title: Heart Failure and Midrange Ejection Fraction: Implications of Recovered Ejection Fraction for Exercise Tolerance and Outcomes.
abstract: BACKGROUND
  Evidence-based therapies for heart failure (HF) differ significantly according to left ventricular ejection fraction (LVEF). However, few data are available on the phenotype and prognosis of patients with HF with midrange LVEF of 40% to 55%, and the impact of recovered systolic function on the clinical features, functional capacity, and outcomes of this population is not known.
  
  
  RESULTS
  We studied 944 patients with HF who underwent clinically indicated cardiopulmonary exercise testing. The study population was categorized according to LVEF as follows: HF with reduced LVEF (HFrEF; LVEF<40%; n=620); HF with midrange ejection fraction and no recovered ejection fraction (LVEF was consistent between 40% and 55%; n=107); HF with recovered midrange ejection fraction (LVEF, 40%-55% but previous LVEF<40%; n=170); and HF with preserved LVEF (HFpEF; LVEF>55%; n=47). HF with midrange ejection fraction and no recovered ejection fraction and HF with recovered midrange ejection fraction had similar clinical characteristics, which were intermediate between those of HFrEF and HFpEF, and comparable values of predicted peak oxygen consumption and minute-ventilation/carbon dioxide production slope, which were better than HFrEF and similar to HFpEF. After a median of 4.4 (2.9-5.7) years, there were 253 composite events (death, left ventricular assistant device implantation, or transplantation). In multivariable Cox-regression analysis, HF with recovered midrange ejection fraction had lower risk of composite events than HFrEF (hazard ratio, 0.25; 95% confidence interval, 0.13-0.47) and HF with midrange ejection fraction and no recovered ejection fraction (hazard ratio, 0.31; 95% confidence interval, 0.15-0.67), and similar prognosis when compared with HFpEF. In contrast, HF with midrange ejection fraction and no recovered ejection fraction tended to show intermediate risk of outcomes in comparison with HFpEF and HFrEF, albeit not reaching statistical significance in fully adjusted analyses.
  
  
  CONCLUSIONS
  Patients with HF with midrange LVEF demonstrate a distinct clinical profile from HFpEF and HFrEF patients, with objective measures of functional capacity similar to HFpEF. Within the midrange LVEF HF population, recovered systolic function is a marker of more favorable prognosis.
authors.affiliation: From the Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (W.N., E.W., H.S., J.D.G., A.M.S.); Department of Internal Medicine, University of Campinas, Campinas, Brazil (W.N.); Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine of University of Porto, Porto, Portugal (M.S.); and Department of Medicine, Section of Geriatric Cardiology, University of Pittsburgh Medical Center, PA (D.E.F.).
authors.forename: Wilson
authors.initials: W
authors.lastname: Nadruz
authors.affiliation: From the Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (W.N., E.W., H.S., J.D.G., A.M.S.); Department of Internal Medicine, University of Campinas, Campinas, Brazil (W.N.); Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine of University of Porto, Porto, Portugal (M.S.); and Department of Medicine, Section of Geriatric Cardiology, University of Pittsburgh Medical Center, PA (D.E.F.).
authors.forename: Erin
authors.initials: E
authors.lastname: West
authors.affiliation: From the Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (W.N., E.W., H.S., J.D.G., A.M.S.); Department of Internal Medicine, University of Campinas, Campinas, Brazil (W.N.); Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine of University of Porto, Porto, Portugal (M.S.); and Department of Medicine, Section of Geriatric Cardiology, University of Pittsburgh Medical Center, PA (D.E.F.).
authors.forename: Mário
authors.initials: M
authors.lastname: Santos
authors.affiliation: From the Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (W.N., E.W., H.S., J.D.G., A.M.S.); Department of Internal Medicine, University of Campinas, Campinas, Brazil (W.N.); Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine of University of Porto, Porto, Portugal (M.S.); and Department of Medicine, Section of Geriatric Cardiology, University of Pittsburgh Medical Center, PA (D.E.F.).
authors.forename: Hicham
authors.initials: H
authors.lastname: Skali
authors.affiliation: From the Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (W.N., E.W., H.S., J.D.G., A.M.S.); Department of Internal Medicine, University of Campinas, Campinas, Brazil (W.N.); Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine of University of Porto, Porto, Portugal (M.S.); and Department of Medicine, Section of Geriatric Cardiology, University of Pittsburgh Medical Center, PA (D.E.F.).
authors.forename: John D
authors.initials: JD
authors.lastname: Groarke
authors.affiliation: From the Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (W.N., E.W., H.S., J.D.G., A.M.S.); Department of Internal Medicine, University of Campinas, Campinas, Brazil (W.N.); Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine of University of Porto, Porto, Portugal (M.S.); and Department of Medicine, Section of Geriatric Cardiology, University of Pittsburgh Medical Center, PA (D.E.F.).
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Forman
authors.affiliation: From the Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (W.N., E.W., H.S., J.D.G., A.M.S.); Department of Internal Medicine, University of Campinas, Campinas, Brazil (W.N.); Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine of University of Porto, Porto, Portugal (M.S.); and Department of Medicine, Section of Geriatric Cardiology, University of Pittsburgh Medical Center, PA (D.E.F.). ashah11@partners.org.
authors.forename: Amil M
authors.initials: AM
authors.lastname: Shah
mesh_terms: D000328:Adult; D000368:Aged; D016009:Chi-Square Distribution; D005080:Exercise Test; D017079:Exercise Tolerance; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy; D016027:Heart Transplantation; D006353:Heart-Assist Devices; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010101:Oxygen Consumption; D016016:Proportional Hazards Models; D012123:Pulmonary Ventilation; D020127:Recovery of Function; D012307:Risk Factors; D013318:Stroke Volume; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left
keywords: heart failure oxygen consumption; ventricular ejection fraction; ventricular function, left