Concomitant β-blocker therapy is associated with a lower occurrence of ventricular arrhythmias in patients with decompensated heart failure

The usefulness of β-blockers has been questioned for patients who have hypertension without a prior manifestation of coronary heart disease or heart failure. In addition, sex-based differences in the efficacy of β-blockers for prevention of heart failure during acute myocardial ischemia have never been evaluated. We explored whether the effect of β-blocker therapy varied according to the sex among patients with hypertension who have no prior history of cardiovascular disease. Data were drawn from the ISACS (International Survey of Acute Coronary Syndromes)-Archives. The study population consisted of 13 764 patients presenting with acute coronary syndromes. There were 2590 patients in whom hypertension was treated previously with β-blocker (954 women and 1636 men). Primary outcome measure was the incidence of heart failure according to Killip class classification. Subsidiary analyses were conducted to estimate the association between heart failure and all-cause mortality at 30 days. Outcome rates were assessed using the inverse probability of treatment weighting and logistic regression models. Estimates were compared by test of interaction on the log scale. Among patients taking β-blockers before admission, there was an absolute difference of 4.6% between women and men in the rate of heart failure (Killip ≥2) at hospital presentation (21.3% versus 16.7%; relative risk ratio, 1.35 [95% CI, 1.10–1.65]). On the opposite, the rate of heart failure was approximately similar among women and men who did not receive β-blockers (17.2% versus 16.1%; relative risk ratio, 1.09 [95% CI, 0.97–1.21]). The test of interaction identified a significant ( P =0.034) association between sex and β-blocker therapy. Heart failure was predictive of mortality at 30-day either in women (odds ratio, 7.54 [95% CI, 5.78–9.83]) or men (odds ratio, 9.62 [95% CI, 7.67–12.07]). In conclusion, β-blockers use may be an acute precipitant of heart failure in new-onset coronary heart disease among women, but not men. Heart failure increases the risk of death. Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT04008173.

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Long-Term Functional and Clinical Follow-Up of Patients With Heart Failure With Recovered Left Ventricular Ejection Fraction After β-Blocker Therapy

Circulation Heart Failure ◽

10.1161/circheartfailure.113.000813 ◽

2014 ◽

Vol 7 (3) ◽

pp. 434-439 ◽

Cited By ~ 53

Author(s):

Pascal de Groote ◽

Marie Fertin ◽

Anju Duva Pentiah ◽

Céline Goéminne ◽

Nicolas Lamblin ◽

...

Keyword(s):

Heart Failure ◽

Left Ventricular Ejection Fraction ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Blocker Therapy ◽

Patients With Heart Failure ◽

Β Blocker

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S49G and R389G polymorphisms of the β1-adrenergic receptor influence signaling via the cAMP-PKA and ERK pathways

Physiological Genomics ◽

10.1152/physiolgenomics.00087.2013 ◽

2013 ◽

Vol 45 (23) ◽

pp. 1186-1192 ◽

Cited By ~ 12

Author(s):

Fan Zhang ◽

Susan F. Steinberg

Keyword(s):

Heart Failure ◽

Lipid Raft ◽

Adrenergic Receptor ◽

Hek293 Cells ◽

Blocker Therapy ◽

Erk Activation ◽

Camp Pathway ◽

Biochemical Fractionation ◽

Allele Specific ◽

Β Blocker

Two functionally important β1-adrenergic receptor (β1AR) polymorphisms have been identified. The R389G polymorphism influences coupling to the Gs-cAMP pathway. R389-β1ARs display enhanced activation of cAMP/PKA; they provide short-term inotropic support but also cause a predisposition to cardiomyopathic decompensation. A second S49G polymorphism is implicated in the evolution of heart failure, but the mechanism remains uncertain. This study shows that position 49 and 389 polymorphisms function in a coordinate manner to influence agonist-dependent cAMP/PKA and ERK responses. cAMP/PKA and ERK responses are more robust in HEK293 cells that heterologously overexpress G49-β1ARs, compared with S49-β1ARs. However, this phenotype is most obvious on a G389-β1AR background; the more robust agonist-dependent cAMP/PKA and ERK responses in R389-β1AR cells effectively obscure the effect of the S49G polymorphism. We also show that isoproterenol (Iso) and carvedilol activate ERK via a similar EGFR-independent mechanism in cells expressing various β1AR haplotypes. However, Iso activates ERK via an Src-independent pathway, but carvedilol-dependent ERK activation requires Src. Since the S49G polymorphism has been linked to changes in β1AR trafficking, we examined whether β1AR polymorphisms influence partitioning to lipid raft membranes. Biochemical fractionation studies show that all four β1AR variants are recovered in buoyant flotillin-enriched membranes; the distinct signaling phenotypes of the different β1AR variants could not be attributed to any gross differences in basal compartmentalization to lipid raft membranes. The allele-specific differences in β1AR signaling phenotypes identified in this study could underlie interindividual differences in responsiveness to β-blocker therapy and clinical outcome in heart failure.

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