Age-dependent differences in clinical phenotype and prognosis in heart failure with mid-range ejection compared with heart failure with reduced or preserved ejection fraction

  • Xiaojing ChenEmail author
  • Gianluigi Savarese
  • Ulf Dahlström
  • Lars H. Lund
  • Michael Fu
Original Paper



HFmrEF has been recently proposed as a distinct HF phenotype. How HFmrEF differs from HFrEF and HFpEF according to age remains poorly defined. We aimed to investigate age-dependent differences in heart failure with mid-range (HFmrEF) vs. preserved (HFpEF) and reduced (HFrEF) ejection fraction.

Methods and results

42,987 patients, 23% with HFpEF, 22% with HFmrEF and 55% with HFrEF, enrolled in the Swedish heart failure registry were studied. HFpEF prevalence strongly increased, whereas that of HFrEF strongly decreased with higher age. All cardiac comorbidities and most non-cardiac comorbidities increased with aging, regardless of the HF phenotype. Notably, HFmrEF resembled HFrEF for ischemic heart disease prevalence in all age groups, whereas regarding hypertension it was more similar to HFpEF in age ≥ 80 years, to HFrEF in age < 65 years and intermediate in age 65–80 years. All-cause mortality risk was higher in HFrEF vs. HFmrEF for all age categories, whereas HFmrEF vs. HFpEF reported similar risk in ≥ 80 years old patients and lower risk in < 65 and 65–80 years old patients. Predictors of mortality were more likely cardiac comorbidities in HFrEF but more likely non-cardiac comorbidities in HFpEF and HFmrEF with < 65 years. Differences among HF phenotypes for comorbidities were less pronounced in the other age categories.


HFmrEF appeared as an intermediate phenotype between HFpEF and HFrEF, but for some characteristics such as ischemic heart disease more similar to HFrEF. With aging, HFmrEF resembled more HFpEF. Prognosis was similar in HFmrEF vs. HFpEF and better than in HFrEF.


HFmrEF HFrEF HFpEF Age Prognosis 



This study is supported by the Swedish Heart–Lung Foundation, the Swedish agreement between the government and the county councils concerning economic support for providing an infrastructure for research and education of doctors (ALF) and the Regional Development Fund, Västra Götaland County, Sweden (FOU-VGR).

Compliance with ethical standards

Conflict of interest

Xiaojing Chen: none. Gianluigi Savarese: none relevant for the present work. Unrelated to the present work: Research funding from the Italian Society of Cardiology on behalf of MSD Italia-Merck Sharp & Dohme Corporation; travel grants from Heart and Lung Foundation. Ulf Dahlström: none. Lars H. Lund: research grants to author’s institution: AstraZeneca, Novartis, Boston Scientiifc; speaker’s honoraria: AstraZeneca, Novartis, StJude, Merck; consulting honoraria: AstraZeneca, Novartis, Sanofi, Bayer, Vifor Pharma, Relypsa, Merck, HeartWare. Micheal Fu: none relevant for the present work. Unrelated to the present work: research funding and/or honoraria from AstraZeneca, Novartis, TRIOMED, and SERVIER.

Supplementary material

392_2019_1477_MOESM1_ESM.docx (40 kb)
Supplementary material 1 (DOCX 40 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of CardiologyWest China Hospital, Sichuan UniversityChengduChina
  2. 2.Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden
  3. 3.Division of Cardiology, Department of MedicineKarolinska InstitutetStockholmSweden
  4. 4.Department of Cardiology and Department of Medical and Health SciencesLinköping UniversityLinköpingSweden
  5. 5.Heart and Vascular ThemeKarolinska University HospitalStockholmSweden

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