Improvement of Vagal Tone by ACE Inhibition: A Mechanism of Cardioprotection in Patients with Mild-to-Moderate Heart Failure

A total of 35 patients in sinus rhythm and with mild-to-moderate congestive heart failure (CHF) (NYHA II-III) aged 53 (+/- 3) years were examined before therapy with angiotensin-converting enzyme (ACE) inhibitors. Of these patients, 16 were reexamined after therapy with ACE inhibitors for 17 +/- 3 days. The relation of hemodynamic alterations to vagal tone was assessed and the influence of parasympathetic (baroreflex activation) tone on survival was evaluated. Only hemodynamic responders to ACE inhibition showed a significant increase of vagal tone from 1.4 +/- 0.4 to 3.6 +/- 1.2 ms/mm Hg (p < 0.01). The magnitude of increase of vagal tone was dependent on the baseline level. All 35 patients were discharged on ACE inhibitors and were followed for 56 months or longer. We compared patients whose hearts survived (20 patients) with those whose hearts did not (15 patients). Twelve patients died and three underwent cardiac transplantation. The two groups differed (p < 0.05) in terms of mean arterial blood pressure (98 +/- 3 vs. 90 +/- 3 mm Hg), heart rate (82 +/- 2 vs. 93 +/- 4 beats/min), and mean pulmonary artery pressure (24 +/- 3 vs. 35 +/- 2 mm Hg). Cardiac index, stroke volume index, and right atrial pressures were not different. Heart survivors had lower (p < 0.05) renin values (3.6 +/- 0.8 vs. 9.0 +/- 3.6 Ang-I/ml/h) but norepinephrine values at baseline were not different. Baroreflex sensitivity was lower (p < 0.02) in survivors than in nonsurvivors (1.3 +/- 0.2 vs. 2.3 +/- 0.3 ms/mm Hg). We then calculated the mortality risk in relation to baroreflex sensitivity at the median BS of 1.6 ms/mm Hg. Survival was different (p < 0.004) between the resulting two groups: 2 of 15 subjects (13%) with high baroreflex sensitivity died, and 13 of 20 patients (65%) whose baroreflex sensitivity was less than 1.6 ms/mm Hg died. When systemic blood pressure, pulmonary artery pressure, stroke volume index, plasma norepinephrine concentrations, and baroreflex sensitivity were entered into a Cox proportional hazards regression, only systolic blood pressure and plasma norepinephrine values predicted survival (p < 0.001). We concluded that high vagal tone is correlated with a good prognosis in patients with CHF. ACE inhibitor therapy can increase the vagal tone significantly. This may alter the incidence of sudden cardiac death and thereby improve prognosis.