Myocardial efficiency and sympathetic reinnervation after orthotopic hearttransplantation - A noninvasive study with positron emission tomography

Background-The lack of cardiac catecholamine uptake and storage caused by s ympathetic denervation may influence performance of the transplanted heart. Reinnervation, occurring late after transplantation, may partially resolve these effects. In this study, oxidative metabolism and its relation to car diac work were compared in allografts and normal and failing hearts, and th e effects of sympathetic reinnervation were evaluated. Methods and Results-Twenty-seven nonrejecting, symptom-free transplant reci pients, 11 healthy control subjects, and 10 patients with severe dilated ca rdiomyopathy underwent PET with C-11 acetate for assessment of oxidative me tabolism by the clearance constant k(mono) and radionuclide angiography or MRI for measurement of ventricular function, geometry, and work. Efficiency was estimated noninvasively by a work-metabolic index [WMI = (stroke volum e X heart ratexsystolic pressure)/k(mono)]. In 14 of 27 transplants, presen ce of regional reinnervation was identified with PET and the catecholamine analogue C-11 hydroxyephedrine (extent, 24 +/- 14% of left ventricle). The WMI was comparable in normal subjects and reinnervated and denervated trans plants (6.2 +/-2.3 versus 4.9 +/-2.0 versus 4.9 +/-1.2 . 10(6) mm Hg mt; P= NS) and significantly lower in cardiomyopathy patients (3.0 +/-1.3 . 10(6) mm Hg mt; P<0.001). For normal subjects and transplant recipients, the WMI was significantly correlated with afterload (peripheral vascular resistance ; r=-0.65, P<0.01), preload (end-diastolic volume; r=0.78, P<0.01), and str oke volume (r=0.81, P<0.01) but not with hydroxyephedrine retention (transp lants only; r=0.09, P=NS). Conclusions-After transplantation, cardiac efficiency is improved compared with failing hearts and comparable to normal hearts. Differences between de nervated and reinnervated allografts were not surveyed. Additionally, the d ependency on loading conditions and contractility was preserved, suggesting that normal regulatory interactions for efficiency are intact and that sym pathetic tone does not play a role under resting conditions.