[Skip to Content]
[Skip to Content Landing]

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

Educational Objective
To describe key aspects of coronary physiological testing and the role of coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) in heart failure with preserved ejection fraction (HFpEF).
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.

Abstract

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.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 Credit(s)™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: February 15, 2021.

Published Online: June 23, 2021. doi:10.1001/jamacardio.2021.1825

Corresponding Author: John J. V. McMurray, MB, ChB, MD, British Heart Foundation Cardiovascular Research Centre, University of Glasgow, 126 University Pl, Glasgow G12 8TA, United Kingdom (john.mcmurray@glasgow.ac.uk).

Author Contributions: Dr Rush had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Rush, Berry, Murphy, Lang, Jhund, Campbell, McMurray, Petrie.

Acquisition, analysis, or interpretation of data: Rush, Berry, Oldroyd, Rocchiccioli, Lindsay, Touyz, Murphy, Ford, Sidik, McEntegart, Lang, McMurray, Petrie.

Drafting of the manuscript: Rush, Berry, Murphy, McMurray, Petrie.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Rush, Ford, Jhund.

Obtained funding: Rush, Touyz, Petrie.

Administrative, technical, or material support: Berry, Rocchiccioli, Lindsay, Ford, Sidik, Lang, Petrie.

Supervision: Berry, Oldroyd, Rocchiccioli, Murphy, Ford, McEntegart, Lang, Jhund, Campbell, McMurray, Petrie.

Conflict of Interest Disclosures: Dr Berry reported receiving grants from the Chief Scientist Office of the Scottish government as a coapplicant during the conduct of the study; grants from Abbott Vascular, AstraZeneca, GSK, Novartis, and HeartFlow to the University of Glasgow, which holds research and consultancy agreements with these companies for work outside the summitted research; nonfinancial support from Coroventis and Siemens to the University of Glasgow, which holds research and consultancy agreements with these companies for work outside the submitted research; and the British Heart Foundation and Chief Scientist Office research grants. Dr Oldroyd reported receiving personal fees from Abbott Vascular during the conduct of the study and personal fees from Abbott Vascular outside the submitted work. Dr Touyz reported receiving personal fees from Novartis Consultancy and a British Heart Foundation grant and personal chair outside the submitted work. Dr Murphy reported receiving grants from the Chief Scientist Office during the conduct of the study; other from Novartis Travel, accommodation and registration costs received for an international conference; a research and innovation grant from AstraZeneca, and grants from Heart Research UK outside the submitted work. Dr Ford reported receiving personal fees from Abbott Vascular outside the submitted work. Dr Lang reported receiving speakers’ fees from AstraZeneca; advisory board fees from Vifor Pharma; speakers’ fees from Novartis; and speakers’ fees from Roche outside the submitted work. Dr Jhund reported receiving fees from AstraZeneca to the University of Glasgow has been for working on the DAPA-HF and DELIVER trials and Novartis for working on the PARADIGM-HF and PARAGON-HF trials; grants from Boehringer Ingelheim; advisory board fees from Boehringer Ingelheim; and advisory board and speakers’ fees from Novartis and AstraZeneca outside the submitted work. Dr McMurray reported receiving nonfinancial support from AstraZeneca as principal investigator. Glasgow University has been paid by AstraZeneca (which markets dapagliflozin) for time spent as principal investigator of DAPA-HF and co-principal investigator of DELIVER (trials using dapagliflozin) in heart failure and meetings related to the trial, as an executive committee member for the DETERMINE and PRIORITIZE trials, and as an advisory board member for the AZD9977 trial. AstraZeneca has also paid travel and accommodation for these meetings, and these payments were made through a consultancy with Glasgow University and Dr McMurray did not receive personal payments in relation to this trial/this drug; nonfinancial support from Bayer, with payment to Glasgow University for time spent as a steering committee member for the FINEARTS-HF trial (using finerenone in heart failure), and Dr McMurray did not receive personal payments in relation to this trial/drug; nonfinancial support from Amgen, with Glasgow University paid by Amgen for time spent as steering committee member for the GALACTIC-HF trial and meetings related to this trial. Amgen also paid travel and accommodation fees for some of these meetings. These payments were made through a consultancy with Glasgow University, and Dr McMurray did not receive personal payments in relation to these trials/this drug; nonfinancial support from Oxford University/Bayer, with Glasgow University paid by Oxford University (who has received a grant from Bayer who manufactures acarbose) for time spent as steering committee member for the ACE trial (using acarbose) and meetings related to this trial. Oxford University also paid travel and accommodation for some of these meetings, with payments made through a consultancy with Glasgow University, and Dr McMurray did not receive personal payments in relation to this trial/this drug; nonfinancial support from Theracos, with Glasgow University paid by Theracos for time spent as principal investigator for the BEST trial and meetings related to this trial; Theracos has also paid travel and accommodations for some of these meetings, with payments made through a consultancy with Glasgow University, and Dr McMurray did not receive personal payments in relation to this trial/this drug; nonfinancial support from DalCor Pharmaceuticals, with payment to Glasgow University for time spent as steering committee member for the Dal-GenE trial and meetings related to this trial, with payments made through a consultancy with Glasgow University, and Dr McMurray did not receive personal payments in relation to this trial/this drug; nonfinancial support from Merck, with payment to Glasgow University for time spent on the data safety monitoring committee for the MK-3102 program and for the VICTORIA trial and meetings related to these trials, with payments made through a consultancy with Glasgow University, and Dr McMurray did not receive personal payments in relation to this trial/this drug; nonfinancial support from GlaxoSmithKline, with payment to Glasgow University for time spent as coprincipal investigator and steering committee member for the Harmony-Outcomes trial (albiglutide) and 2 trials, ASCEND-D and ASCEND-ND, using daprodustat, and meetings related to these trials, and GlaxoSmithKline also paid travel and accommodations for some of these meetings, with payments made through a consultancy with Glasgow University, and Dr McMurray did not receive personal payments in relation to these trials/drugs; payment from Bristol Myers Squibb to Glasgow University for time spent as a steering committee member for the STAND-UP clinical trial (using an HNO donor) in heart failure and meetings related to this trial, with payments made through a consultancy with Glasgow University, and Dr McMurray did not receive personal payments in relation to this trial/this drug; nonfinancial support, with payment from Vifor-Fresenius to Glasgow University paid by Kings College Hospital (who received a grant from KRUK and Vifor-Fresenius who manufacture intravenous iron) for time spent as steering committee member for the PIVOTAL trial (using intravenous iron) and for running the end point adjudication committee for this trial, as well as meetings related to PIVOTAL. Kings College Hospital also paid for travel and accommodations for some of these meetings with payments made through a consultancy with Glasgow University, and Dr McMurray did not receive personal payments in relation to this trial/this drug; nonfinancial support from Kidney Research UK (KRUK) with payment made to Glasgow University by Kings College Hospital (who received a grant from KRUK and Vifor-Fresenius who manufactures intravenous iron) for time spent as a steering committee member for the PIVOTAL trial (using intravenous iron) and for running the end point adjudication committee for this trial, as well as meetings related to the PIVOTAL trial, with Kings College Hospital also paying for travel and accommodations for some of these meetings through a consultancy with Glasgow University, and Dr McMurray did not receive personal payments in relation to this trial/this drug; payment from Alnylam to Glasgow University for time spent on the advisory board committee for the ALN-AGT trial and meetings related to this trial, with payments made through a consultancy with Glasgow University, and Dr McMurray did not receive personal payments in relation to this trial/this drug; nonfinancial support from AbbVie, with Glasgow University paid by AbbVie (who manufactures atrasentan) for time spent as a steering committee member for the SONAR trial (using atrasentan) and meetings related to this trial, with AbbVie also paying for travel and accommodations for some of these meetings and payments made through a consultancy with Glasgow University, and Dr McMurray did not receive personal payments in relation to this trial/this drug; payment for advice about development of praliciguat as a potential therapy for heart failure from Cyclerion to Glasgow University, has been paid by Cyclerion, other from Cardurion My employer, Glasgow University, has been paid by Cardurion for participation in a company advisory board about development of a PDE 9 inhibitor in heart failure; has received nonfinancial support from Novartis, who paid Glasgow University for time spent as an executive committee member and then coprincipal investigator of ATMOSPHERE, coprincipal investigator of the PARADIGM-HF trial, and executive/steering committee member for PARACHUTE-HF, PARADISE-MI, and PERSPECTIVE trials (with sacubitril/valsartan), and meetings/presentations related to these trials and aliskiren and sacubitril/valsartan, including payment for travel and accommodations for some of these meetings through a consultancy with Glasgow University, and Dr McMurray did not received personal payments in relation to these trials/drugs; Glasgow University has also been paid by Novartis for Dr McMurray’s participation in a company advisory board that meets twice per year and covers the cardiometabolic field; nonfinancial support from Servier, with payment to Glasgow University for activities related to role as steering committee member for the GALACTIC-HF trial through a consultancy with Glasgow University, and Dr McMurray did not receive personal payments in relation to these trials/this drug; and lecture fees from Abbott, Hickma, Sun Pharmaceuticals, and Servier outside the submitted work. No other disclosures were reported.

Funding/Support: This project was funded by the Chief Scientist Office of the Scottish government, reference TCS/16/25.

Role of the Funder/Sponsor: The funding organization had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 credit toward the CME [and Self-Assessment requirements] of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Close
Close

Lookup An Activity

or

My Saved Searches

You currently have no searches saved.

Close

My Saved Courses

You currently have no courses saved.

Close