Transforming growth factor beta and myocardial dysfunction following hearttransplantation

Objective: We analyzed the role of transforming growth factor-beta (TGF-bet a), a fibrogenic cytokine, in the development of left ventricular diastolic dysfunction following heart transplantation. Methods: We studied 152 heart transplant recipients who had survived for at least 24 months. We compared histopathological findings (staining of endomyocardial biopsy specimens us ing Heamatoxlin Eosin and polyclonal antibodies), left ventricular function (Doppler echocardiography) and clinical course (NYHA status}. Patients are classified into group A (n = 56 recipients) with immunohistochemical TGF-b eta staining score >7 and group B (n = 96 recipients) with a staining score <7. Results: Doppler echocardiographic evaluation demonstrated greater imp airment of left ventricular diastolic function in recipients with higher TG F-beta staining score. The average mitral deceleration time was 129 +/- 6 m s for recipients group A compared to 167 +/- 15 ms in group B. While the me an isovolumic relaxation rime was 65 +/- 8 ms for patients in group A compa red with 82 +/- 6 ms for recipients in group B (P = 0.0004 and 0.005, respe ctively). Immunohistochemical scoring correlated inversely with both mitral deceleration and isovolumic relaxation times (r = -0.74, P = 0.0004 and r = -0.66, P = 0.004, respectively). Mean NYHA status was 2.7 +/- 1.3 for gro up A compared to 1.17 +/- 0.4 in group 8 was (P = 0.002). Five years follow -up revealed persistent left ventricular diastolic impairment for recipient s with higher immunohistochemical staining score. Mitral deceleration time and isovolumic relaxation time were 118 +/- 11 and 62 +/- 7 ms for group A compared to 156 +/- 12 and 80 +/- 5 ms for group B, P = 0.006 and P = 0.01, respectively. The actuarial development of subsequent coronary artery dise ase (> 50% stenosis) was 17 and 29% for recipients in group A compared to 4 and 6% for recipients in group B at 3 and 5 years follow-up, respectively (P = 0.01 and P = 0.005, respectively). Conclusions: TGF-beta expression in cardiac allografts is associated with impaired graft function and limited survival. The pathogenesis of diastolic dysfunction may be an aberrant repa ir process following rejection due to increased TGF-beta expression in tran splant recipients. (C) 2001 Elsevier Science B.V. All rights reserved.