Abstract 4147797: Clinical Correlations with Longitudinal Echocardiography and Global Longitudinal Strain in the First and Second Genetically Modified Porcine to Human Cardiac Xenotransplantation

Background: Our institution performed the first and second genetically modified porcine cardiac xenotransplantation in a human in the world. Our laboratory performed serial and longitudinal transthoracic echocardiograms (TTE) with global longitudinal strain (GLS) for both patients for clinical surveillance and to identify any evidence of xenograft failure. For both recipients, marked myocardial hypertrophy with worsening GLS were noted at the time of graft failure. Study Aim: The aim of this study is to identify noninvasive measurements which may help predict early graft failure and mortality in cardiac xenotransplantation. We hypothesize that a ratio of papillary muscle measurement (PPM) to end diastolic diameter (EDD) measured on TTE with GLS may predict xenotransplant graft failure and mortality. Methods: Echocardiographic measurements were made in both xenotransplanted patients, which included PPM, EDD, and GLS. Serial echocardiographic measurements and ratios were subsequently compared to endomyocardial biopsies (EMBx) and clinical correlation, including terminal graft failure and death. Results: From post-operative day (POD) 1 of xenotransplant to end-of-life for both recipients, PPM thickness increased by 84.5% (CI 78.8-95.2%) while EDD decreased by 40.2% (CI 20.3-64.1%). For the first recipient, PPM/EDD progressively increased from 0.23 (POD 1) to 0.57 (POD 58), when the xenotransplant terminally failed from a restrictive myopathy (LVEF 55%, GLS -7.7) confirmed by EMBx. For the second recipient, PPM/EDD progressively increased from 0.26 (POD 1) to 1.00 (POD 40) (Figure 1), when the graft terminally failed due to combined systolic and diastolic dysfunction (LVEF 25%, GLS -7.6), also confirmed by EMBx. For both xenografts, the global longitudinal strain (GLS) worsened (more positive) by an average of 42.3% (CI 42.2 - 42.4%) when the PPM/EDD ratio reached between 0.5 and 0.6. Conclusion: Increased ratio of PPM to EDD is associated with worsening GLS, cardiac xenotransplant graft failure, and recipient mortality. TTE with GLS provided real-time clinical and noninvasive histological correlation in the first and second transgenic cardiac xenotransplants. Given the interest in cardiac xenotransplantation, serial noninvasive measurements identifying early graft failure will be important for future monitoring and management.