BACKGROUND: Sympathetic hyperactivity and parasympathetic withdrawal in patients with congestive heart failure correlate closely with disease severity and overall survival. The modulating effects of drugs on the autonomic dysfunction may contribute to improve survival. Low-dose scopolamine has a vagomimetic effect in normal subjects and patients after acute myocardial infarction. We assessed whether transdermal scopolamine would increase vagal activity in patients with congestive heart failure. METHODS AND RESULTS: Heart rate variability was assessed at baseline, 24 hours after one patch of transdermal scopolamine, and 48 hours after scopolamine withdrawal in 21 patients with moderate to severe heart failure. Scopolamine increased both time- and frequency-domain parameters of heart rate variability. Specifically, the mean RR interval and its SD increased by 5.5% (P < .001) and 45% (P < .001), respectively. The change remained significant when corrected for mean heart rate with a 39% (P < .01) increase of the coefficient of variation. The absolute power of the high-frequency component was also significantly augmented. All the parameters returned to baseline after scopolamine withdrawal. Individual analysis showed that in the 7 patients in whom scopolamine did not increase mean RR interval, heart rate variability did not change. CONCLUSIONS: Transdermal scopolamine increases vagal activity as assessed by heart rate variability in patients with congestive heart failure. This autonomic modulation does not occur in all patients and can be predicted by RR interval changes. Whether such restoration of the autonomic balance might have beneficial effects in the long-term management of patients with congestive heart failure remains to be determined.
BACKGROUND: Sympathetic hyperactivity and parasympathetic withdrawal in patients with congestive heart failure correlate closely with disease severity and overall survival. The modulating effects of drugs on the autonomic dysfunction may contribute to improve survival. Low-dose scopolamine has a vagomimetic effect in normal subjects and patients after acute myocardial infarction. We assessed whether transdermal scopolamine would increase vagal activity in patients with congestive heart failure. METHODS AND RESULTS: Heart rate variability was assessed at baseline, 24 hours after one patch of transdermal scopolamine, and 48 hours after scopolamine withdrawal in 21 patients with moderate to severe heart failure. Scopolamine increased both time- and frequency-domain parameters of heart rate variability. Specifically, the mean RR interval and its SD increased by 5.5% (P < .001) and 45% (P < .001), respectively. The change remained significant when corrected for mean heart rate with a 39% (P < .01) increase of the coefficient of variation. The absolute power of the high-frequency component was also significantly augmented. All the parameters returned to baseline after scopolamine withdrawal. Individual analysis showed that in the 7 patients in whom scopolamine did not increase mean RR interval, heart rate variability did not change. CONCLUSIONS: Transdermal scopolamine increases vagal activity as assessed by heart rate variability in patients with congestive heart failure. This autonomic modulation does not occur in all patients and can be predicted by RR interval changes. Whether such restoration of the autonomic balance might have beneficial effects in the long-term management of patients with congestive heart failure remains to be determined.
Authors: Alex P Carll; Mehdi S Hazari; Christina M Perez; Q Todd Krantz; Charly J King; Najwa Haykal-Coates; Wayne E Cascio; Daniel L Costa; Aimen K Farraj Journal: Toxicol Sci Date: 2013-07-19 Impact factor: 4.849