Showing papers on "Ejection fraction published in 2021"
3,645 citations
TL;DR: In this paper, a double-blind trial was conducted to evaluate the effect of empagliflozin on the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a reduced ejection fraction.
Abstract: Background Sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with heart failure and a preserved ejection fraction are uncertain. Methods In this double-blind trial, we randomly assigned 5988 patients with class II-IV heart failure and an ejection fraction of more than 40% to receive empagliflozin (10 mg once daily) or placebo, in addition to usual therapy. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure. Results Over a median of 26.2 months, a primary outcome event occurred in 415 of 2997 patients (13.8%) in the empagliflozin group and in 511 of 2991 patients (17.1%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.69 to 0.90; P Conclusions Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection fraction, regardless of the presence or absence of diabetes. (Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Preserved ClinicalTrials.gov number, NCT03057951).
1,506 citations
TL;DR: In this paper, the authors summarized the impact of obesity on the diagnosis, clinical management, and outcomes of atherosclerotic cardiovascular disease, heart failure, and arrhythmias, especially sudden cardiac death and atrial fibrillation.
Abstract: The global obesity epidemic is well established, with increases in obesity prevalence for most countries since the 1980s. Obesity contributes directly to incident cardiovascular risk factors, including dyslipidemia, type 2 diabetes, hypertension, and sleep disorders. Obesity also leads to the development of cardiovascular disease and cardiovascular disease mortality independently of other cardiovascular risk factors. More recent data highlight abdominal obesity, as determined by waist circumference, as a cardiovascular disease risk marker that is independent of body mass index. There have also been significant advances in imaging modalities for characterizing body composition, including visceral adiposity. Studies that quantify fat depots, including ectopic fat, support excess visceral adiposity as an independent indicator of poor cardiovascular outcomes. Lifestyle modification and subsequent weight loss improve both metabolic syndrome and associated systemic inflammation and endothelial dysfunction. However, clinical trials of medical weight loss have not demonstrated a reduction in coronary artery disease rates. In contrast, prospective studies comparing patients undergoing bariatric surgery with nonsurgical patients with obesity have shown reduced coronary artery disease risk with surgery. In this statement, we summarize the impact of obesity on the diagnosis, clinical management, and outcomes of atherosclerotic cardiovascular disease, heart failure, and arrhythmias, especially sudden cardiac death and atrial fibrillation. In particular, we examine the influence of obesity on noninvasive and invasive diagnostic procedures for coronary artery disease. Moreover, we review the impact of obesity on cardiac function and outcomes related to heart failure with reduced and preserved ejection fraction. Finally, we describe the effects of lifestyle and surgical weight loss interventions on outcomes related to coronary artery disease, heart failure, and atrial fibrillation.
656 citations
TL;DR: This document summarizes current capabilities, research and operational priorities, and plans for further studies that were established at the 2015 USGS workshop on quantitative hazard assessments of earthquake-triggered landsliding and liquefaction in the Czech Republic.
458 citations
TL;DR: In this paper, a universal definition of heart failure (HF) was proposed, with symptoms and signs caused by structural and functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion.
Abstract: In this document, we propose a universal definition of heart failure (HF) as a clinical syndrome with symptoms and/or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion. We also propose revised stages of HF as: At risk for HF (Stage A), Pre-HF (Stage B), Symptomatic HF (Stage C) and Advanced HF (Stage D). Finally, we propose a new and revised classification of HF according to left ventricular ejection fraction (LVEF). This includes HF with reduced ejection fraction (HFrEF): symptomatic HF with LVEF ≤40%; HF with mildly reduced ejection fraction (HFmrEF): symptomatic HF with LVEF 41-49%; HF with preserved ejection fraction (HFpEF): symptomatic HF with LVEF ≥50%; and HF with improved ejection fraction (HFimpEF): symptomatic HF with a baseline LVEF ≤40%, a ≥10 point increase from baseline LVEF, and a second measurement of LVEF > 40%.
400 citations
University of California1, Duke University2, University of Glasgow3, University of Brescia4, Harvard University5, University of North Carolina at Chapel Hill6, University of Minnesota7, University of Copenhagen8, Saarland University9, Medical University of Vienna10, Imperial College London11, Pontifical Catholic University of Chile12, Linköping University13, University of Utah14, National and Kapodistrian University of Athens15, Nova Southeastern University16, Comenius University in Bratislava17, Sofia Medical University18, Henry Ford Hospital19, Peking Union Medical College20, Middlemore Hospital21, St. Vincent's Health System22, Moscow State University23, Université de Montréal24, Wrocław Medical University25, University of São Paulo26, Vilnius University27, University of Cape Town28, Masaryk University29, University Hospital of Bern30, St John of God Health Care31, Carol Davila University of Medicine and Pharmacy32, University of Groningen33, Dokuz Eylül University34, University of Lorraine35, Amgen36
TL;DR: Among patients with heart failure and a reduced ejection, patients who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo.
Abstract: Background The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect ...
341 citations
TL;DR: A universal definition of heart failure (HF) was proposed in this article, which is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and or objective evidence of pulmonary or systemic congestion.
267 citations
TL;DR: In this paper, the authors used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients, including myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22%, and dual pathology in 6% (9/148).
Abstract: Background 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. Methods and results 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). Conclusions 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.
235 citations
University of Cambridge1, Hospital Sant Joan de Déu Barcelona2, Guy's and St Thomas' NHS Foundation Trust3, Boston Children's Hospital4, University of Lyon5, Medical University of Warsaw6, Ghent University Hospital7, University Hospitals Bristol NHS Foundation Trust8, Glenfield Hospital9, King's College London10
TL;DR: Compared to adults with Covid-19, mortality in children with MIS-C is uncommon despite multi-system involvement, very elevated inflammatory markers and need for intensive care support.
Abstract: Background: The aim of the study was to document cardiovascular clinical findings, cardiac imaging and laboratory markers in children presenting with the novel multisystem inflammatory syndrome (MIS-C) associated with COVID-19 infection. Methods: A real-time internet-based survey endorsed by the Association for European Paediatric and Congenital Cardiologists (AEPC) Working Groups for Cardiac Imaging and Cardiovascular Intensive Care. Inclusion criteria was children 0-18 years admitted to hospital between February 1 and June 6, 2020 with diagnosis of an inflammatory syndrome and acute cardiovascular complications. Results: A total of 286 children from 55 centers in 17 European countries were included. The median age was 8.4 years (IQR 3.8-12.4 years) and 67% were males. The most common cardiovascular complications were shock, cardiac arrhythmias, pericardial effusion and coronary artery dilatation. Reduced left ventricular ejection fraction was present in over half of the patients and a vast majority of children had raised cardiac troponin (cTnT) when checked. The biochemical markers of inflammation were raised in majority of patients on admission: elevated CRP, serum ferritin, procalcitonin, NT-proBNP, IL-6 level and D-dimers. There was a statistically significant correlation between degree of elevation in cardiac and biochemical parameters and need for intensive care support (p <0.05). Polymerase chain reaction (PCR) for SARS-CoV-2 was positive in 33.6% while IgM and IgG antibodies were positive in 15.7% and IgG 43.6 % cases, respectively when checked. One child died in the study cohort. Conclusions: Cardiac involvement is common in children with multisystem inflammatory syndrome associated with Covid-19 pandemic. A majority of children have significantly raised levels of NT pro-BNP, ferritin, D-dimers and cardiac troponin in addition to high CRP and procalcitonin levels. Compared to adults with Covid-19, mortality in children with MIS-C is uncommon despite multi-system involvement, very elevated inflammatory markers and need for intensive care support.
234 citations
TL;DR: Empagliflozin administration to non-diabetic HFrEF patients significantly improves LV volumes, LV mass, LV systolic function, functional capacity, and quality of life when compared with placebo.
234 citations
University of Missouri–Kansas City1, Mayo Clinic2, Wake Forest University3, Northwestern University4, Emory University5, Cardiovascular Institute of the South6, Johns Hopkins University School of Medicine7, NorthShore University HealthSystem8, University of Utah9, University of Maryland, Baltimore10, Stormont Vail Health11, Allegheny Health Network12, Eastern Virginia Medical School13, Harvard University14, University of Southern California15
TL;DR: In this paper, the authors evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of KCCQ-CS, a measure of heart failure-related health status, at 12 weeks after treatment initiation.
Abstract: Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of heart failure-related health status, at 12 weeks after treatment initiation. Secondary endpoints included the 6-minute walk test (6MWT), KCCQ Overall Summary Score (KCCQ-OS), clinically meaningful changes in KCCQ-CS and -OS, and changes in weight, natriuretic peptides, glycated hemoglobin and systolic blood pressure. In total, 324 patients were randomized to dapagliflozin or placebo. Dapagliflozin improved KCCQ-CS (effect size, 5.8 points (95% confidence interval (CI) 2.3–9.2, P = 0.001), meeting the predefined primary endpoint, due to improvements in both KCCQ total symptom score (KCCQ-TS) (5.8 points (95% CI 2.0–9.6, P = 0.003)) and physical limitations scores (5.3 points (95% CI 0.7–10.0, P = 0.026)). Dapagliflozin also improved 6MWT (mean effect size of 20.1 m (95% CI 5.6–34.7, P = 0.007)), KCCQ-OS (4.5 points (95% CI 1.1–7.8, P = 0.009)), proportion of participants with 5-point or greater improvements in KCCQ-OS (odds ratio (OR) = 1.73 (95% CI 1.05–2.85, P = 0.03)) and reduced weight (mean effect size, 0.72 kg (95% CI 0.01–1.42, P = 0.046)). There were no significant differences in other secondary endpoints. Adverse events were similar between dapagliflozin and placebo (44 (27.2%) versus 38 (23.5%) patients, respectively). These results indicate that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF. In a multicenter, randomized trial, the SGLT2 inhibitor dapagliflozin improved the health status and exercise function of patients with heart failure with preserved ejection fraction (HFpEF), a condition for which effective treatments are lacking.
TL;DR: In this paper, a series of febrile pediatric patients with acute heart failure potentially associated with SARS-CoV-2 infection and the multisystem inflammatory syndrome in children as defined by the US Centers for Disease Control and Prevention were reported.
Charité1, University of Mississippi2, National and Kapodistrian University of Athens3, RWTH Aachen University4, National University of Singapore5, Boehringer Ingelheim6, Saarland University7, Heidelberg University8, University of São Paulo9, Wrocław Medical University10, Harvard University11, University of Toronto12, University of London13, Baylor University Medical Center14, Imperial College London15
TL;DR: In EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction), empaglif Lozin significantly improved cardiovascular and renal outcomes in patients with heart failure and a reduced ejection fraction, independent of baseline diabetes status and across the continuum of HbA1c.
Abstract: Background: Sodium-glucose cotransporter 2 inhibitors improve outcomes in patients with heart failure with reduced ejection fraction, but additional information is needed about whether glycemic sta...
University of Glasgow1, Brigham and Women's Hospital2, University Medical Center Groningen3, University of Minnesota4, Saarland University5, Max Super Speciality Hospital6, Fudan University7, Semmelweis University8, Montreal Heart Institute9, University of Toronto10, Yale University11, Copenhagen University Hospital12, The George Institute for Global Health13, University of Missouri–Kansas City14, National University of Cordoba15, Wrocław Medical University16, AstraZeneca17
TL;DR: Baseline kidney function did not modify the benefits of dapagliflozin on morbidity and mortality in HFrEF, and dapgliflozar slowed the rate of decline in eGFR, including in patients without diabetes.
Abstract: Background: Many patients with heart failure and reduced ejection fraction (HFrEF) have chronic kidney disease that complicates pharmacological management and is associated with worse outcomes. We ...
Baylor University Medical Center1, Imperial College London2, Charité3, University of Mississippi4, National and Kapodistrian University of Athens5, University of Lorraine6, University of London7, Veterans Health Administration8, University of Minnesota9, University of Florida10, San Francisco VA Medical Center11, University of California, San Diego12, Boehringer Ingelheim13
TL;DR: In patients with heart failure and a reduced ejection fraction, empagliflozin reduced the risk and total number of inpatient and outpatient worsening heart failure events, with benefits seen early after initiation of treatment and sustained for the duration of double-blind therapy.
Abstract: Background: Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, with or without diabetes, but...
Vanderbilt University Medical Center1, Medical University of South Carolina2, Brigham and Women's Hospital3, Montreal Heart Institute4, Integris Baptist Medical Center5, Ochsner Medical Center6, University of California, San Diego7, East Carolina University8, University of Kansas9, Louisiana State University10, Providence Hospital11
TL;DR: The GUIDE-HF trial as discussed by the authors was designed to evaluate whether haemodynamic-guided management using remote pulmonary artery pressure monitoring could reduce heart failure events and mortality in patients with heart failure across the spectrum of symptom severity.
TL;DR: The interplay of mitochondrial hyperacetylation and inflammation as a key driver in HFpEF pathogenesis is identified and can be ameliorated by promoting β-hydroxybutyrate abundance.
Abstract: Rationale: Over 50% of patients with heart failure have preserved ejection fraction (HFpEF), rather than reduced ejection fraction. Complexity of its pathophysiology and the lack of animal models h...
TL;DR: LBBAP provides remarkably low and stable pacing thresholds and was associated with improved clinical and echocardiographic outcomes and provides an alternative option for CRT.
TL;DR: Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure with preserved ejection fraction, but additional data are need for validation as discussed by the authors.
Abstract: Background: Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure with preserved ejection fraction, but additional data are need...
TL;DR: Over one in three previously healthy college-athletes recovering from COVID-19 infection showed imaging features of a resolving pericardial inflammation, although subtle changes in myocardial structure and function were identified.
Abstract: Objectives This study sought to explore the spectrum of cardiac abnormalities in student athletes who returned to university campus in July 2020 with uncomplicated coronavirus disease 2019 (COVID-19). Background There is limited information on cardiovascular involvement in young individuals with mild or asymptomatic COVID-19. Methods Screening echocardiograms were performed in 54 consecutive student athletes (mean age 19 years; 85% male) who had positive results of reverse transcription polymerase chain reaction nasal swab testing of the upper respiratory tract or immunoglobulin G antibodies against severe acute respiratory syndrome coronavirus type 2. Sequential cardiac magnetic resonance imaging was performed in 48 (89%) subjects. Results A total of 16 (30%) athletes were asymptomatic, whereas 36 (66%) and 2 (4%) athletes reported mild and moderate COVID-19 related symptoms, respectively. For the 48 athletes completing both imaging studies, abnormal findings were identified in 27 (56.3%) individuals. This included 19 (39.5%) athletes with pericardial late enhancements with associated pericardial effusion. Of the individuals with pericardial enhancements, 6 (12.5%) had reduced global longitudinal strain and/or an increased native T1. One patient showed myocardial enhancement, and reduced left ventricular ejection fraction or reduced global longitudinal strain with or without increased native T1 values was also identified in an additional 7 (14.6%) individuals. Native T2 findings were normal in all subjects, and no specific imaging features of myocardial inflammation were identified. Hierarchical clustering of left ventricular regional strain identified 3 unique myopericardial phenotypes that showed significant association with the cardiac magnetic resonance findings (p = 0.03). Conclusions More than 1 in 3 previously healthy college athletes recovering from COVID-19 infection showed imaging features of a resolving pericardial inflammation. Although subtle changes in myocardial structure and function were identified, no athlete showed specific imaging features to suggest an ongoing myocarditis. Further studies are needed to understand the clinical implications and long-term evolution of these abnormalities in uncomplicated COVID-19.
TL;DR: This study is the first clinical trial of an antisense drug in HF patients and CDR132L was safe and well tolerated, confirmed linear plasma pharmacokinetics with no signs of accumulation, and suggests cardiac functional improvements.
Abstract: Aims Cardiac microRNA-132-3p (miR-132) levels are increased in patients with heart failure (HF) and mechanistically drive cardiac remodelling processes. CDR132L, a specific antisense oligonucleotide, is a first-in-class miR-132 inhibitor that attenuates and even reverses HF in preclinical models. The aim of the current clinical Phase 1b study was to assess safety, pharmacokinetics, target engagement, and exploratory pharmacodynamic effects of CDR132L in patients on standard-of-care therapy for chronic ischaemic HF in a randomized, placebo-controlled, double-blind, dose-escalation study (NCT04045405). Methods and results Patients had left ventricular ejection fraction between ≥30% and 125 ng/L at screening. Twenty-eight patients were randomized to receive CDR132L (0.32, 1, 3, and 10 mg/kg body weight) or placebo (0.9% saline) in two intravenous infusions, 4 weeks apart in four cohorts of seven (five verum and two placebo) patients each. CDR132L was safe and well tolerated, without apparent dose-limiting toxicity. A pharmacokinetic/pharmacodynamic dose modelling approach suggested an effective dose level at ≥1 mg/kg CDR132L. CDR132L treatment resulted in a dose-dependent, sustained miR-132 reduction in plasma. Patients given CDR132L ≥1 mg/kg displayed a median 23.3% NT-proBNP reduction, vs. a 0.9% median increase in the control group. CDR132L treatment induced significant QRS narrowing and encouraging positive trends for relevant cardiac fibrosis biomarkers. Conclusion This study is the first clinical trial of an antisense drug in HF patients. CDR132L was safe and well tolerated, confirmed linear plasma pharmacokinetics with no signs of accumulation, and suggests cardiac functional improvements. Although this study is limited by the small patient numbers, the indicative efficacy of this drug is very encouraging justifying additional clinical studies to confirm the beneficial CDR132L pharmacodynamic effects for the treatment of HF.
TL;DR: In this paper, the authors evaluated the effect of dapagliflozin 10 mg compared with placebo, once daily, in addition to standard of care, in patients with chronic heart failure and left ventricular ejection fraction (LVEF).
Abstract: Background:
Sodium glucose co-transporter type 2 (SGLT2) inhibitors, originally developed as glucose lowering agents, have been shown to reduce heart failure hospitalizations in patients with type 2 diabetes without established heart failure, and in patients with heart failure with and without diabetes. Their role in patients with heart failure with preserved and mildly reduced ejection fraction remains unknown.
Design and Methods:
Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure (DELIVER) is an international, multi-center, parallel group, event-driven, randomized, double-blind trial in patients with chronic heart failure and left ventricular ejection fraction (LVEF) greater than 40%, comparing the effect of dapagliflozin 10 mg, compared with placebo, once daily, in addition to standard of care. Patients with or without diabetes, with signs and symptoms of heart failure, a left ventricular ejection fraction > 40%, elevation in natriuretic peptides and evidence of structural heart disease are eligible. The primary endpoint is time to first cardiovascular death or worsening heart failure event (heart failure hospitalization or urgent heart failure visit), and will be assessed in dual primary analyses – the full population and in those with LVEF < 60%. The study is event drive and will target 1117 primary events. A total of 6263 patients have been randomized.
Conclusions:
DELIVER will determine the efficacy and safety of the SGLT2 inhibitor dapagliflozin, added to conventional therapy, in patients with heart failure and preserved and mildly reduced ejection fraction. Clinicaltrials.gov NCT03619213.
TL;DR: In EMPEROR-Reduced, empagliflozin had a beneficial effect on the key efficacy outcomes and slowed the rate of kidney function decline in patients with and without CKD, and regardless of the severity of kidney impairment at baseline.
Abstract: Background: In EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction), empagliflozin reduced cardiovascular death or heart failure (HF) ...
TL;DR: It is suggested that heart injury caused by CO VID-19 infection might be an important cause of severe clinical phenotypes or adverse events in affected patients, and early measurements of cardiac damage via biomarkers following hospitalization for COVID-19 infections in a patient with preexisting CVD are recommended.
Abstract: Introduction Coronavirus disease 2019 (COVID-19) has the characteristics of high transmission, diverse clinical manifestations, and a long incubation period. In addition to infecting the respiratory system, COVID-19 also has adverse effects on the cardiovascular system. COVID-19 causes acute myocardial injuries, as well as chronic damage to the cardiovascular system. Areas covered The present review is aimed at providing current information on COVID-19 and the cardiovascular system. PubMed, Scopus, Science direct, and Google Scholar were searched. Expert opinion It is suggested that heart injury caused by COVID-19 infection might be an important cause of severe clinical phenotypes or adverse events in affected patients. Myocardial damage is closely related to the severity of the disease and even the prognosis in patients with COVID-19. In addition to disorders that are caused by COVID-19 on the cardiovascular system, more protection should be employed for patients with preexisting cardiovascular disease (CVD). Hence, it is very important that once relevant symptoms appear, patients with COVID-19 be rapidly treated to reduce mortality. Thus, early measurements of cardiac damage via biomarkers following hospitalization for COVID-19 infections in a patient with preexisting CVD are recommended, together with careful monitoring of any myocardial injury that might be caused by the infection.Abbreviations: ICU: An intensive care unit; 2019-nCoV: 2019 novel coronavirus; ACEI: ACE inhibitor; ACS: Acute coronary syndrome; ARDS: Acute respiratory distress syndrome; AT1R: Ang II type 1 receptor; ATP: Adenosine triphosphate; ACC: American College of Cardiology; ACE: Angiotensin converting enzyme; Ang II: Angiotensin II; ARB: Angiotensin II receptor blocker; AV block: Atrioventricular block; CAD: Coronary artery disease; CVD: Cardiovascular disease; CT: Computerized tomography; CHF: Congestive heart failure; CHD: Coronary heart disease; CK-MB: Creatine kinase isoenzyme-MB; CRP: C-reactive protein; cTnI: Cardiac troponin I; EAT: Epicardial adipose tissue; ECMO: Extracorporeal membrane oxygenation; FDA: Food and Drug Administration; G-CSF: Granulocyte colony-stimulating factor; HFrEF: HF with a reduced ejection fraction; synhACE2: Human isoform of ACE2; IL: Interleukin; IABP: Intra-aortic balloon counterpulsation; IP10: Interferon γ-induced protein 10 kDa; LPC: Lysophosphatidylcholine; Mas: Mitochondrial assembly receptor; MCP1: Monocyte chemoattractant protein-1; MERS: Middle East respiratory syndrome; MIP1a: macrophage inflammatory protein 1a: MOF: Multiple organ failure; MI: Myocardial infarction; MRI: Magnetic resonance imaging; MYO: Myohe-moglobin; NT-proBNP: N-terminal pro-brain natriuretic peptide; PCPS: Percutaneous cardiopulmonary assistance; rhACE2: Recombinant human ACE2; SARS: Severe acute respiratory syndrome; Th: T helper; RAS: Renin-angiotensin system; TNF-α: Tumor necrosis factor-α; WHO: World Health Organization.
University of Porto1, University of Brescia2, Saarland University3, Hannover Medical School4, Rabin Medical Center5, Cairo University6, National and Kapodistrian University of Athens7, Vilnius University8, University of Cyprus9, University of Ferrara10, Queen's University Belfast11, Wrocław Medical University12, Utrecht University13, Linköping University14, University of Ljubljana15, The Volgograd State Medical University16, Karolinska University Hospital17, University of Zagreb18, University of Hasselt19, University of Lisbon20, Charité21, Serbian Academy of Sciences and Arts22, University of Belgrade23, University of Warwick24
TL;DR: In this article, the authors identified nine patient profiles that may be relevant for treatment implementation in heart failure patients with a reduced ejection fraction, taking into account heart rate ( 70 bpm), the presence of atrial fibrillation, symptomatic low blood pressure, estimated glomerular filtration rate ( 30 mL/min/1.73 m2 ), or hyperkalaemia.
Abstract: Despite guideline recommendations and available evidence, implementation of treatment in heart failure (HF) is poor. The majority of patients are not prescribed drugs at target doses that have been proven to positively impact morbidity and mortality. Among others, tolerability issues related to low blood pressure, heart rate, impaired renal function or hyperkalaemia are responsible. Chronic kidney disease plays an important role as it affects up to 50% of patients with HF. Also, dynamic changes in estimated glomerular filtration rate may occur during the course of HF, resulting in inappropriate dose reduction or even discontinuation of decongestive or neurohormonal modulating therapy in clinical practice. As patients with HF are rarely naive to pharmacologic therapies, the challenge is to adequately prioritize or select the most appropriate up-titration schedule according to patient profile. In this consensus document, we identified nine patient profiles that may be relevant for treatment implementation in HF patients with a reduced ejection fraction. These profiles take into account heart rate ( 70 bpm), the presence of atrial fibrillation, symptomatic low blood pressure, estimated glomerular filtration rate ( 30 mL/min/1.73 m2 ) or hyperkalaemia. The pre-discharge patient, frequently still congestive, is also addressed. A personalized approach, adjusting guideline-directed medical therapy to patient profile, may allow to achieve a better and more comprehensive therapy for each individual patient than the more traditional, forced titration of each drug class before initiating treatment with the next.
TL;DR: In this paper, a case series of children younger than 19 years hospitalized with myocarditis within 30 days of BNT162b2 messenger RNA COVID-19 vaccine was presented.
Abstract: Importance The BNT162b2 (Pfizer-BioNTech) messenger RNA COVID-19 vaccine was authorized on May 10, 2021, for emergency use in children aged 12 years and older. Initial reports showed that the vaccine was well tolerated without serious adverse events; however, cases of myocarditis have been reported since approval. Objective To review results of comprehensive cardiac imaging in children with myocarditis after COVID-19 vaccine. Design, setting, and participants This study was a case series of children younger than 19 years hospitalized with myocarditis within 30 days of BNT162b2 messenger RNA COVID-19 vaccine. The setting was a single-center pediatric referral facility, and admissions occurred between May 1 and July 15, 2021. Main outcomes and measures All patients underwent cardiac evaluation including an electrocardiogram, echocardiogram, and cardiac magnetic resonance imaging. Results Fifteen patients (14 male patients [93%]; median age, 15 years [range, 12-18 years]) were hospitalized for management of myocarditis after receiving the BNT162b2 (Pfizer) vaccine. Symptoms started 1 to 6 days after receipt of the vaccine and included chest pain in 15 patients (100%), fever in 10 patients (67%), myalgia in 8 patients (53%), and headache in 6 patients (40%). Troponin levels were elevated in all patients at admission (median, 0.25 ng/mL [range, 0.08-3.15 ng/mL]) and peaked 0.1 to 2.3 days after admission. By echocardiographic examination, decreased left ventricular (LV) ejection fraction (EF) was present in 3 patients (20%), and abnormal global longitudinal or circumferential strain was present in 5 patients (33%). No patient had a pericardial effusion. Cardiac magnetic resonance imaging findings were consistent with myocarditis in 13 patients (87%) including late gadolinium enhancement in 12 patients (80%), regional hyperintensity on T2-weighted imaging in 2 patients (13%), elevated extracellular volume fraction in 3 patients (20%), and elevated LV global native T1 in 2 patients (20%). No patient required intensive care unit admission, and median hospital length of stay was 2 days (range 1-5). At follow-up 1 to 13 days after hospital discharge, 11 patients (73%) had resolution of symptoms. One patient (7%) had persistent borderline low LV systolic function on echocardiogram (EF 54%). Troponin levels remained mildly elevated in 3 patients (20%). One patient (7%) had nonsustained ventricular tachycardia on ambulatory monitor. Conclusions and relevance In this small case series study, myocarditis was diagnosed in children after COVID-19 vaccination, most commonly in boys after the second dose. In this case series, in short-term follow-up, patients were mildly affected. The long-term risks associated with postvaccination myocarditis remain unknown. Larger studies with longer follow-up are needed to inform recommendations for COVID-19 vaccination in this population.
TL;DR: The UNTOUCHED trial was designed to evaluate the IAS rate in a more typical, contemporary ICD patient population implanted with the S-ICD using standardized programming and enhanced discrimination algorithms and demonstrates high efficacy and safety despite the relatively high incidence of comorbidities.
Abstract: Background: The subcutaneous (S) implantable cardioverter-defibrillator (ICD) is safe and effective for sudden cardiac death prevention. However, patients in previous S-ICD studies had fewer comorb...
TL;DR: Empagliflozin ameliorates diastolic function in a nondiabetic HF porcine model, mitigates histological and molecular remodeling, and reduces both left ventricle and cardiomyocyte stiffness.
Abstract: Objectives The purpose of this study was to investigate the effect of empagliflozin on diastolic function in a nondiabetic heart failure with reduced ejection fraction (HFrEF) scenario and on the pathways causing diastolic dysfunction. Background This group demonstrated that empagliflozin ameliorates adverse cardiac remodeling, enhances myocardial energetics, and improves left ventricular systolic function in a nondiabetic porcine model of HF. Whether empagliflozin also improves diastolic function remains unknown. Hypothetically, empagliflozin would improve diastolic function in HF mediated both by a reduction in interstitial myocardial fibrosis and an improvement in cardiomyocyte stiffness (titin phosphorylation). Methods HF was induced in nondiabetic pigs by 2-h balloon occlusion of proximal left anterior descending artery. Animals were randomized to empagliflozin or placebo for 2 months. Cardiac function was evaluated with cardiac magnetic resonance (CMR), 3-dimensional echocardiography, and invasive hemodynamics. In vitro relaxation of cardiomyocytes was studied in primary culture. Myocardial samples were obtained for histological and molecular evaluation. Myocardial metabolite consumption was analyzed by simultaneous blood sampling from coronary artery and coronary sinus. Results Despite similar initial ischemic myocardial injury, the empagliflozin group showed significantly improved diastolic function at 2 months, assessed by conventional echocardiography (higher e′ and color M-mode propagation velocity, lower E/e′ ratio, myocardial performance Tei index, isovolumic relaxation time, and left atrial size), echocardiography-derived strain imaging (strain imaging diastolic index, strain rate at isovolumic relaxation time and during early diastole, and untwisting), and CMR (higher peak filling rate, larger first filling volume). Invasive hemodynamics confirmed improved diastolic function with empagliflozin (better peak LV pressure rate of decay (–dP/dt), shorter Tau, lower end-diastolic pressure-volume relationship (EDPVR), and reduced filling pressures). Empagliflozin reduced interstitial myocardial fibrosis at the imaging, histological and molecular level. Empagliflozin improved nitric oxide signaling (endothelial nitric oxide synthetase [eNOS] activity, nitric oxide [NO] availability, cyclic guanosine monophosphate (cGMP) content, protein kinase G [PKG] signaling) and enhanced titin phosphorylation (which is responsible for cardiomyocyte stiffness). Indeed, isolated cardiomyocytes exhibited better relaxation in empagliflozin-treated animals. Myocardial consumption of glucose and ketone bodies negatively and positively correlated with diastolic function, respectively. Conclusions Empagliflozin ameliorates diastolic function in a nondiabetic HF porcine model, mitigates histological and molecular remodeling, and reduces both left ventricle and cardiomyocyte stiffness.
TL;DR: Pancarditis with cardiac dysfunction is common and associated with myocardial oedema and patients require close monitoring due to coronary artery dilatation and the risk of thrombotic myocardIAL infarction.
Abstract: AIMS: Following the peak of the UK COVID-19 epidemic, a new multisystem inflammatory condition with significant cardiovascular effects emerged in young people. We utilized multimodality imaging to provide a detailed sequential description of the cardiac involvement. METHODS AND RESULTS: Twenty consecutive patients (mean age 10.6 ± 3.8 years) presenting to our institution underwent serial echocardiographic evaluation on admission (median day 5 of illness), the day coinciding with worst cardiac function (median day 7), and the day of discharge (median day 15). We performed cardiac computed tomography (CT) to assess coronary anatomy (median day 15) and cardiac magnetic resonance imaging (CMR) to assess dysfunction (median day 20). On admission, almost all patients displayed abnormal strain and tissue Doppler indices. Three-dimensional (3D) echocardiographic ejection fraction (EF) was <55% in half of the patients. Valvular regurgitation (75%) and small pericardial effusions (10%) were detected. Serial echocardiography demonstrated that the mean 3D EF deteriorated (54.7 ± 8.3% vs. 46.4 ± 8.6%, P = 0.017) before improving at discharge (P = 0.008). Left main coronary artery (LMCA) dimensions were significantly larger at discharge than at admission (Z score -0.11 ± 0.87 vs. 0.78 ± 1.23, P = 0.007). CT showed uniform coronary artery dilatation commonly affecting the LMCA (9/12). CMR detected abnormal strain in all patients with global dysfunction (EF <55%) in 35%, myocardial oedema in 50%, and subendocardial infarct in 5% (1/20) patients. CONCLUSIONS: Pancarditis with cardiac dysfunction is common and associated with myocardial oedema. Patients require close monitoring due to coronary artery dilatation and the risk of thrombotic myocardial infarction.