Clinical, Echocardiographic, and Longitudinal Characteristics Associated With Heart Failure With Improved Ejection Fraction

Heart failure with improved ejection fraction (HFimpEF) has better outcomes than HF with reduced EF (HFrEF). However, factors contributing to HFimpEF remain unclear. This study aimed to evaluate clinical and longitudinal characteristics associated with subsequent HFimpEF. This was a single-center retrospective HFrEF cohort study. Data were collected from 2014 to 2022. Patients with HFrEF were identified using International Classification of Diseases codes, echocardiographic data, and natriuretic peptide levels. The main end points were HFimpEF (defined as EF >40% at ≥3 months with ≥10% increase) and mortality. Cox proportional hazards and mixed effects models were used for analyses. The study included 1,307 patients with HFrEF with a median follow-up of 16.3 months (interquartile range 8.0 to 30.6). The median age was 65 years; 68% were male whereas 57% were White. On follow-up, 38.7% (n = 506) developed HFimpEF, whereas 61.3% (n = 801) had persistent HFrEF. A multivariate Cox regression model identified gender, race, co-morbidities, echocardiographic, and natriuretic peptide as significant covariates of HFimpEF (p <0.05). The HFimpEF group had better survival compared with the persistent HFrEF group (p <0.001). Echocardiographic and laboratory trajectories differed between groups. In this HFrEF cohort, 38.7% transitioned to HFimpEF and approximately 50% met the definition within the first 12 months. In a HFimpEF model, gender, co-morbidities, echocardiographic parameters, and natriuretic peptide were associated with subsequent HFimpEF. The model has the potential to identify patients at risk of subsequent persistent or improved HFrEF, thus informing the design and implementation of targeted quality-of-care improvement interventions. Heart failure with improved ejection fraction (HFimpEF) has better outcomes than HF with reduced EF (HFrEF). However, factors contributing to HFimpEF remain unclear. This study aimed to evaluate clinical and longitudinal characteristics associated with subsequent HFimpEF. This was a single-center retrospective HFrEF cohort study. Data were collected from 2014 to 2022. Patients with HFrEF were identified using International Classification of Diseases codes, echocardiographic data, and natriuretic peptide levels. The main end points were HFimpEF (defined as EF >40% at ≥3 months with ≥10% increase) and mortality. Cox proportional hazards and mixed effects models were used for analyses. The study included 1,307 patients with HFrEF with a median follow-up of 16.3 months (interquartile range 8.0 to 30.6). The median age was 65 years; 68% were male whereas 57% were White. On follow-up, 38.7% (n = 506) developed HFimpEF, whereas 61.3% (n = 801) had persistent HFrEF. A multivariate Cox regression model identified gender, race, co-morbidities, echocardiographic, and natriuretic peptide as significant covariates of HFimpEF (p <0.05). The HFimpEF group had better survival compared with the persistent HFrEF group (p <0.001). Echocardiographic and laboratory trajectories differed between groups. In this HFrEF cohort, 38.7% transitioned to HFimpEF and approximately 50% met the definition within the first 12 months. In a HFimpEF model, gender, co-morbidities, echocardiographic parameters, and natriuretic peptide were associated with subsequent HFimpEF. The model has the potential to identify patients at risk of subsequent persistent or improved HFrEF, thus informing the design and implementation of targeted quality-of-care improvement interventions. For a subset of patients with heart failure with reduced ejection fraction (HFrEF), some improvement in EF occurs. To be formally classified as HF with improved EF (HFimpEF), however, the patients must have a baseline left ventricular EF (LVEF) of ≤40% and subsequent LVEF >40% at ≥3 months, with ≥10% absolute increase.1Wilcox JE Fang JC Margulies KB Mann DL Heart failure with recovered left ventricular ejection fraction: JACC scientific expert panel.J Am Coll Cardiol. 2020; 76: 719-734Crossref PubMed Scopus (134) Google Scholar, 2Bozkurt B Coats AJS Tsutsui H Abdelhamid CM Adamopoulos S Albert N Anker SD Atherton J Böhm M Butler J Drazner MH Michael Felker G Filippatos G Fiuzat M Fonarow GC Gomez-Mesa JE Heidenreich P Imamura T Jankowska EA Januzzi J Khazanie P Kinugawa K Lam CSP Matsue Y Metra M Ohtani T Francesco Piepoli M Ponikowski P Rosano GMC Sakata Y Seferović P Starling RC Teerlink JR Vardeny O Yamamoto K Yancy C Zhang J Zieroth S Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure: endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and Chinese Heart Failure Association.Eur J Heart Fail. 2021; 23: 352-380Crossref PubMed Scopus (494) Google Scholar, 3Heidenreich PA Bozkurt B Aguilar D Allen LA Byun JJ Colvin MM Deswal A Drazner MH Dunlay SM Evers LR Fang JC Fedson SE Fonarow GC Hayek SS Hernandez AF Khazanie P Kittleson MM Lee CS Link MS Milano CA Nnacheta LC Sandhu AT Stevenson LW Vardeny O Vest AR Yancy CW 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-e421Crossref PubMed Scopus (624) Google Scholar The prognosis and outcomes for HFimpEF tend to be better as compared with persistent HFrEF. Patients with HFimpEF have significantly lower rates of mortality, cardiac hospitalizations, all-cause hospitalizations, and composite events.4Basuray A French B Ky B Vorovich E Olt C Sweitzer NK Cappola TP Fang JC Heart failure with recovered ejection fraction: Clinical description, biomarkers, and outcomes.Circulation. 2014; 129: 2380-2387Crossref PubMed Scopus (230) Google Scholar, 5Kalogeropoulos AP Fonarow GC Georgiopoulou V Burkman G Siwamogsatham S Patel A Li S Papadimitriou L Butler J Characteristics and outcomes of adult outpatients with heart failure and improved or recovered ejection fraction.JAMA Cardiol. 2016; 1: 510-518Crossref PubMed Google Scholar, 6Lupón J Díez-López C de Antonio M Domingo M Zamora E Moliner P González B Santesmases J Troya MI Bayés-Genís A. Recovered heart failure with reduced ejection fraction and outcomes: a prospective study.Eur J Heart Fail. 2017; 19: 1615-1623Crossref PubMed Scopus (139) Google Scholar, 7Ghimire A Fine N Ezekowitz JA Howlett J Youngson E McAlister FA Frequency, predictors, and prognosis of ejection fraction improvement in heart failure: an echocardiogram-based registry study.Eur Heart J. 2019; 40: 2110-2117Crossref PubMed Scopus (58) Google Scholar, 8Park CS Park JJ Mebazaa A Oh IY Park HA Cho HJ Lee HY Kim KH Yoo BS Kang SM Baek SH Jeon ES Kim JJ Cho MC Chae SC Oh BH Choi DJ Characteristics, outcomes, and treatment of heart failure with improved ejection fraction.J Am Heart Assoc. 2019; 8e011077Crossref Scopus (56) Google Scholar, 9Perry AS Mudigonda P Huang GS Qureshi B Cheng RK Levy WC Li S Long-term outcomes and risk stratification of patients with heart failure with recovered ejection fraction.Am J Cardiol. 2022; 173: 80-87Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar Moreover, HFimpEF patients have lower rates of cardiac transplantation, LV assist device and a significant in of P J Zhang M T J JE O L B Fang JC JA J of in patients with heart failure with recovered ejection fraction.JAMA Cardiol. 2021; PubMed Scopus Google Scholar However, the and factors to HFimpEF The improvement in EF in HFimpEF be of the of device or a of JE Fang JC Margulies KB Mann DL Heart failure with recovered left ventricular ejection fraction: JACC scientific expert panel.J Am Coll Cardiol. 2020; 76: 719-734Crossref PubMed Scopus (134) Google MM Mann DL and of of left ventricular in Heart PubMed Scopus Google T SD in heart 23: PubMed Scopus Google Scholar clinical characteristics or to HFimpEF as the of the gender, and have to EF improvement and subsequent clinical A Fine N Ezekowitz JA Howlett J Youngson E McAlister FA Frequency, predictors, and prognosis of ejection fraction improvement in heart failure: an echocardiogram-based registry study.Eur Heart J. 2019; 40: 2110-2117Crossref PubMed Scopus (58) Google Scholar Echocardiographic on HFimpEF patients have an better LV and compared with patients with persistent CS Park JJ Mebazaa A Oh IY Park HA Cho HJ Lee HY Kim KH Yoo BS Kang SM Baek SH Jeon ES Kim JJ Cho MC Chae SC Oh BH Choi DJ Characteristics, outcomes, and treatment of heart failure with improved ejection fraction.J Am Heart Assoc. 2019; 8e011077Crossref Scopus (56) Google AS Mudigonda P Huang GS Qureshi B Cheng RK Levy WC Li S Long-term outcomes and risk stratification of patients with heart failure with recovered ejection fraction.Am J Cardiol. 2022; 173: 80-87Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar However, the of a on the echocardiographic, and factors associated with EF improvement a A better of factors patients at risk of persistent HFrEF or HFimpEF. 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Recovered heart failure with reduced ejection fraction and outcomes: a prospective study.Eur J Heart Fail. 2017; 19: 1615-1623Crossref PubMed Scopus (139) Google Scholar, 7Ghimire A Fine N Ezekowitz JA Howlett J Youngson E McAlister FA Frequency, predictors, and prognosis of ejection fraction improvement in heart failure: an echocardiogram-based registry study.Eur Heart J. 2019; 40: 2110-2117Crossref PubMed Scopus (58) Google Scholar, 8Park CS Park JJ Mebazaa A Oh IY Park HA Cho HJ Lee HY Kim KH Yoo BS Kang SM Baek SH Jeon ES Kim JJ Cho MC Chae SC Oh BH Choi DJ Characteristics, outcomes, and treatment of heart failure with improved ejection fraction.J Am Heart Assoc. 2019; 8e011077Crossref Scopus (56) Google Scholar, 9Perry AS Mudigonda P Huang GS Qureshi B Cheng RK Levy WC Li S Long-term outcomes and risk stratification of patients with heart failure with recovered ejection fraction.Am J Cardiol. 2022; 173: 80-87Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar the persistent group and and were and This were to patients with In the multivariate Cox regression characteristics were associated with HFimpEF and in in with A Fine N Ezekowitz JA Howlett J Youngson E McAlister FA Frequency, predictors, and prognosis of ejection fraction improvement in heart failure: an echocardiogram-based registry study.Eur Heart J. 2019; 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