Analysis of an ECG Record Database Reveals QT Interval Prolongation Potential of Famotidine in a Large Korean Population

Abstract

Some non-antiarrhythmic drugs have the undesirable property of delaying cardiac repolarization, an effect that can be measured empirically as a prolongation of the QT interval by surface electrocardiogram (ECG). The QT prolongation and proarrhythmia potential of famotidine are largely unknown, particularly in individuals that have cardiovascular risk factors such as abnormal electrolyte levels. Based on an analysis of QT/QTc intervals from a database of ECG recordings from a large Korean population (ECG-ViEW, 710,369 ECG recordings from 371,401 individuals), we observed that famotidine administration induced a prolonged QTc interval (above 480 ms, p < 0.05 compared to before-treatment, based on a McNemar test). Furthermore, famotidine induced QT prolongations in 10 out of 14 patients with hypocalcemia and 11 out of 13 patients with hypomagnesemia [difference of mean between before and after famotidine administration; 38.00 ms (95% confidence interval 2.72-73.28) and 67.08 ms (95% confidence interval 24.94-109.21), p < 0.05 and p < 0.01 by paired t test, respectively]. In vitro, the IC50 of famotidine for human-ether-a-go-go gene (hERG) channel inhibition was higher than 100 μM as determined by automated patch clamp hERG current assay, implying that hERG channel inhibition is not the underlying mechanism for QT prolongation. These results suggest that famotidine administration increases a proarrhythmic potential, especially in subjects with electrolytes imbalance.

The Association between Work-Related Stress and Autonomic Imbalance among Call Center Employees in Japan

“…In this sense, there are few reports using objective outcomes (Collins et al 2005;Otsuka et al 2009;Maeda et al 2015). QT intervals, as well as heart rate variability (HRV) and heart rate, have been considered as an objective marker of the development of ventricular arrhythmia or of the susceptibility to sudden death (El-Sherif and Turitto 2003;Jouven et al 2005), because QT intervals represent the duration between ventricular depolarization and subsequent repolarization (Yun et al 2015) while the corrected QT interval (Bazett 1920), by comparison with QT index (Rautaharju et al 2009), tends to depend on heart rate . In this study, we investigated the impact of work-related stress, as well as home stress, on autonomic nervous function among call center employees undergoing electrocardiography (ECG) at the time of their annual health checkups.…”

ECG-ViEW II, a freely accessible electrocardiogram database

“…The database is already being used to evaluate adverse drug reactions that result in QT interval prolongation. After examining the association of the QTc interval with certain drugs, Yun et al [11] suggested that famotidine administration can prolong the QTc interval and increase the proarrhythmic potential. Additionally, Park et al [13] concluded that selective serotonin reuptake inhibitors are less likely to be associated with QTc interval prolongation.…”

“…From July 2012 to July 2016, there were many data requests (approximately 90) from 13 countries in Asia, North America, and Europe (S1 Table). In addition, two papers were published using the previous ECG-ViEW database [11,12]. However, ECG-ViEW contains only QT/QTc data; it does not provide the PR interval, QRS duration, and cardiac axis data.…”

Liver Fibrosis Is Associated With Corrected QT Prolongation During Ledipasvir/Sofosbuvir Treatment for Patients With Chronic Hepatitis C

“…reported that 1.1% (4/360) of patients experienced QT prolongation (QT interval >550 milliseconds) after the administration of quinidine. Yun etal . reported that 15.5% (56/362) of patients experienced QTc prolongation (QTc interval >450 milliseconds) after the administration of famotidine.…”