Heart Failure Across the Range of Mildly Reduced and Preserved Ejection Fraction in the United States.

HomeCirculation: Heart FailureVol. 16, No. 5Heart Failure Across the Range of Mildly Reduced and Preserved Ejection Fraction in the United States Open AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toOpen AccessLetterPDF/EPUBHeart Failure Across the Range of Mildly Reduced and Preserved Ejection Fraction in the United States Stephen J. Greene, John A. Spertus, Wenxi Tang, Amiee Kang, Yue Zhong, Michael C. Myers, Sophie Shen, Jenny Jiang, Xuejun Liu, David R. Steffen, Marta G. Viola and G. Michael Felker Stephen J. GreeneStephen J. Greene Correspondence to: Stephen J. Greene, MD, Duke Clinical Research Institute, 300 W Morgan St, Durham, NC 27701. Email E-mail Address: [email protected] https://orcid.org/0000-0001-6912-7374 Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (S.J.G., G.M.F.). Division of Cardiology, Duke University School of Medicine, Durham, NC (S.J.G., G.M.F.). Search for more papers by this author , John A. SpertusJohn A. Spertus https://orcid.org/0000-0002-2839-2611 University of Missouri–Kansas City’s Healthcare Institute for Innovations in Quality and Saint Luke’s Mid America Heart Institute (J.A.S.). Search for more papers by this author , Wenxi TangWenxi Tang Analysis Group Inc, NY (W.T., D.R.S., M.G.V.). Search for more papers by this author , Amiee KangAmiee Kang Bristol Myers Squibb, Lawrenceville, NJ (A.K., Y.Z., M.C.M., S.S., J.J., X.L.). Search for more papers by this author , Yue ZhongYue Zhong https://orcid.org/0000-0002-9839-0160 Bristol Myers Squibb, Lawrenceville, NJ (A.K., Y.Z., M.C.M., S.S., J.J., X.L.). Search for more papers by this author , Michael C. MyersMichael C. Myers https://orcid.org/0000-0002-7895-1397 Bristol Myers Squibb, Lawrenceville, NJ (A.K., Y.Z., M.C.M., S.S., J.J., X.L.). Search for more papers by this author , Sophie ShenSophie Shen Bristol Myers Squibb, Lawrenceville, NJ (A.K., Y.Z., M.C.M., S.S., J.J., X.L.). Search for more papers by this author , Jenny JiangJenny Jiang https://orcid.org/0000-0003-0341-1385 Bristol Myers Squibb, Lawrenceville, NJ (A.K., Y.Z., M.C.M., S.S., J.J., X.L.). Search for more papers by this author , Xuejun LiuXuejun Liu https://orcid.org/0000-0003-3787-3537 Bristol Myers Squibb, Lawrenceville, NJ (A.K., Y.Z., M.C.M., S.S., J.J., X.L.). Department of Health Policy and Management, Gillings School of Global Public Health, University of North Carolina at Chapel Hill (X.L.). Search for more papers by this author , David R. SteffenDavid R. Steffen Analysis Group Inc, NY (W.T., D.R.S., M.G.V.). Search for more papers by this author , Marta G. ViolaMarta G. Viola Analysis Group Inc, NY (W.T., D.R.S., M.G.V.). Search for more papers by this author and G. Michael FelkerG. Michael Felker https://orcid.org/0000-0002-5931-1239 Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (S.J.G., G.M.F.). Division of Cardiology, Duke University School of Medicine, Durham, NC (S.J.G., G.M.F.). Search for more papers by this author Originally published20 Apr 2023https://doi.org/10.1161/CIRCHEARTFAILURE.123.010430Circulation: Heart Failure. 2023;16Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: April 20, 2023: Ahead of Print Although efficacy of multiple heart failure (HF) medications is now proven to extend to patients with left ventricular ejection fraction (LVEF) >40%, the clinical benefits are often attenuated as LVEF increases within this range.1,2 Understanding the real-world patient profile across the range of mildly reduced and preserved LVEF may inform implementation and applicability of clinical trial data to routine practice. The current study sought to leverage a large real-world dataset to compare patient characteristics, treatment patterns, and in-hospital and postdischarge outcomes among US patients hospitalized for HF with LVEF 41% to 49%, 50% to 59%, and ≥60%.The data used in this analysis cannot be made publically available by the authors. This study utilized the Optum electronic medical record database (Eden Prairie, MN) to identify US adults hospitalized between January 2010-December 2020 for a primary diagnosis of HF (as defined by International Classification of Diseases, Ninth Revision/International Classification of Diseases, Tenth Revision codes) with LVEF>40%. To further verify HF as primary diagnosis, eligible patients received intravenous diuretics within 2 days of hospital admission.3 For patients with multiple hospitalizations meeting inclusion criteria, the first hospitalization was selected.Given the intent to inform care for the large majority of patients who are hemodynamically stable at presentation and initially treated with intravenous diuretics, prespecified exclusion criteria (as defined by International Classification of Diseases codes) included (1) severe acute HF/cardiogenic shock at initial hospital presentation (defined as mechanical support or intravenous inotropes, or diagnosis code for cardiogenic shock on admission day), (2) acute coronary syndrome during index hospitalization, and (3) end-stage kidney disease or estimated glomerular filtration rate <15 mL/(min·1.73 m2) on day 1 or 2 of hospitalization before initiation of intravenous diuretics. Eligible patients were categorized into 3 prespecified LVEF groups, defined as LVEF 41% to 49% (ie, HFmrEF), LVEF 50% to 59%, and LVEF ≥60%. LVEF was measured by echocardiogram during index hospitalization or within prior 6 months.Study outcomes were in-hospital mortality, as well as 30-day and 12-month postdischarge outcomes of all-cause mortality, HF hospitalization, all-cause hospitalization, composite all-cause mortality or HF hospitalization, and major adverse cardiovascular events (defined as composite of death, myocardial infarction, stroke, or HF hospitalization events). Institutional review board approval was not needed because this work involved secondary analysis of deidentified data.Among 47 026 eligible patients with LVEF >40%, 6335 (13.5%) patients had LVEF 41-49%, 18 603 (39.6%) patients had LVEF 50% to 59%, and 22 088 (47.0%) patients had LVEF ≥60% (Figure). Overall, median age of the population was 77 years, 58.1% were women, and 83.7% were White. LVEF ≥60% included the highest proportion of women (64.9%), the lowest NT-proBNP (N-terminal pro-B-type natriuretic peptide) concentration (median NT-proBNP 2234 pg/mL), and lowest rates of coronary artery disease (31.5%) and atrial fibrillation (34.4%). LVEF 41% to 49% had the lowest proportion of women (45.2%) and had the highest NT-proBNP concentration (median, 4221 pg/mL).Download figureDownload PowerPointFigure. Heart failure across the range of mildly reduced and preserved ejection fraction in the United States. ACE indicates angiotensin-converting enzyme; ACS, acute coronary syndrome; ARB, angiotensin II receptor blocker; ARNI, angiotensin-receptor neprilysin inhibitor; BMI, body mass index; CAD, coronary artery disease; EF, ejection fraction; ESKD, end-stage kidney disease; HF, heart failure; IV, intravenous; LVEF, left ventricular ejection fraction; MACE, major adverse cardiovascular event; MI, myocardial infarction; MRA mineralocorticoid receptor antagonist; and SGLT2i, sodium-glucose cotransporter-2 inhibitor.From day 2 or later during hospitalization, use of mechanical therapy (ie, ventilatory, circulatory, or kidney support; 4.7%–5.5%) and intravenous inotropes (1.6%–2.0%) were similar across LVEF groups. During hospitalization, median duration of intravenous diuretic therapy was 3 (interquartile range, 2–5) days in each group.Overall rates of mineralocorticoid receptor antagonist and angiotensin-receptor neprilysin inhibitor at discharge were 10.5% and 0.3%, respectively, and modestly higher among patients with LVEF 41% to 49% (Figure). Median length of stay was 4 (interquartile range, 3–7) days and consistent across LVEF groups. In-hospital mortality and postdischarge outcomes at 30 days and 12 months were similar across LVEF groups.In this large contemporary population of US patients hospitalized for HF with LVEF >40%, nearly half (47%) had LVEF ≥60%. Despite differences in clinical profile, outcomes were similarly poor, irrespective of LVEF. Although the current study excluded patients presenting with concurrent ACS, end-stage kidney disease, or need for vasopressors or mechanical support on day of hospital admission, ≈5% of patients in each LVEF strata ultimately required mechanical ventilatory, circulatory, or kidney support during hospitalization. Regardless of LVEF group, more than 1 in 4 patients died, >1 in 2 were rehospitalized, and >1 in 2 experienced a major adverse cardiovascular event over 12-month follow-up.Limitations should be noted. These observational data cannot determine cause-effect relationships. Discharge use of medical therapy should be interpreted in the context of a study period before the 2022 United States HF guidelines. Longitudinal data on LVEF were not available, thus characterization of patients with current LVEF >40% but former LVEF ≤40% could not be assessed. Data regarding cause-specific death were not available.In the 2022 American College of Cardiology/American Heart Association/Heart Failure Society of America HF guidelines, apart from Class 2A recommendations for sodium-glucose cotransporter-2 inhibitor therapy, multiple medications traditionally indicated for HFrEF now carry class 2B recommendations for HF with mildly reduced LVEF and HFpEF.4 These class 2B recommendations note that medications should be considered “particularly among patients with LVEF on the lower end of this spectrum.”4 Among patients in the current analysis with true HFpEF ≥50%, more than half (54%) had LVEF ≥60%, which may inform applicability or anticipated population-level benefit with implementation of new class 2B medication recommendations for HFpEF.4 There remains a substantial need to improve care and outcomes for patients with HF across the range of mildly reduced and preserved LVEF, including the large subset with LVEF ≥60% who may be less responsive to medical therapies other than sodium-glucose cotransporter-2 inhibitors.5Article InformationSources of FundingThis study was supported by Bristol Myers Squibb (Lawrenceville, NJ).Disclosures Dr Greene has received research support from the Duke University Department of Medicine Chair’s Research Award, the American Heart Association (award 929502), Amgen, AstraZeneca, Bristol Myers Squibb (BMS), Cytokinetics, Merck, Novartis, Pfizer, and Sanofi; has served on advisory boards for Amgen, AstraZeneca, BMS, Boehringer Ingelheim/Lilly, Cytokinetics, Roche Diagnostics, scPharmaceuticals, and Sanofi; has received speaker fees from Boehringer Ingelheim, Cytokinetics, and Roche Diagnostics; and serves as a consultant for Amgen, Bayer, BMS, Corteria Pharmaceuticals, CSL Vifor, Merck, PharmaIN, Roche Diagnostics, Sanofi, Tricog Health, and Urovant Pharmaceuticals. Dr. Spertus discloses providing consultative services on patient-reported outcomes and evidence evaluation to Alnylam, AstraZeneca, Bayer, Merck, Janssen, BMS, Edwards, Kineksia, 4DT Medical, Terumo, Cytokinetics, Imbria, and United Healthcare. He holds research grants from BMS, Abbott Vascular, and Janssen. He owns the copyright to the Seattle Angina Questionnaire, Kansas City Cardiomyopathy Questionnaire, and Peripheral Artery Questionnaire and serves on the Board of Directors for Blue Cross Blue Shield of Kansas City. W. Tang, D.R. Steffen, and M.G. Viola are employees of Analysis Group Inc, which has received consultancy fees from BMS for this study. Drs Zhong, Myers, and Shen and A. Kang, J. Jiang, and X. Liu are employees of BMS. Dr Felker has received research grants from the National Heart, Lung, and Blood Institute, the American Heart Association, Amgen, Bayer, BMS, Merck, Cytokinetics, and CSL-Behring; has acted as a consultant to Novartis, Amgen, BMS, Cytokinetics, Medtronic, Cardionomic, Boehringer Ingelheim, American Regent, Abbott, AstraZeneca, Reprieve, Myovant, Sequana, Windtree Therapeutics, and Whiteswell; and has served on clinical end point committees/data safety monitoring boards for Amgen, Merck, Medtronic, EBR Systems, V-Wave, LivaNova, Siemens, and Rocket Pharma.FootnotesFor Sources of Funding and Disclosures, see page 455.Correspondence to: Stephen J. Greene, MD, Duke Clinical Research Institute, 300 W Morgan St, Durham, NC 27701. Email stephen.[email protected]eduReferences1. Kondo T, McMurray JJV. Re-emergence of heart failure with a normal ejection fraction?Eur Heart J. 2022; 43:427–429. doi: 10.1093/eurheartj/ehab828CrossrefMedlineGoogle Scholar2. 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Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American college of cardiology/American heart association joint committee on clinical practice guidelines.J Am Coll Cardiol. 2022; 79:e263–e421. doi: 10.1016/j.jacc.2021.12.012CrossrefMedlineGoogle Scholar5. Shah KS, Xu H, Matsouaka RA, Bhatt DL, Heidenreich PA, Hernandez AF, Devore AD, Yancy CW, Fonarow GC. Heart failure with preserved, borderline, and reduced ejection fraction: 5-year outcomes.J Am Coll Cardiol. 2017; 70:2476–2486. doi: 10.1016/j.jacc.2017.08.074CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails May 2023Vol 16, Issue 5 Advertisement Article InformationMetrics © 2023 The Authors and Bristol Myers Squibb. Circulation: Heart Failure is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.https://doi.org/10.1161/CIRCHEARTFAILURE.123.010430PMID: 37078276 Originally publishedApril 20, 2023 Keywordshospitalizationheart failureUnited StatespatientsPDF download Advertisement