Bhalla, Jaideep Singh

Introduction: The incidence and risk factors for sudden cardiac death (SCD) in patients with systemic right ventricle (sRV) and D-TGA palliated with atrial switch procedures is not well understood. Methods: This cohort was examined retrospectively for the composite end point of SCD, sustained ventricular tachycardia (VT) >30 s or appropriate ICD therapy for VT. Clinical characteristics of those with and without the end point were compared using the Kruskal-Wallis or Chi-square test as appropriate. Results: The composite end point occurred in 15 of 148 (10%) patients (63.5% male) at a mean age of 36.4 (SD 10.3) years. SCD occurred in 6 patients (n=2 successfully resuscitated), sustained VT in 6 patients and ICD therapy for VT in 3 patients who had previously received a primary prevention ICD. Patients with SCD/VT had lower sRV ejection fraction (EF) compared to patients without SCD/VT [28±11 vs 40±10%, P<0.001]. The odds ratio of SCD/VT in patients with sRVEF≤35% compared to sRVEF>35% was 13.3 (95% CI 2.8 - 64.4). Kaplan Meier analysis of time to SCD/VT stratified by sRV EF is presented in figure. QRS duration, QRS fragmentation, QTc and history of systemic AV valve surgery were not significantly associated with SCD/VT. Non-sustained ventricular tachycardia (NSVT) on Holter monitoring occurred more frequently in SCD/VT patients (80 vs 39%, p=0.003). All 11 survivors of SCD/VT received an ICD; appropriate ICD therapy occurred in 27% of these patients during follow-up. Conclusion: SCD or VT occurred in one-tenth of D-TGA patients palliated with atrial switch, predominantly in 3 rd and 4 th decade of life. Reduced sRV EF was the most important association and ICD implantation for primary prevention of SCD is a reasonable consideration in those with reduced sRV EF.

e14591 Background: Combined immune checkpoint inhibitors (ICPI) have revolutionized treatment of solid tumors. Their use can lead to treatment-related adverse events (TRAEs) resulting in hospital admissions, treatment discontinuation and increased morbidity. We aim to evaluate gastrointestinal (GI) TRAEs of different combination ICPI. Methods: A comprehensive search of multiple databases from inception to October 2021 was performed. Phase 2 and 3 trials assessing safety and efficacy of combined ICPI in solid tumors were included. Trials reporting concurrent use of chemotherapy, immunosuppressants, targeted therapy, or sequential ICPI therapy were excluded. Primary outcome was pooled luminal, hepatic and pancreatic TRAEs. A meta-analysis of proportions was done for outcomes using a random-effects model. I2 % was used to assess heterogeneity. Results: Out of 3696 citations screened, 53 trials reporting TRAEs in 6186 patients were included. Data from 41 study arms of 35 trials in nivolumab plus ipilimumab (N+I), 15 study arms of 15 trials in durvalumab plus tremelimumab (D+T), 4 study arms of 3 trials in pembrolizumab plus ipilimumab (P+I). The most common indications for combined ICPI were melanoma (26.4%) and lung cancer (24.5%). Pooled GI TRAE rates from the D+T, P+I and two different dosing combinations of N+I are shown in the table. Conclusions: Our study provides pooled data of TRAEs from different combination ICPI use in solid tumors and demonstrates high incidence of all grades and ≥ 3 GI TRAEs. Combined ICPI related TRAEs should be recognized early, as it may require treatment discontinuation. Further studies are required to assess overall impact of TRAEs on treatment course and outcomes.[Table: see text]