Tissue Doppler imaging detects severely abnormal myocardial velocities that identify children with pre-terminal cardiac graft failure after heart transplantation.
BACKGROUND: Children with orthotopic heart transplants (OHT) may die or require retransplantation due to chronic graft failure usually due to severe coronary allograft vasculopathy (CAV). Non-invasive detection of chronic transplant failure has been problematic due to lack of specific echocardiographic findings. Tissue Doppler Imaging (TDI) is a non-invasive ultrasound methodology, which measures myocardial contraction and relaxation velocities. The purposes of this study were to: 1. Determine quantitative changes of longitudinal TDI velocities characteristic to "pre-terminal" patients who subsequently either died or were listed for re-transplantation due to graft failure; 2. to define the time course of these changes, and 3. to show whether RV and LV velocities were equally effected. METHODS: 53 heart transplantation recipients were evaluated. Of these, 45 were "well" patients. They ranged in age at enrollment from 0.5 to 20.1 (mean 10.21) years, age at transplantation from 0.2 to 18 (mean 5.7) years. The time from transplantation to enrollment was 1 day to 14.9 (mean 4.5) years. There were 8 "pre-terminal" (test group) patients who died or were listed for re-transplantation within 9 months after TDI echo. These ranged in age from 2.6 to 17 (mean 11.6) years, age at transplant from 1 month to 15.9 (mean 8.1) years, and time from transplant to enrollment was 0.7 to 9.8 (mean 3.6) years. TDI was performed in the apical four-chamber view. Systolic (S, cm/s) and diastolic early (E, cm/s) and late (A, cm/s) velocity. Mitral and tricuspid annular TDI velocities were measured. Tricuspid regurgitation and LV ejection fraction were also compared. RESULTS: Pre-terminal patient's Left Ventricular Ejection Fraction began diverging from controls at 3 to 6 months prior to endpoint (p < 0.001). Tricuspid TDI S velocities of pre-terminal patients diverged by 2.0 cm/sec from controls (p < 0.002) 6 months prior to, and reduced further by 2.9 cm/sec 3 months prior to endpoint (p < 0.001). Tricuspid TDI E velocities diverged 3 to 6 months before endpoint, by 1.9 cm/sec (p < 0.02) and by 3.7 cm/sec 0-3 months prior to endpoint, (p < 0.001). Mitral S velocities diverged from controls by 1.5 cm/sec at 0 to 3 months before terminal endpoints (p = 0.002). Mitral E velocities were statistically similar at all time intervals (p > or = 0.15). Septal S velocities equaled controls 6 months (p = 0.92) and between 3 to 6 months (p = 0.83) but diverged by 1.6 cm/sec 0 to 3 months before terminal endpoints (p = 0.01). Septal E velocities equaled controls. Mortality Prediction: LVEF, tricuspid annulus systolic and diastolic velocities, and tricuspid regurgitation severity were significant in predicting mortality. Coronary angiography was performed in 26 patients, 5 had severe coronary artery disease and all were pre-terminal. DISCUSSION: The TDI data reported here show 3 to 6 months before the terminal graft failure, tricuspid, but not mitral, S and E TDI velocities, deteriorated to uniquely low levels not seen in other clinically well pediatric transplant recipients. Further RV deterioration occurred during the final 3 months before death and severely reduced left ventricular velocities then occurred. Small decreases in LVEF and progressive increases in the severity of tricuspid regurgitation were also detectable and predicted an increased likelihood of mortality. Seven of the 8 preterminal patients had angiograms 5 of which showed severe CAV. These data suggest that there is a critical "pre-terminal" window of time in which children demonstrate uniquely reduced right and subsequently left sided myocardial velocities at approximately 6 months prior to graft failure. The practice of annual catheterization and coronary angiography may not allow caregivers an opportunity to intervene early in the process of graft dysfunction. Therefore, a strategy of tissue Doppler echocardiography 2 or 3 times each year might be an appropriate regimen to survey for graft impairment.