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Original Investigation
June 23, 2021

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

Author Affiliations
  • 1British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
  • 2Golden Jubilee National Hospital, Clydebank, United Kingdom
  • 3Royal Alexandra Hospital, Paisley, United Kingdom
JAMA Cardiol. Published online June 23, 2021. doi:10.1001/jamacardio.2021.1825
Key Points

Question  What is the prevalence of obstructive epicardial coronary artery disease and coronary microvascular dysfunction in hospitalized patients with heart failure with preserved ejection fraction?

Findings  In a cohort study, 106 consecutive participants with preserved ejection fraction were evaluated with coronary angiography, invasive coronary physiologic and vasoreactivity testing, and cardiac magnetic resonance imaging. A total of 51% of the study participants had obstructive epicardial coronary artery disease, 66% had endothelium-independent coronary microvascular dysfunction, and 24% had endothelium-dependent coronary microvascular dysfunction.

Meaning  The findings of this study suggest that obstructive epicardial coronary artery disease and coronary microvascular dysfunction are common and often unrecognized in hospitalized patients with heart failure with preserved ejection fraction and may be therapeutic targets.


Importance  Coronary 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 Participants  A 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 Measures  The prevalence of obstructive epicardial CAD, CMD, and myocardial ischemia, infarction, and fibrosis.

Results  Of 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 ≥25) 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 Relevance  In 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.

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