Coronary Microvascular Rarefaction and Myocardial Fibrosis in Heart Failure With Preserved Ejection Fraction

TLDR

Myocardial structural changes in HFpEF are poorly characterized due to limited human tissue, but cardiac hypertrophy, CAD, microvascular rarefaction, and fibrosis are suspected contributors. The study used autopsy data from 124 HFpEF patients and 104 controls, measuring heart weight, CAD severity, and quantifying microvascular density and fibrosis in full‑thickness left‑ventricular sections with whole‑field digital microscopy and automated algorithms. HFpEF hearts were heavier, had more CAD, greater fibrosis, and lower microvascular density than controls; fibrosis correlated inversely with MVD, and adjusting for MVD reduced group differences, indicating that hypertrophy, CAD, microvascular rarefaction, and fibrosis collectively contribute to diastolic dysfunction.

Abstract

Characterization of myocardial structural changes in heart failure with preserved ejection fraction (HFpEF) has been hindered by the limited availability of human cardiac tissue. Cardiac hypertrophy, coronary artery disease (CAD), coronary microvascular rarefaction, and myocardial fibrosis may contribute to HFpEF pathophysiology.We identified HFpEF patients (n=124) and age-appropriate control subjects (noncardiac death, no heart failure diagnosis; n=104) who underwent autopsy. Heart weight and CAD severity were obtained from the autopsy reports. With the use of whole-field digital microscopy and automated analysis algorithms in full-thickness left ventricular sections, microvascular density (MVD), myocardial fibrosis, and their relationship were quantified. Subjects with HFpEF had heavier hearts (median, 538 g; 169% of age-, sex-, and body size-expected heart weight versus 335 g; 112% in controls), more severe CAD (65% with ≥1 vessel with >50% diameter stenosis in HFpEF versus 13% in controls), more left ventricular fibrosis (median % area fibrosis, 9.6 versus 7.1) and lower MVD (median 961 versus 1316 vessels/mm(2)) than control (P<0.0001 for all). Myocardial fibrosis increased with decreasing MVD in controls (r=-0.28, P=0.004) and HFpEF (r=-0.26, P=0.004). Adjusting for MVD attenuated the group differences in fibrosis. Heart weight, fibrosis, and MVD were similar in HFpEF patients with CAD versus without CAD.In this study, patients with HFpEF had more cardiac hypertrophy, epicardial CAD, coronary microvascular rarefaction, and myocardial fibrosis than controls. Each of these findings may contribute to the left ventricular diastolic dysfunction and cardiac reserve function impairment characteristic of HFpEF.