Levetiracetam-Induced Ventricular Tachycardia: A Rare Adverse Reaction Warranting Caution in Patients with Atrial Fibrillation

Dear Editor, Levetiracetam is a widely prescribed broad-spectrum antiseizure medication with a favorable neurocognitive and systemic safety profile. Cardiovascular adverse effects are extremely rare, with sporadic reports of conduction abnormalities or arrhythmias.[1] We report a case of refractory ventricular tachycardia (VT) temporally related to levetiracetam initiation, resolving on withdrawal, and highlight the potential need for vigilance in patients with atrial fibrillation (AF) or other arrhythmia histories. A 75-year-old woman, follow-up case of recurrent ischemic stroke (old infarcts in left temporal and right frontal lobes) presented in emergency room with generalized tonic–clonic seizures and a two years history of paroxysmal AF (CHA2DS2-VASc score = 6 on oral antithrombotic). She was on amiodarone 150 mg once daily for since then. She presented following a cluster of five seizures in 24 hours. Her baseline cardiac evaluation, including echocardiogram, electrolytes, and resting electrocardiography (ECG), had been normal six months earlier. The patient had multiple vascular risk factors including advanced age and prior ischemic strokes, but no history of diabetes mellitus, hypertension, or smoking. There was no family history of sudden cardiac death, inherited arrhythmia syndromes, or cardiomyopathy. There was no history of ischemic heart disease, structural cardiomyopathy, or ventricular arrhythmia in the case. On admission, serum electrolytes were within normal limits: serum sodium 138 mmol/L, potassium 4.2 mmol/L, corrected calcium 9.1 mg/dL, and magnesium 1.9 mg/dL. Renal and hepatic function tests were normal (serum creatinine 0.9 mg/dL; AST 28 IU/L, ALT 32 IU/L). Cardiac biomarkers including high-sensitivity troponin I were negative (0.012 ng/mL). Thyroid function tests were normal (TSH 2.1 μIU/mL). The patient was receiving oral anticoagulation for atrial fibrillation along with amiodarone 150 mg once daily for the preceding 2 years, without recent dose modification. No other QT-prolonging or proarrhythmic medications were being taken. A baseline electrocardiogram obtained at presentation showed sinus rhythm with a ventricular rate of 76 beats/min, PR interval 168 ms, QRS duration 92 ms, and a corrected QT (QTc, Bazett) interval of 420 ms, with no ischemic changes or conduction abnormalities. She was initiated on intravenous levetiracetam (loading dose 1.5 g, followed by 750 mg twice daily) for acute seizure control. Eighteen hours after initiation, she developed palpitations, diaphoresis, and dizziness. She had blood pressure of 70/40 mm of Hg. Her ECG revealed 5 episodes of refractory monomorphic VT at a rate of 170 bpm [Figure 1]. She was given DC cardioversion and again had VT. Lidocaine (1mg/kg) administration was done. Troponin I, and thyroid profile were within normal limits. A 2D echocardiogram showed preserved ejection fraction (60%) with no structural abnormalities.Figure 1: (a) ECG strip showing sustained monomorphic ventricular tachycardia at 170 bpm occurring 18 hours after levetiracetam initiation (b) ECG strip showing normal rhythm after DC cardioversionLevetiracetam was immediately discontinued, and intravenous amiodarone was administered, resulting in reversion to sinus rhythm within 30 minutes. No recurrence was noted during the next 72 hours. The patient was switched to sodium valproate and remained arrhythmia-free. Causality assessment using the Naranjo Adverse Drug Reaction Probability Scale [Table 1] yielded a score of 7, suggesting a “probable” adverse drug reaction. An interictal electroencephalogram performed after stabilization demonstrated focal epileptiform discharges over the left temporal region, without concurrent electrocardiographic abnormalities on simultaneous ECG recording. No ictal EEG–ECG correlation suggestive of primary cardiogenic syncope was observed.Table 1: Naranjo adverse drug reaction probability scale applied to this caseLevetiracetam is not classically associated with proarrhythmia, unlike sodium channel–blocking antiseizure drugs. However, its binding to synaptic vesicle protein 2A and modulation of neurotransmitter release may indirectly influence cardiac autonomic tone. Experimental studies suggest possible effects on calcium handling and ion channel kinetics in cardiomyocytes though human evidence remains sparse.[2] A PubMed search (January 2000–June 2025) combining “levetiracetam” AND “ventricular tachycardia” yielded only three prior case reports of VT/Torsades temporally linked to levetiracetam, both resolving on drug discontinuation or causing death before intervention. Neither explicitly addressed AF comorbidity.[3-5] In our patient, pre-existing AF may have represented a background of atrial and ventricular conduction heterogeneity, potentially lowering the threshold for drug-induced arrhythmia. While AF itself does not directly precipitate VT, overlapping risk factors—such as atrial remodeling, fibrosis, or channelopathies—can predispose to ventricular arrhythmias under pharmacologic stress. Neuroimaging in our patient revealed chronic infarcts involving the left temporal lobe and right frontal lobe, without acute ischemic changes. Notably, there was no radiological evidence of insular cortex involvement. Although seizures originating from the insula are known to produce profound cardiac autonomic disturbances and ictal arrhythmias, the absence of insular involvement in our patient strengthens the likelihood of a drug-induced mechanism rather than seizure-related autonomic dysfunction. Furthermore, many AF patients are on antiarrhythmic or rate-control agents that may interact with repolarization pathways, compounding the risk. We propose that AF, especially when associated with structural heart disease or prolonged baseline QTc, may represent a subgroup in whom levetiracetam warrants cautious initiation especially when loading. Baseline ECG, electrolyte optimization, and avoidance of concomitant QT-prolonging drugs are prudent. In high-risk patients, telemetry during initiation could detect early arrhythmias. The rarity of such events should not obscure their potential severity. Pharmacovigilance databases may underestimate incidence due to underreporting. Given levetiracetam’s widespread use in older adults—many of whom have AF—the true burden of subclinical or transient arrhythmias may be higher than recognized. In conclusion, levetiracetam-induced VT is exceedingly rare but potentially life-threatening. This case suggests that patients with AF may constitute a higher-risk subgroup for such adverse events. Clinicians should remain vigilant, perform baseline cardiac assessments, and consider ECG monitoring during initiation in susceptible individuals. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given consent for his clinical information and images to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.