title: Prognostic Importance of Impaired Systolic Function in Heart Failure With Preserved Ejection Fraction and the Impact of Spironolactone.
abstract: BACKGROUND
  Impairment in left ventricular systolic function has been described in heart failure (HF) with preserved ejection fraction (HFpEF), but its prognostic relevance is not known. We determined whether left ventricular longitudinal strain (LS) is predictive of cardiovascular outcomes in HFpEF beyond clinical and conventional echocardiographic measures.
  
  
  RESULTS
  LS was assessed by 2-dimensional speckle-tracking echocardiography at baseline in 447 patients with HFpEF enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. At a median follow-up of 2.6 years (interquartile range, 1.5-3.9 years), 115 patients experienced the primary composite outcome of cardiovascular death, HF hospitalization, or aborted cardiac arrest. Impaired LS, defined as an absolute LS <15.8%, was present in 52% of patients and was predictive of the composite outcome (adjusted hazard ratio, 2.14; 95% confidence interval, 1.26-3.66; P=0.005), cardiovascular death alone (adjusted hazard ratio, 3.20; 95% confidence interval, 1.44-7.12; P=0.004), and HF hospitalization alone (adjusted hazard ratio, 2.23; 95% confidence interval, 1.16-4.28; P=0.016) after adjustment for clinical and conventional echocardiographic variables. LS was the strongest echocardiographic predictor of the composite outcome. Exploratory analysis in a subset of 131 patients with follow-up LS assessed after 12 to 18 months demonstrated a trend toward improvement in LS associated with spironolactone in patients enrolled in the Americas but not in Russia or Georgia.
  
  
  CONCLUSIONS
  Impaired left ventricular systolic function is a powerful predictor of HF hospitalization, cardiovascular death, or aborted cardiac arrest in HFpEF independent of clinical predictors. Impaired LS represents a novel imaging biomarker to identify patients with HFpEF at particularly high risk for cardiovascular morbidity and mortality.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.
authors.affiliation: From Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.M.S., B.C., L.L., M.A.P., S.D.S.); Sarver Heart Center, University of Arizona College of Medicine, Tucson (N.K.S.); Cardiology Division, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.); Cardiovascular Division, VA Medical Center, Minneapolis, MN (I.S.A.); and Cardiology Division, University of Michigan School of Medicine, Ann Arbor (B.P.). ashah11@partners.org.
authors.forename: Amil M
authors.initials: AM
authors.lastname: Shah
authors.affiliation: From Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.M.S., B.C., L.L., M.A.P., S.D.S.); Sarver Heart Center, University of Arizona College of Medicine, Tucson (N.K.S.); Cardiology Division, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.); Cardiovascular Division, VA Medical Center, Minneapolis, MN (I.S.A.); and Cardiology Division, University of Michigan School of Medicine, Ann Arbor (B.P.).
authors.forename: Brian
authors.initials: B
authors.lastname: Claggett
authors.affiliation: From Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.M.S., B.C., L.L., M.A.P., S.D.S.); Sarver Heart Center, University of Arizona College of Medicine, Tucson (N.K.S.); Cardiology Division, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.); Cardiovascular Division, VA Medical Center, Minneapolis, MN (I.S.A.); and Cardiology Division, University of Michigan School of Medicine, Ann Arbor (B.P.).
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Sweitzer
authors.affiliation: From Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.M.S., B.C., L.L., M.A.P., S.D.S.); Sarver Heart Center, University of Arizona College of Medicine, Tucson (N.K.S.); Cardiology Division, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.); Cardiovascular Division, VA Medical Center, Minneapolis, MN (I.S.A.); and Cardiology Division, University of Michigan School of Medicine, Ann Arbor (B.P.).
authors.forename: Sanjiv J
authors.initials: SJ
authors.lastname: Shah
authors.affiliation: From Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.M.S., B.C., L.L., M.A.P., S.D.S.); Sarver Heart Center, University of Arizona College of Medicine, Tucson (N.K.S.); Cardiology Division, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.); Cardiovascular Division, VA Medical Center, Minneapolis, MN (I.S.A.); and Cardiology Division, University of Michigan School of Medicine, Ann Arbor (B.P.).
authors.forename: Inder S
authors.initials: IS
authors.lastname: Anand
authors.affiliation: From Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.M.S., B.C., L.L., M.A.P., S.D.S.); Sarver Heart Center, University of Arizona College of Medicine, Tucson (N.K.S.); Cardiology Division, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.); Cardiovascular Division, VA Medical Center, Minneapolis, MN (I.S.A.); and Cardiology Division, University of Michigan School of Medicine, Ann Arbor (B.P.).
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: From Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.M.S., B.C., L.L., M.A.P., S.D.S.); Sarver Heart Center, University of Arizona College of Medicine, Tucson (N.K.S.); Cardiology Division, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.); Cardiovascular Division, VA Medical Center, Minneapolis, MN (I.S.A.); and Cardiology Division, University of Michigan School of Medicine, Ann Arbor (B.P.).
authors.forename: Bertram
authors.initials: B
authors.lastname: Pitt
authors.affiliation: From Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.M.S., B.C., L.L., M.A.P., S.D.S.); Sarver Heart Center, University of Arizona College of Medicine, Tucson (N.K.S.); Cardiology Division, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.); Cardiovascular Division, VA Medical Center, Minneapolis, MN (I.S.A.); and Cardiology Division, University of Michigan School of Medicine, Ann Arbor (B.P.).
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pfeffer
authors.affiliation: From Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.M.S., B.C., L.L., M.A.P., S.D.S.); Sarver Heart Center, University of Arizona College of Medicine, Tucson (N.K.S.); Cardiology Division, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.); Cardiovascular Division, VA Medical Center, Minneapolis, MN (I.S.A.); and Cardiology Division, University of Michigan School of Medicine, Ann Arbor (B.P.).
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006323:Heart Arrest / Q000453:epidemiology; D054143:Heart Failure, Systolic / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D038622:Internationality; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D011379:Prognosis; D013148:Spironolactone / Q000494:pharmacology / Q000627:therapeutic use*; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology*; D015996:Survival Rate; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology*
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone
keywords: clinical trial; heart failure; heart ventricles; preserved left ventricular function; spironolactone; strain