Obstructive epicardial coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) are common—-but most likely unrecognized—in patients hospitalized with heart failure with preserved ejection fraction (HFpEF), according to results from a recent study. In fact, researchers found that 91% of these patients had either CAD, CMD, or both, and nearly all of those without obstructive CAD had CMD.
“Myocardial ischemia due to epicardial CAD, CMD, or both, may represent a disease mechanism and therapeutic target in some patients with HFpEF,” wrote Christopher J. Rush, MB, ChB, PhD, and colleagues in JAMA Cardiology. “…to our knowledge, the prevalence of epicardial CAD, CMD, and coronary endothelial dysfunction have not been systematically studied in patients with HFpEF. We performed comprehensive invasive and noninvasive assessments of epicardial and microvascular function to evaluate the prevalence of CAD, CMD, and coronary endothelial dysfunction in prospectively recruited hospitalized patients with HFpEF.”
In this prospective, multicenter study, they enrolled 106 patients (mean age: 72 years; 50% women) who had been hospitalized with HFpEF. In all, 75 patients underwent coronary angiography, 62 had an assessment of coronary microvascular function, and 41 underwent coronary vasoreactivity testing, and 52 cardiac MRI.
Obstructive epicardial CAD was seen in 38 of 75 patients (51%) who underwent coronary angiography; 53% had 1-vessel, 34% 2-vessel, and 13% 3-vessel disease. Nineteen of these 38 patients (50%) had no history of CAD. Patients with obstructive CAD were more often men and more likely to have a history of CAD, MI, coronary revascularization, and chronic kidney disease compared with those without obstructive disease. They also tended to have higher estimated left ventricular filling pressures and less likely to have mild-to-moderate valve disease.
Endothelium-independent CMD was found in 41 of the 62 patients (66%) who underwent coronary microvascular functional assessment. This was defined as coronary flow reserve <2.0 and/or index of microvascular resistance ≥25. CMD prevalence was similar in those with obstructive CAD and those without (62% versus 69%). Any CMD—endothelium independent or dependent—occurred in 45 of 53 patients (85%), and in 29 of 36 patients (81%) without obstructive epicardial CAD.
Twenty-nine of the 41 patients undergoing coronary vasoreactivity testing (71%) had impaired global myocardial perfusion, and 14 of 46 patients had visual perfusion defects (30%).
Among the 52 patients who underwent late gadolinium enhancement (LGE) multiparametric cardiac magnetic resonance imaging (CMRI), 14 (27%) had subendocardial or transmural LGE in coronary artery regions consistent with previous myocardial infarction. Eight of these patients had no clinical history of myocardial infarction.
During follow-up, significantly more patients with obstructive CAD had more adverse events compared with those without obstructive CAD (74% versus 46%, respectively).
“In this exploratory analysis, we found that patients with obstructive epicardial CAD had higher rates of adverse clinical outcomes than those without obstructive disease, predominantly related to hospitalizations, although there were few events overall. To our knowledge, the most appropriate medical therapy and the potential role of revascularization in HFpEF have never been investigated in randomized clinical trials,” wrote Rush and colleagues.
“CMD is emerging as an important entity in the evaluation of patients with suspected ischemic myocardial syndromes. Observational data suggest that CMD is associated with increased risk of major adverse cardiovascular events, including HFpEF, in a manner that is independent of conventional risk factors and ischemic or atherosclerotic disease burden and mediated by the presence of myocardial injury and left ventricular (LV) diastolic dysfunction,” wrote Viviany R. Taqueti, MD, MPH, of Brigham and Women’s Hospital, Harvard Medical School, Boston, in an accompanying editorial.
After noting some of the limitations of the study from Rush et al, Taqueti added that “the suggestion that invasive angiography may be necessary to diagnose CAD in patients with HFpEF should be taken with caution, because many alternative noninvasive testing modalities for detection of flow-limiting CAD are widely available.”
Study limitations include the exclusion of most hospitalized HFpEF patients due to their failure to meet inclusion criteria or agree to participate, that all study procedures were not completed by all enrolled patients, delays between study recruitment and coronary assessments, and failure to adjudicate clinical outcomes.
“Despite these limitations, and taking care not to overinterpret the study results, these are welcome and much-needed supportive data in 2 key clinical cardiovascular areas (HFpEF and CMD) that have proven both diagnostically and therapeutically challenging. The authors are to be commended for their bold study design bringing together emerging invasive and noninvasive tools to probe the unrecognized outsize role of the coronary microcirculation,” Taqueti concluded.
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Obstructive epicardial coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) are common and often unrecognized in hospitalized patients with heart failure with preserved ejection fraction (HFpEF) and may be therapeutic targets.
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A full 91% of hospitalized HFpEF patients had either CAD, CMD, or both.
Liz Meszaros, Deputy Managing Editor, BreakingMED™
This project was funded by the Chief Scientist Office of the Scottish government.
Rush and Taqueti reported no disclosures.
Cat ID: 3
Topic ID: 74,3,730,3,192,925
