Title : Cardiac myosin inhibitors – New pharmacological approach for obstructive hypertrophic cardiomyopathy treatment
Abstract:
The modern knowledge of hypertrophic cardiomyopathy (HCM) rapidly evolved over the past twenty years, where the thorough understanding of HCM pathophysiology, combined with innovative therapeutic solutions, finally allowed us to achieve some excellent outcomes, including in obstructive HCM (oHCM). Currently, septal reduction therapies are largely confined to patients with oHCM who have advanced symptoms, as defined by New York Heart Association (NYHA) Class III or IV. Unfortunately, worldwide, many patients with oHCM are managed in institutions with limited or no expertise in septal reduction therapies. The initial approach to the treatment of symptomatic patients with oHCM includes beta?blockers, non?dihydropyridine calcium channel blockers, and disopyramide. Although generally effective, all these agents are commonly associated with specific adverse drug reactions. Therefore, the development of pioneering, disease?aimed therapies, represents a major change for oHCM patients. It was recently confirmed that HCM?associated mutations affecting sarcomere protein genes most probably cause myocardial hyper?contractility, due to excessive availability of myosin heads ready to form cross?bridges with actin, with a reduced proportion remaining in the energy?sparing super?relaxed state not available for engagement. Consequently, cardiac myosin inhibitors (CMI) represent a new class of medications being developed for patients with oHCM. The first one just recently approved was mavacamten, which reduces cardiac muscle contractility by inhibiting excessive myosin-actin cross-bridge formation. The main objectives of this presentation will be to clarify pharmacological properties of mavacamten, including pharmacodynamics, pharmacokinetics, indications and contraindications for use, adverse drug reactions, as well as the most important drug interactions. This will provide better understanding of this ground-breaking drug for oHCM, thus helping clinicians in appropriate prescribing and its adequate clinical use.
