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American Journal of Cardiovascular... Sep 2023Aficamten is a novel cardiac myosin inhibitor that has demonstrated its ability to safely lower left ventricular outflow tract (LVOT) gradients and improve heart failure... (Review)
Review
Aficamten is a novel cardiac myosin inhibitor that has demonstrated its ability to safely lower left ventricular outflow tract (LVOT) gradients and improve heart failure symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM). Based on the REDWOOD-HCM open label extension (OLE) study, participants receiving aficamten had significantly reduced resting and Valsalva LVOT gradient within 2 weeks after initiating treatment, with ongoing improvements over 24 weeks, and recent evidence suggests effects can sustain up to 48 weeks. While beta-blockers, calcium channel blockers, and disopyramide have shown some benefits in managing HCM, they have limited direct impact on the underlying disease process in patients with obstructive HCM. Aficamten achieves its therapeutic effect by reducing hypercontractility and improving diastolic function in obstructive HCM. Mavacamten was the first cardiac myosin inhibitor approved for symptomatic obstructive HCM. However, aficamten has a shorter human half-life (t) and fewer drug-drug interactions, making it a preferable treatment option. This review evaluates the long-term clinical value and safety of aficamten in patients with obstructive HCM based on available data from completed and ongoing clinical trials. Additionally, the molecular basis of sarcomere-targeted therapy in reducing LVOT gradients is explored, and its potential in managing obstructive HCM is discussed.
Topics: Humans; Cardiomyopathy, Hypertrophic; Calcium Channel Blockers; Adrenergic beta-Antagonists; Cardiac Myosins
PubMed: 37526885
DOI: 10.1007/s40256-023-00599-0 -
Future Cardiology Oct 2023Hypertrophic cardiomyopathy (HCM) is a phenotypically heterogeneous disease with a genetic basis and variable penetrance. The hallmarks of HCM include dynamic left... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is a phenotypically heterogeneous disease with a genetic basis and variable penetrance. The hallmarks of HCM include dynamic left ventricular outflow tract obstruction, typically caused by asymmetric septal hypertrophy. However, abnormal papillary muscle placement, abnormal mitral valve and subvalvular apparatus and apical hypertrophic forms have also been described. Typical medical treatment has been stagnant for decades, although there have been significant advances in surgical treatment of patients with obstructive HCM. Herein, we describe a new class of drugs targeting the specific pathophysiology of HCM.
Topics: Humans; Cardiomyopathy, Hypertrophic; Cardiomyopathy, Hypertrophic, Familial; Heart Valve Diseases; Ventricular Outflow Obstruction, Left
PubMed: 37933625
DOI: 10.2217/fca-2023-0056 -
Expert Opinion on Investigational Drugs 2023Hypertrophic cardiomyopathy (HCM), a phenotypically variable disorder with a genetic basis, was first described in the late 1800s. Since the discovery of the disease,... (Review)
Review
INTRODUCTION
Hypertrophic cardiomyopathy (HCM), a phenotypically variable disorder with a genetic basis, was first described in the late 1800s. Since the discovery of the disease, various medical and surgical treatments have been proposed with surgical treatments proving to be of more benefit than medical in patients with severe symptoms. Although beta blockers, calcium channel blockers, and disopyramide have been used for their negative inotropic effect, the data behind utilization of these medications is weak at best.
AREAS COVERED
Herein, we describe a first-in-man class of medications called cardiac myosin inhibitors (CMI), which have been recently approved by the Food and Drug Administration (FDA) for the treatment of symptomatic patients with obstructive HCM. PubMed was the primary database searched.
EXPERT OPINION
Whether these medications will stand the test of time remains to be seen. They do appear to provide significant benefit and disease modification in early randomized trials with the drawback of decreasing contractility and ejection fraction. In our opinion, this new class of medications is an option for patients with NYHA class II-III symptoms from obstructive HCM who have EF ≥ 55%.
Topics: Humans; Drugs, Investigational; Cardiomyopathy, Hypertrophic; Adrenergic beta-Antagonists; Calcium Channel Blockers; Myosins
PubMed: 37787068
DOI: 10.1080/13543784.2023.2263362 -
Progress in Cardiovascular Diseases 2023Hypertrophic cardiomyopathy (HCM) is a genetic condition with multiple different genetic and clinical phenotypes. As awareness for HCM increases, it is important to also... (Review)
Review
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. Typically for obstructive forms of the disease, in which increased septal hypertrophy, abnormally placed papillary muscles, abnormalities in mitral valve or subvalvular apparatus, lead to dynamic left ventricular outflow tract (LVOT) obstruction, treatment is targeted at decreasing obstructive gradients and therefore symptoms. Medications like beta blockers, calcium channel blockers, disopyramide can often accomplish this. However, in patients with severe obstruction or symptoms refractory to medical therapy, either surgical correction of the LVOT obstruction or percutaneous via alcohol septal ablation, are treatment options. In this review, we will focus on the invasive treatment of hypertrophic obstructive cardiomyopathy.
PubMed: 37652213
DOI: 10.1016/j.pcad.2023.08.003 -
Circulation Nov 2023Atrial fibrillation (AF) is the most common sustained arrhythmia in hypertrophic cardiomyopathy (HCM) with clinical and subclinical episodes occurring in nearly one-half... (Review)
Review
Atrial fibrillation (AF) is the most common sustained arrhythmia in hypertrophic cardiomyopathy (HCM) with clinical and subclinical episodes occurring in nearly one-half of patients. AF in HCM historically has been characterized as a decisive disease complication associated with substantial risk for thromboembolic stroke and increased morbidity and mortality. However, there have been many advances in treatment strategy resulting in improved outcomes for this patient group. For example, stroke risk in HCM has been greatly reduced by using systemic oral anticoagulation initiated after the first clinical (symptomatic) AF episode, usually with preference given to direct anticoagulants over warfarin. In contrast, stroke risk scoring systems (such as CHADS-VASc score) are not informative in HCM given the substantial potential for stroke events in patients with low scores, and therefore should not be used for anticoagulation decisions in this disease. A novel risk score specifically designed for HCM (HCM-AF score) can reliably identify most patients with HCM at risk for future AF. Although a strategy focused on controlling ventricular rate is effective in asymptomatic (or minimally symptomatic) patients with AF, restoring and maintaining sinus rhythm is required for most patients with marked AF symptom burden and impaired quality of life. Several antiarrhythmic drugs such as sotalol, disopyramide, and amiodarone, can be effective in suppressing AF episodes; albeit safe, long-term efficacy is supported by only limited data. Catheter AF ablation has emerged as an important treatment option for some patients, although freedom from AF after a single ablation is relatively low (35% at 3 years), multiple ablations and the concomitant use of antiarrhythmic drugs can control AF with more than two-thirds of patients maintaining sinus rhythm at 5 years. Surgical AF ablation with biatrial Cox-Maze IV performed as an adjunctive procedure during myectomy can reduce symptomatic AF episodes (70% of patients free from AF at 5 years). For the vast majority of patients who have HCM with AF, the implementation of contemporary therapies has allowed for improved quality of life and low HCM-related mortality.
Topics: Humans; Atrial Fibrillation; Anti-Arrhythmia Agents; Quality of Life; Risk Factors; Anticoagulants; Stroke; Cardiomyopathy, Hypertrophic; Catheter Ablation; Treatment Outcome
PubMed: 38011245
DOI: 10.1161/CIRCULATIONAHA.123.065037 -
The Medical Letter on Drugs and... Jan 2024
Topics: Humans; Atrial Fibrillation
PubMed: 38180321
DOI: 10.58347/tml.2024.1693a -
Cardiology Research Aug 2023Hypertrophic cardiomyopathy is one of the most common genetic inherited diseases of myocardium, which is caused by mutation in genes encoding proteins for the cardiac... (Review)
Review
Hypertrophic cardiomyopathy is one of the most common genetic inherited diseases of myocardium, which is caused by mutation in genes encoding proteins for the cardiac sarcomere. It is the most frequent cause of sudden death in young people and trained athletes. All diagnostic methods, including heart catheterization, transthoracic and transesophageal echocardiography, magnetic resonance imaging, genetic counseling and tissue biopsy are required for risk and therapy stratification and should be individualized depending on phenotype and genotype. Current therapy has not been tested adequately. Beta-blockers and verapamil can cause hypotension which can make hypertrophic cardiomyopathy worse. Disopyramide has been inadequately studied, and mavacamten was only studied in small trials. More definitive trials are currently ongoing. Novel invasive and noninvasive diagnostics, medical therapies, interventional and surgical approaches tend to influence the natural history of the disease, favoring a better future for this patient population.
PubMed: 37559708
DOI: 10.14740/cr1514 -
Journal of Cardiac Failure Nov 2023
Topics: Humans; Disopyramide; Sequoia; Heart Failure; Anti-Arrhythmia Agents; Cardiomyopathy, Hypertrophic
PubMed: 37473912
DOI: 10.1016/j.cardfail.2023.07.003