Cardiovasc Toxicol. 2026 May 13;26(5):50. doi: 10.1007/s12012-026-10125-8.
ABSTRACT
Cardiac toxicity from QT-prolonging drugs can precipitate malignant ventricular arrhythmias in susceptible individuals, and family screening may clarify inherited risk. We report a 33-year-old woman with a history of postpartum cardiac arrest treated with a secondary-prevention implantable cardioverter-defibrillator (ICD) who developed an electrical storm after self-administration of a single low dose of amitriptyline (12.5 mg). ICD interrogation documented 176 episodes of ventricular fibrillation requiring repeated shocks, followed by complete battery depletion, hemodynamic collapse, and the need for venoarterial extracorporeal membrane oxygenation and continuous renal replacement therapy. The admission electrocardiogram showed marked QT prolongation (QTc 651 ms), with previously documented prolonged baseline QTc values. Targeted next-generation sequencing identified a novel SCN5A missense variant (NM_000335.5:c.5738G > A) and a rare pathogenic KCNQ1 splice variant (NM_000218.3:c.1032G > C), cascade testing across the family demonstrated variable expressivity among carriers. Given a suspected contribution of late sodium current, a mechanism-based strategy was implemented with mexiletine added to propranolol and overdrive pacing (90 bpm). This case underscores the risk of malignant ventricular arrhythmias after exposure to QT-prolonging agents even at low doses, and supports genotype-informed, mechanism-based therapy to mitigate arrhythmic risk in patients with marked QT prolongation.
PMID:42126717 | DOI:10.1007/s12012-026-10125-8