Assessment of Coronary Flow Reserve in a Mouse Model of Heart Failure with Preserved Ejection Fraction Using Doppler Echocardiography.

Abstract

Heart failure with preserved ejection fraction (HFpEF) constitutes a considerable global health burden and a major clinical challenge due to the absence of effective therapies, and the underlying pathophysiology remains elusive. Coronary microvascular dysfunction (CMD), which is highly prevalent in patients with HFpEF, triggers myocardial ischemia that impairs both left ventricular diastolic and systolic function. Given that microvascular dysfunction is a central feature of HFpEF, CMD is now considered an important factor in its pathogenesis. Coronary flow reserve (CFR), defined as the ratio of maximal hyperemic to resting blood flow velocity, is a highly valuable marker of myocardial ischemia. Furthermore, it serves as a comprehensive indicator of coronary vasomotor dysfunction, measuring the combined hemodynamic effects of both epicardial and microvascular coronary arteries on myocardial perfusion. This protocol focused on assessing the changes in CFR in a mouse model of HFpEF using Doppler echocardiography. In this study, control mice showed a greater than twofold increase in peak coronary blood flow velocity with isoflurane-induced vasodilation compared to resting values, whereas this response was significantly attenuated in HFpEF mice. In HFpEF, a reduced CFR predicts adverse outcomes and reflects underlying microvascular dysfunction, positioning it as a key tool for studying disease progression and guiding patient selection.