Abstract

Abstract Background Denervation at heart transplant (HTx) results in attenuated heart rate (HR) control and limited exercise tolerance. Purpose The aim of this study was to assess longitudinal changes in the HR response to exercise in HTx recipients. We compared the results with those of healthy controls. Methods Seventy-four HTx recipients were enrolled in a cardiopulmonary exercise trial. The HR response to maximal exercise was tested at 11 weeks and at 1- and 3-years follow-up post HTx, and compared with the HR response in 50 age and gender matched controls. The HR was measured at rest, at 25-, 50-, 75-, and 100% of VO2peak, and 30 sec, 1, 2, and 4 min after peak exercise on a treadmill or bicycle ergometer. We also assessed the HR reserve and the chronotropic response index (CRI). Results Elleven weeks after HTx, the HR response to exercise was blunted, but improved significantly during follow-up. The change in HR from rest to peak exercise increased by 53% (41 bpm vs 62 bpm; p<0.001) from inclusion to 12 months follow-up, but levelled off between 12- and 36 months (62 bpm vs 65 bpm; p=0.59) (Figure 1). In comparison, the exercise-induced increase in HR in healthy controls was 117 bpm. In HTx recipients, approximately 40% of the total increase in HR occurred between rest and 25% of VO2peak at inclusion (Figure). In contrast, only 31% of the increase in HR in healthy controls occurred between rest and 25% of VO2peak (p<0.001). The fall in HR during the first 4 minutes after exercise increased over the duration of the study (p<0.001 for all comparisons between inclusion and 12 months, and 12- and 36 months at 30 sec, 1, 2, 3 and 4 min after exercise). During the first minute after the end of exercise, the HR rose 2 bpm at baseline, but fell 10 bpm at 12 months (p for difference <0.001). However, even at 36 months, the decline in HR after exercise remained less rapid than in healthy controls (p<0.001) (Figure). CRI increased between baseline and 12 months, but levelled off between the 12-month visit and 36 months (0.50±0.2 vs 0.79±0.3; p<0.001 and 0.79±0.3 vs 0.81±0.3; p=0.51). The chronotropic response was normalized (>0.85) in 44% of the HTx recipients at 1 year and in 51% at 3 year after HTx. Conclusion The increase and decrease in HR during exercise are considerably muted in de novo HTx recipients. The HR response improves during the first year after surgery, and thereafter levels off. In contrast the decline in HR after exercise seems to increase with time, which may be related to the effect of exercise. This suggests that partial re-innervation takes place. Whether this response continues to improve in the longer term remains to be determined. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): South-Eastern Norway Regional Health Authority

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