Letter by Nikolova et al Regarding Article, “Heart Failure With Preserved Ejection Fraction in Perspective”

Abstract

We would like to congratulate Pfeffer et al 1 for their excellent review of the current state of knowledge of the complex syndrome of heart failure with preserved ejection fraction (HFpEF). The authors provide a comprehensive historical and epidemiological perspective on the evolution in our understanding of this syndrome. However, we would like to point out that there is a fundamental pathophysiological process supported by animal and human data that should be included when considering this disorder. In particular, the authors discuss the importance of calcium homeostatic changes as a major contributor to the development of diastolic relaxation abnormalities and myocardial stiffness. A major component of pathological calcium homeostasis is remodeling of the transverse tubule (TT) network. TTs are richly folded membrane structures in cardiomyocytes, which harbor calcium (Ca 2+) signaling microdomains. 2-4 Synchrony of Ca 2+ transients and excitation-contraction coupling are dependent on the maintenance of the precise architectural organization of theses Ca 2+ microdomains, which are disrupted in HFpEF. 5-7 Disclosures None.