Publications by authors named "Stephen Heitner"
Background: Standard-of-care (SoC) medications for the treatment of obstructive hypertrophic cardiomyopathy (oHCM) are recommended as first-line therapy despite the lack of evidence from controlled clinical trials and well known off-target side effects.
Objectives: We describe the impact of SoC therapy downtitration and withdrawal in patients already receiving aficamten in FOREST-HCM (Follow-Up, Open-Label, Research Evaluation of Sustained Treatment with Aficamten in Hypertrophic Cardiomyopathy; NCT04848506).
Methods: Patients receiving SoC therapy (beta-blocker, nondihydropyridine calcium-channel blocker, and/or disopyramide) were eligible for protocol-guided SoC downtitration and withdrawal at the discretion of the investigator and after achieving a stable dose of aficamten for ≥4 weeks.
Article Synopsis
- The study evaluates the accuracy of the Eko murmur analysis software (EMAS) in detecting valvular heart disease (VHD) by comparing it to echocardiography (ECHO) results.
- Data from 1,029 individuals were analyzed, revealing that EMAS had a sensitivity of 39.4% and a specificity of 82.4% for detecting murmurs related to VHD.
- While EMAS shows better sensitivity for certain VHD types, its overall limited sensitivity suggests it may not be reliable as a screening tool for all forms of VHD.
Background: Aficamten is a cardiac myosin inhibitor that mitigates left ventricular outflow gradients in obstructive hypertrophic cardiomyopathy (oHCM). The clinical efficacy of aficamten across multiple outcome domains in oHCM has not been fully defined.
Objectives: This responder analysis from the SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM) trial characterizes the clinical impact of aficamten.
Objective: Hypertrophic cardiomyopathy (HCM), including obstructive HCM (oHCM), is the most common inherited cardiomyopathy causing lifestyle-limiting symptoms. Data are lacking about patients' perspectives on the daily impact of their symptoms. This qualitative interview study was conducted to better understand patients' experiences with oHCM.
View Article and Find Full Text PDFArticle Synopsis
- The SEQUOIA-HCM trial examines the effectiveness of aficamten, a new cardiac myosin inhibitor, in improving exercise capacity in adults suffering from symptomatic obstructive hypertrophic cardiomyopathy (HCM).
- The study involves a double-blind, placebo-controlled design, with participants recruited from 101 sites across 14 countries, focusing on those with objectively measured exertional intolerance.
- The main goal is to assess changes in integrated exercise performance after 24 weeks of treatment using a combination of peak oxygen uptake and ventilation efficiency, along with monitoring clinical health outcomes.
Background: A primary goal in treating obstructive hypertrophic cardiomyopathy (oHCM) is to improve patients' health status: their symptoms, function, and quality of life. The health status benefits of aficamten, a novel cardiac myosin inhibitor, have not been comprehensively described.
Objectives: This study sought to determine the effect of aficamten on patient-reported health status, including symptoms of fatigue, shortness of breath, chest pain, physical and social limitations, and quality of life.
Background: Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by left ventricular (LV) hypertrophy, LV outflow tract obstruction, and left atrial dilation, which can be associated with progressive heart failure, atrial fibrillation, and stroke. Aficamten is a next-in-class cardiac myosin inhibitor that reduces outflow tract obstruction by modulating cardiac contractility, with the potential to reverse pathological remodeling and, in turn, reduce cardiovascular events.
Objectives: This study sought to investigate the effect of aficamten on cardiac remodeling compared with placebo using cardiovascular magnetic resonance (CMR) and its association with key clinical endpoints in the SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM) CMR substudy.
Background: Aficamten, a next-in-class cardiac myosin inhibitor, improved peak oxygen uptake (pVO) and lowered resting and Valsalva left ventricular outflow (LVOT) gradients in adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) in SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM), a phase 3, multicenter, randomized, double-blinded, placebo-controlled study.
Objectives: The authors sought to evaluate the effect of aficamten on echocardiographic measures of cardiac structure and function in SEQUOIA-HCM.
Methods: Serial echocardiograms were performed over 28 weeks in patients randomized to receive placebo or aficamten in up to 4 individually titrated escalating doses (5-20 mg daily) over 24 weeks based on Valsalva LVOT gradients and left ventricular ejection fraction (LVEF).
Article Synopsis
- The study analyzed the role of biomarkers NT-proBNP and hs-cTnI in managing obstructive hypertrophic cardiomyopathy (oHCM) and how they relate to treatment effects of aficamten.
- Baseline levels of NT-proBNP correlated with the left ventricular outflow tract gradient (LVOT-G) and diastolic function, while hs-cTnI correlated with left ventricular thickness.
- After 8 weeks of aficamten treatment, NT-proBNP decreased by 79% and hs-cTnI by 41%, with these reductions linked to improvements in heart function, health status, and exercise capacity, suggesting that these biomarkers are useful for tracking treatment response.
Article Synopsis
- Aficamten is a new drug that helps reduce heart issues in patients with obstructive hypertrophic cardiomyopathy by targeting heart muscle contractility and maintaining safe blood flow levels.
- * In a clinical trial involving 282 patients, those receiving aficamten were able to maintain effective heart function with minimal side effects, including a stable reduction in heart muscle contraction without significant adverse events.
- * The findings suggest that using a tailored dosing strategy for aficamten is effective and safe, improving cardiovascular health without worsening conditions like heart failure.
Aims: The aim of this study was to report safety and efficacy of aficamten in patients with non-obstructive hypertrophic cardiomyopathy (nHCM) over 36 weeks in the ongoing FOREST-HCM trial.
Methods And Results: Patients were started on aficamten 5 mg daily, with doses adjusted in 5-mg increments (5-20 mg) at ≥2-week intervals according to site-read left ventricular ejection fraction (LVEF). Aficamten dose was increased if LVEF ≥55%, maintained if LVEF 50-54%, decreased if LVEF 40-<50%, and temporarily interrupted if LVEF <40%.
Background: One of the major determinants of 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 is an oral selective cardiac myosin inhibitor that reduces left ventricular outflow tract gradients by mitigating cardiac hypercontractility.
Methods: In this phase 3, double-blind trial, we randomly assigned adults with symptomatic obstructive HCM to receive aficamten (starting dose, 5 mg; maximum dose, 20 mg) or placebo for 24 weeks, with dose adjustment based on echocardiography results.
Article Synopsis
- This phase 2 trial assessed the safety and effectiveness of a medication called aficamten in patients suffering from nonobstructive hypertrophic cardiomyopathy (nHCM).
- 41 patients participated, and after 10 weeks of treatment, over half showed improvement in heart failure symptoms, with many reaching a better functional class.
- While some patients experienced a slight decrease in heart function (LVEF), the overall results indicated that aficamten is generally safe and effective in improving symptoms and relevant heart health markers.
Background: Tricuspid regurgitation (TR) is common and is associated with poor outcomes in patients with heart failure (HF). However, data with adjudicated events from fully characterized patients with heart failure with reduced ejection fraction (HFrEF) are lacking.
Objectives: This study sought to explore the association between mild or moderate/severe TR and clinical outcomes of patients with HFrEF.
Background: Omecamtiv mecarbil improves outcomes in patients with heart failure and reduced ejection fraction (HFrEF). We examined the relationship between baseline troponin levels, change in troponin levels over time and the treatment effect of omecamtiv mecarbil in patients enrolled in the Global Approach to Lowering Adverse Cardiac Outcomes through Improving Contractility in Heart Failure (GALACTIC-HF) trial (NCT02929329).
Methods: GALACTIC-HF was a double-blind, placebo-controlled trial that randomized 8256 patients with symptomatic HFrEF to omecamtiv mecarbil or placebo.
Background: Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM), an increasingly recognized cause of heart failure (HF), often remains undiagnosed until later stages of the disease.
Methods And Results: A previously developed machine learning algorithm was simplified to create a random forest model based on 11 selected phenotypes predictive of ATTRwt-CM to estimate ATTRwt-CM risk in hypothetical patient scenarios. Using U.
Patients with obstructive hypertrophic cardiomyopathy (oHCM) have increased risk of arrhythmia, stroke, heart failure, and sudden death. Contemporary management of oHCM has decreased annual hospitalization and mortality rates, yet patients have worsening health-related quality of life due to impaired exercise capacity and persistent residual symptoms. Here we consider the design of clinical trials evaluating potential oHCM therapies in the context of SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM).
View Article and Find Full Text PDFBackground: In the Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial, omecamtiv mecarbil, compared with placebo, reduced the risk of worsening heart failure (HF) events, or cardiovascular death in patients with HF and reduced ejection fraction. The primary aim of this prespecified analysis was to evaluate the safety and efficacy of omecamtiv mecarbil by randomization setting, that is, whether participants were enrolled as outpatients or inpatients.
Methods And Results: Patients were randomized either during a HF hospitalization or as an outpatient, within one year of a worsening HF event (hospitalization or emergency department visit).
Article Synopsis
- A significant portion of heart failure patients in the U.S. do not qualify for advanced therapies, yet most have severely reduced ejection fractions (EF ≤30%).
- Patients with severely reduced EF tend to be younger, more likely to be Black, and receive higher rates of guideline-directed medical therapy compared to those with EF between 31% and 40%.
- However, these patients face a greater risk of death and heart failure hospitalization within 12 months after discharge, and their healthcare costs are also notably higher.
Range of DNA repair in response to double-strand breaks induced in human preimplantation embryos remains uncertain due to the complexity of analyzing single- or few-cell samples. Sequencing of such minute DNA input requires a whole genome amplification that can introduce artifacts, including coverage nonuniformity, amplification biases, and allelic dropouts at the target site. We show here that, on average, 26.
View Article and Find Full Text PDFBackground: Omecamtiv mecarbil improves cardiovascular outcomes in patients with heart failure (HF) with reduced ejection fraction (EF). Consistency of drug benefit across race is a key public health topic.
Objectives: The purpose of this study was to evaluate the effect of omecamtiv mecarbil among self-identified Black patients.
Background: Left ventricular outflow tract (LVOT) obstruction is a major determinant of heart failure symptoms in obstructive hypertrophic cardiomyopathy (oHCM). Aficamten, a next-in-class cardiac myosin inhibitor, may lower gradients and improve symptoms in these patients.
Objectives: This study aims to evaluate the safety and efficacy of aficamten in patients with oHCM.
Efficacy of omecamtiv mecarbil in heart failure with reduced ejection fraction according to N-terminal pro-B-type natriuretic peptide level: insights from the GALACTIC-HF trial.
Eur J Heart Fail
February 2023
Aim: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is predictive of both outcomes and response to treatment in patients with heart failure with reduced ejection fraction (HFrEF). The aim of this study was to examine the effect of the cardiac myosin activator omecamtiv mecarbil according to baseline NT-proBNP level in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure trial (GALACTIC-HF).
Methods And Results: The primary outcome was the composite of a worsening heart failure event (urgent clinic visit, emergency department visit, or hospitalization) or cardiovascular death.