A5016225435- Cardiomyopathy and Myosin Studies
- Cardiovascular Function and Risk Factors
- Cardiovascular Effects of Exercise
- Congenital heart defects research
- Cardiac pacing and defibrillation studies
- Congenital Heart Disease Studies
- Viral Infections and Immunology Research
- Cardiac Arrhythmias and Treatments
- Cardiac Structural Anomalies and Repair
- Muscle Physiology and Disorders
- Galectins and Cancer Biology
- Trypanosoma species research and implications
- Genetic Associations and Epidemiology
- Protein Tyrosine Phosphatases
- Williams Syndrome Research
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Parathyroid Disorders and Treatments
- Cardiac tumors and thrombi
- Genomics and Rare Diseases
- Mitochondrial Function and Pathology
- Cardiovascular Issues in Pregnancy
- Cardiac Imaging and Diagnostics
- RNA modifications and cancer
- Studies on Chitinases and Chitosanases
- Coronary Artery Anomalies
Erasmus University Rotterdam
2016-2025
Erasmus MC
2016-2025
ERN GUARD-Heart
2023-2025
Sequoia (United States)
2024
SEQUOIA (Italy)
2024
Brigham and Women's Hospital
2017-2024
Lahey Medical Center
2024
Baim Institute for Clinical Research
2024
Harvard University
2024
Oregon Health & Science University
2024
Mutations in the MYBPC3 gene, encoding cardiac myosin-binding protein C (cMyBP-C), are a frequent cause of familial hypertrophic cardiomyopathy. In present study, we investigated whether composition and function sarcomere altered homogeneous cardiomyopathy patient group with frameshift mutations (MYBPC3(mut)).Comparisons were made between samples from mutant carriers (c.2373dupG, n=7; c.2864_2865delCT, n=4) nonfailing donors (n=13). Western blots use antibodies directed against cMyBP-C did...
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...
Hypertrophic cardiomyopathy is the leading cause of sudden cardiac death (SCD) in children and young adults. Our objective was to develop validate a SCD risk prediction model pediatric hypertrophic guide prevention strategies. In an international multicenter observational cohort study, phenotype-positive patients with isolated <18 years age at diagnosis were eligible. The primary outcome variable time from composite events 5-year follow-up: SCD, resuscitated arrest, aborted that is,...
BackgroundOne of the major determinants exercise intolerance and limiting symptoms among patients with obstructive hypertrophic cardiomyopathy (HCM) is an elevated intracardiac pressure resulting from left ventricular outflow tract obstruction. Aficamten oral selective cardiac myosin inhibitor that reduces gradients by mitigating hypercontractility.MethodsIn this phase 3, double-blind trial, we randomly assigned adults symptomatic HCM to receive aficamten (starting dose, 5 mg; maximum 20 mg)...
Abstract Aims Genetic hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomere protein-encoding genes (i.e. genotype-positive HCM). In an increasing number of patients, HCM occurs the absence a mutation genotype-negative Mitochondrial dysfunction thought to be key driver pathological remodelling HCM. Reports mitochondrial respiratory function and specific disease-modifying treatment options patients with are scarce. Methods results Respirometry was performed on septal myectomy...
Left ventricular (LV) noncompaction (LVNC) is a distinct cardiomyopathy featuring thickened bilayered LV wall consisting of thick endocardial layer with prominent intertrabecular recesses thin, compact epicardial layer. Similar to hypertrophic and dilated cardiomyopathy, LVNC genetically heterogeneous was recently associated mutations in sarcomere genes. To contribute the genetic classification for LVNC, systematic cardiological family study performed cohort 58 consecutively diagnosed...
The impact of alcohol septal ablation (ASA)-induced scar is not known. This study sought to examine the long-term outcome ASA among patients with obstructive hypertrophic cardiomyopathy.Ninety-one consecutive (aged 54+/-15 years) cardiomyopathy underwent ASA. Primary end point was a composite cardiac death and aborted sudden including appropriate cardioverter-defibrillator discharges for fast ventricular tachycardia/ventricular fibrillation. Secondary points were noncardiac other nonfatal...
High-myofilament Ca(2+) sensitivity has been proposed as a trigger of disease pathogenesis in familial hypertrophic cardiomyopathy (HCM) on the basis vitro and transgenic mice studies. However, myofilament depends protein phosphorylation muscle length, at present, data humans are scarce.To investigate whether high perturbed length-dependent activation characteristics for human HCM with mutations thick thin filament proteins.Cardiac samples from patients harboring genes encoding (MYH7,...
Background— The recently released 2014 European Society of Cardiology guidelines hypertrophic cardiomyopathy (HCM) use a new clinical risk prediction model for sudden cardiac death (SCD), based on the HCM Risk-SCD study. Our study is first external and independent validation this model. Methods Results— population consisted consecutive cohort 706 patients with without prior SCD event, from 2 tertiary referral centers. primary end point was composite appropriate implantable...
Hypertrophic cardiomyopathy (HCM), typically characterized by asymmetrical left ventricular hypertrophy, frequently is caused mutations in sarcomeric proteins. We studied if changes properties HCM depend on the underlying protein mutation.Comparisons were made between cardiac samples from patients carrying a MYBPC3 mutation (MYBPC3(mut); n=17), negative without an identified sarcomere (HCM(mn); n=11), and nonfailing donors (n=12). All had normal systolic function, but impaired diastolic...
<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...
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....
Disease mechanisms regarding hypertrophic cardiomyopathy (HCM) are largely unknown and disease onset varies. Sarcomere mutations might induce energy depletion for which until now there is no direct evidence at sarcomere level in human HCM. This study investigated if genes encoding myosin-binding protein C (MYBPC3) myosin heavy chain (MYH7) underlie changes the energetic cost of contraction development HCM disease. Energetic was studied vitro by measurements force ATPase activity cardiac...
Childhood-onset hypertrophic cardiomyopathy (HCM) is far less common than adult-onset disease, thus natural history not well characterized. We aim to describe the characteristics and outcomes of childhood-onset HCM.We performed an observational cohort study 7677 HCM patients from Sarcomeric Human Cardiomyopathy Registry (SHaRe). Hypertrophic were stratified by age at diagnosis [<1 year (infancy), 1-18 years (childhood), >18 (adulthood)] assessed for composite endpoints reflecting heart...
Background: Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. While ≈50% of patients with HCM carry a sarcomere gene mutation (sarcomere mutation-positive, SMP ), background unknown in other half mutation-negative, SMN ). Genotype-specific differences have been reported cardiac function. Moreover, later disease onset and better prognosis than patients. To define if genotype-specific derailments at protein level may explain heterogeneity development, we performed...
Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by left ventricular (LV) hypertrophy, LV outflow tract obstruction, and atrial dilation, which can be associated with progressive heart failure, fibrillation, stroke. Aficamten a next-in-class cardiac myosin inhibitor that reduces obstruction modulating contractility, the potential to reverse pathological remodeling and, in turn, reduce cardiovascular events. This study sought investigate effect of aficamten on compared placebo...
Abstract Background Cardiac sarcoidosis (CS) is associated with poor prognosis, making early diagnosis and treatment important. This study evaluated the results of a diagnostic approach in patients known suspected cardiac involvement tertiary centre their long-term outcomes. Methods We included 180 clinical suspicion CS. In addition to an electrocardiogram (ECG)/transthoracic echocardiogram (TTE), cardiovascular magnetic resonance imaging (CMR) positron emission tomography (PET) were...