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

•Heart failure is subclassified based on reduced or preserved ejection fraction.•Treatments targeting cardiomyocyte Ca2+ homeostasis are effective in HFrEF.•Half of all heart failure patients are diagnosed with HFpEF.•Phamacological treatment of HFpEF is largely ineffective.

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.