Plasma Galectin-3 and Heart Failure Outcomes in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy)

Craig M. Stolen, Aram Adourian, Timothy E. Meyer, Kenneth M. Stein, Scott D. Solomon
2014 Journal of Cardiac Failure  
Elevated circulating levels of the protein galectin-3, a mediator of fibrogenesis, have previously been associated with adverse outcomes in heart failure (HF) patients and appear to modify response to certain pharmacologic therapies. This study investigated the relationship between galectin-3 level and clinical outcomes in HF patients randomized to implantable cardioverter defibrillator (ICDonly) or cardiac resynchronization therapy (CRT-D). Methods and Results: Plasma galectin-3 concentrations
more » ... were measured in 654 New York Heart Association functional class I/II patients participating in the MADIT-CRT trial. A heterogeneity of response was detected between pre-implantation galectin-3 and randomization group (CRT-D or ICD-only) on the primary MADIT-CRT trial end point of nonfatal HF event or death (P 5 .045). Among patients with baseline galectin-3 levels in the top quartile of the distribution, CRT-D was associated with a 65% reduction in risk of the primary end point (hazard ratio [HR] 0.35, 95% confidence interval [CI] 0.19e0.67), whereas among patients with lower baseline galectin-3 values CRT-D was associated with a 25% decrease in risk (HR 0.75, 95% CI. 0.51e1.11). Baseline galectin-3 level also was observed to be an independent predictor of the primary end point (multivariable adjusted HR per log unit increase: 1.55; 95% CI 1.01e2.38; P 5 .043). Conclusions: Elevated galectin-3 was found to be an independent predictor of adverse HF outcome in patients with mildly symptomatic HF. A significant interaction of device randomization group with preimplantation galectin-3 level was detected, with HF patients with the highest baseline galectin-3 levels deriving a disproportionately larger benefit from CRT-D. (J Cardiac Fail 2014;20:793e799)
doi:10.1016/j.cardfail.2014.07.018 pmid:25106783 fatcat:fiarogorhrbytb3i24gqdp32aa