Low-dose but not high-dose captopril increases parasympathetic activity in patients with heart failure

Parasympathetic nervous activity (PSNA) is an important determinant of the risk of sudden death and outcome in patients with cardiovascular disease, so the effects of drug therapy on PSNA may be of prognostic importance in patients with chronic heart failure (CHF). The angiotensin-converting enzyme (ACE) inhibitors are the only drugs that are reasonably accepted to improve prognosis in such patients. Accordingly we determined PSNA by heart-rate variability (HRV) analysis in nine patients (four women and five men, aged 73.6 +/- 6 yrs) with heart failure (NYHA Classes II-III) and in sinus rhythm. HRV was determined during 20-40 min supine rest at baseline and then at 2-weekly intervals during incremental dosing of oral captopril, 12.5 mg b.i.d., 25 mg b.i.d., and 50 mg b.i.d. Poincaré plot and conventional time- and frequency-domain measures were used to analyze the data. Low-dose captopril (12.5 mg b.i.d.) resulted in an increase in SD delta RR (16.0 +/- 6.6 to 22.0 +/- 9.1 ms; p < 0.05). We previously validated this as a measure of PSNA. Higher dose captopril (25 mg b.i.d.) also produced an increase in PSNA activity (16.0 +/- 6.6 to 18.7 +/- 7.8 ms), although this failed to reach statistical significance. However, the highest dose of captopril (50 mg b.i.d.) reduced PSNA activity to near-baseline values, as shown by measures of HRV in both the time and frequency domains. These data suggest that only a low dose of captopril augments PSNA in patients with heart failure. Dosing of ACE inhibitors may be important in optimizing their benefit in CHF.