Implications of Potential Undiagnosed HFpEF on Symptomatic Response With Coronary Revascularization.

BACKGROUND

Although patients with heart failure with preserved ejection fraction (HFpEF) have poor quality of life (QoL) and a high coronary artery disease (CAD) burden, there remains limited evidence guiding revascularization in these patients, in part related to complexity in diagnosis.

OBJECTIVES

This study aims to determine the prevalence of likely undiagnosed HFpEF in patients with CAD and a positive stress test result, as well as its therapeutic interaction with an invasive strategy on QoL.

METHODS

Patients without known heart failure (HF) from the ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial were stratified by the Rose Dyspnea Scale questionnaire and HFpEF-ABA (heart failure with preserved ejection fraction algorithm using age, body mass index, and history of atrial fibrillation) probability into 3 groups: 1) probable HFpEF (dyspnea and HFpEF-ABA ≥75%); 2) possible HFpEF (dyspnea and HFpEF-ABA <75%); and 3) no HFpEF (no dyspnea). The effect of an invasive strategy on health status was determined using mixed models. The study independently tested the prevalence of HFpEF by using exercise right-sided heart catheterization in a validation cohort of patients with dyspnea, stress testing, and angiography.

RESULTS

Among 4,986 participants, 53.4% had dyspnea and were at risk for HFpEF: 9.0% (n = 450) with probable HFpEF and 44.4% (n = 2,213) with possible HFpEF. Patients in the probable HFpEF group had the worst exercise capacity, angina, dyspnea, and QoL, despite having less obstructive CAD (P < 0.0001 for all). An invasive strategy improved Rose Dyspnea Scale, SAQ (Seattle Angina Questionnaire) QoL, and Euro-QoL-5D results consistently across the 3 groups (P = 0.009; P < 0.0001, and P = 0.05, respectively; interaction P > 0.20 for all), with greater benefits on physical limitation and angina in the probable HFpEF group (SAQ Summary, SAQ Physical Limitation, and SAQ Angina Frequency score interaction P = 0.01; P = 0.01, and P = 0.08, respectively). The probable HFpEF group demonstrated an increased risk of HF hospitalization (HR: 7.2 [95% CI: 3.7-13.8]; P < 0.0001) vs no HFpEF (HR: 5.0 [95% CI: 2.7-9.0]; P < 0.0001) vs possible HFpEF), but an invasive strategy did not mitigate this risk (HR: 1.5 [95% CI: 0.7-3.5]; P = 0.34). In the validation cohort (n = 237), of those patients with positive stress test results and dyspnea, 85% had HFpEF, and 68% of these patients had elevated left-sided heart filling pressures even at rest.

CONCLUSIONS

More than one-half of patients with CAD and ischemia have dyspnea, with a high risk of undiagnosed HFpEF in one-tenth of these patients. In this study, patients with a high HFpEF probability had the greatest risk for HF hospitalization, the poorest exercise tolerance, and the most severe symptoms, and they derived the greatest benefit from an invasive strategy for physical limitation and angina. However, despite these improvements, residual dyspnea, QoL impairments, and elevated HF hospitalization risk persisted after revascularization. These data suggest a potential role for independent evaluation of coexisting HFpEF in patients with CAD and dyspnea.