84.0) years; 33.9% (n=80 884) ST-elevation myocardial infarction (STEMI)) and 65.5% (n=452 801) men (median age 67.1 (IQR 56.9-77.2) years; 42.5% (n=192 229) STEMI).,Women less frequently received 13 of the 16 quality indicators compared with men, including timely reperfusion therapy for STEMI (76.8% vs 78.9%; p<0.001), timely coronary angiography for non-STEMI (24.2% vs 36.7%; p<0.001), dual antiplatelet therapy (75.4% vs 78.7%) and secondary prevention therapies (87.2% vs 89.6% for statins, 82.5% vs 85.6% for ACE inhibitor/angiotensin receptor blockers and 62.6% vs 67.6% for beta-blockers; all p<0.001).,Median 30-day Global Registry of Acute Coronary Events risk score adjusted mortality was higher for women than men (median: 5.2% (IQR 1.8%-13.1%) vs 2.3% (IQR 0.8%-7.1%), p<0.001).,An estimated 8243 (95% CI 8111 to 8375) deaths among women could have been prevented over the study period if their quality indicator attainment had been equal to that attained by men.,According to the ESC ACCA AMI quality indicators, women in England and Wales less frequently received guideline-indicated care and had significantly higher mortality than men.,Greater attention to the delivery of recommended AMI treatments for women has the potential to reduce the sex-AMI mortality gap.

Women with ST‐segment-elevation myocardial infarction (STEMI) have higher mortality rates than men.,We investigated whether sex‐related differences in timely access to care among STEMI patients may be a factor associated with excess risk of early mortality in women.,We identified 6022 STEMI patients who had information on time of symptom onset to time of hospital presentation at 41 hospitals participating in the ISACS‐TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry (NCT01218776) from October 2010 through April 2016.,Patients were stratified into time‐delay cohorts.,We estimated the 30‐day risk of all‐cause mortality in each cohort.,Despite similar delays in seeking care, the overall time from symptom onset to hospital presentation was longer for women than men (median: 270 minutes [range: 130-776] versus 240 minutes [range: 120-600]).,After adjustment for baseline variables, female sex was independently associated with greater risk of 30‐day mortality (odds ratio: 1.58; 95% confidence interval, 1.27-1.97).,Sex differences in mortality following STEMI were no longer observed for patients having delays from symptom onset to hospital presentation of ≤1 hour (odds ratio: 0.77; 95% confidence interval, 0.29-2.02).,Sex difference in mortality following STEMI persists and appears to be driven by prehospital delays in hospital presentation.,Women appear to be more vulnerable to prolonged untreated ischemia.,URL: https://www.clinicaltrials.gov/.,Unique identifier: NCT01218776.

To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died.,Retrospective case series.,Tongji Hospital in Wuhan, China.,Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed.,Data were collected until 28 February 2020.,Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms.,The median age of deceased patients (68 years) was significantly older than recovered patients (51 years).,Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%).,Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)).,Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)).,The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days.,Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively.,Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients.,Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%).,Patients with cardiovascular comorbidity were more likely to develop cardiac complications.,Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients.,Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk.,Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

Coronavirus disease 2019 (COVID-19) has been demonstrated to be the cause of pneumonia.,Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis.,A 63-year-old male was admitted with pneumonia and cardiac symptoms.,He was genetically confirmed as having COVID-19 according to sputum testing on the day of admission.,He also had elevated troponin I (Trop I) level (up to 11.37 g/L) and diffuse myocardial dyskinesia along with a decreased left ventricular ejection fraction (LVEF) on echocardiography.,The highest level of interleukin-6 was 272.40 pg/ml.,Bedside chest radiographs showed typical ground-glass changes indicative of viral pneumonia.,Laboratory test results for viruses that cause myocarditis were all negative.,The patient conformed to the diagnostic criteria of the Chinese expert consensus statement for fulminant myocarditis.,After receiving antiviral therapy and mechanical life support, Trop I was reduced to 0.10 g/L, and interleukin-6 was reduced to 7.63 pg/mL.,Moreover, the LVEF of the patient gradually recovered to 68%.,The patient died of aggravation of secondary infection on the 33rd day of hospitalization.,COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure.,This is the first report of COVID-19 complicated with fulminant myocarditis.,The mechanism of cardiac pathology caused by COVID-19 needs further study.

There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2).,We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive.,Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class.,A difference of at least 10 percentage points was prespecified as a substantial difference.,Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness.,A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness.,There was no association between any single medication class and an increased likelihood of a positive test.,None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive.,We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.

This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury.

Supplemental Digital Content is available in the text.,Severe acute respiratory syndrome corona virus 2 infection causes severe pneumonia (coronavirus disease 2019 [COVID-19]), but the mechanisms of subsequent respiratory failure and complicating renal and myocardial involvement are poorly understood.,In addition, a systemic prothrombotic phenotype has been reported in patients with COVID-19.,A total of 62 subjects were included in our study (n=38 patients with reverse transcriptase polymerase chain reaction-confirmed COVID-19 and n=24 non-COVID-19 controls).,We performed histopathologic assessment of autopsy cases, surface marker-based phenotyping of neutrophils and platelets, and functional assays for platelet, neutrophil functions, and coagulation tests, as well.,We provide evidence that organ involvement and prothrombotic features in COVID-19 are linked by immunothrombosis.,We show that, in COVID-19, inflammatory microvascular thrombi are present in the lung, kidney, and heart, containing neutrophil extracellular traps associated with platelets and fibrin.,Patients with COVID-19 also present with neutrophil-platelet aggregates and a distinct neutrophil and platelet activation pattern in blood, which changes with disease severity.,Whereas cases of intermediate severity show an exhausted platelet and hyporeactive neutrophil phenotype, patients severely affected with COVID-19 are characterized by excessive platelet and neutrophil activation in comparison with healthy controls and non-COVID-19 pneumonia.,Dysregulated immunothrombosis in severe acute respiratory syndrome corona virus 2 pneumonia is linked to both acute respiratory distress syndrome and systemic hypercoagulability.,Taken together, our data point to immunothrombotic dysregulation as a key marker of disease severity in COVID-19.,Further work is necessary to determine the role of immunothrombosis in COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children.,A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation.,The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology.,We apply systems-level analyses of blood immune cells, cytokines, and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2, and children presenting with MIS-C.,We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage.,Finally, autoantibody profiling suggests multiple autoantibodies that could be involved in the pathogenesis of MIS-C.,•Hyperinflammation in MIS-C differs from that of acute COVID-19•T cell subsets discriminate Kawasaki disease patients from MIS-C•IL-17A drives Kawasaki but not MIS-C hyperinflammation•Global profiling reveals candidate autoantibodies with pathogenic potential,Hyperinflammation in MIS-C differs from that of acute COVID-19,T cell subsets discriminate Kawasaki disease patients from MIS-C,IL-17A drives Kawasaki but not MIS-C hyperinflammation,Global profiling reveals candidate autoantibodies with pathogenic potential,A systems immunology approach describes how multisystem inflammatory syndrome in children (MIS-C) is distinct from Kawasaki disease as well as the cytokine storm associated with severe COVID-19 in terms of its molecular and immune profiles.

No studies investigated the prevalence of arrhythmias among clinically‐stable patients affected by COVID‐19 infection.,We assessed prevalence, type, and burden of arrhythmias, by a single‐day snapshot in seven non‐intensive COVID Units at a third‐level center.,We enrolled 132 inhospital patients (mean age 65±14y; 66% males) newly diagnosed with COVID‐19 infection.,Arrhythmic episodes were detected in 12 patients (9%).,In detail, 8 had atrial fibrillation, and 4 self‐limiting supraventricular tachyarrhythmias.,There were no cases of ventricular arrhythmias or new‐onset atrioventricular blocks.,In addition, we report no patients with QTc interval >450 ms.,Our single‐day snapshot survey suggests that the prevalence of arrhythmias among clinically stable COVID‐19 patients is low.,In particular, no life‐threatening arrhythmic events occurred.

This document is an update to the 2013 publication of the Society for Cardiovascular Magnetic Resonance (SCMR) Board of Trustees Task Force on Standardized Protocols.,Concurrent with this publication, 3 additional task forces will publish documents that should be referred to in conjunction with the present document.,The first is a document on the Clinical Indications for CMR, an update of the 2004 document.,The second task force will be updating the document on Reporting published by that SCMR Task Force in 2010.,The 3rd task force will be updating the 2013 document on Post-Processing.,All protocols relative to congenital heart disease are covered in a separate document.,The section on general principles and techniques has been expanded as more of the techniques common to CMR have been standardized.,A section on imaging in patients with devices has been added as this is increasingly seen in day-to-day clinical practice.,The authors hope that this document continues to standardize and simplify the patient-based approach to clinical CMR.,It will be updated at regular intervals as the field of CMR advances.

Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined.,We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients.,One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days.,Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%).,Late gadolinium enhancement and/or ischaemia was found in 54% (80/148).,This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148).,Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis.,Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia).,Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease.,There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms).,During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence.,In a proportion of patients, there is evidence of possible ongoing localized inflammation.,A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history.,Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined.,Diffuse oedema or fibrosis was not detected.

There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2).,We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive.,Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class.,A difference of at least 10 percentage points was prespecified as a substantial difference.,Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness.,A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness.,There was no association between any single medication class and an increased likelihood of a positive test.,None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive.,We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.

What are the cardiovascular effects in unselected patients with recent coronavirus disease 2019 (COVID-19)?,In this cohort study including 100 patients recently recovered from COVID-19 identified from a COVID-19 test center, cardiac magnetic resonance imaging revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), which was independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.,This cohort study evaluates the presence of myocardial injury in unselected patients recently recovered from coronavirus disease 2019 (COVID-19).,Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide.,Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown.,To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness.,In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020.,Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription-polymerase chain reaction on swab test of the upper respiratory tract.,Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained.,Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor-matched patients (n = 57).,Of the 100 included patients, 53 (53%) were male, and the mean (SD) age was 49 (14) years.,The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days.,Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization.,At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 patients (5%).,Compared with healthy controls and risk factor-matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, and raised native T1 and T2.,A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), or pericardial enhancement (n = 22).,There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms; P = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL; P = .002) but not for native T2 mapping.,None of these measures were correlated with time from COVID-19 diagnosis (native T1: r = 0.07; P = .47; native T2: r = 0.14; P = .15; hsTnT: r = −0.07; P = .50).,High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.33; P < .001) and native T2 mapping (r = 0.18; P = .01).,Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation.,Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19-related myocardial pathology.,In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.

To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died.,Retrospective case series.,Tongji Hospital in Wuhan, China.,Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed.,Data were collected until 28 February 2020.,Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms.,The median age of deceased patients (68 years) was significantly older than recovered patients (51 years).,Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%).,Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)).,Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)).,The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days.,Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively.,Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients.,Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%).,Patients with cardiovascular comorbidity were more likely to develop cardiac complications.,Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients.,Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk.,Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

Previous reports suggest that radiation therapy for breast cancer (BC) can cause ischemic heart disease, with the radiation-related risk increasing linearly with mean whole heart dose (MWHD).,This study aimed to validate these findings in younger BC patients and to investigate additional risk factors for radiation-related myocardial infarction (MI).,A nested case-control study was conducted within a cohort of BC survivors treated during 1970 to 2009.,Cases were 183 patients with MI as their first heart disease after BC.,One control per case was selected and matched on age and BC diagnosis date.,Information on treatment and cardiovascular risk factors was abstracted from medical and radiation charts.,Cardiac doses were estimated for each woman by reconstructing her regimen using modern 3-dimensional computed tomography planning on a typical patient computed tomography scan.,Median age at BC of cases and controls was 50.2 years (interquartile range, 45.7-54.7).,Median time to MI was 13.6 years (interquartile range, 9.9-18.1).,Median MWHD was 8.9 Gy (range, 0.3-35.2 Gy).,MI rate increased linearly with increasing MWHD (excess rate ratio [ERR] per Gy, 6.4%; 95% confidence interval, 1.3%-16.0%).,Patients receiving ≥20 Gy MWHD had a 3.4-fold (95% confidence interval, 1.5-7.6) higher MI rate than unirradiated patients.,ERRs were higher for younger women, with borderline significance (ERR<45years, 24.2%/Gy; ERR≥50years, 2.5%/Gy; Pinteraction = .054).,Whole heart dose-volume parameters did not modify the dose-response relationship significantly.,MI rate after radiation for BC increases linearly with MWHD.,Reductions in MWHD are expected to contribute to better cardiovascular health of BC survivors.

The risk of heart disease subsequent to breast cancer radiotherapy was examined with particular focus on women receiving anthracycline-containing chemotherapy.,Women diagnosed with early-stage breast cancer in Denmark, 1977-2005, were identified from the register of the Danish Breast Cancer Cooperative Group, as was information on cancer-directed treatment.,Information on heart disease was sought from the Danish National Patient and Cause of Death Registries.,Incidence rate ratios were estimated comparing left-sided with right-sided cancer (IRR, LvR), stratified by calendar year, age, and time since breast cancer radiotherapy.,Among 19,464 women receiving radiotherapy, the IRR, LvR, was 1.11 (95% CI 1.03-1.20, p = 0.005) for all heart disease and among those also receiving anthracyclines the IRR, LvR, was 1.32 (95% CI 1.02-1.70, p = 0.03).,This risk was highest if the treatment was given before the age of 50 years (IRR, LvR, 1.44, (95% CI 1.04-2.01) but there was no significant trend with age or time since treatment.,Radiotherapy for left-sided breast cancer is associated with a higher risk of heart disease than for right-sided with the largest increases seen in women who also received anthracycline-containing chemotherapy.

Supplemental Digital Content is available in the text.,Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension.,To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19.,This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57-69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020.,In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19-0.92]; P=0.03).,In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15-0.89]; P=0.03).,Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12-0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension.,Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers.,While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.

The dysfunction of the renin-angiotensin system (RAS) has been observed in coronavirus infection disease (COVID-19) patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs), are associated with clinical outcomes remains unknown.,COVID-19 patients with hypertension were enrolled to evaluate the effect of RAS inhibitors.,We observed that patients receiving ACEI or ARB therapy had a lower rate of severe diseases and a trend toward a lower level of IL-6 in peripheral blood.,In addition, ACEI or ARB therapy increased CD3 and CD8 T cell counts in peripheral blood and decreased the peak viral load compared to other antihypertensive drugs.,This evidence supports the benefit of using ACEIs or ARBs to potentially contribute to the improvement of clinical outcomes of COVID-19 patients with hypertension.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic in just a few months, causing millions infected.,Nearly 20% of COVID-19 patients present severe coagulation abnormalities, which may occur in almost all of the severe and critical ill COVID-19 cases.,Concomitant venous thromboembolism (VTE), a potential cause of unexplained deaths, has been frequently reported in COVID-19 cases, but its management is still challenging due to the complexity between antithrombotic therapy and coagulation disorders.,Based on frontline practical experience and comprehensive literature review, here a panel of experts and physicians from China and Europe developed an evidence and opinion-based consensus on the prophylaxis and management of VTE associated with COVID-19.,This statement aims for clinicians treating COVID-19 and provides practical recommendations in detailed situations, for example, how to choose thromboprophylactic measures for patients with diverse severity of disease and bleeding risk, or which kind of anticoagulant should be prescribed.,With limited experience on COVID19-associated VTE, this expert consensus statement should be helpful for clinicians worldwide with specific suggestions.

COVID-19 predisposes patients to a prothrombotic state with demonstrated microvascular involvement.,The degree of hypercoagulability appears to correlate with outcomes; however, optimal criteria to assess for the highest-risk patients for thrombotic events remain unclear; we hypothesized that deranged thromboelastography measurements of coagulation would correlate with thromboembolic events.,Patients admitted to an ICU with COVID-19 diagnoses who had thromboelastography analyses performed were studied.,Conventional coagulation assays, d-dimer levels, and viscoelastic measurements were analyzed using a receiver operating characteristic curve to predict thromboembolic outcomes and new-onset renal failure.,Forty-four patients with COVID-19 were included in the analysis.,Derangements in coagulation laboratory values, including elevated d-dimer, fibrinogen, prothrombin time, and partial thromboplastin time, were confirmed; viscoelastic measurements showed an elevated maximum amplitude and low lysis of clot at 30 minutes.,A complete lack of lysis of clot at 30 minutes was seen in 57% of patients and predicted venous thromboembolic events with an area under the receiver operating characteristic curve of 0.742 (p = 0.021).,A d-dimer cutoff of 2,600 ng/mL predicted need for dialysis with an area under the receiver operating characteristic curve of 0.779 (p = 0.005).,Overall, patients with no lysis of clot at 30 minutes and a d-dimer > 2,600 ng/mL had a venous thromboembolic event rate of 50% compared with 0% for patients with neither risk factor (p = 0.008), and had a hemodialysis rate of 80% compared with 14% (p = 0.004).,Fibrinolysis shutdown, as evidenced by elevated d-dimer and complete failure of clot lysis at 30 minutes on thromboelastography predicts thromboembolic events and need for hemodialysis in critically ill patients with COVID-19.,Additional clinical trials are required to ascertain the need for early therapeutic anticoagulation or fibrinolytic therapy to address this state of fibrinolysis shutdown.

The impact of atrial arrhythmias on coronavirus disease 2019 (COVID‐19)‐associated outcomes are unclear.,We sought to identify prevalence, risk factors and outcomes associated with atrial arrhythmias among patients hospitalized with COVID‐19.,An observational cohort study of 1053 patients with severe acute respiratory syndrome coronavirus 2 infection admitted to a quaternary care hospital and a community hospital was conducted.,Data from electrocardiographic and telemetry were collected to identify atrial fibrillation (AF) or atrial flutter/tachycardia (AFL).,The association between atrial arrhythmias and 30‐day mortality was assessed with multivariable analysis.,Mean age of patients was 62 ± 17 years and 62% were men.,Atrial arrhythmias were identified in 166 (15.8%) patients, with AF in 154 (14.6%) patients and AFL in 40 (3.8%) patients.,Newly detected atrial arrhythmias occurred in 101 (9.6%) patients.,Age, male sex, prior AF, renal disease, and hypoxia on presentation were independently associated with AF/AFL occurrence.,Compared with patients without AF/AFL, patients with AF/AFL had significantly higher levels of troponin, B‐type natriuretic peptide, C‐reactive protein, ferritin and d‐dimer.,Mortality was significantly higher among patients with AF/AFL (39.2%) compared to patients without (13.4%; p < .001).,After adjustment for age and co‐morbidities, AF/AFL (adjusted odds ratio [OR]: 1.93; p = .007) and newly detected AF/AFL (adjusted OR: 2.87; p < .001) were independently associated with 30‐day mortality.,Atrial arrhythmias are common among patients hospitalized with COVID‐19.,The presence of AF/AFL tracked with markers of inflammation and cardiac injury.,Atrial arrhythmias were independently associated with increased mortality.

Early studies suggest that coronavirus disease 2019 (COVID-19) is associated with a high incidence of cardiac arrhythmias.,Severe acute respiratory syndrome coronavirus 2 infection may cause injury to cardiac myocytes and increase arrhythmia risk.,The purpose of this study was to evaluate the risk of cardiac arrest and arrhythmias including incident atrial fibrillation (AF), bradyarrhythmias, and nonsustained ventricular tachycardia (NSVT) in a large urban population hospitalized for COVID-19.,We also evaluated correlations between the presence of these arrhythmias and mortality.,We reviewed the characteristics of all patients with COVID-19 admitted to our center over a 9-week period.,Throughout hospitalization, we evaluated the incidence of cardiac arrests, arrhythmias, and inpatient mortality.,We also used logistic regression to evaluate age, sex, race, body mass index, prevalent cardiovascular disease, diabetes, hypertension, chronic kidney disease, and intensive care unit (ICU) status as potential risk factors for each arrhythmia.,Among 700 patients (mean age 50 ± 18 years; 45% men; 71% African American; 11% received ICU care), there were 9 cardiac arrests, 25 incident AF events, 9 clinically significant bradyarrhythmias, and 10 NSVTs.,All cardiac arrests occurred in patients admitted to the ICU.,In addition, admission to the ICU was associated with incident AF (odds ratio [OR] 4.68; 95% confidence interval [CI] 1.66-13.18) and NSVT (OR 8.92; 95% CI 1.73-46.06) after multivariable adjustment.,Also, age and incident AF (OR 1.05; 95% CI 1.02-1.09) and prevalent heart failure and bradyarrhythmias (OR 9.75; 95% CI 1.95-48.65) were independently associated.,Only cardiac arrests were associated with acute in-hospital mortality.,Cardiac arrests and arrhythmias are likely the consequence of systemic illness and not solely the direct effects of COVID-19 infection.