Emerging pharmacologic and structural therapies for hypertrophic cardiomyopathy

Abstract

Hypertrophic cardiomyopathy is the most common inherited heart disease. Although it was first described over 50 years ago, there has been little in the way of novel disease-specific therapeutic development for these patients. Current treatment practice largely aims at symptomatic control using old drugs made for other diseases and does little to modify the disease course. Septal reduction by surgical myectomy or percutaneous alcohol septal ablation are well-established treatments for pharmacologic-refractory left ventricular outflow tract obstruction in hypertrophic cardiomyopathy patients. In recent years, there has been a relative surge in the development of innovative therapeutics, which aim to target the complex molecular pathophysiology and resulting hemodynamics that underlie hypertrophic cardiomyopathy. Herein, we review the new and emerging therapeutics for hypertrophic cardiomyopathy, which include pharmacologic attenuation of sarcomeric calcium sensitivity, allosteric inhibition of cardiac myosin, myocardial metabolic modulation, and renin-angiotensin-aldosterone system inhibition, as well as structural intervention by percutaneous mitral valve plication and endocardial radiofrequency ablation of septal hypertrophy. In conclusion, while further development of these therapeutic strategies is ongoing, they each mark a significant and promising advancement in treatment for hypertrophic cardiomyopathy patients.

Transcriptomic Validation of the Protective Effects of Aqueous Bark Extract of Terminalia arjuna (Roxb.) on Isoproterenol-Induced Cardiac Hypertrophy in Rats

“…(Liu and Molkentin, 2016;Wang and Cai, 2017;Gibb and Hill, 2018;Sciarretta et al, 2018). While these signaling networks are highly interactive and complex, the categorical goal of pharmacological science is to target the nodal points and the effectors (Walters et al, 2016;Philipson et al, 2017).…”

Hypertrophic cardiomyopathy: modern aspects of pharmacologic treatment

“…Дизрегуляция в передаче сигнала по кальциевым каналам в миоците миокарда играет крайне важную роль в патофизиологии ГКМП: вносит свой вклад в развитие как диастолической дисфункции, так и аритмогенности, часто предшествует гипертрофии и началу симптомов у пациентов с ГКМП [25].…”

“…Использование дилтиазема в качестве агента, модифицирующего заболевание, может потенциально изменять аномальный внутриклеточный обмен ионов кальция и последующую экспрессию фенотипа ГКМП. Для дальнейшего изучения роли дилтиазема необходимы дополнительные клинические исследования [25].…”

“…De Pasquale и соавт. систематизированы современные экспериментальные стратегии медикаментозной терапии ГКМП [25]. Новейшие перспективные подходы для фармакологического воздействия отражены в табл.…”

Dysfunctional network and mutation genes of hypertrophic cardiomyopathy

“…In recent years, research on complex molecular pathophysiology of hypertrophic cardiomyopathy has increased rapidly (14). Gene testing has become more accessible and is increasingly being included in the care of patients with hypertrophic cardiomyopathy (15).…”