*Purpose: Genetically engineered (GE) pigs are thought to be an alternative organ source for patients in end-stage heart failure unable to receive a timely allograft. However, cardiac xenografts exhibit life-limiting diastolic failure within a short period without addressing potential causes of xenograft growth. Questions remain regarding whether this phenomenon is caused by individual cardiomyocyte hypertrophy.

*Methods: GE pig hearts were transplanted orthotopically into weight-matched baboons between 15-30kg, utilizing continuous perfusion preservation prior to implantation (n=8). Neither Temsirolimus nor afterload reducing agents were administered to control for potential causes of post-transplantation growth. GE xenografts contained multiple knockouts ± knockout (KO) for growth hormone receptor (GHR), to address intrinsic xenograft growth and human transgene expression (table 1). TTEs were obtained longitudinally to quantify post-transplantation xenograft growth. Cardiomyocyte cross-sectional area was tabulated and compared to non-transplanted, age-matched controls to measure cellular hypertrophy and compared as ratios (cardiomyocyte transplanted xenograft:non-transplanted control).

*Results: GHRKO xenografts had a reduced LV mass % increase compared GHR intact xenografts (58.4% ± 27.6 vs. 140.7% ± 58.1, respectively, p=0.041) up to 9 months after transplantation. All cardiomyocytes increased after transplantation, compared to age-matched controls (figure 1a). There was no difference in cardiomyocyte cross-sectional area ratios between GHRKO and GHR intact xenografts (1.9 ± 0.4 and 1.6 ± 0.1, respectively (p=0.38)) (figure 1b).

*Conclusions: These data suggest that individual cardiomyocyte cross-sectional area increases after xenotransplantation regardless of GHR status and does not seem to largely contribute to xenograft growth. Other factors should be considered as more dominant etiologies.

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