Pushing the Limits of Medical Management in HCM: A Review of Current Pharmacological Therapy Options

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiac disease with a highly variable phenotypic expression, ranging from asymptomatic to drug refractory heart failure (HF) presentation. Pharmacological therapy is the first line of treatment, but options are currently limited to nonspecific medication like betablockers or calcium channel inhibitors, with frequent suboptimal results. While being the gold standard practice for the management of drug refractory HCM patients, septal reduction therapy (SRT) remains an invasive procedure with associated surgical risks and it requires the expertise of the operating centre, thus limiting its accessibility. It is therefore with high interest that researchers look for pharmacological alternatives that could provide higher rates of success. With new data gathering these past years as well as the development of a new drug class showing promising results, this review provides an up-to-date focused synthesis of existing medical treatment options and future directions for HCM pharmacological treatment.

Mavacamten, a First-in-Class Cardiac Myosin Inhibitor for Obstructive Hypertrophic Cardiomyopathy

“…Figure 2 adapts the American Heart Association/American College of Cardiology treatment recommendations for patients with symptomatic HCM and outflow obstruction to include the potential role of mavacamten. 1,[3][4][5][6][7][8][9][10][11]26 βblockers and non-dihydropyridine calcium channel blockers are relatively safe and well-tolerated therapies and were employed in most patients before they were started on additional disopyramide or septal reduction therapies. 1,[4][5][6]9 Similarly, mavacamten was mostly studied in patients who were on baseline therapy or were intolerant to β-blockers or non-dihydropyridine calcium channel blockers.…”

“…In a study of 503 patients undergoing myomectomy for drug refractory HCM, extensive hypertrophy (≥30 mm, P < 0.01) and younger age (40 vs 53 years, P < 0.001) were the most significant predictors of nonresponsiveness and may portend the need for subsequent medical intervention with mavacamten or disopyramide. 26…”

“…In a study of 503 patients undergoing myomectomy for drug refractory HCM, extensive hypertrophy (≥30 mm, P < 0.01) and younger age (40 vs 53 years, P < 0.001) were the most significant predictors of nonresponsiveness and may portend the need for subsequent medical intervention with mavacamten or disopyramide. 26 Whether to start mavacamten or disopyramide as the first add-on drug therapy is not an easy decision. Disopyramide has not been well studied and that provides limited confidence for it providing strong and sustained benefits.…”

The efficacy and safety of pharmacological treatments in patients with hypertrophic cardiomyopathy: a network meta-analysis

“…Trimetazidine prevents the accumulation of protons, sodium, and calcium in muscle cells by reducing the production of free radicals. Spironolactone and N-acetylcysteine [7] also improved myocardial brosis. Mavacamten is the rst drug speci cally developed for HCM [8] .…”

The consolidation of surgery for hypertrophic obstructive cardiomyopathy in Asia and the Pacific Rim

“…( 12 ) Pharmacological therapies remain the first line of therapy although the options are still limited to nonspecific medications, frequently offering suboptimal results. ( 13 ) Myosin modulation with Macavamtem (Bristol Myers Squibb, New York, USA) is currently being investigated by the community, although the only Phase III trial only compared the investigational drug with placebo. ( 14 ) This, at the moment, raises important doubts and questions as this trial has only confirmed that with Mavacamten, the persistence of obstruction was high in a less symptomatic population, improvement in pVO 2 was suboptimal in a young study cohort (mean age 58 years), and the lifetime tolerance remains unassessed.…”