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

Abstract

Background Characterization of myocardial structural changes in heart failure (HF) with preserved ejection fraction (HFpEF) has been hindered by limited availability of human cardiac tissue. Cardiac hypertrophy, coronary artery disease (CAD), coronary microvascular rarefaction and myocardial fibrosis may contribute to HFpEF pathophysiology. Methods and Results We identified HFpEF patients (n=124) and age-appropriate control patients (non-cardiac death, no HF diagnosis; n=104) who underwent autopsy. Heart weight and CAD severity were obtained from the autopsy reports. Using whole field digital microscopy and automated analysis algorithms in full thickness left ventricular (LV) sections, microvascular density (MVD), myocardial fibrosis and their relationship were quantified. Subjects with HFpEF had heavier hearts (median 538 g; 169% of age/sex/body size expected heart weight vs. 335 g; 112% in controls), more severe CAD (65% with ≥ one vessel with >50% diameter stenosis in HFpEF vs 13% in controls), more LV fibrosis (median % area fibrosis, 9.6 vs. 7.1) and lower MVD (median 961 vs. 1316 vessels per mm2) 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 vs without CAD. Conclusions 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 LV diastolic dysfunction and cardiac reserve function impairment characteristic of HFpEF.

Clinical Phenotypes in Heart Failure With Preserved Ejection Fraction

“…Coronary microvascular rarefaction was found to correlate with the ante mortem severity of LVH and diastolic dysfunction, as assessed by Doppler echocardiography 205. Whether coronary microvascular rarefaction and LV dyssynchrony are related in patients with HFpEF and narrow QRS has not been investigated 206.…”

EPA, not DHA, prevents fibrosis in pressure overload-induced heart failure: potential role of free fatty acid receptor 4

“…In that regard, the lower overall levels of 3-PUFA uptake, particularly prior to surgery (8 weeks prior to surgery previously, only 2 weeks in this study) might explain the inability to prevent contractile dysfunction in this study. In addition, a recent report examining pathology in human HFpEF indicated that while fi brosis was significantly increased in HFpEF patients, fi brosis alone could not account for systolic and diastolic dysfunction in HF, and other parameters contribute to contractile dysfunction ( 29 ). levels of 3-PUFAs (supplementary Table 2).…”

Impaired Myocardial Sympathetic Innervation Is Associated with Diastolic Dysfunction in Heart Failure with Preserved Ejection Fraction: 11C-Hydroxyephedrine PET Study

“…Therefore, both global and regional impairment of sympathetic innervation may reflect heterogeneous microvascular dysfunction in HFpEF. In fact, HFpEF patients showed more severe cardiac hypertrophy and coronary microvascular rarefaction than control subjects in an autopsy study (25). It is possible that microvascular dysfunction may cause heterogeneous reduction in myocardial sympathetic innervation and diastolic dysfunction.…”