Diastolic Function in Heart Failure

Abstract

Heart failure has reached epidemic proportions, and diastolic heart failure or heart failure with preserved ejection fraction (HFpEF) constitutes about 50% of all heart failure admissions. Long-term prognosis of both reduced ejection fraction heart failure and HFpEF are similarly dismal. No pharmacologic agent has been developed that actually treats or repairs the physiologic deficit(s) responsible for HFpEF. Because the physiology of diastole is both subtle and counterintuitive, its role in heart failure has received insufficient attention. In this review, the focus is on the physiology of diastole in heart failure, the dominant physiologic laws that govern the process in all hearts, how all hearts work as a suction pump, and, therefore, the elucidation and characterization of what actually is meant by “diastolic function”. The intent is for the reader to understand what diastolic function actually is, what it is not, and how to measure it. Proper measurement of diastolic function requires one to go beyond the usual E/A, E/E′, etc. phenomenological metrics and employ more rigorous causality (mathematical modeling) based parameters of diastolic function. The method simultaneously provides new physiologic insight into the meaning of in vivo “equilibrium volume” of the left ventricle (LV), longitudinal versus transverse volume accommodation of the chamber, diastatic “ringing” of the mitral annulus, and the mechanism of L-wave generation, as well as availability of a load-independent index of diastolic function (LIIDF). One important consequence of understanding what diastolic function is, is the recognition that all that current therapies can do is basically alter the load, rather than actually “repair” the functional components (chamber stiffness, chamber relaxation). If beneficial (biological/structural/metabolic) remodeling due to therapy does manifest ultimately as improved diastolic function, it is due to resumption of normal physiology (as in alleviation of ischemia) or activation of compensatory pathways already devised by evolution. In summary, meaningful quantitative characterization of diastolic function in any clinical setting, including heart failure, requires metrics based on physiologic mechanisms that quantify the suction pump attribute of the heart. This requires advancing beyond phenomenological global indexes such as E/A, E/E′, Vp, etc. and employing causality (mathematical modeling) based parameters of diastolic function easily obtained via the parametrized diastolic function (PDF) formalism.