Background/Purpose: Sotalol is a class III antiarrhythmic requiring inpatient monitoring due to the risk of QT prolongation and proarrhythmias. Obesity may alter pharmacokinetics through changes in volume of distribution and renal clearance estimation. While actual body weight (ABW) is recommended per package insert to calculate creatinine clearance (CrCl), this may overestimate renal function in obese patients, potentially leading to drug accumulation and increased proarrhythmic risk. The purpose of this study was to compare the composite rate of inpatient sotalol discontinuation or dose reduction due to QT/QTc prolongation between obese and non-obese patients during monitored initiation. Methods: This retrospective cohort study evaluated adult patients admitted for sotalol initiation at a hospital system in Northeast Tennessee and Southwest Virginia from July 2020–June 2025. Patients were stratified by obesity status (BMI ≥30 kg/m2defined as obese). The primary outcome was the composite of inpatient sotalol discontinuation or dose reduction due to QT/QTc prolongation. Secondary outcomes included all-cause discontinuation, all-cause dose reduction, any dose adjustment, bradycardia (HR <50 bpm), sinus rhythm at discharge, serial QT/QTc trends across up to six doses (QT interval applied when HR <60 bpm; QTc applied when HR ≥60 bpm), and differences in CrCl calculated by ABW versus adjusted body weight (AdjBW). Categorical variables were compared using Fisher’s exact test; continuous variables using Mann-Whitney U test. Results: A total of 150 patients were included: 91 obese and 59 non-obese. Obese patients were younger (median 69 [IQR 59.5–75] vs. 74 [67–78] years, p=0.003) with significantly higher ABW-based CrCl (102.6 [85.8–140.4] vs. 73.3 [57.1–88.8] mL/min, p<0.001); the median CrCl overestimation using ABW versus AdjBW was 23.8 mL/min in obese patients compared to 7.7 mL/min in non-obese patients (p<0.001). Baseline serum creatinine, electrolytes, QT/QTc, heart rate, rhythm distribution, and starting sotalol dose were similar between groups. The primary composite outcome of discontinuation or dose reduction due to QT/QTc prolongation occurred in 4 obese patients (4.4%) and 3 non-obese patients (5.1%) (OR 0.86 (95% CI 0.19-3.98); p=1). All composite events were discontinuations; no dose reductions attributable to QT/QTc prolongation occurred in either group. All-cause inpatient discontinuation was similar between groups (14.3% vs. 11.9%, p=0.81). All-cause dose reductions were significantly more frequent in non-obese patients (16.9% vs. 3.3%, p=0.006), driven by bradycardia and hypotension rather than QT prolongation. Any dose adjustment did not differ significantly (23.7% vs. 15.4%, p=0.21). Bradycardia rates (18.6% vs. 13.2%, p=0.37), sinus rhythm at discharge (64.4% vs. 58.2%, p=0.5), and serial QT/QTc values at all time points were comparable between groups. Conclusions: Obesity was not associated with an increased composite rate of sotalol discontinuation or dose reduction due to QT/QTc prolongation during monitored inpatient initiation. Despite a clinically meaningful overestimation of CrCl using ABW in obese patients, this did not translate into greater QT-mediated adverse events or higher discontinuation rates. Notably, all-cause dose reductions were more frequent in non-obese patients and were driven by bradycardia and hypotension rather than QT prolongation. These findings suggest that obesity alone may not confer additional proarrhythmic risk during standard inpatient sotalol initiation and support current renal dosing guidance regardless of BMI.
