Vijeta Bhambhani1,2, Jorge R Kizer3, Joao A C Lima4, Pim van der Harst5, Hossein Bahrami6, Matthew Nayor2, Christopher R de Filippi7, Danielle Enserro8, Michael J Blaha9, Mary Cushman10, Thomas J Wang11, Ron T Gansevoort12, Caroline S Fox13, Hanna K Gaggin2, Willem J Kop14, Kiang Liu15, Ramachandran S Vasan8,13,16, Bruce M Psaty17,18, Douglas S Lee19, Frank P Brouwers5, Hans L Hillege5, Traci M Bartz20, Emelia J Benjamin13,16, Cheeling Chan15, Matthew Allison21, Julius M Gardin22, James L Januzzi2, Daniel Levy13,23, David M Herrington24, Wiek H van Gilst5, Alain G Bertoni25, Martin G Larson13,26, Rudolf A de Boer5, John S Gottdiener27, Sanjiv J Shah28, Jennifer E Ho1,2. 1. Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA. 2. Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. 3. Department of Medicine and Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA. 4. Department of Medicine and Cardiology, Heart and Vascular Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA. 5. Department of Cardiology, University of Groningen, University Medical Center Groningen, The Netherlands. 6. Division of Cardiovascular Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA. 7. Inova Heart and Vascular Institute, Falls Church, VA, USA. 8. Department of Preventive Medicine, Boston University School of Medicine, Boston, MA, USA. 9. Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins University, Baltimore, MD, USA. 10. University of Vermont Larner College of Medicine, Burlington, VT, USA. 11. Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. 12. Department of Internal Medicine, University of Groningen, University Medical Center Groningen, The Netherlands. 13. Framingham Heart Study, Framingham, MA, USA. 14. Center of Research on Psychology in Somatic Diseases, Department of Medical and Clinical Psychology, Tilburg University, Tilburg, The Netherlands. 15. Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 16. Cardiovascular Medicine Section, Department of Medicine, Boston University School of Medicine, Boston, MA, USA. 17. Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, WA, USA. 18. Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA. 19. Institute for Clinical Evaluative Sciences, Toronto, Canada. 20. Department of Biostatistics, University of Washington, Seattle, WA, USA. 21. University of California, San Diego, Department of Family Medicine and Public Health, La Jolla, CA, USA. 22. Division of Cardiology, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA. 23. Population Sciences Branch of the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. 24. Section on Cardiovascular Medicine, Wake Forest School of Medicine Winston Salem, NC, USA. 25. Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine Winston Salem, NC, USA. 26. Department of Mathematics and Statistics, Boston University, Boston, MA, USA. 27. Division of Cardiology, Department of Medicine, University of Maryland, Baltimore, MD, USA. 28. Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Abstract
AIMS: 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). CONCLUSIONS: 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.
AIMS: 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). CONCLUSIONS: 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.
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