Sympathetic Reinnervation After Heart Transplantation Assessed by Iodine-123 Metaiodobenzylguanidine (123I-MIBG) Imaging and Heart Rate Response to Exercise

Abstract

<h3>Purpose</h3> The extent of sympathetic reinnervation of transplanted hearts varies among recipients. The purpose of this study is to investigate the relation between the functional response of the left ventricular (LV) myocardium to adrenergic stimulation and the findings of [¹²³I]metaiodobenzylguanidine (MIBG) scintigraphy in cardiac transplant recipients. <h3>Methods</h3> MIBG scintigraphy was performed in 20 heart transplant recipients (mean of 7.6 years after transplantation) and in 20 age-matched individuals with hemodynamically stable (NYHA functional class I) dilated cardiomyopathy (DCM). Heart rate and blood pressure as well as the ECG during exercise- or dobutamine-induced stress tests were measured in all patients. All patients also underwent endomyocardial biopsy, and some of the biopsy specimens were subjected to mRNA analysis. LV isovolumic contraction (<i>dP/dt</i>_max) and relaxation (tau) were measured simultaneously during stress tests in six transplant recipients and five patients with DCM. <h3>Results</h3> MIBG uptake was virtually undetectable in transplant recipients, with the exception of one individual who showed evidence of reinnervation in the anteroseptal region. The heart-to-mediastinum ratio was significantly smaller in transplant recipients than in patients with DCM (1.32 ± 0.6. vs. 2.22 ± 0.3, <i>p</i> < 0.0001). The change in <i>dP/dt</i>_max at peak heart rate during stress tests did not differ significantly between the two groups (83 ± 26 vs. 93 ± 20%, <i>p</i> = 0.335), whereas that in tau was smaller in transplant recipients than in DCM patients (31 ± 8 vs. 42 ± 9%, <i>p</i> < 0.05). RT-PCR analysis revealed that the amount of β-adrenergic receptor kinase-1 mRNA in the ventricular myocardium tended to be smaller in recipients who showed an attenuated response in stress tests than in those with a good response <h3>Conclusion</h3> LV contractility during adrenergic stimulation by dobutamine or exercise was preserved, whereas LV relaxation was attenuated, in transplant recipients. The discrepancy between the responses of LV myocardial contractility and relaxation to adrenergic stimulation and MIBG scintigraphic findings may provide insight into the reinnervation of transplanted hearts.