Relationship between regional cardiac hyperinnervation and ventricular arrhythmia

Background-Sympathetic nerve activity is known to be important in ventricul ar arrhythmogenesis, but there is little information on the relation betwee n the distribution of cardiac sympathetic nerves and the occurrence of spon taneous ventricular arrhythmias in humans. Methods and Results-We studied 53 native hearts of transplant recipients, 5 hearts obtained at autopsy of patients who died of noncardiac causes, and 7 ventricular tissues that had been surgically resected from the origin of ventricular tachycardia. The history was reviewed to determine the presence (group 1A) or absence (group 1B) of spontaneous ventricular arrhythmias. I mmunocytochemical staining for S100 protein, neurofilament protein, tyrosin e hydroxylase, and protein gene product 9.5 was performed to study the dist ribution and the density of sympathetic nerves. The average left ventricula r ejection fraction was 0.22+/-0.07. A total of 30 patients had documented ventricular arrhythmias, including ventricular tachycardia and sudden cardi ac death. A regional increase in sympathetic nerves was observed around the diseased myocardium and blood vessels in all 30 hearts. The density of ner ve fibers as determined morphometrically was significantly higher in group 1A patients (total nerve number 19.6+/-11.2/mm(2), total nerve length 3.3+/ -3.0 mm/mm(2)) than in group 1B patients (total nerve number 13.5+/-6.1/mm( 2) total nerve length 2.0+/-1.1 mm/mm(2), P<0.05 and P<0.01, respectively). Conclusions-There is an association between a history of spontaneous ventri cular arrhythmia and an increased density of sympathetic nerves in patients with severe heart failure. These findings suggest that abnormally increase d postinjury sympathetic nerve density may be in part responsible for the o ccurrence of ventricular arrhythmia and sudden cardiac death in these patie nts.