Effect of Sympathetic Reinnervation on Cardiac Performance after Heart Transplantation

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Abstract
Late after cardiac transplantation, limited reinnervation of the transplanted heart may occur, but little is known about the effect of reinnervation on cardiac function and exercise performance. We quantified the extent of myocardial reinnervation noninvasively in 29 cardiac-transplant recipients, using positron-emission tomography and the catecholamine analogue [11C]hydroxyephedrine. Global and regional ventricular function at rest and during standardized exercise testing was measured with the use of radionuclide angiography, and the results were compared with those in 10 healthy controls. Sympathetic reinnervation, mainly in the anteroseptal wall, was present in 16 of the 29 transplant recipients. At rest, hemodynamic differences were not observed between the patients with reinnervation and those with denervation. However, the latter group had a shorter mean (±SD) exercise time (6.1±1.5 minutes, vs. 8.2±1.2 in the group with reinnervation; P<0.01) and a lower peak heart rate (121±13 vs. 143±15 beats per minute, P<0.01). The contractile response to exercise was significantly enhanced in transplant recipients with reinnervation and similar to that of normal controls. In a multivariate analysis, hydroxyephedrine retention was the only independent determinant of the exercise-induced increase in the ejection fraction. In heart-transplant recipients, the restoration of sympathetic innervation is associated with improved responses of the heart rate and contractile function to exercise. These results support the functional importance of reinnervation in transplanted hearts.