Doppler echocardiography for surveillance of acute cardiac allograft rejection: a 28-year single-center experience

Abstract

Background: Endomyocardial biopsies (EMB) are recommended for the detection of acute cardiac rejection (ACR) despite limited sensitivity. We report the long-term post-transplant results of Doppler echocardiography as a noninvasive alternative of routine EMB.

Methods: Two cohorts of heart transplantation (HT) recipients were chronologically defined as follows: the Dual Monitoring Cohort (DMC) from January 1990 to December 1997 included patients who underwent routine EMB and Doppler echocardiography within 24 hours for ACR surveillance; and the "Echo-First Cohort" (EFC), including patients transplanted from January 1998 to December 2018 with Doppler echocardiography as first-line approach for ACR surveillance. Echocardiographic measurements of interest were collected: early diastolic (E) wave peak velocity; pressure half time (PHT) and isovolumetric relaxation time (IVRT). Post-transplant outcomes were reviewed and the Kaplan-Meier approach was used for survival estimates. Inter-operator variability for ultrasound measurements was investigated. Data were collected from medical records from January 2019 to December 2020.

Results: A total of 228 patients were included, 99 patients in the DMC and 129 in the EFC. Overall, 5-, 10- and 15-year survival rates were 65.4%, 55.5% and 44.1% respectively, without any significant difference between the two cohorts (log rank test, P=0.71). Echocardiography variables and EMB findings were associated with a mean area under the receiver operating characteristic curve (AUC-ROC) of 0.73 [95% confidence interval (CI): 0.54-0.91], 0.74 (95% CI: 0.54-0.94) and 0.75 (95% CI: 0.57-0.94) respectively for E wave, PHT and IVRT. IVRT and PHT were significantly decreased, and E wave significantly increased, in case of histologically proven ACR. Inter-operator variability was not significant for E wave and IVRT measurements (P=0.13 and 0.30 respectively).

Conclusions: Doppler echocardiography as a first-line method for surveillance of ACR did not impair long-term results after HT. These findings suggest that this non-invasive approach might be a reasonable alternative to systematic EMB, limiting risk and improving the quality of life.

Keywords: Heart transplantation (HT); acute rejection; echocardiography; endomyocardial biopsy (EMB); long-term outcomes.

Figure 1

Flow chart illustrating the study design. The Dual Monitoring Cohort included patients transplanted from January 1990 to December 1997 with conventional endomyocardial biopsies screening. The Echo-First Cohort included patients transplanted from January 1998 to December 2018 who undergo Doppler echocardiography as first-line approach for surveillance of acute allograft rejection. yo, years old.

Figure 2

Survival analysis using Kaplan-Meier approach (95% confidence interval) for the study population (A) and comparison of survival curves between the Dual Monitoring Cohort and the Echo-First Cohort (B). Censoring is indicated by a vertical mark.

Figure 3

Temporal diagram of repeated ultrasound measurements in case of negative biopsy (Biop0) or positive biopsy (Biop1), for the 10 first samples (mean value and 95% confidence interval). IVRT, isovolumetric relaxation time; PHT, pressure half time.

Figure 4

Receiver operative characteristics curves for ultrasound measurements considering the first event (A), the second event (B) and the third event (C). These figures show a clinically relevant relationship between ultrasound parameters and histologically-proven acute allograft rejection at the second and third events after transplant with areas under the curve ≥0.65 for all parameters. AUC, area under the curve; CI, confidence interval; IVRT, isovolumetric relaxation time; PHT, pressure half time.