Pulmonary Hypertension (PAH) is frequent in patient with advanced Heart Failure (HF). One of the underlying mechanisms of this pathogenic pathway could be a reduced ability of the arteriolar vascular smooth muscle to relax. The cGMP plays an important in the regulation of pulmonary vascular tone and its clearance is dependant of phosphodiesterase 5 (PDE 5). The aim of this study was to investigate whether or not the PDE 5 G(-1142)T genotype was associated with PAH and could affect the NO-inhaled response in HF.
HF patients underwent VO2, echocardiography 24h before the right side cardiac catheterization. Hemodynamic parameters, cGMP plasma level (n=12) were made after Air and 20ppm NO gas breathing. The PCR-restriction fragment length polymorphism method was used to determine the PDE5 G/T gene.
Subjects: We included 72 HF patients. Most of the patients had a ischemic cardiomyopathy (54 %). The mean LVEF was 29±1 and age was 53±1. The mean pulmonary artery pressure was 25.5±1.3mmHg. The genotype TT, GT, GG and G(-1142) allele frequency distribution was respectively 38.9 %, 41.7 %, 19.4 % and 40.3 %.
Baseline characteristics were similar between the three genotypes except for the cGMP which was significantly decrease in TT genotype versus GG-GT group (p=0.02) Furthermore the pulmonary capillary wedge pressure (PCWP) trend to decrease in TT genotype (p=0.09). These results suggested that PDE 5 activity is increase in patient with TT genotype and may increase the pulmonary artery tone. NO-inhaled PVR was significantly different between the three subgroups (Anova for repeated measures: p=0.002) and was more important in the TT group with a decrease of PVR of 33 % versus 1.6 % in GG and 0 % in GT subgroups. The PVR decrease is explained by a superior increase in PCWP in TT genotype after NO inhalation. Our hypothesis is that the greatest NO-inhaled response in TT genotype is due to a greater degree of pulmonary vasoconstriction tone at baseline.
We first demonstrate that G(-1142) polymorphism of PDE 5 is functional and may regulate the basal pulmonary artery tone at baseline and increase the NO-inhaled response in Heart Failure.Le texte complet de cet article est disponible en PDF.