Re-innervation after heart transplantation:: A multidisciplinary study

Background: Several authors have demonstrated the existence and implications of re-innervation in the transplanted heart. Our aim was to study this phenomenon using 3 different techniques and to analyze the correlation among them. Methods: The study population consisted of 55 patients who had undergone heart transplantation 0.5 to 160 months earlier. We used a control group of 10 healthy individuals for comparison. To detect re-innervation, we used 1) planar and single photon emission computed tomography (SPECT) scintigraphic imaging of cardiac sympathetic activity with I-123-metaiodobenzylguanidine (MIBG), 2) analysis of heart-rate variability based on 24-hour Holter recordings; and 3) immunohistochemical study of endomyocardial biopsy specimens with anti-S100 antibody. Results: The SPECT images showed evidence of sympathetic re-innervation in 17 patients (31%), predominantly in the anterior and in the septal regions of the left ventricle. Sympathetic activity increased during the post-transplant time course (r = 0.32; p = 0.017), although it did not reach normal values. We found a correlation between the low-frequency component of heart-rate variability (a marker of sympathetic activity) and the degree of MIBG uptake according to scintigraphy (r = 0.32; p = 0.015). Immunostaining study demonstrated the existence of nerve fibers in 36 patients (65%) who had greater values of heart-rate variability parameters reflecting parasympathetic activity. Conclusions: The 3 techniques evidenced re-innervation after heart transplantation. A correlation exists between sympathetic activity detected using MIBG scintigraphy and analysis of heart-rate variability. Patients in whom endomyocardial biopsy specimen reveals the presence of nerve fibers show more parasympathetic activity in the heart-rate variability analysis.