The impact of primary immunization route on the outcome of infection with SARS-CoV-2 in a hamster model of COVID-19.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has resulted in over 6.7 million deaths worldwide. COVID-19 vaccines administered parenterally via intramuscular or subcutaneous (SC) routes have reduced the severity of respiratory infections, hospitalization rates, and overall mortality.

Arrhythmic sudden death survival prediction using deep learning analysis of scarring in the heart.

Sudden cardiac death from arrhythmia is a major cause of mortality worldwide. Here, we develop a novel deep learning (DL) approach that blends neural networks and survival analysis to predict patient-specific survival curves from contrast-enhanced cardiac magnetic resonance images and clinical covariates for patients with ischemic heart disease. The DL-predicted survival curves offer accurate predictions at times up to 10 years and allow for estimation of uncertainty in predictions.

Diabetes and Risk of Sudden Death in Coronary Artery Disease Patients Without Severe Systolic Dysfunction.

Objectives: This study sought to determine the absolute and relative associations of diabetes mellitus (DM) and hemoglobin A (HbA) with sudden and/or arrhythmic death (SAD) versus other modes of death in patients with coronary artery disease (CAD) who do not qualify for implantable cardioverter-defibrillators.

Background: Patients with CAD and DM are at elevated risk for SAD; however, it is unclear whether these patients would benefit from implantable cardioverter-defibrillators given competing causes of death and/or whether HbA might augment SAD risk stratification.

Methods: In the PRE-DETERMINE study of 5,764 patients with CAD with left ventricular ejection fraction (LVEF) of >30% to 35%, competing risk analyses were used to compare the absolute and relative risks of SAD versus non-SAD by DM status and HbA level and to identify risk factors for SAD among 1,782 patients with DM.

Validation of electrocardiographic criteria for identifying left ventricular dysfunction in patients with previous myocardial infarction.

Background: Eleven criteria correlating electrocardiogram (ECG) findings with reduced left ventricular ejection fraction (LVEF) have been previously published. These have not been compared head-to-head in a single study. We studied their value as a screening test to identify patients with reduced LVEF estimated by cardiac magnetic resonance (CMR) imaging.

Simple electrocardiographic measures improve sudden arrhythmic death prediction in coronary disease.

Aims: To determine whether the combination of standard electrocardiographic (ECG) markers reflecting domains of arrhythmic risk improves sudden and/or arrhythmic death (SAD) risk stratification in patients with coronary heart disease (CHD).

Methods And Results: The association between ECG markers and SAD was examined in a derivation cohort (PREDETERMINE; N = 5462) with adjustment for clinical risk factors, left ventricular ejection fraction (LVEF), and competing risk. Competing outcome models assessed the differential association of ECG markers with SAD and competing mortality.

Estimating Myocardial Infarction Size With a Simple Electrocardiographic Marker Score.

Background Myocardial infarction (MI) size is a key predictor of prognosis in post-MI patients. Cardiovascular magnetic resonance (CMR) is the gold standard test for MI quantification, but the ECG is less expensive and more widely available. We sought to quantify the relationship between ECG markers and cardiovascular magnetic resonance infarct size.

Ethical rejections of xenotransplantation? The potential and challenges of using human-pig chimeras to create organs for transplantation.

Xenotransplantation using organs from human‐pig chimeras has great potential to alleviate the shortage of donor organs and benefit patients. However, scientific, ethical and financial issues need to be resolved before clinical testing can begin. [Image: see text]

Sudden Death in Patients With Coronary Heart Disease Without Severe Systolic Dysfunction.

Importance: The majority of sudden and/or arrhythmic deaths (SAD) in patients with coronary heart disease occur in those without severe systolic dysfunction, for whom strategies for sudden death prevention are lacking.

Objective: To provide contemporary estimates of SAD vs other competing causes of death in patients with coronary heart disease without severe systolic dysfunction to search for high-risk subgroups that might be targeted in future trials of SAD prevention.

Design, Setting, And Participants: This prospective observational cohort study included 135 clinical sites in the United States and Canada.

Implantable cardioverter-defibrillators in heart failure patients with reduced ejection fraction and diabetes.

Aim: There is limited information on the outcomes after primary prevention implantable cardioverter-defibrillator (ICD) implantation in patients with heart failure (HF) and diabetes. This analysis evaluates the effectiveness of a strategy of ICD plus medical therapy vs. medical therapy alone among patients with HF and diabetes.

Device Therapies Among Patients Receiving Primary Prevention Implantable Cardioverter-Defibrillators in the Cardiovascular Research Network.

Background: Primary prevention implantable cardioverter-defibrillators (ICDs) reduce mortality in selected patients with left ventricular systolic dysfunction by delivering therapies (antitachycardia pacing or shocks) to terminate potentially lethal arrhythmias; inappropriate therapies also occur. We assessed device therapies among adults receiving primary prevention ICDs in 7 healthcare systems.

Methods And Results: We linked medical record data, adjudicated device therapies, and the National Cardiovascular Data Registry ICD Registry.

Outer Limits of Biotechnologies: A Jewish Perspective.

A great deal of biomedical research focuses on new biotechnologies such as gene editing, stem cell biology, and reproductive medicine, which have created a scientific revolution. While the potential medical benefits of this research may be far-reaching, ethical issues related to non-medical applications of these technologies are demanding. We analyze, from a Jewish legal perspective, some of the ethical conundrums that society faces in pushing the outer limits in researching these new biotechnologies.

Comparison of Inappropriate Shocks and Other Health Outcomes Between Single- and Dual-Chamber Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death: Results From the Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter-Defibrillators.

Background: In US clinical practice, many patients who undergo placement of an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death receive dual-chamber devices. The superiority of dual-chamber over single-chamber devices in reducing the risk of inappropriate ICD shocks in clinical practice has not been established. The objective of this study was to compare risk of adverse outcomes, including inappropriate shocks, between single- and dual-chamber ICDs for primary prevention.

New York Heart Association class and the survival benefit from primary prevention implantable cardioverter defibrillators: A pooled analysis of 4 randomized controlled trials.

Background: Primary prevention implantable cardioverter defibrillator (ICD) reduce all-cause mortality by reducing sudden cardiac death. There are conflicting data regarding whether patients with more advanced heart failure derive ICD benefit owing to the competing risk of nonsudden death.

Methods: We performed a patient-level meta-analysis of New York Heart Association (NYHA) class II/III heart failure patients (left ventricular ejection fraction ≤35%) from 4 primary prevention ICD trials (MADIT-I, MADIT-II, DEFINITE, SCD-HeFT).

Predicting appropriate shocks in patients with heart failure: Patient level meta-analysis from SCD-HeFT and MADIT II.

Background: No precise tools exist to predict appropriate shocks in patients with a primary prevention ICD. We sought to identify characteristics predictive of appropriate shocks in patients with a primary prevention implantable cardioverter defibrillator (ICD).

Methods: Using patient-level data from the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), we identified patients with any appropriate shock.

Associations of Sex Hormones With Surface Electrocardiogram J Point Amplitude in Healthy Volunteers.

Gender differences in J point height exist. Previous studies suggest male sex hormones mediate effects on cardiovascular disease through myocardial repolarization. Our objective was to assess whether male and female sex hormones are associated with J point amplitude in healthy subjects.

Primary Prevention Implantable Cardioverter Defibrillators in Patients With Nonischemic Cardiomyopathy: A Meta-analysis.

Importance: Conflicting data have emerged on the efficacy of implantable cardioverter defibrillators (ICDs) for primary prevention of sudden cardiac death (primary prevention ICDs) in patients with nonischemic cardiomyopathy.

Objective: To investigate the association of primary prevention ICDs with all-cause mortality in patients with nonischemic cardiomyopathy.

Data Sources: PubMed was searched from January 1, 2000, through October 31, 2016, for the terms implantable defibrillator OR implantable cardioverter defibrillator AND non-ischemic cardiomyopathy.

Orthogonal decomposition of left ventricular remodeling in myocardial infarction.

Background: Left ventricular size and shape are important for quantifying cardiac remodeling in response to cardiovascular disease. Geometric remodeling indices have been shown to have prognostic value in predicting adverse events in the clinical literature, but these often describe interrelated shape changes. We developed a novel method for deriving orthogonal remodeling components directly from any (moderately independent) set of clinical remodeling indices.

Kidney function and appropriateness of device therapies in adults with implantable cardioverter defibrillators.

Objective: Patients with chronic kidney disease (CKD) have higher risk of sudden cardiac death; however, they may not receive implantable cardioverter defibrillators (ICDs), in part due to higher risk of complications. We evaluated whether CKD is associated with greater risk of device-delivered shocks/antitachycardia pacing (ATP) therapies among patients receiving a primary prevention ICD.

Methods: We studied participants in the observational Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter Defibrillators.

Inflammatory Mediators and Clinical Outcome in Patients With Advanced Heart Failure Receiving Cardiac Resynchronization Therapy.

Expression of different cytokines and growth factors after myocardial injury has been associated with fibroplasia and dilatation versus reverse remodeling and myocardial repair. Specifically, the proinflammatory/fibrotic mediators: interleukin (IL)-6, epidermal growth factor, and fibroblast growth factor (FGF)-2 cause fibroplasia, whereas reparative cytokines including: IL-1α, IL-1β, IL-4, and IL-13 can limit fibrosis. In appropriate patients, cardiac resynchronization therapy (CRT) reverses cardiomyopathy and improves outcome.

Information maximizing component analysis of left ventricular remodeling due to myocardial infarction.

Background: Although adverse left ventricular shape changes (remodeling) after myocardial infarction (MI) are predictive of morbidity and mortality, current clinical assessment is limited to simple mass and volume measures, or dimension ratios such as length to width ratio. We hypothesized that information maximizing component analysis (IMCA), a supervised feature extraction method, can provide more efficient and sensitive indices of overall remodeling.

Methods: IMCA was compared to linear discriminant analysis (LDA), both supervised methods, to extract the most discriminatory global shape changes associated with remodeling after MI.

Association of BNP and Troponin Levels with Outcome among Cardiac Resynchronization Therapy Recipients.

Background: We conducted a prospective multicenter study to assess the prognostic value of combined baseline preimplant plasma levels of the biomarkers cardiac troponin T (TnT) and B-type natriuretic peptide (BNP) among cardiac resynchronization therapy (CRT) with or without defibrillator capability (CRT-D) recipients.

Methods: At CRT-D implant, patients were stratified based on detectable TnT (≥0.01 ng/mL) and elevated BNP (predefined as >440 pg/mL) levels.