Comparison of Conventional Beta-Blockers and A New Pioneer, Mavacamten (MYK-461): A Cardiac Myosin Modulator, in Management of Hypertrophic Obstructive Cardiomyopathy View PDF

Cardiovascular disease (CVD), is one of the leading causes of global morbidity and mortality. It is most commonly associated with Hypertrophic obstructive cardiomyopathy (HOCM) [1]. The incidence of HOCM is 1:500 in the adult population [2,3]. According to a study conducted in 2016-2018, 2.7% of males and 1.6% of females are having HOCM. The incidence of HOCM is increasing with advancing age, as 0.36/per 10,000 people under the age of 18 and 4.28 per 10,000 persons the age of 55-64 years [4]. HOCMs are mainly autosomal dominant but metabolic storage diseases and neuromuscular diseases also account for its development [5]. Mutations in one of the genes encoding cardiac sarcomere, Z-disc, and calcium-controlling proteins are linked to HOCM development. Twenty genes have been identified so far, however, the two most often mutated genes are myosin-binding protein C and -myosin heavy chain (MYH7) (MYBPC3) [6,7]. HOCM is the primary non-ischemic disease, considered to be one of the major factors for sudden cardiac failure and death [2]. HOCM is characterized by an enlarged left ventricle, hyperdynamic contraction, and poor relaxation due to abundant cardiac-actin and myosin interactions [1,8]. Left ventricular hypertrophy includes, septal hypertrophy that causes high left ventricular outflow tract, which in turn leads to suction effect and traction of mitral valve cusps towards the anterior interventricular septum. This traction consequently produces sub-aortic systolic gradient and left ventricular outflow tract obstruction (LVOTO) [6]. A ventricular gradient larger than 30 mmHg is referred to as LVOTO, which remains symptomless unless 50mmHg. At rest, it affects 25% of individuals with hypertrophic cardiomyopathies and can worsen in 30% of patients during activity (dynamic LVOTO) [9,10]. Myocardial hypertrophy or systolic anterior movement (SAM) of the mitral valve (MV) leaflet are the two factors that contribute to obstruction. Symptoms associated with HOCM include dyspnea, chest pain and syncope, resulting in major concerns for one’s life [1,5, and 11].

The management of HOCM can be pharmacological or interventional. Pharmacological measures have been used since past many years as the recommended old standard guidelines. These included Beta-blockers, non-dihydropyridine calcium channel blockers [1,12]. In non-responsive patients to the above therapy, disopyramide is usually administered.1 Beta-blockers are considered to be the first line of management, unless contra-indicated. Betablockers decrease the heart rate and improve the ejection fraction [13]. Contraindications include asthma, hypoglycemia, and the administration in a person on antiarrhythmic drugs [14]. The side effects associated with all of the diseases are least tolerable compared to the efficacy, so inclination towards the surgical intervention of septal reduction is considered. Unfortunately, no prospective data on postsurgical intervention is available that can modulate the perspective of pharmacological superiority [15]. Recently, a reversible, selective inhibitor of cardiac myosin ATPase, mavacamten (MYK-461), has been introduced.1 According to New York Heart Association, class II and III adult patients of HOCM, with symptomatic heart failure, are legible for MYK-461 use [16]. This drug decreases the actin-myosin crossbridges, so demolishing the likelihood of systolic and diastolic crossbridging, which is the hallmark of HOCM [16,17]. MYK-461 reduces the LVOT obstruction, hence increasing the cardiac filling pressure. IT selectively reduces cardiac contractility by restoring the normal ratio of myosin heads to a relaxed state [17,18]. This drug has a half-life of 8 days with 85% bioavailability [16,19]. This drug is under consideration for many clinical trials and has provided efficient results compared to conventional pharmacological measurements, as discussed in the results. Keeping in mind the escalating rise in HOCM with advancing age, particularly in developing countries, there is an urgent need of deciding the efficient management plans, with fewer adverse effects.

Aim of this study is to compare the efficacy, side effects and prognosis of two different drugs for HOCM, the conventional beta-blockers and Mavacamten, a novel myosin inhibitor.

The rational of this review is to compare Mavacamten and beta blockers in HOCM to help clinicians in deciding the best management plan, and if found significant, incorporate them in departmental protocol to decrease the global burden of this disease.