Untangling the pathophysiologic link between coronary microvascular dysfunction and heart failure with preserved ejection fraction

Coronary microvascular disease (CMD), characterized by impaired coronary flow reserve (CFR), is a common finding in patients with stable angina. Impaired CFR, in the absence of obstructive coronary artery disease, is also present in up to 75% of patients with heart failure with preserved ejection fraction (HFpEF). Heart failure with preserved ejection fraction is a heterogeneous syndrome comprising distinct endotypes and it has been hypothesized that CMD lies at the centre of the pathogenesis of one such entity: the CMD-HFpEF endotype. This article provides a contemporary review of the pathophysiology underlying CMD, with a focus on the mechanistic link between CMD and HFpEF. We discuss the central role played by subendocardial ischaemia and impaired lusitropy in the development of CMD-HFpEF, as well as the clinical and research implications of the CMD-HFpEF mechanistic link. Future prospective follow-up studies detailing outcomes in patients with CMD and HFpEF are much needed to enhance our understanding of the pathological processes driving these conditions, which may lead to the development of physiology-stratified therapy to improve the quality of life and prognosis in these patients.

Automated summary

CMD, characterized by impaired coronary flow reserve (CFR), plays a central role in the pathogenesis of HFpEF, involving subendocardial ischemia and impaired lusitropy. Future prospective follow-up studies are essential for a better understanding of these diseases and may lead to the development of tailored therapies to improve quality of life and prognosis in patients with CMD and HFpEF.