Influence of angiotensin converting enzyme inhibitor treatment on cardiac autonomic modulation in patients receiving haemodialysis

BACKGROUND: Cardiovascular disease mortality among patients with end stage renal disease (ESRD) exceeds that which is predicted by traditional risk factors. Sudden death accounts for up to 15-38% of patients with ESRD found dead at home. Heart rate variability (HRV) is a reliable measure of autonomic modulation and has a very strong predictive value for ventricular arrhythmias and sudden death. A lower HRV is associated with increased risk. Modifying autonomic tone pharmacologically reduces death from dysrhythmia in the general population but has not been studied in ESRD. METHODS: We examined the effect of ramipril, an angiotensin converting enzyme inhibitor (ACEI) known in the general population to increase HRV, on cardiac function and heart rate variability in patients with renal failure. Eligible subjects on haemodialysis underwent a 2-week washout period free of ACEI or beta blockers, during which time hypertension was treated with amlodipine, which has been shown not to affect HRV. Haemodynamic and HRV measurements were obtained at baseline and after subjects were treated for 4 weeks with an ACEI. RESULTS: Haemodynamics did not differ at 0 and 4 weeks. Baseline HRV values were markedly below those found in the general population, indicating pronounced predominance of sympathetic tone over vagal tone. Actual worsening of HRV with ACEI treatment was evident in several major time domains. The time domain SDNN (the standard deviation of all normal RR intervals) fell from 42.0 +/- 24.8 ms to 20.1 +/- 16.1 ms (P = 0.004) and the triangulation index fell from 178.0 +/- 94.0 to 115 +/- 59.2 (P = 0.01). A trend toward reduced HRV was seen in several other time domains. CONCLUSION: These findings suggest that, unlike the general population, treatment of ESRD patients with an angiotensin converting enzyme inhibitor may cause a deleterious shift toward increased cardiac sympathetic nervous system tone.