Evolution of the chronotropic response to exercise after cardiac transplantation

The chronotropic response to exercise is abnormal in cardiac transplant recipients as a result of autonomic denervation. Differences in the response between recent transplant recipients and longer-term survivors have been described in previous cross-sectional studies. These changes have not been assessed directly using serial studies. The effect of sinus node dysfunction on the chronotropic response has not previously been determined. Thirty-one transplant recipients underwent serial treadmill exercise tests using the chronotropic exercise assessment protocol 3 and 6 weeks and 3 and 6 months after transplantation. Sinus node function was assessed using standard electrophysiologic techniques. The chronotropic response increased between 3 and 6 weeks after transplantation in all subjects. Six months after transplantation, there was a further marked increase in the response in a subgroup of 5 subjects. These subjects also had a dramatic decrease in heart rate on cessation of exercise. Three subjects had abnormal sinus node function. Although heart rates and chronotropic response were below average in these subjects, 2 other subjects with normal sinus node function on electrophysiologic testing had lower heart rates and worse chronotropic responses. Thus, the chronotropic response to exercise evolves over the first 6 weeks after cardiac transplantation in all subjects. In a number of recipients (16%), there is a marked increase in chronotropic response between 3 and 6 months, which suggests efferent sympathetic reinnervation. There was no clear difference in chronotropic response between subjects with and without evidence of sinus node dysfunction.