Hypertrophic cardiomyopathy dysfunction mimicked in human engineered heart tissue and improved by SGLT2 inhibitors.
Paul J M WijnkerRafeeh DinaniNico C van der LaanSila AlgülBjorn C KnollmannArjan C HouwelingCarol Ann RemmeCoert J ZuurbierDiederik W D KusterJolanda van der VeldenPublished in: Cardiovascular research (2024)
HCM is the most common inherited cardiomyopathy and treatment to prevent mutation-induced cardiac dysfunction is lacking. Early HCM characteristics are diastolic dysfunction and hypercontractility. We show in hiPSC-CM models that SGLT2i represent a potential therapy to correct cardiomyocyte dysfunction induced by HCM sarcomere mutations. SGLT2i acutely enhanced relaxation and altered Ca2+ handling in HCM hiPSC-CMs, targeting important early HCM disease hallmarks.