BACKGROUND AND AIMS: Echocardiographic grading of left ventricular diastolic function is recommended to guide diagnostic evaluation of heart failure with preserved ejection fraction (HFpEF). A new algorithm for diastolic function interpretation has been proposed, but it has not yet been systematically evaluated in HFpEF.
Objectives: To determine the false-negative rate of the 2025 ASE algorithm among invasively confirmed ambulatory HFpEF, assess temporal changes in diastolic grades between decompensated and recompensated hospitalized HFpEF, and, secondarily, to compare diagnostic discrimination with existing HFpEF algorithms and prognostic associations.
METHODS: Echocardiography was performed in two HFpEF cohorts: (1) ambulatory, compensated patients undergoing invasive hemodynamic exercise testing as part of a prospective cohort study, with an external validation cohort, and (2) hospitalized/decompensated patients both acutely and following recompensation. For secondary analyses, we included non-cardiac dyspnea controls and compared performance with existing algorithms.
RESULTS: In the ambulatory/compensated HFpEF cohort, 248/756 (32.8%) were graded normal, 263/756 (34.8%) Grade 1 diastolic dysfunction, 219/756 (30.0%) Grades 2-3, and 26/756 (3.4%) indeterminate. Among those labeled normal or Grade 1, >60% had resting pulmonary artery wedge pressure ≥15 mmHg at catheterization. In decompensated HFpEF, 22/88 (25.0%) showed normal or Grade 1, and this proportion increased to 45/88 (51.1%) after recompensation. In HFpEF with Grade 1 undergoing simultaneous hemodynamic exercise testing with stress imaging, only 11/116 (9.5%) met the ASE-recommended stress criteria, resulting in a 90.5% false-negative rate. Similar findings were observed in the external validation cohort. The 2025 ASE algorithm poorly discriminated HFpEF from non-cardiac dyspnea (AUC 0.61). Patients with HFpEF labeled as normal or Grade 1 had 5-fold higher risk for all-cause death or heart failure hospitalization compared with controls (HR 5.37, 95% CI 1.27-22.6).
CONCLUSIONS: Among patients with invasively-proven HFpEF, the 2025 ASE algorithm frequently assigns normal or low diastolic grades, and the recommended stress criteria detect only a minority of cases. While echocardiography remains essential to guide HFpEF evaluation, current algorithms proposed to inform its interpretation have inadequate sensitivity. Diastolic function grades must be interpreted in the context of pre-test probability and HFpEF-specific, evidence-based frameworks, rather than used in isolation to exclude disease.
Editors
Editor-in-Chief
Harlan M. Krumholz, MD, SM, FACC
CME Editor
Ragavendra R. Baliga, MD
Author
Barry A. Borlaug, MD
Important Dates
Date of Release: March 17, 2026
Term of Approval/Date of CME/MOC Expiration: March 16, 2027