Publications by authors named "Veselka J"
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.
Article 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.
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.
Article Synopsis
- The study examined a large group of patients (1468) diagnosed with hypertrophic cardiomyopathy (HCM) to understand the relationship between genetic status (genotype positive [G+] or negative [G-]) and clinical outcomes over an average follow-up of 7.8 years.
- It found no significant differences in mortality rates or adverse heart events between G+ and G- patients, indicating that genetic factors did not influence the clinical course of the disease.
- The researchers concluded that genotype status should not guide clinical management or predictions regarding outcomes in HCM patients, with age being the only significant factor affecting mortality and heart failure progression.
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.
Background Recent trials support the role of cardiac CT in the evaluation of symptomatic patients suspected of having coronary artery disease (CAD); however, body mass index (BMI) has been reported to negatively impact CT image quality. Purpose To compare initial use of CT versus invasive coronary angiography (ICA) on clinical outcomes in patients with stable chest pain stratified by BMI category. Materials and Methods This prospective study represents a prespecified BMI subgroup analysis of the multicenter Diagnostic Imaging Strategies for Patients with Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial conducted between October 2015 and April 2019.
View Article and Find Full Text PDFBackground: The use of beta-blockers in hypertrophic obstructive cardiomyopathy (HOCM) patients after alcohol septal ablation (ASA) lacks data support. We aimed to evaluate the effect of metoprolol on exercise capacity, hemodynamic and laboratory parameters, and quality of life in HOCM patients after ASA.
Methods: This was a prospective randomized single-center open-label crossover trial in 21 HOCM patients after ASA.
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 PDFIn the 30 years since Dr Sigwart's first pioneering procedures, alcohol septal ablation (ASA) has become the standard catheterisation procedure to reduce or eliminate obstruction in the left ventricular outflow tract. This procedure reduces the pressure gradient by 70%-80%, and only 10%-20% of patients have a residual gradient > 30 mm Hg after ASA. The mortality rate of the procedure is < 1%, and ∼ 10% of patients require permanent pacemaker implantation for higher degrees of atrioventricular block.
View Article and Find Full Text PDFBackground: We present an uncommon case of a patient with hypertrophic obstructive cardiomyopathy and idiopathic pulmonary fibrosis. The case demonstrates the importance of pre-transplant cardiology workup and the need of interdisciplinary approach in diagnosing the cause of dyspnoea.
Case Summary: The 52-year-old male patient was diagnosed with idiopathic pulmonary fibrosis in 2019 and gradually became oxygen dependent due to progression of dyspnoea.
Objective: To compare cardiac computed tomography (CT) with invasive coronary angiography (ICA) as the initial strategy in patients with diabetes and stable chest pain.
Research Design And Methods: This prespecified analysis of the multicenter DISCHARGE trial in 16 European countries was performed in patients with stable chest pain and intermediate pretest probability of coronary artery disease. The primary end point was a major adverse cardiac event (MACE) (cardiovascular death, nonfatal myocardial infarction, or stroke), and the secondary end point was expanded MACE (including transient ischemic attacks and major procedure-related complications).
Invasive therapies for symptomatic obstructive hypertrophic cardiomyopathy.
Prog Cardiovasc Dis
August 2023
Hypertrophic cardiomyopathy (HCM) is a genetic condition with multiple different genetic and clinical phenotypes. As awareness for HCM increases, it is important to also be familiar with potential treatment options for the disease. Treatment of HCM can be divided into two different categories, medical and interventional.
View Article and Find Full Text PDFBackground: The current ACC/AHA guidelines on hypertrophic cardiomyopathy (HCM) caution that alcohol septal ablation (ASA) might be less effective in patients with left ventricular outflow tract obstruction (LVOTO) ≥ 100 mm Hg.
Methods: We used a multinational registry to evaluate the outcome of ASA patients according to baseline LVOTO.
Results: A total of 1346 ASA patients were enrolled and followed for 5.
Introduction: The role of eicosanoids, metabolites of arachidonic acid with cardio-renal activity, remains unclear in human heart failure (HF).
Methods: We enrolled 50 patients with HF to measure plasma 14,15-EET and 14,15-DHET levels using commercial ELISA kits and compared them with 25 age- and sex-matched controls.
Results: Both of the measured eicosanoids were significantly higher in the HF group: 14,15-EET (91.
Background: Association of congestive heart failure (CHF) and chronic kidney disease (CKD) worsens the patient's prognosis and results in poor survival rate. The aim of this study was to examine if addition of endothelin type A (ET) receptor antagonist to the angiotensin-converting enzyme inhibitor (ACEi) will bring additional beneficial effects in experimental rats.
Methods: CKD was induced by 5/6 renal mass reduction (5/6 NX) and CHF was elicited by volume overload achieved by creation of aorto-caval fistula (ACF).
Lessons We Learned About Sudden Death in Hypertrophic Cardiomyopathy.
JACC Clin Electrophysiol
November 2022
Objective: Evaluation of the effect of endothelin type A (ET A ) receptor blockade on the course of volume-overload heart failure in rats with angiotensin II-dependent hypertension.
Methods: Ren-2 renin transgenic rats (TGR) were used as a model of hypertension. Heart failure was induced by creating an aorto-caval fistula (ACF).
Article Synopsis
- Atrioventricular block is a common complication following alcohol septal ablation (ASA) in patients with hypertrophic obstructive cardiomyopathy, leading to some requiring a permanent pacemaker (PPM).
- In a study involving 1,814 patients using the Euro-ASA registry, 9.4% underwent PPM implantation within 30 days after the procedure, with a follow-up averaging 4 years.
- Long-term outcomes revealed that while survival and functional class were similar between groups, those with PPM had a lower left ventricular outflow gradient and lower likelihood of needing further interventions.