title: Defining Advanced Heart Failure: A Systematic Review of Criteria Used in Clinical Trials.
abstract: BACKGROUND
  Enrollment criteria used in advanced heart failure (HF) clinical trials might identify a common set of widely accepted quantitative characteristics as the basis of a consensus definition for advanced HF, which is currently lacking.
  
  
  METHODS
  We reviewed all clinical trials investigating interventions in patients with advanced HF as of July 31, 2015. Eligible publications (N = 134) reported original data from clinical trials explicitly defining advanced HF in adults.
  
  
  RESULTS
  New York Heart Association (NYHA) class was the most common criterion (119 trials, 88.8%; classes ranged from II to IV), followed by left ventricular ejection fraction (LVEF) (84 trials, 62.7%; cutoff range, 20% to 45%; mode 35%). Other criteria included inotrope-dependent status (12.7%), peak oxygen consumption (10.4%), ≥1 previous HF admissions (10.4%), cardiac index (10.4%), pulmonary capillary wedge pressure (9.0%), left ventricular end-diastolic diameter (6.0%), and transplant listing status (5.2%). Cutoff points for quantitative criteria varied considerably. Previous HF admission was more frequently required in recent trials (P = .007 for temporal trend), whereas use of hemodynamic criteria decreased over time (P = .050 for temporal trend). Average LVEF among participants increased over time.
  
  
  CONCLUSIONS
  There is considerable variation in the definition of advanced HF for clinical trial purposes. Beyond NYHA and LVEF, a wide array of criteria has been used, with little consistency both in criteria selection and quantitative cutoff points.
authors.affiliation: Emory University, Atlanta, Georgia.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Bjork
authors.affiliation: Emory University, Atlanta, Georgia.
authors.forename: Kristina K
authors.initials: KK
authors.lastname: Alton
authors.affiliation: Emory University, Atlanta, Georgia.
authors.forename: Vasiliki V
authors.initials: VV
authors.lastname: Georgiopoulou
authors.affiliation: Stony Brook University, Stony Brook, New York.
authors.forename: Javed
authors.initials: J
authors.lastname: Butler
authors.affiliation: Emory University, Atlanta, Georgia. Electronic address: akaloge@emory.edu.
authors.forename: Andreas P
authors.initials: AP
authors.lastname: Kalogeropoulos
mesh_terms: D002986:Clinical Trials as Topic; D006333:Heart Failure / Q000145:classification* / Q000175:diagnosis / Q000503:physiopathology; D006801:Humans; D018579:Patient Selection; D013318:Stroke Volume
keywords: Heart failure; advanced heart failure; clinical trials; systematic review