Non-invasive assessment of rejection in pediatric transplant patients: Serologic and echocardiographic prediction of biopsy-proven myocardial rejection

Background: Cardiac allograft rejection is a multifocal immune process that is currently assessed using biopsy-guided histologic classification system s (International Society for Heart and Lung Transplantation). Cardiac tropo nin T and I are established serologic markers of global myocyte damage, The use of load-independent measures of contractility have also been shown to accurately assess the presence of ventricular dysfunction. Little is known about their utility in accurately predicting rejection in the pediatric age group. We undertook the present study to compare rejection grade with echo cardiographic and serologic estimates of transplant rejection-related myoca rdial damage. Methods: We compared histologic rejection grades (0 to 4) with patient char acteristics, echocardiographic measurements, catheterization measurements, and biochemical markers for 86 evaluations in 37 transplant recipients at C hildren's Hospital. Results: In univariate analyses, biopsy scores correlated (p < 0.05) invers ely with left ventricular systolic function (shortening fraction) and contr actility (stress velocity index, SVI), and directly with mitral E-wave ampl itude. In multivariate analyses, lower contractility and higher mitral E-wa ve amplitude remained significantly (p less than or equal to 0.01) associat ed with rejection (SVI, p = 0.002, odds ratio = 0.393; E wave, p = 0.0002, odds ratio = 228). Most rejection episodes were associated with elevation o f biochemical markers of myocardial injury. Although troponin I was weakly associated with differences between rejection grades (p = 0.034), troponin T, creatine kinase-MB fraction, and C-reactive protein did not differ with biopsy-rejection scores. Serum markers had a poor predictive capacity for b iopsy-detected rejection. Conclusion: Progressively depressed left ventricular contractility and dias tolic function are found with worsening pediatric heart transplant rejectio n-biopsy score; however, sensitive and specific serum markers do not corres pond to the degree of active myocardial injury. The use of echocardiographi c measures of contractility is associated with a specificity of 91.8% but l ow sensitivity of 66.7%. Overall we found poor concordance between serum ma rkers and grade of rejection. It is unclear whether myocardial injury as as sessed by serum markers, echocardiography, or histologic scoring is more im portant for assessment of acute rejection or long-term outcome, but it does not appear that serum and tissue markers of rejection can be used intercha ngeably.