Of the five missense variants we identified in the exons of the ADRB1, ADRB2, and GRK5 genes, only ADRB2 Arg16Gly A > G (G being the minor allele, with a frequency of 38.2% in our HF cohort) was significantly associated with heterogeneity in the primary end point and an individual end point of cardiovascular deaths (both P < 0.001 by Log rank test) (Fig. 2a, b). This evidence concerns the gene GRK5 and hydrops fetalis.