An Insight of Novel Pharmacological Therapies in Hypertrophic Cardiomyopathy

Esteban      Orenes-Pinero; Diana      Hernandez-Romero; Eva      Jover; Gonzalo      de la Morena; Mariano      Valdes; Francisco      Marin

Abstract

Hypertrophic cardiomyopathy (HCM) is microscopically characterized by cardiomyocyte hypertrophy, myofibrillar disarray, and fibrosis. During the evolvement of the hypertrophic disease, myocardium suffers a heterogeneous remodeling which includes enhancement of extracellular matrix. The most commonly used pharmacological agents are β- blockers and verapamil, a calcium antagonist, which are the mainstay of therapy. Their proposed mechanisms of effect include improved ventricular relaxation, and increased diastolic filling time but its impact on HCM pathophysiology remains unclear. The results of genetic and pharmacological studies in animal models suggest that cardiac hypertrophy and fibrosis in HCM are potentially reversible. However, current pharmacological treatments of HCM in patients, while are effective for symptomatic improvement, have not been established to prevent, ameliorate, or reverse cardiac hypertrophy in patients. An effective treatment of HCM has to target the molecular mechanisms that are involved in the pathogenesis of the phenotype and novel pharmacological therapies are moving in that direction. In this review, we analyse potential beneficial effects of specific experimental pharmacological agents on decreasing myocardial hypertrophy, regression of fibrosis or improving myocardial metabolic efficiency.

Keywords: Hypertrophic cardiomyopathy, fibrosis, losartan, spironolactone, statins, calcineurin inhibitors, perhexiline, Nacetylcysteine, HCM, HMG-CoA, NF-AT3, CsA, TGF