Cardiomyocyte Ca2+ homeostasis as a therapeutic target in heart failure with reduced and preserved ejection fraction

Abstract

Heart failure is a highly prevalent syndrome of multiple etiologies and associated comorbidities, and aberrant intracellular Ca²⁺ homeostasis is a hallmark finding in heart failure patients. The cyclical changes in Ca²⁺ concentration within cardiomyocytes control cycles of cardiac contraction and relaxation, and dysregulation of Ca²⁺ handling processes leads to systolic dysfunction, diastolic dysfunction, and adverse remodeling. For this reason, greater understanding of Ca²⁺ handling mechanisms in heart failure is critical for selection of appropriate treatment strategies. In this review, we summarize the mechanisms of altered Ca²⁺ handling in two subsets of heart failure, heart failure with reduced ejection fraction and heart failure with preserved ejection fraction, and outline current and experimental treatments that target cardiomyocyte Ca²⁺ handling processes.