Pandya, Krutarth K

Introduction: Obesity is associated with a higher burden of atrial fibrillation (AF) and related complications. Hypothesis: Bariatric surgery in patients with AF is associated with a reduction in mortality and long-term complications at 1 year. Methods: Patients with AF who underwent bariatric surgery were identified by analyzing the nationwide readmission database and incorporating the validated ICD-10 CM codes from October 2015 to December 2019. We performed the propensity score matching to adjust the confounders and cox proportional hazard regression to generate hazard ratios. Moreover, we generated Kaplan Meier curves for time-to-event analysis. The primary endpoint was all-cause mortality at 1 year, whereas secondary endpoints were ischemic stroke, major bleeding, and AF readmission at 1 year. Results: Out of 892488 obese patients with AF, 18766 underwent bariatric surgery. After propensity score matching, 18764 patients were identified in each group. At 1-year, patients undergoing bariatric surgery had a significant reduction in mortality (2.18% vs. 2.73%, HR: 0.91, 95% CI: 0.85-0.96, p=0.001). Additionally, risk of ischemic stroke was also reduced (1.98% vs. 2.29%, HR: 0.91, 95% CI: 0.86-0.97, p=0.01), whereas no difference was noted in AF readmissions (4.02% vs. 3.34%, HR: 0.97, 95% CI: 0.92-1.04, p=0.49) and risk of major bleeding was increased (5.74% vs. 3.42%, HR: 1.17, 95% CI: 1.10-1.25, p<0.0001) at 1 year in AF patients with bariatric surgery. (Figure 1) Conclusions: Bariatric surgery in patients with AF was associated with a reduction in 1-year mortality and ischemic stroke. However, the risk of major bleeding was noted to be increased and no difference was noted in AF readmission at 1 year.

Background: Different arrhythmias have been reported in patients with COVID-19 due to the complication of the disease, and medications used in the management of COVID-19. Remdesivir was approved by FDA for the management of COVID-19 patients in October 2020. There are several case reports suggesting remdesivir causing bradyarrhythmia in COVID-19 patients. Objective: To increase the knowledge and awareness among healthcare professions (HCPs) about the risk of arrhythmias associated with the use of remdesivir. Methods: We used the FDA Adverse Events Reporting System (FAERS) database to find bradyarrhythmia as a reported adverse event (AE) due to remdesivir until October,2021. Total 6,504 events were reported, out of which 5,996 (92.2%) were reported by HCPs. These AEs were included and further analyzed. Results: Out of 5,996 AEs reported with remdesivir, total 537 (9.0%) events were bradyarrhythmia. There were 74 (1.27%) events reported for atrial fibrillation, and 24 (0.04%) for ventricular tachycardia attributed to the use of remdesivir. Reported events of bradyarrhythmia were further divided and analyzed into men vs women, and different age groups of years 18-64, 65-85, &gt;85. Total events of bradyarrhythmia among men (238, 6.5%) vs women (141, 6.4%) were not significantly different. Among all the age groups, more events were reported in younger women in the age group of 18-64 (12.3%) vs 65-85 (7.9%) vs &gt;85 (6.9%). Conclusion: Multiple studies have shown COVID-19 associated tachyarrhythmias, likely secondary to the myocardial damage due to hypoxia. Few studies have also suggested bradyarrhythmias in these patients. Our analysis of the FAERS database also showed many reported AEs of bradyarrhythmia attributed to the use of remdesivir. Postulated mechanisms include; medication side effects, damage to the SA node as a complication of the COVID-19 disease process, and electrolyte imbalance due to the renal failure. Close surveillance of these patients with early diagnosis can lead to prompt discontinuation of the medication, which can further decrease the mortality related to bradyarrhythmias. Further studies are required to identify the at-risk population and to better understand the risk of bradyarrhythmia associated with remdesivir.

Background: Sacubitril-valsartan is a combination of a neprilysin inhibitor and an angiotensin II receptor blocker respectively. Sacubitril-valsartan has become a standard of care in the treatment of patients with Congestive Heart Failure (CHF) with reduced EF. During its clinical trials and upon review of U.S. Food and Drug Administration (FDA) approval, sacubitril-valsartan exhibited a side effect profile including hyperkalemia, hypotension, renal dysfunction, and angioedema. Recently, sacubitril-valsartan was also approved for the treatment of CHF patients with preserved EF. Objective: In view of new indications and increased usage, it is important to establish the updated safety profile of sacubitril-valsartan in the general population since the PARADIGM-HF trial. Methods: We explored reported Adverse Events (AEs) of sacubitril-valsartan using the FDA Adverse Event Reporting System. A total of 57,958 AEs were reported until August 2021. Total of 16,658 (28.7%) AEs were reported by HCPs, which were further analyzed. AEs were analyzed in men (56.7%) vs women (25.3%), and also in 3 age groups of 18-64, 65-85, >85. Results: Out of 16,658 AEs, the most frequently reported AE was hypotension (17.2%). Other commonly reported AEs were renal dysfunction (14.3%), allergic reactions including angioedema (10.8%), GI distress (8.8%), tachyarrhythmias (5.8%), hyperkalemia (4.5%), and cough (3.0%). Out of 16,658 AEs, 11,631 (69%) were deemed serious and 4,422 (26.5%) resulted in hospitalization. Deaths were attributed to 3,909 serious AEs (23.5%). In the age group of 18-64, events of atrial fibrillation were less among women compared to men (1% vs 3%), while total events of ventricular tachycardia were noted more among men compared to women (2% vs 0.5%). Conclusion: Most of the reported AEs were consistent with the observed AEs from PARADIGM-HF except for tachyarrhythmia. There are few reports documenting arrhythmias followed by the use of sacubitril-valsartan, however, the clear mechanism is unknown. Despite the wide use of sacubitril-valsartan, there is currently limited data on the safety profile. In future with the increasing use, further randomized controlled trials (RCTs) are needed to better understand the safety profile of the medication.