Phosphodiesterase-5 Is Elevated in Failing Single Ventricle Myocardium and Affects Cardiomyocyte Remodeling In Vitro.

Background Single ventricle (SV) congenital heart disease is fatal without intervention, and eventual heart failure is a major cause of morbidity and mortality. Although there are no proven medical therapies for the treatment or prevention of heart failure in the SV heart disease population, phosphodiesterase-5 inhibitors (PDE5i), such as sildenafil, are increasingly used. Although the pulmonary vasculature is the primary target of PDE5i therapy in patients with SV heart disease, the effects of PDE5i on the SV heart disease myocardium remain largely unknown.

Dose Response of β-Blockers in Adrenergic Receptor Polymorphism Genotypes.

Background In heart failure (HF) with reduced ejection fraction, 2 clinical trials, the BEST (β-Blocker Evaluation of Survival Trial) and HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), have reported an effectiveness interaction between the ADRB1 (β-1 adrenergic receptor) Arg389Gly polymorphism and β-blockers (BBs). HF-ACTION additionally reported a dose-related interaction of unclear origin. If confirmed and pharmacogenetically resolved, these findings may have important implications for HF with reduced ejection fraction precision therapy.

Sex-related differences in age-associated downregulation of human ventricular myocardial β1-adrenergic receptors.

Background: With increasing age, human ventricular myocardium exhibits selective downregulation of β1-adrenergic receptors (β1-ARs). We tested the hypothesis that sex differences exist in age-related changes in β1-ARs.

Methods: Left (LV) and right (RV) ventricular tissue was obtained from 61 unplaceable potential organ donor hearts ages 1 to 71 years with no known cardiac history and from LVs removed from 56 transplant recipients with idiopathic dilated cardiomyopathy.