Cholinergic stimulation with pyridostigmine reduces ventricular arrhythmia and enhances heart rate variability in heart failure.
BACKGROUND
Increased ventricular arrhythmia density and reduced heart rate variability are associated with risk of death in patients with heart failure. Cholinesterase inhibition with pyridostigmine bromide increases heart rate variability in normal subjects, but its effect on patients with heart failure is unknown. In this study, we tested the hypothesis that short-term administration of pyridostigmine bromide, a cholinesterase inhibitor, reduces ventricular arrhythmia density and increases heart rate variability in patients with congestive heart failure.


METHODS
Patients with heart failure and in sinus rhythm participated in a double-blind, cross-over protocol, randomized for placebo and pyridostigmine (30 mg orally 3 times daily for 2 days). Twenty-four hour electrocardiographic recordings were performed for arrhythmia analysis and for the measurement of time domain indices of heart rate variability. Patients were separated into 2 groups, according to their ventricular arrhythmia density. The arrhythmia group (n = 11) included patients with >10 ventricular premature beats (VPBs) per hour (VPBs/h), and the heart rate variability group (n = 12) included patients with a number of VPBs in 24 hours not exceeding 1% of the total number of R-R intervals.


RESULTS
For the arrhythmia group, pyridostigmine resulted in a 65% reduction of ventricular ectopic activity (placebo 266 +/- 56 VPBs/h vs pyridostigmine 173 +/- 49 VPBs/h, P =.03). For the heart rate variability group, pyridostigmine administration increased mean R-R interval (placebo 733 +/- 22 ms vs pyridostigmine 790 +/- 33 ms, P =.01), and in the time domain indices of heart rate variability root-mean-square of successive differences (placebo 21 +/- 2 ms vs pyridostigmine 27 +/- 3 ms, P =.01) and percentage of pairs of adjacent R-R intervals differing by >50 ms (placebo 3% +/- 1% vs pyridostigmine 6% +/- 2%, P =.03).


CONCLUSIONS
In patients with heart failure, pyridostigmine reduced ventricular arrhythmia density and increased heart rate variability, most likely due to its cholinomimetic effect. Long-term trials with pyridostigmine in heart failure should be conducted.
Behling
Alice
A
Division of Cardiology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Moraes
Ruy S
RS
Rohde
Luis E
LE
Ferlin
Elton L
EL
Nóbrega
Antonio C L
AC
Ribeiro
Jorge P
JP
D000284:Administration, Oral; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D002303:Cardiac Output, Low / Q000188:drug therapy / Q000503:physiopathology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D011729:Pyridostigmine Bromide / Q000008:administration & dosage*; D018709:Statistics, Nonparametric; D013997:Time Factors
D002800:Cholinesterase Inhibitors; D011729:Pyridostigmine Bromide