Transforming growth factor β and diastolic left ventricular dysfunction after heart transplantation:: Echocardiographic and histologic evidence

Background: The mechanism for chronic left ventricular diastolic dysfunction in the non-rejecting cardiac allograft has not been fully studied. Objectives: The purposes of this study were to analyze the significance and frequency of left ventricular diastolic dysfunction after heart transplantation and to examine the involvement of fibrotic cytokines (transforming growth factor beta [TGF-beta]) in development of clinical and echocardiographic changes in, cardiac allograft recipients. Methods: We studied 152 heart transplant recipients who had survived for at least 24 months. We compared histopathologic findings. (staining of endomyocardial biopsy specimens using hematoxylin and eosin, and polyclonal antibodies expressed as TGF-beta score), left ventricular function (Doppler echocardiography), and clinical course (New York Heart Association [NYHA] status). We classified patients into Group 1 (n = 41 recipients) with a restrictive filling pattern, mitral, deceleration time (MDT) < 140 milliseconds, and Group 2 (n = 111 recipients), MDT greater than or equal to 140 milliseconds. Results: The MDT was 122 +/- 7 milliseconds in Group 1 compared with an MDT of 177 17 milliseconds in Group 2 (p = 0.0003). Group I showed significant immunohistochemical staining in endomyocardial biopsy specimens (a mean TGF-beta score of 9.1 +/- 1.2 for Group 1 compared with a mean TGF-beta score of 3.6 +/- 0.8 for Group 2 p = 0.001). The TGF-beta expression correlated inversely with both MDT and isovolumic relaxation time, (r = 0.77, p = 0.0004, and r = -0.69, p = 0.004, respectively). Mean NYHA status in Group 1 recipients was 2.2 +/- 1.1 compared with 1.37 +/- 0.6 for Group 2 (p = 0.006).