Hazard ratios or relative change ratios for bucindolol/placebo (95% confidence intervals), number of events, and log-rank <i>P</i> values for clinical endpoints and norepinephrine change by genotype combination groups.

<p>Abbreviations: ACM, all-cause mortality; B, bucindolol; CI, confidence interval; CVH, cardiovascular hospitalization; CVM, cardiovascular mortality; HFH, heart failure hospitalization; HFP, heart failure progression (composite of heart failure death, cardiac transplantation, heart failure hospitalization, or an emergency department visit for treatment of heart failure involving administration of intravenous heart failure medication); HR, hazard ratio; P, placebo; NE, norepinephrine; RCR, relative change ratio; RES, relative effect size.</p>A<p>Number of events presented are using the unadjusted analysis, which differs slightly from covariate-adjusted because adjusted analyses are transplant-censored.</p>B<p>All genotypes.</p>C<p>β₁389 Arg/Arg+α_{2C Wt/}Wt.</p>D<p>β₁389 Arg/Arg+α_{2C Del} carrier.</p>E<p>β₁389 Arg/Arg+any α_2C.</p>F<p>β₁389 Gly carrier+α_{2C Wt/}Wt.</p>G<p>β₁389 Gly carrier+α_{2C Del} carrier.</p>H<p>Interaction <i>P</i> value≤0.20, >0.10.</p>I<p>Interaction <i>P</i> value≤0.10, >0.05.</p>J<p>Relative change ratio.</p>K<p>[1−HR or RCR]×100.</p>L<p>RES = Ln HR (genotype group)/Ln (DNA substudy cohort).</p>M<p>See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044324#s2" target="_blank">Methods</a>.</p

Time to all-cause mortality or cardiac transplantation for Group 1/2 (A), Group 3 (B), and Group 4 (C), and time to heart failure progression (combination endpoint of heart failure mortality, cardiac transplantation, heart failure hospitalization, or emergency department care that includes intravenous therapy not requiring hospitalization) for Group 1/2 (D), Group 3 (E), and Group 4 (F).

<p>Abbreviations: AC, all-cause; BUC, bucindolol; Del, deletion; HF, heart failure; PBO, placebo.</p

Baseline characteristics by genotype combination groups.

<p>Data presented as means ± standard deviations, unless otherwise noted.</p><p>Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; BP, blood pressure; CHF, chronic heart failure; HF, heart failure; LVEF, left ventricular ejection fraction; NE, norepinephrine; NYHA, New York Heart Association.</p>A<p>β<b>₁</b>389 Arg/Arg+α<b>_2C</b>_Wt/Wt.</p>B<p>β<b>₁</b>389 Arg/Arg+α<b>_2C</b>_Del carrier.</p>C<p>β<b>₁</b>389 Gly carrier+α_{2c Wt/}Wt.</p>D<p>β<b>₁</b>389 Gly carrier+α<b>_2C</b>_Del carrier.</p>E<p><i>P</i><0.05 by ANOVA (ANalysis Of Variance).</p>F<p><i>P</i><0.0083 by Bonferroni for all pair wise comparisons.</p>G<p><i>P</i><0.05 by Chi-square test.</p>H<p><i>P</i><0.0083 by Bonferroni vs. Group 4.</p>I<p><i>P</i><0.0083 by Bonferroni vs. Group 1.</p>J<p><i>P</i><0.0083 by Bonferroni vs. Group 2.</p

Representative competition curves between 50 pM ¹²⁵[I]CYP and L-NE at increasing concentrations, in the absence and presence of 30 µM Gpp(NH)p in membranes from a non-failing human left ventricle with 77% β₁ AR that was β₁389 Arg/Arg genotype (A) and in membranes from a non-failing human heart with 77% β₁ AR that was β₁389 Arg/Gly genotype (B); mean±SEM (%) of high-affinity L-NE binding sites identified in seven β₁389 Arg/Arg, five β₁389 Arg/Gly, and five β₁389 Gly/Gly left ventricles (C).

<p>Abbreviations: AR, adrenergic receptor; CYP, cyanopindolol; Gpp(NH)p, non-hydrolyzable guanine nucleotide; K_H, dissociation constant; K_L, low-affinity binding constant; L-NE, L-norepinephrine; SEM, standard error measurement.</p