Abstract 4365121: Clinical Correlations with Serial Echocardiography and Global Longitudinal Strain in the First and Second Genetically Modified Porcine to Human Cardiac Xenotransplantation

Background: Our institution performed the first two genetically modified porcine cardiac xenotransplantation in humans, conducting serial longitudinal transthoracic echocardiograms (TTE) with global longitudinal strain (GLS). Both recipients exhibited marked right ventricular (RV) hypertrophy and worsening GLS at the time of graft failure. Methods: Serial TTE measurements were made in both xenotransplanted patients, including RV wall thickness (RVWT), end diastolic diameter (EDD), and GLS. Measurement ratios were compared to endomyocardial biopsies (EMBx), clinically correlating to terminal graft failure. Results: From post-operative day (POD) 1 of xenotransplant to end-of-life, RVWT increased 80.9% (CI 95.6-118.5%) while EDD decreased 40.2% (CI 20.3-64.1%). For the first recipient, RVWT/EDD increased from 0.22 (POD 1) to 0.53 (POD 58), when the graft terminally failed from restrictive myopathy (LVEF 55%, GLS -7.7), confirmed by EMBx. For the second recipient, RVWT/EDD increased from 0.18 (POD 1) to 0.68 (POD 40) (Figure 1), when the graft terminally failed due to combined systolic and diastolic dysfunction (LVEF 25%, GLS -7.6), confirmed by EMBx. For both xenografts, GLS worsened by an average of 42.3% (CI 42.2-42.4%) when the RVWT/EDD ratio reached 0.50 - 0.55, demonstrating a linear correlation (r= 0.8). Conclusion: Increased RVWT/EDD ratio is associated with worsening GLS, xenotransplant graft failure, and recipient mortality. TTE provided real-time noninvasive histological correlation in the first two cardiac xenotransplants. In future cardiac xenotransplantation, serial noninvasive measurements identifying early graft failure will be essential for monitoring and management.