A5083767342- Cardiomyopathy and Myosin Studies
- Cardiovascular Effects of Exercise
- Cardiovascular Function and Risk Factors
- Congenital Heart Disease Studies
- Congenital heart defects research
- Cardiac pacing and defibrillation studies
- Cardiac electrophysiology and arrhythmias
- Viral Infections and Immunology Research
- Atrial Fibrillation Management and Outcomes
- Williams Syndrome Research
- Adipose Tissue and Metabolism
- Muscle Physiology and Disorders
- Cardiac Structural Anomalies and Repair
- Ion channel regulation and function
- Genomics and Rare Diseases
- Cardiovascular and exercise physiology
- Trypanosoma species research and implications
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Heat shock proteins research
- Peptidase Inhibition and Analysis
- Protease and Inhibitor Mechanisms
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Genetic Associations and Epidemiology
University of Pennsylvania
2014-2025
Cardiovascular Institute of the South
2021-2025
University of Michigan
2014-2024
Hospital of the University of Pennsylvania
2020-2024
Medline (United States)
2024
Advisory Board Company (United States)
2022-2023
Philadelphia University
2019-2023
State Street (United States)
2021
American Heart Association
2021
American College of Cardiology
2021
A better understanding of the factors that contribute to heterogeneous outcomes and lifetime disease burden in hypertrophic cardiomyopathy (HCM) is critically needed improve patient management outcomes. The Sarcomeric Human Cardiomyopathy Registry (SHaRe) was established provide scale data required address these issues, aggregating longitudinal datasets curated by eight international HCM specialty centers.
Hypertrophic cardiomyopathy (HCM) is caused by pathogenic variants in sarcomere protein genes that evoke hypercontractility, poor relaxation, and increased energy consumption the heart patient risks for arrhythmias failure. Recent studies show missense myosin, molecular motor of sarcomere, are clustered residues participate dynamic conformational states proteins. We hypothesized these conformations essential to adapt contractile output conservation pathophysiology HCM results from...
<h3>Importance</h3> Formulating exercise recommendations for patients with hypertrophic cardiomyopathy is challenging because of concern about triggering ventricular arrhythmias and a clinical benefit has not been previously established in this population. <h3>Objective</h3> To determine whether moderate-intensity training improves capacity adults cardiomyopathy. <h3>Design, Setting, Participants</h3> A randomized trial involving 136 was conducted between April 2010 October 2015 at 2...
The "2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy" provides recommendations to guide clinicians in management patients with hypertrophic cardiomyopathy.
The term "end stage" has been used to describe hypertrophic cardiomyopathy (HCM) with left ventricular systolic dysfunction (LVSD), defined as occurring when ejection fraction is <50%. prognosis of HCM-LVSD reportedly poor, but because its relative rarity, the natural history remains incompletely characterized.
Importance Whether vigorous intensity exercise is associated with an increase in risk of ventricular arrhythmias individuals hypertrophic cardiomyopathy (HCM) unknown. Objective To determine whether engagement increased for and/or mortality HCM. The a priori hypothesis was that participants engaging activity were not more likely to have arrhythmic event or die than those who reported nonvigorous activity. Design, Setting, and Participants This investigator-initiated, prospective cohort...
Background— The ubiquitin proteasome system maintains a dynamic equilibrium of proteins and prevents accumulation damaged misfolded proteins, yet its role in human cardiac dysfunction is not well understood. present study evaluated function heart failure hypertrophic cardiomyopathy (HCM). Methods Results— Proteasome was studied nonfailing donor hearts, explanted failing myectomy samples from patients with HCM. proteolytic activities were markedly reduced HCM hearts compared ( P <0.01)....
Mild hypertrophy but increased arrhythmic risk characterizes the stereotypic phenotype proposed for hypertrophic cardiomyopathy (HCM) caused by thin-filament mutations. However, whether such clinical profile is different from more prevalent thick-filament–associated disease unresolved. This study aimed to assess features and outcomes in a large cohort of patients with HCM associated mutations compared thick-filament HCM. Adult (age >18 years), 80 150 mutations, were followed an average 4.5...
Histone H3 lysine 4 (H3K4me) methyltransferases and their cofactors are essential for embryonic development the establishment of gene expression patterns in a cell-specific heritable manner. However, importance such epigenetic marks maintaining adults initiating human disease is unclear. Here, we addressed this question using mouse model which could inducibly ablate PAX interacting (with transcription-activation domain) protein 1 (PTIP), key component H3K4me complex, cardiac cells. Reducing...
Significance Genetic variants in human β-cardiac myosin, which causes muscle contraction the heart, can lead to hypertrophic cardiomyopathy (HCM), an inherited heart disease that cause sudden death. New technologies have generated sequence data for large numbers of patients with HCM and unaffected individuals. In this study, we compare protein structural locations genetic general population identify spatial regions myosin a higher than expected proportion associated earlier age at diagnosis....
<h3>Importance</h3> Patients with hypertrophic cardiomyopathy (HCM) are prone to body weight increase and obesity. Whether this predisposes these individuals long-term adverse outcomes is still unresolved. <h3>Objective</h3> To describe the association of mass index (BMI, calculated as in kilograms divided by height meters squared) patients HCM terms overall disease progression, heart failure symptoms, arrhythmias. <h3>Design, Setting, Participants</h3> In cohort study, retrospective data...
International guidelines for variant interpretation in Mendelian disease set stringent criteria to report a as (likely) pathogenic, prioritising control of false-positive rate over test sensitivity and diagnostic yield. Genetic testing is also more likely informative individuals with well-characterised variants from extensively studied European-ancestry populations. Inherited cardiomyopathies are relatively common diseases that allow empirical calibration assessment this framework. We...
Cardiovascular genetics is a rapidly evolving subspecialty within cardiovascular medicine, and its growth attributed to advances in genome sequencing genetic testing the expanding understanding of basis multiple cardiac conditions, including arrhythmias (channelopathies), heart failure (cardiomyopathies), lipid disorders, complications neuromuscular vascular disease, aortopathies. There have also been great clinical diagnostic methods, as well therapies ameliorate symptoms, slow progression...