1. In this cohort study, 91% of patients with preserved ejection fraction heart failure had evidence of epicardial coronary artery disease and/or coronary microvascular dysfunction.
2. Due to the high prevalence of these conditions, coronary artery disease and coronary microvascular dysfunction may be unrecognized and underdiagnosed in patients hospitalized with heart failure with preserved ejection fraction and serve as important therapeutic targets.
Evidence Rating Level: 2 (Good)
Study Rundown: Coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) may represent a pathophysiologic mechanism and therapeutic target in patients with heart failure with preserved ejection fraction (HFpEF). However, the prevalence of epicardial CAD, CMD, and coronary endothelial dysfunction among patients with HFpEF is largely unknown. This prospective cohort study used comprehensive invasive and noninvasive assessments of epicardial and microvascular function to assess the prevalence of CAD, CMD, and coronary endothelial dysfunction in hospitalized patients with HFpEF. The main outcome and measure of the analysis was the prevalence of obstructive epicardial CAD, CMD, and myocardial ischemia, infarction, and fibrosis among the cohort. Comprehensive patient assessment was completed via coronary angiography, invasive coronary physiologic and vasoreactivity testing, and cardiac magnetic resonance imaging (CMRI). Among 106 prospectively recruited hospitalized patients with HFpEF, 51% (38 of 75 participants) had obstructive epicardial CAD, 66% (41 of 62) had endothelium-independent CMD, and 24% (10 of 41) had endothelium-dependent CMD. These results suggest that obstructive epicardial CAD and/or CMD are prevalent in patients with HFpEF and often go unrecognized in hospital. Thus, therapeutic targeting of this patient population may be beneficial for mortality and lead to better clinical outcomes and quality of life. A limitation of this study was that not all enrolled patients underwent the planned procedures as part of the comprehensive assessment. Several patients dropped out prior to invasive and noninvasive assessments while a decision was made to exclude severely frail patients from invasive investigations due to risks of the procedure. This limited the study’s ability to compare coronary evaluation modalities across patient cohorts and the overall generalizability of the study results.
Relevant Reading: A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation
In-Depth [prospective cohort]: In this multicenter, prospective cohort study, 106 consecutive patients (53 [50%] women; mean [SD] age, 72  years) hospitalized with HFpEF were enrolled and assessed between January 2017 and August 2018 with data analysis completed in September 2019. As part of the comprehensive assessment, 75 patients had coronary angiography, 62 received assessment of coronary microvascular function, 41 underwent coronary vasoreactivity testing (via intracoronary infusions of acetylcholine), and 52 received CMRI. Obstructive epicardial CAD was present in 38 of 75 participants (51%, 95%CI, 39%-62%) with 19 of the 38 patients (50%; 95%CI, 34%-66%) never having had a history of CAD. Endothelium-independent CMD (where coronary flow reserve <2.0 and/or index of microvascular resistance ≥25) was present in 41 of 62 participants (66%; 95%CI, 53%-77%) while endothelium-dependent CMD (abnormal coronary vasoreactivity) was identified in 10 of 41 participants (24%; 95%CI, 13%-40%). In total, CMD was evident in 45 of 53 participants (85%; 95%CI, 72%-92%) while 29 of 36 participants (81%; 95%CI, 64%-91%) without obstructive epicardial CAD had CMD. On CMRI, 29 of 41 patients (71%; 95%CI, 54%-83%) had a myocardial-perfusion reserve index less than or equal to 1.84 (impaired global myocardial perfusion), 14 of 46 patients (30%; 95%CI, 19%-46%) presented visual perfusion defects, 14 of 52 patients (27%; 95%CI, 16%-41%) presented ischemic late gadolinium enhancement (myocardial infarction), and 20 of 48 patients (42%; 95%CI, 28%-56%) had extracellular volume greater than 30% (diffuse myocardial fibrosis). Lastly, patients with obstructive CAD presented with more adverse events during follow-up (28 [74%]) than those without (17 [46%]).
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