Cardiac Troponin T Isoform Expression Correlates With Pathophysiological Descriptors in Patients Who Underwent Corrective Surgery for Congenital Heart Disease

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Abstract
Background This study examined cardiac troponin T (cTnT) isoform expression in patients who had undergone surgery at Duke University Medical Center (Durham, NC) between December 1, 1993, and January 31, 1995, to correct congenital heart defects. The human heart expresses four cTnT isoforms (cTnT 1 through cTnT 4 ) whose sequence differences result from combinatorial alternative splicing of two exons. We have previously shown that cTnT 4 is expressed at higher levels in severely failing hearts from transplant patients. In this study, we tested the hypothesis that congenital heart defects that have a more negative effect on myocardial function increase cTnT 4 expression. We used the presence or absence of drug treatment for heart failure or congested circulation before surgery and the duration of inotropic support after corrective surgery as indicators of the pathophysiological state of the heart just before surgery. Methods and Results Right atrial appendage tissue was collected from 34 patients, 6 days to 35 years old (median age, 3.4 months). The amounts of the cTnT 1 through cTnT 4 isoforms, measured as a percentage of total cTnT, were determined from Western blots probed with MAb13-11, a cTnT-specific monoclonal antibody. We found that cTnT 4 expression correlated positively with the duration of inotropic support and was higher in patients who received drug treatment before surgery than in those who did not. Furthermore, we found that the percent of cTnT 4 was significantly higher in hearts with congenital defects that caused congestive failure than in hearts with tetralogy of Fallot. Conclusions These findings suggest that in patients with congenital cardiac defects, cTnT 4 expression is modulated by heart failure and is increased in hearts that are more hemodynamically stressed.