Abstract Body (Do not enter title and authors here): Background: Amiodarone is commonly prescribed to manage arrhythmias in Left Ventricular Assist Devices (LVADs) patients. However, its safety profile in this population remains unclear.

Hypothesis: Amiodarone use may be associated with differences in mortality and adverse clinical outcomes among patients with LVADs.

Aim: To evaluate the association between amiodarone use and clinical outcomes in LVAD patients using real-world data.

Methods: A retrospective cohort study was conducted using the TriNetX Network, selecting patients with LVAD. Amiodarone users were matched 1:1 with non-users through propensity score matching, considering demographics, medical conditions, and medications. The primary outcome was mortality. Secondary outcomes were stroke, device thrombosis, hepatitis, hypothyroidism, and arrhythmias.

Results: From 17,457 amiodarone-treated and 20,151 untreated LVAD patients, 14,138 pairs were successfully matched. Amiodarone use was associated with a significantly increased 1-year all-cause mortality (Risk Difference [RD]: 13.0%; Hazard Ratio [HR]: 2.13; 95% CI: 2.01–2.26; p<0.001). The risk of device thrombosis was also higher in the amiodarone group (RD: 2.2%; HR: 2.55; 95% CI: 2.17–2.98), as was the risk of ischemic stroke (RD: 1.9%; HR: 1.37; 95% CI: 1.24–1.51). In addition, amiodarone was strongly associated with increased incidence of ventricular arrhythmias, including ventricular tachycardia (RD: 13.9%; HR: 2.58; 95% CI: 2.40–2.78) and ventricular fibrillation (RD: 6.7%; HR: 3.94; 95% CI: 3.47–4.48), as well as atrial fibrillation (RD: 16.3%; HR: 2.86; 95% CI: 2.66–3.08). Elevated risks of hypothyroidism (RD: 2.6%; HR: 1.65; 95% CI: 1.48–1.84) and hepatitis (RD: 0.4%; p=0.003) were also observed. All reported associations were statistically significant.

Conclusion: In this large real-world cohort, amiodarone use in LVAD patients was consistently associated with increased risks of mortality and several clinically significant adverse events. These findings warrant cautious consideration of amiodarone use in this vulnerable population and suggest the need for closer monitoring and potential alternative therapies.