The prognostic value of cardiopulmonary exercise testing and HFA-PEFF in patients with unexplained dyspnea and preserved left ventricular ejection fraction

Background: HFA-PEFF and cardiopulmonary exercise testing (CPET) are comprehensive diagnostic tools for heart failure with preserved ejection fraction (HFpEF). We aimed to investigate the incremental prognostic value of CPET for the HFA-PEFF score among patients with unexplained dyspnea with preserved ejection fraction (EF). Methods: Consecutive patients with dyspnea and preserved EF (n = 292) were enrolled between August 2019 and July 2021. All patients underwent CPET and comprehensive echocardiography, including two-dimensional speckle tracking echocardiography in the left ventricle, left atrium and right ventricle. The primary outcome was defined as a composite cardiovascular event including cardiovascular-related mortality, acute recurrent heart failure hospitalization, urgent repeat revascularization/myocardial infarction or any hospitalization due to cardiovascular events. Results: The mean age was 58 ± 14.5 years, and 166 (56.8%) participants were male. The study population was divided into three groups based on the HFA-PEFF score: < 2 (n = 81), 2–4 (n = 159), and ≥ 5 (n = 52). HFA-PEFF score ≥ 5, VE/VCO₂ slope, peak systolic strain rate of the left atrium and resting diastolic blood pressure were independently associated with composite cardiovascular events. Furthermore, the addition of VE/VCO₂ and HFA-PEFF to the base model showed incremental prognostic value for predicting composite cardiovascular events (C-statistic 0.898; integrated discrimination improvement 0.129, p = 0.032; net reclassification improvement 1.043, p ≤ 0.001). Conclusions: CPET could be exploited for the HFA-PEFF approach in terms of incremental prognostic value and diagnosis among patients with unexplained dyspnea with preserved EF.