Myocardial efficiency and sympathetic reinnervation after orthotopic heart transplantation: A noninvasive study with positron emission tomography

Background - The lack of cardiac catecholamine uptake and storage caused by sympathetic 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 cardiac work were compared in allografts and normal and failing hearts, and the effects of sympathetic reinnervation were evaluated. Methods and Results - Twenty-seven nonrejecting, symptom-free transplant recipients, 11 healthy control subjects, and 10 patients with severe dilated cardiomyopathy underwent PET with ¹¹C acetate for assessment of oxidative metabolism 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 volume×heart rate×systolic pressure)/k(mono)]. In 14 of 27 transplants, presence of regional reinnervation was identified with PET and the catecholamine analogue ¹¹C hydroxyephedrine (extent, 24±14% of left ventricle). The WMI was comparable in normal subjects and reinnervated and denervated transplants (6.2±2.3 versus 4.9±2.0 versus 4.9±1.2 · 10⁶ mm Hg · mL; P=NS) and significantly lower in cardiomyopathy patients (3.0±1.3 · 10⁶ mm Hg · mL; 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 stroke volume (r=0.81, P<0.01) but not with hydroxyephedrine retention (transplants only; r=0.09, P=NS). Conclusions - After transplantation, cardiac efficiency is improved compared with failing hearts and comparable to normal hearts. Differences between denervated and reinnervated allografts were not surveyed. Additionally, the dependency on loading conditions and contractility was preserved, suggesting that normal regulatory interactions for efficiency are intact and that sympathetic tone does not play a role under resting conditions.