B-AB13-04 A PATIENT-SPECIFIC RE-ENGINEERED CARDIOMYOCYTE MODEL CONFIRMS THE CIRCUMSTANCE-DEPENDENT ARRHYTHMIA RISK ASSOCIATED WITH THE AFRICAN-SPECIFIC COMMON SCN5A POLYMORPHISM (P.SER1103TYR): IMPLICATIONS FOR THE INCREASED SUDDEN DEATHS OBSERVED IN BLACKS DURING THE COVID-19 PANDEMIC

During the early stages of COVID-19 pandemic, many cities throughout world observed a marked increase in sudden cardiac death (SCD). The p.S1103Y-SCN5A common variant, present ∼8-10% individuals African descent, may be circumstance-dependent, SCD-predisposing, pro-arrhythmic polymorphism setting hypoxia-induced acidosis or QT-prolonging drug use. In light FDA’s Emergency Use Authorization hydroxychloroquine (HCQ), potential drug, we sought to ascertain effects and HCQ on action duration (APD) patient-specific induced pluripotent stem cell cardiomyocyte (iPSC-CM) model p.S1103Y-SCN5A. iPSC-CMs were generated from 14-year-old p.S1103Y-SCN5A-positive American male. patient’s variant-corrected (isogenic control) using CRISPR/Cas9 technology. FluoVolt voltage sensing dye was used assess APD90 values p.S1103Y-SCN5A-iPSC-CMs compared isogenic control before after an acidotic state (pH 6.9) 24 hours treatment with 10 μM HCQ. Under baseline conditions 7.4), there no significant difference (398 ± 7 ms, n=21) versus (395 6 n=21, p = NS). prolonged significantly (477 5 Δ+79 n=15, < 0.0001) but not (377 Δ-21 NS) at pH 6.9. Notably, while change (394 NS), prolongation (504 8 Δ+106 following Although African-specific variant had effect APD under conditions, physiologic stress either patient-specific, re-engineered heart cells. Further study is needed determine if its circumstance-dependent reduction repolarization reserve has contributed increased rate SCDs racial outcome disparities during pandemic.