Plasma concentration of Fas/Fas ligand and left ventricular function in response to metoprolol in conjunction with standard treatment

Recent studies suggest that cardiac myocyte apoptosis contributes to the progress of CHF (congestive heart failure). In the present study, we tested the hypothesis that metoprolol in conjunction with the standard treatment regime for CHF [an ACE (angiotensin-converting enzyme) inhibitor, diuretics and digoxin] may significantly reduce the plasma concentrations of the apoptotic mediators sFas (soluble Fas) and sFasL (soluble Fas ligand) in patients with CHF. An ELISA was used to determine the plasma concentrations of sFas and sFasL in 106 patients with stable CHF at recruitment. Echocardiography was performed at baseline and after 1 year of treatment with metoprolol in conjunction with the standard treatment regime for CHF (i.e. an ACE inhibitor, diuretics and digoxin). The dose of metoprolol was doubled on a biweekly basis up to 50 mg twice a day or maintained at the maximum tolerated dose. Data after 1 year were available for 92 patients and were analysed. The plasma concentrations of sFas and sFasL in patients with CHF decreased significantly (P<0.01) after 1 year of treatment with metoprolol in conjunction with the standard treatment regime compared with at baseline (5.4±0.2 compared with 3.2±0.1 ng/ml respectively for sFas, and 52.1±2.3 compared with 26.7±1.0 pg/ml respectively for sFasL). Compared with baseline, after 1 year of treatment with metoprolol in conjunction with the standard treatment regime there were significant improvements in LV (left ventricular) ejection fraction (from 32.6±0.9 to 51.5±0.8%; P<0.01), LV end-diastolic dimension (from 69.8±0.6 to 57.7±0.3 mm; P<0.01), LV end-systolic dimension (from 53.9±0.6 to 40.5±0.5 mm; P<0.01), LV end-diastolic volume (from 254.7±5.0 to 164.1±2.2 ml; P<0.01) and LV end-systolic volume (from 142.0±4.2 to 72.2±2.0 ml; P<0.01). In addition, the distance walked in a 6-min walk test increased markedly (P<0.01) from 260.3±5.2 m at baseline to 440.9±5.7 m after 1 year of treatment. In conclusion, we have demonstrated that metoprolol in conjunction with an ACE inhibitor, diuretics and digoxin in patients with CHF can lead to a reverse in LV remodelling potentially through its anti-apoptotic effects.