Non-invasive Myocardial Strain Imaging to Evaluate Graft Failure in Cardiac Xenotransplantation

Abstract

Background: The shortage of human hearts for allotransplantation makes xenotransplantation one possible option for controllable organ providers. To detect acute xenograft rejection, invasive biopsy seems inevitable; sometimes resulting in poor incision wound healing, or infection. So far, a noninvasive imaging for early detecting xenograft rejection is not well established. We hypothesized that ultrasound speckle tracking would better detect xenograft rejection than routine left ventricular (LV) ejection fractions. Methods: From August 2013 to July 2015, a total of 6 cardiac heterotopic xenotransplants (alpha 1, 3-galactosyltransferase gene-knockout porcine heart) into Cynomolgus monkeys were monitored with echocardiography every 3-7 days. M-mode and 2D ejection fraction measurements as well as myocardial strain analyses were performed. Cardiac xenograft pathology was reviewed from the immediate postoperative biopsy as well as the necropsy. Results: Myocardial speckle tracking analysis was feasible in all 6 cases. The longest survival was 43 days. Only one pathology-proven immunologic rejection was contained. Both antibody-mediated rejection (n=1) and sepsis-induced myocardial dysfunction (n=2) revealed decreased radial or circumferential strains but normal-range ejection fractions. Xenograft functional decline was significant with respect to radial or circumferential strain (P = 0.028), but not to conventional M-mode or 2D ejection fractions (P = 0.600, P = 0.340 respectively). Conclusions: Myocardial strain better reflected xenograft failure than conventional ejection fractions, especially in cases with concentric LV remodeling, but the presence of only one xenograft-rejection- related death limits conclusions about its early diagnostic role for xenograft rejection. Further studies are warranted to correlate the strain analysis and immuno-pathologic detail.