Noninvasive monitoring of peak filling rate with acoustic quantification echocardiography accurately detects acute cardiac allograft rejection

Background: Acute cardiac allograft rejection is associated with early dias tolic dysfunction. The development of chronic rejection is dependent on the frequency and severity of acute rejection episodes. Therefore, early diagn osis and therapy influence long-term survival significantly. For the first time, acoustic quantification, a new echocardiographic technology for on-li ne measurement of cardiac volumes and their changes, facilitates quantitati ve assessment of systolic and diastolic function noninvasively. Methods: Since May 1996, all consecutive patients after cardiac transplanta tion (n = 94) underwent 475 endomyocardial biopsies and the same number of echocardiographic studies within 6 hours after biopsy before the histologic al results were available. Results: Nineteen patients showed 23 episodes of acute rejection (ISHLT gre ater than or equal to 2). There was a significant decrease in left ventricu lar peak filling rate (PFR: end-diastolic volume (EDV)/second) as a paramet er of diastolic function during rejection (2.9 +/- 0.4, n 23) as compared t o PFR measured under nonrejection status (4.5 +/- 0.8; n = 452; p < 0.0001) . Most importantly we found that in these 19 patients showing rejection, th e PFR was normal in the last examination before rejection, but was signific antly reduced during rejection (2.9 +/- 0.4 vs 4.5 +/- 0.7 n = 23, p < 0.00 01). After successful rejection therapy, PFR again normalized in all patien ts, with the exception of 1 patient with steroid-refractory humoral rejecti on. We calculated sensitivity and specificity for several cutpoints for the event "first rejection" in 15 patients and plotted them in a receiver oper ating characteristic curve, showing that a PFR greater than or equal to 4.0 EDV/second is never associated with treatable rejection. A decrease of PFR of more than 18% from its prevalue of the last biopsy with no rejection in creases the accuracy for the diagnosis of rejection significantly. Conclusions: We conclude that diastolic dysfunction during acute cardiac al lograft rejection can be accurately detected by noninvasive measurement of peak filling rate with acoustic quantification echocardiography. Monitoring of this parameter provides reliable discrimination between treatable and n ontreatable rejection.