Recognition of Acute Cardiac Allograft Rejection From Serial Integrated Backscatter Analyses in Human Orthotopic Heart Transplant Recipients

Abstract

Background Previous studies showed that moderate and severe acute cardiac rejection (AR) but not mild AR is associated with significant myocardial acoustic changes. This study examines whether serial measurements of end-diastolic two-dimensional integrated backscatter (2D-IB) enhance the diagnostic potential of ultrasonic tissue analysis in AR. Methods and Results Serial endomyocardial biopsies, conventional echocardiograms, and parasternal long-axis radiofrequency signals for determination of posterior wall and septal 2D-IB were performed in 52 transplant patients. Histology showed no AR in 155 biopsy samples, AR grade 1A in 25, AR grade 1B/2 in 27, and AR grade 3A/3B in 13. Whereas no significant 2D-IB changes occurred between AR-free studies and during AR grade 1A, posterior wall and septal 2D-IB increased during AR grade 1B/2 from −47.80±4.36 to −42.97±5.11 dB and from −36.72±7.45 to −32.52±7.98 dB ( P <.001 and P <.05, respectively) and during AR grade 3A/3B from −47.96±4.74 to −38.25±5.32 dB and from −37.92±5.87 to −31.01±4.62 dB ( P <.001 and P <.01, respectively). Changes in posterior wall and septal 2D-IB were greater during AR grade 3A/3B than during AR grade 1B/2 ( P <.01 and P <.05). Increases of 1.5 dB in posterior wall or septal 2D-IB indicated AR grades ≥1B with sensitivities of 88% and 83% and specificities of 89% and 85%; posterior wall and septal 2D-IB increases of 5.5 and 3.8 dB identified AR grades ≥3A with sensitivities of 92% and 79% and specificities of 90% and 84%. Although a weak inverse correlation between posterior wall and septal 2D-IB changes and posterior wall and septal thickening ( r =.41 and r =.39, both P <.001) and fractional diameter shortening ( r =.35, P <.001) was found, significant 2D-IB increases also occurred in some rejecting patients with unaltered contraction. Conclusions Increases in end-diastolic posterior wall and septal 2D-IB in serial studies permit reliable identification not only of moderate and severe AR but also of mild AR. Because 2D-IB increases significantly more in AR with myocyte damage than without such damage, an estimate of AR severity appears feasible. Significant myocardial acoustic changes during AR may occur independently of changes in contractile performance.