Genetic Variants Are Not Associated with Outcome in Patients with Coronary Artery Disease and Left Ventricular Dysfunction: Results of the Genetic Substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) Trials.

  • Cardiovascular Research Unit
January 13, 2015 By:
  • Feldman AM
  • She L
  • McNamara DM
  • Mann DL
  • Bristow MR
  • Maisel AS
  • Wagner DR
  • Andersson B
  • Chiariello L
  • Hayward CS
  • Hendry P
  • Parker JD
  • Racine N
  • Selzman CH
  • Senni M
  • Stepinska J
  • Zembala M
  • Rouleau J
  • Velazquez EJ
  • Lee KL.

Objectives and Background: We evaluated the ability of 23 genetic variants to provide prognostic information in patients enrolled in the Genetic Substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Methods: Patients assigned to STICH Hypothesis 1 were randomized to medical therapy with or without coronary artery bypass grafting (CABG). Those assigned to STICH Hypothesis 2 were randomized to CABG or CABG with left ventricular reconstruction. Results: In patients assigned to STICH Hypothesis 2 (n = 714), no genetic variant met the prespecified Bonferroni-adjusted threshold for statistical significance (p < 0.002); however, several variants met nominal prognostic significance: variants in the beta2-adrenergic receptor gene (beta2-AR Gln27Glu) and in the A1-adenosine receptor gene (A1-717 T/G) were associated with an increased risk of a subject dying or being hospitalized for a cardiac problem (p = 0.027 and 0.031, respectively). These relationships remained nominally significant even after multivariable adjustment for prognostic clinical variables. However, none of the 23 genetic variants influenced all-cause mortality or the combination of death or cardiovascular hospitalization in the STICH Hypothesis 1 population (n = 532) by either univariate or multivariable analysis. Conclusion: We were unable to identify the predictive genotypes in optimally treated patients in these two ischemic heart failure populations. (c) 2015 S. Karger AG, Basel.

2015 Jan. Cardiology.130(2):69-81. Epub 2015 Jan 13.
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