Prevalence of Coronary Artery Disease and Coronary Microvascular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction

Abstract

IMPORTANCECoronary artery disease (CAD) and coronary microvascular dysfunction (CMD) may contribute to the pathophysiologic characteristics of heart failure with preserved ejection fraction (HFpEF). However, the prevalence of CAD and CMD have not been systematically studied.OBJECTIVE To examine the prevalence of CAD and CMD in hospitalized patients with HFpEF. DESIGN, SETTING, AND PARTICIPANTSA total of 106 consecutive patients hospitalized with HFpEF were evaluated in this prospective, multicenter, cohort study conducted between January 2, 2017, and August 1, 2018; data analysis was performed from March 4 to September 6, 2019. Participants underwent coronary angiography with guidewire-based assessment of coronary flow reserve, index of microvascular resistance, and fractional flow reserve, followed by coronary vasoreactivity testing. Cardiac magnetic resonance imaging was performed with late gadolinium enhancement and assessment of extracellular volume. Myocardial perfusion was assessed qualitatively and semiquantitatively using the myocardial-perfusion reserve index. MAIN OUTCOMES AND MEASURESThe prevalence of obstructive epicardial CAD, CMD, and myocardial ischemia, infarction, and fibrosis. RESULTSOf 106 participants enrolled (53 [50%] women; mean [SD] age, 72 [9] years), 75 had coronary angiography, 62 had assessment of coronary microvascular function, 41 underwent coronary vasoreactivity testing, and 52 received cardiac magnetic resonance imaging. Obstructive epicardial CAD was present in 38 of 75 participants (51%, 95% CI, 39%-62%); 19 of 38 (50%; 95% CI, 34%-66%) had no history of CAD. Endothelium-independent CMD (ie, coronary flow reserve <2.0 and/or index of microvascular resistance Ն25) was identified in 41 of 62 participants (66%; 95% CI, 53%-77%). Endothelium-dependent CMD (ie, abnormal coronary vasoreactivity) was identified in 10 of 41 participants (24%; 95% CI, 13%-40%). Overall, 45 of 53 participants (85%; 95% CI, 72%-92%) had evidence of CMD and 29 of 36 (81%; 95% CI, 64%-91%) of those without obstructive epicardial CAD had CMD. Cardiac magnetic resonance imaging findings included myocardial-perfusion reserve index less than or equal to 1.84 (ie, impaired global myocardial perfusion) in 29 of 41 patients (71%; 95% CI, 54%-83%), visual perfusion defect in 14 of 46 patients (30%; 95% CI, 19%-46%), ischemic late gadolinium enhancement (ie, myocardial infarction) in 14 of 52 patients (27%; 95% CI, 16%-41%), and extracellular volume greater than 30% (ie, diffuse myocardial fibrosis) in 20 of 48 patients (42%; 95% CI, 28%-56%). Patients with obstructive CAD had more adverse events during follow-up (28 [74%]) than those without obstructive CAD (17 [46%]). CONCLUSIONS AND RELEVANCEIn this cohort study, 91% of patients with HFpEF had evidence of epicardial CAD, CMD, or both. Of those without obstructive CAD, 81% had CMD. Obstructive epicardial CAD and CMD appear to be common and often unrecognized in hospitalized patients with HFpEF and may be therapeutic targets.

Aetiological classification and prognosis in patients with heart failure with preserved ejection fraction

“…Various researchers have proposed ischaemic HFpEF as a distinct entity. 19 , 20 Shah et al . proposed that abnormalities in coronary microcirculation can support the occurrence of HFpEF in some patients, 21 but there is currently no routine evaluation of microvascular dysfunction in HFpEF patients.…”

“…Recent studies have suggested a high prevalence of coronary microvascular dysfunction in HFpEF patients. 19 Whether abnormal coronary microcirculation occurs in almost all HFpEF patients with evidence of macroscopic CAD deserves further investigations.…”

Predominance of Heart Failure With Preserved Ejection Fraction in Postmenopausal Women: Intra- and Extra-Cardiomyocyte Maladaptive Alterations Scaffolded by Estrogen Deficiency

“…Their expression is characteristic of decreased eNOS activity and NO bioavailability. This encourages the recruitment and trafficking of circulating leukocytes to the subendothelial, which initiates the formation of atherosclerotic lesions formation and the progression of atherosclerosis which hastens the incidence of HFpEF ( Venugopal et al, 2002 ; Kolluru et al, 2010 ; Westermann et al, 2011 ; Rush et al, 2021 ). These aforementioned CME dysfunctionalities have been associated with E2 deficiency.…”

Vasomotor Dysfunction in Patients with Ischemia and Non-Obstructive Coronary Artery Disease: Current Diagnostic and Therapeutic Strategies

“…Apart from vascular events, several studies have shown evidence of CMD in patients with heart failure with preserved ejection fraction (HFpEF), such that it might be a key pathophysiologic player [ 111 , 112 , 113 , 114 , 115 , 116 , 117 ]. Moreover, in patients without flow-limiting epicardial CAD, impaired CFR was independently associated with diastolic dysfunction and adverse events [ 118 , 119 ].…”