Stephen B. Heitner
A5011566295- Cardiomyopathy and Myosin Studies
- Cardiovascular Function and Risk Factors
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Cardiovascular Effects of Exercise
- Cardiac pacing and defibrillation studies
- Heart Failure Treatment and Management
- Congenital Heart Disease Studies
- Parathyroid Disorders and Treatments
- Cardiac Imaging and Diagnostics
- Cardiac Structural Anomalies and Repair
- Cardiac Arrhythmias and Treatments
- Eosinophilic Disorders and Syndromes
- Multiple Myeloma Research and Treatments
- Cardiac Valve Diseases and Treatments
- Viral Infections and Immunology Research
- Cardiac electrophysiology and arrhythmias
- Peptidase Inhibition and Analysis
- Atrial Fibrillation Management and Outcomes
- Congenital heart defects research
- Hemodynamic Monitoring and Therapy
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Acute Myocardial Infarction Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Neuroendocrine Tumor Research Advances
Cytokinetics (United States)
2021-2025
Providence College
2024-2025
Alaska Heart and Vascular Institute
2024-2025
Oregon Health & Science University
2015-2024
Brigham and Women's Hospital
2018-2024
Lahey Medical Center
2024
Baim Institute for Clinical Research
2024
Harvard University
2024
Lahey Hospital and Medical Center
2024
Massachusetts General Hospital
2024
Hereditary transthyretin amyloidosis is caused by pathogenic single-nucleotide variants in the gene encoding (TTR) that induce misfolding and systemic deposition of amyloid. Progressive amyloid accumulation leads to multiorgan dysfunction death. Inotersen, a 2′-O-methoxyethyl–modified antisense oligonucleotide, inhibits hepatic production transthyretin.
Patients with nonobstructive hypertrophic cardiomyopathy (nHCM) often experience a high burden of symptoms; however, there are no proven pharmacological therapies. By altering the contractile mechanics cardiomyocyte, myosin inhibitors have potential to modify pathophysiology and improve symptoms associated HCM.MAVERICK-HCM (Mavacamten in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy) explored safety efficacy mavacamten, first-in-class reversible inhibitor...
Background: Mavacamten, an orally administered, small-molecule modulator of cardiac myosin, targets underlying biomechanical abnormalities in obstructive hypertrophic cardiomyopathy (oHCM). Objective: To characterize the effect mavacamten on left ventricular outflow tract (LVOT) gradient. Design: Open-label, nonrandomized, phase 2 trial. (ClinicalTrials.gov: NCT02842242) Setting: 5 academic centers. Participants: 21 symptomatic patients with oHCM. Intervention: Patients cohort A received...
Transthyretin (TTR) amyloidosis is an underdiagnosed disease caused by destabilization of TTR due to pathogenic mutations or aging. Both and protective illuminate mechanisms potential interventions. AG10 a selective, oral stabilizer under development for transthyretin cardiomyopathy (ATTR-CM) that mimics mutation.This randomized, double-blind, placebo-controlled study evaluated safety, tolerability, pharmacokinetics, pharmacodynamics in ATTR-CM patients with symptomatic, chronic heart...
Left ventricular outflow tract (LVOT) obstruction is a major determinant of heart failure symptoms in obstructive hypertrophic cardiomyopathy (oHCM). Aficamten, next-in-class cardiac myosin inhibitor, may lower gradients and improve these patients.This study aims to evaluate the safety efficacy aficamten patients with oHCM.Patients oHCM LVOT ≥30 mm Hg at rest or ≥50 Valsalva were randomized 2:1 receive (n = 28) placebo 13) 2 dose-finding cohorts. Doses titrated based on ejection fraction...
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)...
Background This open-label phase 2 trial evaluated the safety and efficacy of aficamten in patients with non-obstructive hypertrophic cardiomyopathy (nHCM). Methods Patients symptomatic nHCM (left ventricular outflow tract obstruction gradient ≤30 mmHg, left ejection fraction [LVEF] ≥60%, N-terminal pro-B-type natriuretic peptide [NT-proBNP] >300 pg/mL) received 5–20 mg once daily (doses adjusted according to echocardiographic LVEF) for 10 weeks. Results 41 were enrolled (mean ± SD age 56 16...
In GALACTIC-HF (Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure) (n = 8,256), the cardiac myosin activator, omecamtiv mecarbil, significantly reduced primary composite endpoint (PCE) of time-to-first heart failure event or cardiovascular death patients with and ejection fraction (EF) (≤35%).The purpose this study was evaluate influence baseline EF on therapeutic effect mecarbil.Outcomes treated mecarbil were compared placebo according...
Heart failure with reduced ejection fraction is a progressive clinical syndrome, and many patients' condition worsen over time despite treatment. Patients more severe disease are often intolerant of available medical therapies.
The purpose of this study was to establish whether an artificially intelligent (AI) system can be developed automate stress echocardiography analysis and support clinician interpretation.Coronary artery disease is the leading global cause mortality morbidity remains one most commonly used diagnostic imaging tests.An automated image processing pipeline extract novel geometric kinematic features from echocardiograms collected as part a large, United Kingdom-based prospective, multicenter,...
<h3>Importance</h3> Exercise limitation is a cardinal manifestation of heart failure with reduced ejection fraction (HFrEF) but not consistently improved by any the current guideline-directed medical therapies. <h3>Objective</h3> To determine whether omecamtiv mecarbil, novel direct myosin activator that improves cardiac performance and reduces risk for cardiovascular death or first HF event in HFrEF, can improve peak exercise capacity patients chronic HFrEF. <h3>Design, Setting,...
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...
Background: Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by unexplained left ventricular (LV) hypertrophy associated with dynamic LV outflow tract obstruction. Current medical therapies are nonspecific and have limited efficacy in relieving symptoms. Mavacamten a first-in-class targeted inhibitor of cardiac myosin, which has been shown to reduce obstruction, improve exercise capacity, relieve symptoms oHCM the PIONEER-HCM phase 2 study. Methods: EXPLORER-HCM multicenter,...
Abstract Aim Patients with heart failure reduced ejection fraction and low systolic blood pressure (SBP) have high mortality, hospitalizations, poorly tolerate evidence-based medical treatment. Omecamtiv mecarbil may be particularly helpful in such patients. This study examined its efficacy tolerability patients SBP ≤100 mmHg enrolled the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility Heart Failure (GALACTIC-HF). Methods results The GALACTIC-HF baseline...
•Aficamten is a next-generation cardiac myosin inhibitor (CMI)•CMIs are novel treatment for obstructive hypertrophic cardiomyopathy (oHCM)•We report efficacy and safety of aficamten with disopyramide refractory oHCM•In Cohort 3 REDWOOD-HCM, plus was well tolerated•Patients had improved left ventricular outflow tract gradient NYHA class How this work applies to patients•Disopyramide used help relieve symptoms as second-line option when patients HCM have persistent limiting despite either...
The aim of this study was to report safety and efficacy aficamten in patients with non-obstructive hypertrophic cardiomyopathy (nHCM) over 36 weeks the ongoing FOREST-HCM trial.
Background Aficamten, a novel cardiac myosin inhibitor, reversibly reduces hypercontractility in obstructive hypertrophic cardiomyopathy. We present prespecified analysis of the pharmacokinetics, pharmacodynamics, and safety aficamten SEQUOIA‐HCM (Safety, Efficacy, Quantitative Understanding Obstruction Impact Aficamten HCM). Methods Results A total 282 patients with cardiomyopathy were randomized 1:1 to daily (5–20 mg) or placebo between February 1, 2022, May 15, 2023. dosing targeted...