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Original Investigation
July 13, 2022

Diagnosis of Heart Failure With Preserved Ejection Fraction Among Patients With Unexplained Dyspnea

Author Affiliations
  • 1Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota
  • 2Department of Cardiology, Alfred Hospital, Melbourne, Victoria, Australia
  • 3Department of Cardiology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
  • 4Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston
  • 5Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark
  • 6Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland
  • 7Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida
  • 8Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
  • 9Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium
  • 10Centre for Cardiovascular Diseases, University Hospital Brussels, Jette, Belgium
JAMA Cardiol. 2022;7(9):891-899. doi:10.1001/jamacardio.2022.1916
Key Points

Question  What is the performance of the H2FPEF and HFA-PEFF algorithms to diagnose heart failure with preserved ejection fraction (HFpEF) compared with the invasive gold standard of an elevated pulmonary capillary wedge pressure (PCWP) during exercise?

Findings  In this case-control study of 736 patients, H2FPEF and HFA-PEFF scores provided discriminatory information to identify HFpEF, but there was superior discrimination for the H2FPEF score. The use of an alternative criterion, the PCWP/cardiac output slope, led to potential misclassification in 20% of patients.

Meaning  The findings suggest that the H2FPEF and HFA-PEFF algorithms can discriminate patients with HFpEF from control individuals among ambulatory patients with dyspnea and that the H2FPEF score provides superior diagnostic performance despite fewer input variables.


Importance  Diagnosis of heart failure with preserved ejection fraction (HFpEF) among dyspneic patients without overt congestion is challenging. Multiple diagnostic approaches have been proposed but are not well validated against the independent gold standard for HFpEF diagnosis of an elevated pulmonary capillary wedge pressure (PCWP) during exercise.

Objective  To evaluate H2FPEF and HFA-PEFF scores and a PCWP/cardiac output (CO) slope of more than 2 mm Hg/L/min to diagnose HFpEF.

Design, Setting, and Participants  This retrospective case-control study included patients with unexplained dyspnea from 6 centers in the US, the Netherlands, Denmark, and Australia from March 2016 to October 2020. Diagnosis of HFpEF (cases) was definitively ascertained by the presence of elevated PCWP during exertion; control individuals were those with normal rest and exercise hemodynamics.

Main Outcomes and Measures  Logistic regression was used to evaluate the accuracy of HFA-PEFF and H2FPEF scores to discriminate patients with HFpEF from controls.

Results  Among 736 patients, 563 (76%) were diagnosed with HFpEF (mean [SD] age, 69 [11] years; 334 [59%] female) and 173 (24%) represented controls (mean [SD] age, 60 [15] years; 109 [63%] female). H2FPEF and HFA-PEFF scores discriminated patients with HFpEF from controls, but the H2FPEF score had greater area under the curve (0.845; 95% CI, 0.810-0.875) compared with the HFA-PEFF score (0.710; 95% CI, 0.659-0.756) (difference, −0.134; 95% CI, –0.177 to −0.094; P < .001). Specificity was robust for both scores, but sensitivity was poorer for HFA-PEFF, with a false-negative rate of 55% for low-probability scores compared with 25% using the H2FPEF score. Use of the PCWP/CO slope to redefine HFpEF rather than exercise PCWP reclassified 20% (117 of 583) of patients, but patients reclassified from HFpEF to control by this metric had clinical, echocardiographic, and hemodynamic features typical of HFpEF, including elevated resting PCWP in 66% (46 of 70) of reclassified patients.

Conclusions and Relevance  In this case-control study, despite requiring fewer data, the H2FPEF score had superior diagnostic performance compared with the HFA-PEFF score and PCWP/CO slope in the evaluation of unexplained dyspnea and HFpEF in the outpatient setting.

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