The present study provides the first clear evidence to indicate that even on a genetic background of homozygosity for the risk allele of the α2C-AR Del322-325 variant, the β1-AR gene variant at position 389 does not influence either the risk for the clinical expression of the phenotype for heart failure, the severity of heart failure, or the progression of heart failure independent of β-AR-blocker therapy. Here, ADRB2 is linked to heart failure.