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Remarkably Widened QRS Complex Following a Lethal Dose of Propafenone—An Ominous Sign

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A patient in their 30s who had attempted to commit suicide by taking 20 tablets of oral propafenone (150 mg/tablet) was admitted to the emergency department with impaired consciousness and convulsions that had started 3 hours before admission. No other drug intake was reported by the patient’s family members. Examination revealed a heart rate of 70 beats/min, and blood pressure was 77/46 mm Hg. The patient’s Glasgow Coma Scale score was 3 (range, 3-15, with 3 being the lowest level of consciousness). Laboratory values were as follows: serum creatinine, 98 μmol/L; sodium, 134 mmol/L; potassium, 4.68 mmol/L; and lactate, 11.6 mmol/L. Arterial blood gas analysis revealed a pH of 7.00. An electrocardiogram (ECG) was obtained (Figure, A) and evaluated by the on-call cardiologist.

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Voltage-gated sodium channels in cardiac tissue are located in the cell membrane and open in response to the depolarization of the cell. Propafenone is a class IC antiarrhythmic drug that acts by slowing sodium influx into myocytes through voltage-gated sodium channels and is referred to as a sodium-channel blocker.1 Propafenone binds to the transmembrane channels and decreases the number of channels available for depolarization. The effect produced on the cell is a delay in the entry of sodium ions into the cardiac myocyte, which occurs during phase 0 of depolarization.2

Multiple ECG abnormalities can be observed in the patient with blockage of cardiac sodium channels. The primary manifestation of the blockage, as mentioned previously, is the slowing of the upslope of phase 0 depolarization and thus a widening of the QRS complex (Figure, A). Propafenone blocked the sodium channel of the His-Purkinje system and ventricular muscle fibers, thereby reducing their conduction velocity, with a slightly more pronounced effect on intraventricular conduction. This led to QRS widening with relative preservation of the narrow initial portion of the QRS.3 A QRS duration of more than 200 milliseconds suggested a notable interventricular conduction delay.4 The initial ECG (Figure, A) demonstrated serious propafenone-associated decremental conduction, particularly affecting the intramyocardial conduction, with a QRS duration of 280 milliseconds and preservation of the narrow initial portion of the QRS. This was because the His-Purkinje conduction remained relatively unhampered by the drug. Potential differential diagnoses included the following: left bundle-branch block pattern, QRS prolongation caused by a class IC antiarrhythmic drug, accelerated idioventricular rhythm, and junctional rhythm with left bundle-branch block/intramyocardial conduction block. However, accelerated idioventricular rhythm and junctional rhythm were ruled out because of the presence of P waves preceding each ventricular complex.

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Article Information

Corresponding Author: Min Gao, MD, PhD, Department of Electrocardiogram, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, No.17 Lujiang Rd, Hefei, Anhui, 230001, China (gmbeauty@163.com).

Published Online: August 15, 2022. doi:10.1001/jamainternmed.2022.3367

Conflict of Interest Disclosures: None reported.

Additional Contributions: We would like to thank Professor Yun-Tao Zhao, MD, PhD (Department of Cardiology, Aerospace Center Hospital, Beijing, China), and Professor Xue-Qi Li, MD (Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China), for their assistance with the interpretation of the ECGs. These contributors were compensated for their work.

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Valentino  MA , Panakos  A , Ragupathi  L , Williams  J , Pavri  BB .  Flecainide toxicity: a case report and systematic review of its electrocardiographic patterns and management.   Cardiovasc Toxicol. 2017;17(3):260-266. doi:10.1007/s12012-016-9380-0PubMedGoogle ScholarCrossref
Yang  XY , Song  XT , Zhang  Y .  Wide QRS complex tachycardia with a dominant R wave in lead aVR—is it ventricular tachycardia?   JAMA Intern Med. 2020;180(12):1682-1684. doi:10.1001/jamainternmed.2020.4759PubMedGoogle ScholarCrossref
Brubacher  J .  Bicarbonate therapy for unstable propafenone-induced wide complex tachycardia.   CJEM. 2004;6(5):349-356. doi:10.1017/S1481803500009635PubMedGoogle ScholarCrossref
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