Loperamide is a readily available, over-the-counter medication used to treat diarrhea. At therapeutic doses, loperamide exerts its effects mainly on the intestinal opioid receptors with minimal psychoactive effects; however, at supratherapeutic doses, it reaches central opioid receptors. With tighter regulations on opioid prescriptions, loperamide has emerged as a popular drug of abuse among opioid users. At supratherapeutic doses, loperamide can cause severe cardiac toxicity, resulting in wide QRS rhythms, severe bradycardia, prolonged QTc, polymorphic ventricular tachycardia, and cardiac arrest. We present the case of a 27-year-old female with a history of heroin abuse who suffered torsades de pointes resulting in cardiac arrest in the setting of a loperamide overdose.

UNASSIGNED: The rising prevalence of psychiatric disorders has resulted in a significant increase in the use of antipsychotic medications. These agents may prolong the corrected QT interval (QTc), running the risk of precipitating ventricular arrhythmias, notably Torsades de Pointes (TdP). Current recommendations vary regarding the optimal approach to safe prescribing practices and QTc surveillance for antipsychotics. This review summarizes the current literature addressing these clinical concerns.
UNASSIGNED: The physiologic basis of the QTc interval, mechanisms underlying its susceptibility to pharmacological influence, specific risks associated with atypical antipsychotic agents, and recommendations for safe prescription practices. We performed a literature review using Pubmed and Embase databases, searching for \'antipsychotics\' and \'torsades de pointes.\'
UNASSIGNED: Finding a safe and universally accepted protocol for prescribing antipsychotics remains a persistent challenge in medicine. Predictive models that integrate clinical history with demographic and ECG characteristics can help estimate an individual\'s susceptibility to therapy-associated risks, including QTc prolongation. Agents such as ziprasidone and iloperidone are significantly more likely to prolong the QTc interval compared to others such as brexpiprazole, cariprazine, olanzapine, and clozapine. A personalized approach using low-risk medications when clinically feasible, and at the lowest efficacious dose, offers a promising path toward safer antipsychotic prescribing.
Antipsychotic medications are used to treat conditions such as schizophrenia and bipolar disorder; however, they can also affect cardiac electrical conduction. This effect on cardiac function increases the risk of a dangerous heart rhythm, which can potentially be fatal. Patients and doctors need to be aware of and monitor for these potential heart-related side effects, although antipsychotics can be very helpful for mental health conditions.

An implantable loop recorder (ILR) is now widely used for differential diagnosis of unexplained syncope or recurrent syncope with unknown causes. In the inherited arrhythmia syndromes, ILR may be useful for management of the therapeutic strategies; however, there is no obvious evidence to uncover arrhythmic syncope by ILR in long-QT syndrome (LQTS) patients. Here we experienced a 19-year-old female patient with LQTS type 1 who had recurrent syncope even after beta-blocker therapy but no arrhythmias were documented, and some episodes might be due to non-cardiogenic causes. Implantable cardioverter defibrillator (ICD) therapy was also recommended; however, she could not accept ICD but was implanted with ILR for further continuous monitoring. Two years later, she suffered syncope during a brief run, and ILR recorded an electrocardiogram at that moment. Thus a marked QT interval prolongation as well as T-wave alternance resulting in development of torsades de pointes could be detected. Although ILR is just a diagnostic tool but does not prevent sudden cardiac death, most arrhythmic events in LQTS are transient and sometimes hard to be diagnosed as arrhythmic syncope. ILR may provide direct supportive evidence to select the optimal therapeutic strategy in cases where syncope is difficult to diagnose.
UNASSIGNED: Long-QT syndrome (LQTS) patients often suffer recurrent syncope even after beta-blocker therapy, but torsades de pointes (TdP) is not always detected by standard 12‑lead electrocardiogram or Holter monitoring, and some syncope might be non-cardiogenic. In this case, implantable loop recorder (ILR) documented the evidence of QT interval prolongation and beat-by-beat T-wave alternance subsequent TdP. Thus, ILR may provide useful evidence for the optimal treatment strategy in LQTS cases where syncope is difficult to diagnose.

Numerous non-cardiovascular drugs have a potential to induce life-threatening torsades de pointes (TdP) ventricular cardiac arrhythmias by blocking human ether-à-go-go-related gene (hERG) currents via binding to the channel\'s inner cavity. Identification of the hERG current-inhibiting properties of candidate drugs is performed focusing on binding sites in the channel pore. It has been suggested that biologicals have a low likelihood of hERG current inhibition, since their poor diffusion across the plasma membrane prevents them from reaching the binding site in the channel pore. However, biologicals could influence hERG channel function by binding to \'unconventional\' noncanonical binding sites. This Opinion gives an overview on noncanonical blockers of hERG channels that might be of relevance for the assessment of the possible torsadogenic potential of macromolecular therapeutics.

Hypothyroidism can have a significant impact on cardiac contractility, vascular resistance, blood pressure, and cardiac rhythm. Ventricular arrhythmias induced by hypothyroidism are infrequently reported, especially in pediatric cases. A 15-year-old girl with autoimmune hypothyroidism experienced pulseless ventricular arrhythmias on 2 separate occasions because of nonadherence to levothyroxine medication. Subsequent investigations revealed an SCN5A mutation associated with Brugada syndrome. A loop recorder captured polymorphic ventricular tachycardia (PMVT), specifically Torsades de Pointes during her second event. Both arrhythmias were addressed only after stabilizing her thyroid hormone levels with replacement therapy. Although rare, patients with uncontrolled hypothyroidism may present with ventricular arrhythmias, particularly PMVT. The cornerstone of treatment for hypothyroidism-induced ventricular arrhythmia is thyroid replacement therapy. The identification of an SCN5A mutation unmasked by overt hypothyroidism emphasizes the need for a comprehensive cardiac evaluation in patients with hypothyroidism being assessed for PMVT.

The clinical manifestations of licorice-induced pseudoaldosteronism include muscle weakness, periodic paralysis, hypokalemia, and hypertension. Excessive licorice consumption can lead to adverse reactions affecting multiple systems, including the endocrine, cardiovascular, nervous, digestive, and immune systems. Although licorice is a frequently used Chinese herbal medicine, life-threatening adverse reactions have been reported among its users. This article presents a case of severe hypokalemia, torsade de pointes, severe hypertension, and exacerbation of manic symptoms resulting from an overdose of compound licorice tablets. This study aimed to enhance the understanding of the causes of hypokalemia and raise awareness on the potentially fatal adverse reactions associated with licorice drugs.

UNASSIGNED: Inpatient monitoring is recommended for sotalol initiation.
UNASSIGNED: The purpose of this study was to assess the safety of outpatient sotalol commencement.
UNASSIGNED: This is a multicenter, retrospective, observational study of patients initiated on sotalol in an outpatient setting. Serial electrocardiogram monitoring at day 3, day 7, 1 month, and subsequently as clinically indicated was performed. Corrected QT (QTc) interval and clinical events were evaluated.
UNASSIGNED: Between 2008 and 2023, 880 consecutive patients who were commenced on sotalol were evaluated. Indications were atrial fibrillation/flutter in 87.3% (n = 768), ventricular arrhythmias in 9.9% (n = 87), and other arrhythmias in 2.8% (n = 25). The daily dosage at initiation was 131.0 ± 53.2 mg/d. The QTc interval increased from baseline (431 ± 32 ms) to 444 ± 37 ms (day 3) and 440 ± 33 ms (day 7) after sotalol initiation (P < .001). Within the first week, QTc prolongation led to the discontinuation of sotalol in 4 and dose reduction in 1. No ventricular arrhythmia, syncope, or death was observed during the first week. Dose reduction due to asymptomatic bradycardia occurred in 3 and discontinuation due to dyspnea in 3 within the first week. Overall, 1.1% developed QTc prolongation (>500 ms/>25% from baseline); 4 within 3 days, 1 within 1 week, 4 within 60 days, and 1 after >3 years. Discontinuation of sotalol due to other adverse effects occurred in 41 patients within the first month of therapy.
UNASSIGNED: Sotalol initiation in an outpatient setting with protocolized follow-up is safe, with no recorded sotalol-related mortality, ventricular arrhythmias, or syncope. There was a low incidence of significant QTc prolongation necessitating discontinuation within the first month of treatment. Importantly, we observed a small incidence of late QT prolongation, highlighting the need for vigilant outpatient surveillance of individuals on sotalol.

Safety pharmacology examines the potential for new drugs to have unusual, rare side effects such as torsade de pointes (TdP). Recently, as a part of the Comprehensive in vitro Proarrhythmia Assay (CiPA) project, techniques for predicting the development of drug-induced TdP through computer simulations have been proposed and verified. However, CiPA assessment generally does not consider the effect of cardiac cell inter-individual variability, especially related to metabolic status. The study aimed to explore whether rare proarrhythmic effects may be linked to the inter-individual variability of cardiac cells and whether incorporating this variability into computational models could alter the prediction of drugs\' TdP risks. This study evaluated the contribution of two biological characteristics to the proarrhythmic effects. The first was spermine concentration, which varies with metabolic status; the second was L-type calcium permeability that could occur due to mutations. Twenty-eight drugs were examined throughout this study, and qNet was analyzed as an essential feature. Even though there were some discrepancies of TdP risk predictions from the baseline model, we found that considering the inter-individual variability might change the TdP risk of drugs. Several drugs in the high-risk drugs group were predicted to affect as intermediate and low-risk drugs in some individuals and vice versa. Also, most intermediate-risk drugs were expected to act as low-risk drugs. When compared, the effects of inter-individual variability of L-type calcium were more significant than spermine in altering the TdP risk of compounds. These results emphasize the importance of considering inter-individual variability to assess drugs.

Drug-induced QT prolongation increases the risk of Torsade de Pointes (TdP). Drug-induced QT prolongation is a complex and unpredictable system due to many uncertainties. Risk factors such as electrolyte disturbances, heart failure and genetics play an important role in estimating the effect on QT prolongation. Moreover, the degree of QT prolongation is not always directly related to the risk of TdP and the assessment of the QT-interval is variable depending on the type and timing of QT measurement. Therefore, the variation in QT measurement may be larger than the effect of certain drugs on the QT interval. Because of the potentially lethal risk, several measures are undertaken to reduce the risk of QT prolongation and TdP, while their effect and proportionality are unclear. We suggest we should be less stringent in certain settings when risk of TdP is extremely low given the limited availability of our resources.

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