Prospective evaluation of effect of carvedilol therapy on heart rate variability in patients with dilated cardiomyopathy

The aim of the present study was to assess the effects of carvedilol therap y in addition to conventional heart failure therapy on heart rate variabili ty (HRV) and on left ventricular function in 14 patients with mild to moder ate heart failure due to idiopathic dilated cardiomyopathy (LDC). After a 3 - to 4-week titration period. carvedilol was titrated up to 50 mg daily, or the highest dose tolerated (at least 25 mg daily). Maintenance treatment w as then continued for 8 weeks. Digital 24-hour Holter recordings were obtai ned at baseline and after 8 weeks of carvedilol therapy. HRV for the entire 24-hour period was computed in the time domain using the Oxford Medilog Ex cel 2 analysis system. Measures of HRV included the mean of all coupling in tervals between normal beats (RRm), the standard deviation of all normal RR intervals (SDNN), the square root of the mean of the squared differences b etween adjacent normal RR intervals (rMSSD), and the porportion of adjacent normal RR intervals differing > 50 ms (pNN50). Additional treatment with carvedilol induced a significant increase in HRV: SDNN increased from 77 +/- 21 ms to 110 +/- 22 ms (p = 0.001), rMSSD from 19 +/- 7 ms to 26 +/- 7 ms (p = 0.02), and mean pNN50-value increased from 1.7 +/- 1.3 % to 5.5 +/- 4.5 % (p < 0.01) under therapy with carvedilol. Me an heart rate on carvedilol calculated over 24 hours was 13 beats less than at baseline (75 bpm versus 88 bpm, p < 0.01). After 2 months of additional treatment with carvedilol, both hemodynamic and clinical parameters improv ed: left ventricular ejection fraction increased from 24 +/- 7 % to 30 +/- 10 % (p < 0.05), and New York Heart Association class decreased from 2.5 +/ - 0.8 to 1.8 +/- 0.7 (p < 0.05). In summary, eight weeks of additional carvedilol therapy induced a signific ant increase in HRV parameters related to parasympathetic activity in patie nts with IDC. Whether increased vagal tone may contribute to the protective effect of carvedilol has to be evaluated by further studies.