Phenomapping the Response of Patients With Ischemic Cardiomyopathy With Reduced Ejection Fraction to Surgical Revascularization

Background

Coronary artery bypass grafting (CABG) has demonstrated long-term mortality benefits in patients with HFREF and obstructive coronary artery disease (CAD), but whether phenotypic heterogeneity influences the benefits of CABG is unknown. We applied clustering analysis to STICHES (Surgical Treatment for Ischemic Heart Failure Extension Study) to identify phenogroups with different long-term risk profiles and investigate differences in CABG benefits between phenogroups.

Methods and Results

STICHES was a randomized controlled trial evaluating the effect of CABG in addition to medical therapy versus medical therapy alone. We split the STICHES participants into derivation (n = 753) and validation (n = 459) cohorts. We phenomapped the derivation cohort using penalized model-based clustering. We fit multivariable Cox models to investigate long-term differences in all-cause mortality, cardiovascular (CV) mortality, and a composite of all-cause mortality/CV hospitalization between phenogroups and whether phenogroup assignment modified the effects of CABG on these outcomes. Findings were internally validated on the validation cohort. Four phenogroups were identified in the derivation cohort. The highest-risk group was at a twofold greater risk of death (HR: 2.0, 95% CI: 1.4–2.9, p < 0.001) and CV death (HR: 2.0, 95% CI: 1.3–3.1, p = 0.002), and a 1.5-fold greater risk for death/CV hospitalization (HR: 1.5, 95% CI: 1.1–2.1, p = 0.016). Phenogroup assignment did not modify the effects of CABG on the outcomes (p > 0.05 for all). Similar results were obtained in the validation cohort.

Conclusions

The beneficial effects of CABG on all-cause mortality, CV mortality, and a composite of all-cause mortality and CV hospitalization persist despite phenotypic heterogeneity in HFREF and CAD.