Notably, Parikh et al. [52] demonstrated in a retrospective analysis of prospectively designed DNA sub-studies from Beta-Blocker Evaluation of Survival Trial (BEST) [53] and Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) trial [54] that enhanced efficacy of bucindolol in heart failure with reduced ejection fraction occurs at high doses for individuals with the ADRB1 Arg389Arg genotype compared with Gly389 carriers. This evidence concerns the gene ADRB1 and heart failure.