Arrhythmic Storm in Takotsubo Syndrome: Potential Contribution of Genetic Susceptibility

Background Takotsubo syndrome is an acute and reversible cardiomyopathy traditionally considered benign; however, growing evidence highlights a significant risk of malignant ventricular arrhythmias. Genetic susceptibility, particularly variants associated with channelopathies, may modulate arrhythmic risk and influence management. Case Presentation A 69–year–old woman with a family history of sudden cardiac death and a medical history of arterial hypertension, dyslipidaemia, paroxysmal atrial fibrillation on oral anticoagulation, type 2 diabetes mellitus, and chronic autoimmune thyroiditis presented with non–ST–elevation acute coronary syndrome complicated by hypertensive pulmonary oedema. Previous drug–induced QTc prolongation during amiodarone therapy was reported. Admission electrocardiography showed sinus rhythm with anterior T–wave inversion and prolonged QTc. Transthoracic echocardiography revealed moderate left ventricular systolic dysfunction (LVEF 40%) with apical ballooning and no left ventricular outflow tract obstruction. High–sensitivity troponin I and NT–proBNP levels were markedly elevated. Shortly after admission, the patient developed an arrhythmic storm with recurrent polymorphic ventricular tachycardia without electrolyte abnormalities, requiring electrical defibrillation, intravenous lidocaine, intubation, and deep sedation. Due to persistent electrical instability, the patient was transferred to a tertiary centre. Coronary angiography excluded obstructive coronary artery disease, and ventriculography confirmed Takotsubo cardiomyopathy. After stabilization, QTc progressively normalized, ventricular arrhythmias did not recur, and left ventricular systolic function recovered. Cardiac magnetic resonance supported the diagnosis. Telemetry revealed recurrent atrial fibrillation with rapid ventricular response followed by sinus bradycardia. Given the malignant arrhythmic presentation and pacing requirement, a transvenous implantable cardioverter–defibrillator was implanted. Genetic testing identified a heterozygous RYR2 variant of uncertain significance, prompting genetic counselling. At 6–month follow–up, the patient was asymptomatic, with preserved ventricular function and no arrhythmic recurrences. Conclusions Takotsubo syndrome may trigger malignant ventricular arrhythmias in patients with an underlying arrhythmogenic substrate. Genetic evaluation may add value for risk stratification and individualized management in selected patients.