title: Outcome of super-responders to cardiac resynchronization therapy defined by endpoint-derived parameters of left ventricular remodeling: a two-center retrospective study.
abstract: OBJECTIVE
  Various studies have attempted to identify super-responders to cardiac resynchronization therapy (CRT) by echocardiographic parameters of reverse remodeling. However, scientific evidence regarding those parameters is scarce. This study aimed at validating the definition of super-response to CRT based on the following frequently employed echocardiographic parameters: left ventricular ejection fraction (LVEF), end-diastolic volume index (EDVI), and end-systolic volume index (ESVI).
  
  
  RESULTS
  We retrospectively investigated echocardiographic data and outcomes of 542 patients after CRT implantation. The primary endpoint comprised all-cause mortality, heart transplantation, ventricular assist device implantation (VAD), and hospitalization for heart failure. Secondary endpoints were hospitalization for heart failure, and the combination of all-cause mortality, heart transplantation and VAD. Two approaches were employed defining super-response based on improvement of echocardiographic parameters: one derived from the negative predictive value (NPV) for clinical endpoints, and second from best quartiles of improvement. Using the NPV method, an absolute 25 % increase in LVEF, a relative 38 % reduction in EDVI, and 46 % in ESVI were calculated as optimal cut-offs identifying 4.9, 18.5, and 21.3 % as super-responders. The best quartiles method resulted in lower cut-off values, i.e. 14 % increase in LVEF, 26 % reduction in EDVI, and 36 % in ESVI. All cut-offs except LVEF ≥ 25% were significantly associated with improved outcomes after 5 years (median follow-up 35.7 months).
  
  
  CONCLUSIONS
  NPV- and best quartile-based cut-offs validate previously applied empirical echocardiographic cut-offs to define super-response to CRT. These data provide evidence for using these empirical cut-offs in daily practice and facilitate inter-study comparability.
authors.affiliation: Department of Cardiology, Invasive Electrophysiology and Devices, University Heart Center Zurich, Zurich, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Hürlimann
authors.forename: Susann
authors.initials: S
authors.lastname: Schmidt
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Seifert
authors.forename: Ardan M
authors.initials: AM
authors.lastname: Saguner
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hindricks
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: Frank
authors.initials: F
authors.lastname: Ruschitzka
authors.forename: Jan
authors.initials: J
authors.lastname: Steffel
mesh_terms: D058406:Cardiac Resynchronization Therapy; D004452:Echocardiography / Q000706:statistics & numerical data; D023381:Endpoint Determination / Q000379:methods*; D005260:Female; D006333:Heart Failure / Q000000981:diagnostic imaging* / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D011379:Prognosis; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013318:Stroke Volume; D015996:Survival Rate; D013557:Switzerland / Q000453:epidemiology; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging* / Q000401:mortality / Q000628:therapy*; D020257:Ventricular Remodeling