Repolarization/ST segment characteristics in serial 12-lead EKGS in the worldwide first genetically modified porcine-to human xenotransplant
Oneib Khan1, Mahdokht Parsirad1, Timm Dickfeld1, Calvin Kagan1, Richard Amara1, Likhitesh Jaikumar1, Monodeep Biswas1, Susie Hong-Zohlman1, Manjula Ananthram1, Charles Hong1, Vincent See1, Stephen Shorofsky1, Bartley Griffith2, Muhammad Mohiuddin2.
1Cardiovascular Medicine, University Of Maryland Medical Center, Baltimore, MD, United States; 2Surgery, University Of Maryland Medical Center, Baltimore, MD, United States
Background: The worldwide first genetically modified porcine-to-human cardiac xenotransplantation was performed in January 2022 at the University of Maryland with the recipient surviving 61 days. Repolarization parameters are correlated with increased risk of ventricular arrhythmias and mortality in the human heart but have never been assessed in a porcine xenotransplant.
Methods: Daily 12- lead ECGs were obtained during the post-operative period.
Results: Compared to normal porcine (QTc<370-440ms) or human (QTc<440ms) ECG parameters the first-ever genetically modified cardiac xenotransplant (“pig heart-in-human body”) demonstrated a consistently prolonged QTc of 579±67ms. The first 2 post-operative weeks demonstrated the most striking QTc prolongation (656±60ms; maximum 733ms), which shortened significantly during the further post-operative period (576±47ms; p<0.001). A similar time course was seen for abnormal repolarization with marked T wave inversions in the precordial/inferior leads. Maximum negative T wave amplitude was also most pronounced during the first 2 post-operative weeks (-1.1±0.4mV) and consistently improved over the further post-operative course (-0.4±0.3mV; p<0.001). Analogously, the single marked post-operative ST abnormality occurred during the first 2 weeks: up to 13mm “tomb-stoning” ST elevations were observed in all 3 inferior leads (day 10, >8h duration) with complete resolution and absence of Troponin I elevation (~8ng/mL), lack of regional wall motion abnormality or decrease in left ventricular EF (>65%).
Conclusion: Unexpected and potentially proarrhythmic repolarization/ST abnormalities were observed during the whole post-operative period. However, abnormalities were most pronounced in the immediate 2-week post-operative period with significant improvement over the following weeks. This suggests the presence of possible adaptive and/or compensatory mechanisms that allow partial correction of post-surgical, denervation and medication-related effects on cardiac repolarization and may mitigate the proarrhythmic risk.
