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. 2022 Sep 1;7(9):891-899.
doi: 10.1001/jamacardio.2022.1916.

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

Yogesh N V Reddy  1 , David M Kaye  2 , M Louis Handoko  3 , Arno A van de Bovenkamp  3 , Ryan J Tedford  4 , Carson Keck  4 , Mads J Andersen  5 , Kavita Sharma  6 , Rishi K Trivedi  6 , Rickey E Carter  7 , Masaru Obokata  8 , Frederik H Verbrugge  1   9   10 , Margaret M Redfield  1 , Barry A Borlaug  1
Affiliations

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

Yogesh N V Reddy et al. JAMA Cardiol. .

Abstract

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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Reddy reported receiving grants from Bayer and Sleep Number and an internal competitive grant program from Mayo Clinic Cardiovascular Division. Dr Handoko reported receiving grants from The Dutch Heart Foundation and educational, speaker, and consultancy fees from Novartis, Boehringer Ingelheim, AstraZeneca, Vifor Pharma, Bayer, Merck Sharp & Dohme, Abbott, Daiichi Sankyo, and Quin outside the submitted work. Dr Tedford reported consulting and serving on the steering committee for Abbott, Medtronic, Acceleron Pharma, and Aria CV; consulting for Edwards Gradient, Itamar, CareDx Lexicon Pharmaceuticals, Alleviant Eidos Therapeutics, and United Therapeutics; serving on a research advisory board for Abiomed; and performing hemodynamic core laboratory work for Merck and Actelion. Dr Sharma reported receiving personal fees from Novartis, Bayer, Novo Nordisk, Boehringer Ingelheim, Janssen, and AstraZeneca and grants from Amgen outside the submitted work. Dr Carter reported receiving grants from the National Heart, Lung, and Blood Institute (NHLBI) and the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), and serving on the scientific advisory board for Anumana, Inc outside the submitted work. Dr Obokata reported receiving research grants from the Fukuda Foundation for Medical Technology, Mochida Memorial Foundation for Medical and Pharmaceutical Research, Nippon Shinyaku, Japanese Circulation Society, and Takeda Science Foundation. Dr Verbrugge reported receiving a fellowship from the Belgian American Educational Foundation and Special Research Fund (Bijzonder Onderzoeksfonds) of Hasselt University. Dr Borlaug reported receiving grants from the NHLBI, NIH, and the US Department of Defense; research funding from Axon, AstraZeneca, Corvia, Medtronic, GlaxoSmithKline, Mesoblast, Novartis, and Tenax Therapeutics; and serving on steering committee and consulting for Actelion, Amgen, Aria, Boehringer Ingelheim, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, NGMBio, ShouTi, and VADovations. No other disclosures were reported.

Figures

Figure.
Figure.. Comparison of H2FPEF and HFA-PEFF Scores for Diagnosis of Heart Failure With Preserved Ejection Fraction (HFpEF)
H2FPEF and HFA-PEFF scores of 0 to 1 indicated a low probability of HFpEF; H2FPEF scores of 6 to 9 and HFA-PEFF scores of 5 to 6 indicated a high probability of HFpEF. Intermediate probability of HFpEF required additional exercise testing for diagnosis. C, The P value is for the difference in area under the curve between scores. ROC indicates receiver operating characteristic.
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