A5076454382- Cardiovascular Effects of Exercise
- Cardiomyopathy and Myosin Studies
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Sports injuries and prevention
- Cardiac electrophysiology and arrhythmias
- Parathyroid Disorders and Treatments
- Connective tissue disorders research
- Cardiac pacing and defibrillation studies
- Peptidase Inhibition and Analysis
- Viral Infections and Immunology Research
- Cardiac Structural Anomalies and Repair
- Cardiovascular Function and Risk Factors
- Cardiac Arrhythmias and Treatments
- Cardiac Valve Diseases and Treatments
- Eosinophilic Disorders and Syndromes
- Aortic Disease and Treatment Approaches
- Cardiac Arrest and Resuscitation
- Mechanical Circulatory Support Devices
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Muscle Physiology and Disorders
- Genomics and Rare Diseases
- Nuclear Structure and Function
- Congenital heart defects research
- Medical Imaging and Pathology Studies
- Cellular transport and secretion
Medical University of South Carolina
2017-2025
University College London
2024
BridgeBio (United States)
2024
West Virginia University
2024
Johns Hopkins University
2013-2023
Cairns Hospital
2017-2023
University of Washington
2022
Johns Hopkins Hospital
2010-2022
Oregon Health & Science University
2022
Johns Hopkins Medicine
2011-2021
Transthyretin amyloid cardiomyopathy is caused by the deposition of transthyretin fibrils in myocardium. The occurs when wild-type or variant becomes unstable and misfolds. Tafamidis binds to transthyretin, preventing tetramer dissociation amyloidogenesis.In a multicenter, international, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 441 patients with 2:1:2 ratio receive 80 mg tafamidis, 20 placebo for 30 months. In primary analysis, hierarchically assessed all-cause...
Aortic aneurysm and dissection are manifestations of Marfan syndrome (MFS), a disorder caused by mutations in the gene that encodes fibrillin-1. Selected MFS reflect excessive signaling transforming growth factor-beta (TGF-beta) family cytokines. We show aortic mouse model is associated with increased TGF-beta can be prevented antagonists such as TGF-beta-neutralizing antibody or angiotensin II type 1 receptor (AT1) blocker, losartan. AT1 antagonism also partially reversed noncardiovascular...
PreambleThis international consensus statement provides the state of genetic testing for channelopathies and cardiomyopathies.It summarizes opinion writing group members based on their own experience a general review literature with respect to use role these potentially heritable cardiac conditions.This document focuses primarily 13 distinct entities detailed relative diagnostic, prognostic, therapeutic impact test result each entity.It does not focus management various...
Progressive enlargement of the aortic root, leading to dissection, is main cause premature death in patients with Marfan's syndrome. Recent data from mouse models syndrome suggest that aortic-root caused by excessive signaling transforming growth factor beta (TGF-beta) can be mitigated treatment TGF-beta antagonists, including angiotensin II-receptor blockers (ARBs). We evaluated clinical response ARBs pediatric who had severe enlargement.We identified 18 been followed during 12 47 months...
Mitral valve prolapse (MVP) is a common human phenotype, yet little known about the pathogenesis of this condition. MVP can occur in context genetic syndromes, including Marfan syndrome (MFS), an autosomal-dominant connective tissue disorder caused by mutations fibrillin-1. Fibrillin-1 contributes to regulated activation cytokine TGF-beta, and enhanced signaling consequence fibrillin-1 deficiency. We thus hypothesized that increased TGF-beta may contribute multisystem MFS, development...
Arrhythmogenic right ventricular dysplasia (ARVD) is an inherited cardiomyopathy characterized by dysfunction and arrhythmias. The purpose of our study was to describe the presentation, clinical features, survival, natural history ARVD in a large cohort patients from United States.The patient population included 100 (51 male; median age at 26 [interquartile range {IQR}, 18 38; range, 2 70] years). A familial pattern observed 32 patients. most common presenting symptoms were palpitations,...
Mitral valve prolapse (MVP) is a common human phenotype, yet little known about the pathogenesis of this condition. MVP can occur in context genetic syndromes, including Marfan syndrome (MFS), an autosomal-dominant connective tissue disorder caused by mutations fibrillin-1. Fibrillin-1 contributes to regulated activation cytokine TGF-β, and enhanced signaling consequence fibrillin-1 deficiency. We thus hypothesized that increased TGF-β may contribute multisystem MFS, development myxomatous...
Angiotensin II (AngII) mediates progression of aortic aneurysm, but the relative contribution its type 1 (AT1) and 2 (AT2) receptors remains unknown. We show that loss AT2 expression accelerates aberrant growth rupture aorta in a mouse model Marfan syndrome (MFS). The selective AT1 receptor blocker (ARB) losartan abrogated aneurysm mice; full protection required intact signaling. angiotensin-converting enzyme inhibitor (ACEi) enalapril, which limits signaling through both receptors, was less...
Transforming growth factor–β promotes aortic aneurysm formation through activation of its “noncanonical” signaling pathway.
Background— Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a progressive cardiomyopathy. We aimed to define long-term outcome in transatlantic cohort of 1001 individuals. Methods and Results— Clinical genetic characteristics follow-up data ARVD/C index-patients (n=439, fulfilling 2010 criteria all) family members (n=562) were assessed. Mutations identified 276 (63%). Index-patients presented predominantly with sustained arrhythmias (268; 61%). During median 7 years,...
We sought to determine the influence of genotype on clinical course and arrhythmic outcome among arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C)-associated mutation carriers.Pathogenic mutations in desmosomal non-desmosomal genes were identified 577 patients (241 families) from USA Dutch ARVD/C cohorts. Patients with sudden cardiac death (SCD)/ventricular fibrillation (VF) at presentation (n = 36) younger (median 23 vs. 36 years; P < 0.001) than those presenting sustained...
Marfan syndrome is a connective tissue disorder caused by mutations in the gene encoding fibrillin-1 (FBN1). A dominant-negative mechanism has been inferred based upon dominant inheritance, mulitimerization of monomers to form microfibrils, and dramatic paucity matrix-incorporated seen heterozygous patient samples. Yeast artificial chromosome–based transgenesis was used overexpress disease-associated mutant human (C1663R) on normal mouse background. Remarkably, these mice failed show any...
Each of the cardiomyopathies, classically categorized as hypertrophic cardiomyopathy, dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular has a signature genetic theme. Hypertrophic are largely understood diseases sarcomere or desmosome proteins, respectively. In contrast, >250 genes spanning >10 gene ontologies have been implicated in DCM, representing complex diverse architecture. To clarify this, systematic curation evidence to establish relationship with DCM was conducted.