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. 2024 May 1;9(5):457-465.
doi: 10.1001/jamacardio.2024.0284.

Prognostic Models for Mortality and Morbidity in Heart Failure With Preserved Ejection Fraction

Kirsty McDowell  1 , Toru Kondo  1   2 , Atefeh Talebi  1 , Ken Teh  1 , Erasmus Bachus  3 , Rudolf A de Boer  4 , Ross T Campbell  1 , Brian Claggett  5 , Ashkay S Desai  5 , Kieran F Docherty  1 , Adrian F Hernandez  6 , Silvio E Inzucchi  7 , Mikhail N Kosiborod  8 , Carolyn S P Lam  9   10 , Felipe Martinez  11 , Joanne Simpson  1 , Muthiah Vaduganathan  5 , Pardeep S Jhund  1 , Scott D Solomon  5 , John J V McMurray  1
Affiliations

Prognostic Models for Mortality and Morbidity in Heart Failure With Preserved Ejection Fraction

Kirsty McDowell et al. JAMA Cardiol. .

Erratum in

  • Change to Open Access Status.
    [No authors listed] [No authors listed] JAMA Cardiol. 2024 Sep 1;9(9):861. doi: 10.1001/jamacardio.2024.2464. JAMA Cardiol. 2024. PMID: 39083251 Free PMC article. No abstract available.

Abstract

Importance: Accurate risk prediction of morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF) may help clinicians risk stratify and inform care decisions.

Objective: To develop and validate a novel prediction model for clinical outcomes in patients with HFpEF using routinely collected variables and to compare it with a biomarker-driven approach.

Design, setting, and participants: Data were used from the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial to derive the prediction model, and data from the Angiotensin Receptor Neprilysin Inhibition in Heart Failure With Preserved Ejection Fraction (PARAGON-HF) and the Irbesartan in Heart Failure With Preserved Ejection Fraction Study (I-PRESERVE) trials were used to validate it. The outcomes were the composite of HF hospitalization (HFH) or cardiovascular death, cardiovascular death, and all-cause death. A total of 30 baseline candidate variables were selected in a stepwise fashion using multivariable analyses to create the models. Data were analyzed from January 2023 to June 2023.

Exposures: Models to estimate the 1-year and 2-year risk of cardiovascular death or hospitalization for heart failure, cardiovascular death, and all-cause death.

Results: Data from 6263 individuals in the DELIVER trial were used to derive the prediction model and data from 4796 individuals in the PARAGON-HF trial and 4128 individuals in the I-PRESERVE trial were used to validate it. The final prediction model for the composite outcome included 11 variables: N-terminal pro-brain natriuretic peptide (NT-proBNP) level, HFH within the past 6 months, creatinine level, diabetes, geographic region, HF duration, treatment with a sodium-glucose cotransporter 2 inhibitor, chronic obstructive pulmonary disease, transient ischemic attack/stroke, any previous HFH, and heart rate. This model showed good discrimination (C statistic at 1 year, 0.73; 95% CI, 0.71-0.75) in both validation cohorts (C statistic at 1 year, 0.71; 95% CI, 0.69-0.74 in PARAGON-HF and 0.75; 95% CI, 0.73-0.78 in I-PRESERVE) and calibration. The model showed similar discrimination to a biomarker-driven model including high-sensitivity cardiac troponin T and significantly better discrimination than the Meta-Analysis Global Group in Chronic (MAGGIC) risk score (C statistic at 1 year, 0.60; 95% CI, 0.58-0.63; delta C statistic, 0.13; 95% CI, 0.10-0.15; P < .001) and NT-proBNP level alone (C statistic at 1 year, 0.66; 95% CI, 0.64-0.68; delta C statistic, 0.07; 95% CI, 0.05-0.08; P < .001). Models derived for the prediction of all-cause and cardiovascular death also performed well. An online calculator was created to allow calculation of an individual's risk.

Conclusions and relevance: In this prognostic study, a robust prediction model for clinical outcomes in HFpEF was developed and validated using routinely collected variables. The model performed better than NT-proBNP level alone. The model may help clinicians to identify high-risk patients and guide treatment decisions in HFpEF.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Kondo reported receiving personal fees from Abbott Medical Japan LLC, Ono Pharmaceutical Co Ltd, Otsuka Pharmaceutical Co Ltd, Novartis Pharma, AstraZeneca, Bristol Myers Squibb, and Abiomed Japan outside the submitted work. Dr Bachus reported being an employee of and receiving personal fees from AstraZeneca outside the submitted work. Dr de Boer reported receiving grants from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals GmbH, Novo Nordisk, and Roche and speaker and/or travel fees from Abbott, AstraZeneca, Bristol Myers Squibb, Cardior Pharmaceuticals GmbH, Novo Nordisk, and Roche outside the submitted work. Dr Campbell reported speaker fees from AstraZeneca and consulting fees from Bayer outside the submitted work. Dr Claggett reported receiving consulting fees from Alnylam, Cardurion, Corvia, Cytokinetics, Intellia, Rocket, and CVRX outside the submitted work. Dr Desai reported receiving grants from AstraZeneca, Novartis, Abbott, Alnylam, and Bayer and consulting fees from AstraZeneca, Novartis, Abbott, Alnylam, Axon, Avidity Biopharma, Bayer, GlaxoSmithKline, Medpace, Medtronic, Merck, New Amsterdam, Parexel, Porter Health, Regeneron, River2Renal, Roche, Veristat, Verily, and Zydus outside the submitted work. Dr Docherty reported being an employee of AstraZeneca; receiving grants and personal fees from AstraZeneca; receiving grants from Boehringer Ingelheim and Roche; and receiving personal fees from Pharmacosmos, Bayer, and Us2.AI outside the submitted work. Dr Hernandez reported receiving personal fees from Bayer and Cytokinetics and grants from Boehringer Ingelheim, Eli Lilly, Amgen, AstraZeneca, Novartis, Merck, and American Regent outside the submitted work. Dr Inzucchi reported receiving personal fees from AstraZeneca, Boehringer Ingelheim, Merck, Pfizer, Novo Nordisk, and Bayer outside the submitted work. Dr Kosiborod reported receiving grants from AstraZeneca, Boehringer Ingelheim, Pfizer, 35Pharma, Alnylam, Amgen, and Applied Therapeutics; personal fees from Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Imbria Pharmaceuticals, Janssen, Lexicon Pharmaceuticals, Merck, Novo Nordisk, Pharmacosmos, Pfizer, Sanofi, scPharmaceuticals, Structure Therapeutics, Vifor Pharma, and Youngene Therapeutics; and research support/stock options from AstraZeneca, Artera Health, and Saghmos Therapeutics outside the submitted work. Dr Lam reported receiving grants from Novo Nordisk and Roche Diagnostics; other research support from Alleviant Medical, Allysta Pharma, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CardioRenal, Cytokinetics, Darma Inc., EchoNous Inc, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Quidel Corporation, Radcliffe Group Ltd, Recardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics and Us2.AI; consultant and/or advisory board fees from Us2.AI as cofounder and nonexecutive director and having a patent pending for diagnosis and prognosis of chronic heart failure and a patent issued for automated clinical workflow that recognizes and analyses 2-dimensional and Doppler echo images for cardiac measurements and the diagnosis, prediction and prognosis of heart disease. Dr Martinez reported receiving personal fees from Novartis and AstraZeneca during the conduct of the study. Dr Simpson reported receiving personal fees from Alnylam outside the submitted work. Dr Vaduganathan reported receiving research grant support, advisory board fees, or speaker fees from American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, BMS, Boehringer Ingelheim, Chiesi, Cytokinetics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health and grants from AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics outside the submitted work. Dr Jhund reported receiving speaker and/or advisory fees from Novartis, AstraZeneca, Bayer, NovoNordisk, ALkem metabolomics, and ProAdWise Communications and grants from Analog Devices Inc, Boehringer Ingelheim, and Roche Diagnostics outside the submitted work. Dr Solomon reported receiving grants from AstraZeneca, Novartis, Alexion, Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lilly, Mesoblast, MyoKardia, NIH/NHLBI, Neurotronik, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Theracos, US2.AI, and Edgewise and personal fees from Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boeringer-Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GSK, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, Valo consulting outside the submitted work. Dr McMurray reported committee and/or employee fees from AstraZeneca, Novartis, Amgen, Bayer, Cardurion, Cytokinetics, GSK, and KBP Biosciences, and personal fees from Abbott, Alkem Metabolics, AstraZeneca, Blue Ocean Scientific Solutions Ltd, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharmaceuticals Ltd., Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica Health, Intas Pharmaceuticals, J.B. Chemicals & Pharmaceuticals Ltd, Lupin Pharmaceuticals, Medscape/Heart.Org, ProAdWise Communications, Radcliffe Cardiology, Sun Pharmaceuticals, The Corpus, Translation Research Group, Translational Medicine Academy, Alynylam Pharmaceuticals, Bayer, BMS, Ionis Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, River 2 Renal Corp, Global Clinical Trial Partners Ltd, and George Clinical PTY Ltd outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Observed and Predicted Risk in the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) Trial at 2 Years
Risk for the composite of heart failure hospitalization (HFH) or cardiovascular (CV) death (A), CV death (B), and all-cause death (C) for patients categorized by quintile of risk score. Quintiles of risk score are graded from low risk (1) to high risk (2).
Figure 2.
Figure 2.. Kaplan-Meier Plots for Observed Event Rate at 1 Year According to Quintiles of Risk Score
A, Prognostic Models for Mortality and Morbidity in Heart Failure With Preserved Ejection Fraction (PREDICT-HFpEF) risk score. B, Meta-Analysis Global Group in Chronic (MAGGIC) risk score in the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial. CV indicates cardiovascular; HFH, HF hospitalization.
See this image and copyright information in PMC

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