Author + information
- Received November 10, 2018
- Revision received November 17, 2018
- Accepted November 26, 2018
- Published online March 6, 2019.
- Gianluigi Savarese, MD, PhDa,∗,
- Ola Vedin, MD, PhDb,c,∗∗ (, )
- Domenico D'Amario, MD, PhDd,
- Alicia Uijl, MD, PhDa,e,
- Ulf Dahlström, MD, PhDf,
- Giuseppe Rosano, MD, PhDg,
- Carolyn S.P. Lam, MD, PhDh and
- Lars H. Lund, MD, PhDa
- aDepartment of Medicine, Karolinska Institutet and Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
- bDepartment of Medical Sciences, Uppsala University and Uppsala Clinical Research Center, Uppsala, Sweden
- cBoehringer Ingelheim AB, Stockholm, Sweden
- dInstitute of Cardiology, Fondazione Policlinico Universitario A. Gemelli Institute of Scientific Research and Treatment, Università Cattolica del Sacro Cuore, Rome, Italy
- eJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
- fDepartment of Cardiology and Department of Medical and Health Sciences, Linkoping University, Linkoping, Sweden
- gDepartment of Medical Sciences, IRCCS San Raffaele Hospital, Rome, Italy
- hNational Heart Centre Singapore, Duke-NUS Medical School, and University Medical Centre Groningen, Groningen, the Netherlands
- ↵∗Address for correspondence:
Dr. Ola Vedin, Uppsala Clinical Research Centre, Uppsala Science Park, Dag Hammarskjölds väg 38, 751 85 Uppsala, Sweden.
Objectives This study sought to evaluate the incidence, the predictors, and the associations with outcomes of changes in ejection fraction (EF) in heart failure (HF) patients.
Background EF determines therapy in HF, but information is scarce about incidence, determinants, and prognostic implications of EF change over time.
Methods Patients with ≥2 EF measurements were made in the Swedish Heart Failure Registry were categorized as heart failure with preserved ejection fraction (HFpEF) (EF ≥50%), heart failure with midrange ejection fraction (HFmrEF) (EF 40% to 49%), or heart failure with reduced ejection fraction (HFrEF) (EF <40%). Changes among categories were recorded, and associations among EF changes, predictors, and all-cause mortality and/or HF hospitalizations were analyzed using logistic and Cox regressions.
Results Of 4,942 patients at baseline, 18% had HFpEF, 19% had HFmrEF, and 63% had HFrEF. During follow-up, 21% and 18% of HFpEF patients transitioned to HFmrEF and HFrEF, respectively; 37% and 25% of HFmrEF patients transitioned to HFrEF and HFpEF, respectively; and 16% and 10% of HFrEF patients transitioned to HFmrEF and HFpEF, respectively. Predictors of increased EF included use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, female sex, cases of less severe HF, and comorbidities. Predictors of decreased EF included diabetes, ischemic heart disease, and cases of more severe HF. Increased EF was associated with a lower risk (hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.55 to 0.69) and decreased EF with a higher risk (HR: 1.15; 95% CI: 1.01 to 1.30) of mortality and/or HF hospitalizations. Prognostic implications were most evident for transitions to and from HFrEF.
Conclusions Increases in EF increase occurred in one-fourth of HFrEF and HFmrEF patients, and decreases occurred in more than one-third of patients with HFpEF and HFmrEF. EF change was associated with a wide range of important clinical, treatment, and organizational factors as well as with outcomes, particularly transitions to and from HFrEF.
↵∗ Drs. Savarese and Vedin are joint first authors.
Supported by grants 2013-23897-104604-23 and 523-2014-2336 to Karolinska Institutet from the Swedish Research Council, grants 20120321 and 20150557 from the Swedish Heart Lung Foundation, and grant 20110120 from the Stockholm County Council. No funding agency had any role in the design or conduct of the study, or collection, management, analysis, or interpretation of the data, or in the preparation or approval of the manuscript. Dr. Savarese has received honoraria from Vifor, AstraZeneca, Roche, and Servier; and has received grants from Boehringer Ingelheim, and Merck Sharp & Dohme. Dr. Lam is a paid consultant for National Heart Centre, National Medical Research Council of Singapore, Abbott Diagnostics, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Coarvia, Janssen Research & Development LLC, Medtronics, Menarini, Merck Sharpe & Dohme, Novartis, Stealth BioTherapeutics, and Vifor Pharma; has received grants from National Medical Research Council of Singapore, Boston Scientific, Bayer, Roche Diagnostic, Medtronics, and Vifor Pharma; and is a paid adviser for Roche Diagnostic, AstraZeneca, Movartis, Amgen, Boehringer Ingelheim, and Abbott Diagnostics. Dr. Lund is a consultant for and has received grants from AstraZeneca, Boehringer Ingelheim, Relypsa, Novartis, and Vifor Pharma; a consultant for Sanofi and Bayer; and has received speaker honoraria from Abbott, Novartis, and Vifor Pharma. Dr. Vedin is an employee of Boehringer Ingelheim; and is a paid consultant for and has received speaker fees from Alnylam, Boehringer Ingelheim, Fresenius Medicare, Merck Sharpe & Dohme, Novartis, Orion Pharma, and Servier. Dr. Dahlström has received a research grant from AstraZeneca; and has received consulting and speaker fees from AstraZeneca and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received November 10, 2018.
- Revision received November 17, 2018.
- Accepted November 26, 2018.
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