Predictors and outcomes of heart failure with mid-range ejection fraction

Vijeta Bhambhani, Jorge R. Kizer, Joao A.c. Lima, Pim Van Der Harst, Hossein Bahrami, Matthew Nayor, Christopher R. De Filippi, Danielle Enserro, Michael J. Blaha, Mary Cushman, Thomas J. Wang, Ron T. Gansevoort, Caroline S. Fox, Hanna K. Gaggin, W.J. Kop, Kiang Liu, Ramachandran S. Vasan, Bruce M. Psaty, Douglas S. Lee, Frank P. BrouwersHans L. Hillege, Traci M. Bartz, Emelia J. Benjamin, Cheeling Chan, Matthew Allison, Julius M. Gardin, James L. Januzzi, Daniel Levy, David M. Herrington, Wiek H. Van Gilst, Alain G. Bertoni, Martin G. Larson, Rudolf A. De Boer, John S. Gottdiener, Sanjiv J. Shah, Jennifer E. Ho

Research output: Contribution to journalArticleScientificpeer-review

84 Citations (Scopus)


While heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF) are well described, determinants and outcomes of heart failure with mid-range ejection fraction (HFmrEF) remain unclear. We sought to examine clinical and biochemical predictors of incident HFmrEF in the community.

Methods and results:
We pooled data from four community-based longitudinal cohorts, with ascertainment of new heart failure (HF) classified into HFmrEF [ejection fraction (EF) 41-49%], HFpEF (EF ≥50%), and HFrEF (EF ≤40%). Predictors of incident HF subtypes were assessed using multivariable Cox models. Among 28 820 participants free of HF followed for a median of 12 years, there were 200 new HFmrEF cases, compared with 811 HFpEF and 1048 HFrEF. Clinical predictors of HFmrEF included age, male sex, systolic blood pressure, diabetes mellitus, and prior myocardial infarction (multivariable adjusted P ≤ 0.003 for all). Biomarkers that predicted HFmrEF included natriuretic peptides, cystatin-C, and high-sensitivity troponin (P ≤ 0.0004 for all). Natriuretic peptides were stronger predictors of HFrEF [hazard ratio (HR) 2.00 per 1 standard deviation increase, 95% confidence interval (CI) 1.81-2.20] than of HFmrEF (HR 1.51, 95% CI 1.20-1.90, P = 0.01 for difference), and did not differ in their association with incident HFmrEF and HFpEF (HR 1.56, 95% CI 1.41-1.73, P = 0.68 for difference). All-cause mortality following the onset of HFmrEF was worse than that of HFpEF (50 vs. 39 events per 1000 person-years, P = 0.02), but comparable to that of HFrEF (46 events per 1000 person-years, P = 0.78).

We found overlap in predictors of incident HFmrEF with other HF subtypes. In contrast, mortality risk after HFmrEF was worse than HFpEF, and similar to HFrEF
Original languageEnglish
Pages (from-to)651-659
JournalEuropean Journal of Heart Failure
Issue number4
Publication statusPublished - 2018


  • Aged
  • Cause of Death/trends
  • Echocardiography
  • Female
  • Follow-Up Studies
  • Heart Failure/diagnosis
  • Heart Ventricles/diagnostic imaging
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Risk Assessment
  • Stroke Volume/physiology
  • Survival Rate/trends
  • United States/epidemiology


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