Transforming growth factor beta 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.


OBJECTIVE
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 >or=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 1 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).


CONCLUSIONS
Transforming growth factor beta expression in cardiac allografts is associated with impaired left ventricular diastolic function. The pathogenesis of diastolic dysfunction may be an aberrant repair process after rejection-caused TGF-beta expression in the allograft.
Aziz
Tarek M
TM
Cardiothoracic Transplant Unit, Wythenshawe Hospital, Manchester, United Kingdom. tarekaziz55@hotmail.com
Burgess
Malcolm I
MI
Haselton
Philip S
PS
Yonan
Nizar A
NA
Hutchinson
Ian V
IV
D000328:Adult; D001706:Biopsy; D001794:Blood Pressure / Q000502:physiology; D003971:Diastole / Q000502:physiology; D015150:Echocardiography, Doppler; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000209:etiology / Q000378:metabolism; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D015995:Prevalence; D013223:Statistics as Topic; D013318:Stroke Volume / Q000502:physiology; D013599:Systole / Q000502:physiology; D013995:Time; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology; D014655:Vascular Resistance / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000378:metabolism*
D016212:Transforming Growth Factor beta