Semaglutide-associated Twiddler syndrome

52-year-old woman with cardiac sarcoidosis and a dual-chamber implantable cardioverter defibrillator (ICD) was treated with semaglutide for refractory obesity (body mass index (BMI) of 40.1 (kg/m²)). After rapid weight loss of 25 kg, she developed painful device mobility and right ventricular lead dysfunction. Chest x-ray revealed lead entanglement consistent with Twiddler syndrome, which is a mechanical complication in which a pacemaker or ICD rotates within its pocket, causing the leads to twist or dislodge and resulting in device malfunction. Lead extraction was complicated by cardiac tamponade. After recovery, she underwent successful reimplantation of a single-chamber ICD. Patients with cardiac implantable electronic devices who are treated with glucacon-like-peptide-1 receptor agonists may have an increased risk of Twiddler syndrome, as substantial weight loss can increase generator mobility in the subcutaneous pocket. Clinicians should recognize this rare but potentially life-threatening complication.