In patients with congenital heart disease, myocardial cTnT4 isoform expression correlates with clinical indicators of heart failure and hemodynamic stress.
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 (cTnT1 through cTnT4) whose sequence differences result from combinatorial alternative splicing of two exons. We have previously shown that cTnT4 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 cTnT4 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 cTnT1 through cTnT4 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 cTnT4 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 cTnT4 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, cTnT4 expression is modulated by heart failure and is increased in hearts that are more hemodynamically stressed.
Saba et al. (Thu,) studied this question.