title: The Hospitalization Burden and Post-Hospitalization Mortality Risk in Heart Failure With Preserved Ejection Fraction: Results From the I-PRESERVE Trial (Irbesartan in Heart Failure and Preserved Ejection Fraction).
abstract: OBJECTIVE
  The aim of this study was to investigate prognosis in patients with heart failure (HF) with preserved ejection fraction and the causes of hospitalization and post-hospitalization mortality.
  
  
  BACKGROUND
  Although hospitalizations in patients with HF with preserved ejection fraction are common, there are limited data from clinical trials on the causes of admission and the influence of hospitalizations on subsequent mortality risk.
  
  
  METHODS
  Patients (n = 4,128) with New York Heart Association functional class II to IV HF and left ventricular ejection fractions >45% were enrolled in I-PRESERVE (Irbesartan in Heart Failure and Preserved Ejection Fraction). A blinded events committee adjudicated cardiovascular hospitalizations and all deaths using predefined and standardized definitions. The risk for death after HF, any-cause, or non-HF hospitalization was assessed using time-dependent Cox proportional hazard models.
  
  
  RESULTS
  A total of 2,278 patients had 5,863 hospitalizations during the 49 months of follow-up, of which 3,585 (61%) were recurrent hospitalizations. For any-cause hospitalizations, 26.5% of patients died during follow-up, with an incident mortality rate of 11.1 deaths per 100 patient-years (PYs) and an adjusted hazard ratio of 5.32 (95% confidence interval: 4.21 to 6.23). Overall, 53.6% of hospitalizations were classified as cardiovascular and 43.7% as noncardiovascular, with 2.7% not classifiable. HF was the largest single cause of initial (17.6%) and overall (21.1%) hospitalizations, although, after HF hospitalization, a substantially higher proportion of readmissions were due to primary HF causes (40%). HF hospitalization occurred in 685 patients, with 41% deaths during follow-up, an incident mortality rate of 19.3 deaths per 100 PYs. The adjusted hazard ratio was 2.93 (95% confidence interval: 2.40 to 3.57) relative to patients who were not hospitalized for HF and was greater in those with longer durations of hospitalization. There were 1,593 patients with only non-HF hospitalizations, 21% of whom died during follow-up, with an incident mortality rate of 8.7 deaths per 100 PYs and an adjusted hazard ratio of 4.25 (95% confidence interval: 3.27 to 5.32). The risk for death was highest in the first 30 days and declined over time for all hospitalization categories. Patients not hospitalized for HF or for any cause had observed incident mortality rates of 3.8 and 1.3 deaths per 100 PYs, respectively.
  
  
  CONCLUSIONS
  In I-PRESERVE, HFpEF patients hospitalized for any reason, and especially for HF, were at high risk for subsequent death, particularly early. The findings support the need for careful attention in the post-discharge time period including attention to comorbid conditions. Among those hospitalized for HF, the high mortality rate and increased proportion of readmissions due to HF (highest during the first 30 days), suggest that this group would be an appropriate target for investigation of new interventions.
authors.affiliation: Washington Veterans Affairs Medical Center and Georgetown University, Washington, District of Columbia. Electronic address: peter.carson@med.va.gov.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Carson
authors.affiliation: Veterans Affairs Health Care System and University of Minnesota, Minneapolis, Minnesota.
authors.forename: Inder S
authors.initials: IS
authors.lastname: Anand
authors.affiliation: Veterans Affairs Health Care System and University of Minnesota, Minneapolis, Minnesota.
authors.forename: Sithu
authors.initials: S
authors.lastname: Win
authors.affiliation: Veterans Affairs Health Care System and University of Minnesota, Minneapolis, Minnesota.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rector
authors.affiliation: Theresienkrankenhaus, Mannheim, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Haass
authors.affiliation: Hospital Gregorio Maranon, Madrid, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Lopez-Sendon
authors.affiliation: University of Florida-Jacksonville, Jacksonville, Florida.
authors.forename: Alan
authors.initials: A
authors.lastname: Miller
authors.affiliation: San Francisco Veterans Affairs Medical Center and University of California, San Francisco, San Francisco, California.
authors.forename: John R
authors.initials: JR
authors.lastname: Teerlink
authors.affiliation: Montreal Heart Institute Research Center, Montreal, Quebec, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: White
authors.affiliation: Population Health Research Institute and McMaster University, Hamilton, Ontario, Canada.
authors.forename: Robert S
authors.initials: RS
authors.lastname: McKelvie
authors.affiliation: Université Paris, Pitie Salpetriere Hospital, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Komajda
authors.affiliation: Ralph H. Johnson Veterans Affairs Medical Center and Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Zile
authors.affiliation: British Heart Foundation Glasgow Cardiovascular Research Center, Glasgow, United Kingdom.
authors.forename: John J
authors.initials: JJ
authors.lastname: McMurray
authors.affiliation: San Francisco Veterans Affairs Medical Center and University of California, San Francisco, San Francisco, California.
authors.forename: Barry
authors.initials: B
authors.lastname: Massie
mesh_terms: D000368:Aged; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000401:mortality* / Q000503:physiopathology; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D013318:Stroke Volume / Q000502:physiology
keywords: heart failure; hospitalizations; preserved ejection fraction; prognosis