Background Recently, diastolic stress testing and invasive hemodynamic measurements have been emphasized for diagnosis of heart failure with preserved ejection fraction (HFpEF) because when determined using noninvasive parameters it can fall into a nondiagnostic intermediate range. The current study evaluated the discriminative and prognostic roles of invasive measured left ventricular end-diastolic pressure in the population with suspected HFpEF, particularly for patients with intermediate Heart Failure Association Pre-test Assessment, Echocardiography & Natriuretic Peptide, Functional Testing, Final Etiology (HFA-PEFF) score. Methods and Results A total of 404 patients with symptoms or signs of HF and preserved left ventricular systolic function were enrolled. All subjects underwent left heart catheterization with left ventricular end-diastolic pressure measurement for confirmation of HFpEF (≥16 mm Hg). The primary outcome was all-cause death or readmission due to HF within 10 years. Among the study population, 324 patients (80.2%) were diagnosed as invasively confirmed HFpEF, and 80 patients (19.8%) were as noncardiac dyspnea. The patients with HFpEF showed a significantly higher HFA-PEFF score than the patients with noncardiac dyspnea (3.8±1.8 versus 2.6±1.5, P<0.001). The discriminative ability of the HFA-PEFF score for diagnosing HFpEF was modest (area under the curve, 0.70 [95% CI, 0.64-0.75], P<0.001). The HFA-PEFF score was associated with a significantly higher 10-year risk of death or HF readmission (per-1 increase, hazard ratio [HR], 1.603 [95% CI, 1.376-1.868], P<0.001). Among the 226 patients with an intermediate HFA-PEFF score (2-4), those with invasively confirmed HFpEF had a significantly higher risk of death or HF readmission within 10 years than the patients with noncardiac dyspnea (24.0% versus 6.9%, HR, 3.327 [95% CI, 1.109-16.280], P=0.030). Conclusions The HFA-PEFF score is a moderately useful tool for predicting future adverse events in suspected HFpEF, and invasively measured left ventricular end-diastolic pressure can provide additional information to discriminate patient prognosis, particularly in those with intermediate HFA-PEFF scores. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04505449.

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