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Higher mortality in HFrEF patients compared to those with HFmrEF or HFpEF
Literature - Lam CSP, Gamble GD, Ling LH, et al. - Eur Heart J 2018; published on line ahead of print

Introduction and methods

There are conflicting data regarding the similarity in prevalence and mortality risk of patients with heart failure with reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction (HFpEF) and heart failure with mid-range ejection fraction (HFmrEF) [1-4].

This prospective study compared the survival over a follow-up period of 2 years of patients with HFpEF to that of patients with HFmrEF and HFrEF, using international real world data. Adults from New Zealand and Singapore, with a clinical HF diagnosis within 6 months of an episode of decompensated HF, were included in the study. The endpoints were all-cause death and hospitalization for HF (HFH). Patients with severe valve disease, transient acute pulmonary edema due to an acute coronary syndrome, end-stage renal failure, constrictive pericarditis, congenital heart disease, hypertrophic cardiomyopathy, cardiac amyloidosis, chemotherapy-associated cardiomyopathy, isolated right HF, life-threatening co-morbidity with life expectancy <1 year and inability to provide consent, were excluded from the study.

Main results

  • Out of a total of 2,039 patients, 28% (N=571) of patients had HFpEF, 13% (N=265) had HFmrEF, and 59% (N=1,203) had HFrEF. The median left ventricular ejection fraction (LVEF) was 60% in patients with HFpEF, 44% in those with HFmrEF, and 26% in those with HFrEF.
  • Creatinine, sodium, and hemoglobin values were similar in the 3 groups. The median NT-proBNP was 1184 pg/mL in HFpEF, 1532 pg/mL in HFmrEF, and 2195 pg/mL in HFrEF (P< 0.001).
  • Overall, 14% of HFpEF patients, 12% of HFmrEF patients, and 19% of HFrEF patients died (P=0.0013). The corresponding numbers of death/1,000-patient years were 75 (95%CI: 60–93) for HFpEF, 63 (95%CI: 43–88) for HFmrEF, and 109 (95%CI: 96–124) for HFrEF (P<0.0001).
  • After adjustment for age and gender, patients with HFpEF and HFmrEF had lower mortality compared with those with HFrEF (HR for HFpEF: 0.49; 95%CI: 0.38–0.65; P<0.0001; HR for HFmrEF: 0.50; 95%CI: 0.34–0.73; P=0.0004). Full adjustment led to similar results.
  • The combined endpoint of all-cause death and HFH occurred in 35% of HFpEF patients, 40% of HFmrEF, and 43% of HFrEF patients.
  • Independent predictors of all-cause mortality included age, ischemic etiology, higher NYHA Class (III or IV), lower systolic blood pressure, and higher NT-proBNP. Beta-blockers were independently related to a lower death risk (HR: 0.56; 95%CI: 0.42–0.74; P < 0.0001).


In a prospective real world study conducted in Singapore and New Zealand, the risk of all-cause death was comparable in HFpEF and HFmrEF patients and higher in HFrEF patients. The risk of death or HF hospitalization was lower for HFpEF compared with HFrEF or HFmrEF.


1. Bhatia RS, Tu JV, Lee DS, et al. Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med 2006;355:260–269.

2. Gerber Y, Weston SA, Berardi C, et al. Contemporary trends in heart failure with reduced and preserved ejection fraction after myocardial infarction: a community study. Am J Epidemiol 2013;178:1272–1280.

3. MAGGIC Collaborative Group. The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: an individual patient data meta-analysis. Eur Heart J 2012;33:1750–1757.

4. Chan MM, Lam CS. How do patients with heart failure with preserved ejection fraction die? Eur J Heart Fail 2013;15:604–613.

Find this article online at Eur Heart J

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Schedule17 May 2024