Ventricular Arrhythmias Associated With Over-the-Counter and Recreational Opioids.

Background: Epidemic increases in opioid deaths prompted policies limiting access to prescription opioids in North America. Consequently, the over-the-counter opioids loperamide (Imodium A-D) and mitragynine, the herbal ingredient in kratom, are increasingly used to avert withdrawal or induce euphoria. Arrhythmia events related to these nonscheduled drugs have not been systematically studied.

Huffing and twist: Fatal Torsade de pointes associated with Tetrafluoroethane Inhalation and amphetamine use.

Many volatile chemicals inhaled for a recreational high have a chemical structure similar to chloroform and may lead to Ikr blockade and subsequent torsades de pointes. This is one potential mechanism of action for huffing-associated sudden death.

Psychological factors and cardiac repolarization instability during anger in implantable cardioverter defibrillator patients.

Background: Evidence indicates that emotions such as anger are associated with increased incidence of sudden cardiac death, but the biological mechanisms remain unclear. We tested the hypothesis that, in patients with sudden death vulnerability, anger would be associated with arrhythmic vulnerability, indexed by cardiac repolarization instability.

Methods: Patients with coronary artery disease (CAD) and an implantable cardioverter defibrillator (ICD; n = 41) and healthy controls (n = 26) gave an anger-inducing speech (anger recall), rated their current (state) anger, and completed measures of trait (chronic) levels of Anger and Hostility.

Cardiovascular Complications of Opioid Use: JACC State-of-the-Art Review.

Opioids are the most potent of all analgesics. Although traditionally used solely for acute self-limited conditions and palliation of severe cancer-associated pain, a movement to promote subjective pain (scale, 0 to 10) to the status of a "fifth vital sign" bolstered widespread prescribing for chronic, noncancer pain. This, coupled with rising misuse, initiated a surge in unintentional deaths, increased drug-associated acute coronary syndrome, and endocarditis.

Potent Inhibition of hERG Channels by the Over-the-Counter Antidiarrheal Agent Loperamide.

Objectives: The aim of this study was to determine the in vitro electrophysiological properties of loperamide. The authors' hypothesis was that loperamide is a potent blocker of the current carried by the human ether-à-go-go-related gene (hERG) potassium channel.

Background: Loperamide is a peripherally-acting μ-opioid agonist available worldwide as an over-the-counter treatment for diarrhea.

Cardiovascular disorders associated with naloxone monotherapy and in fixed-dose combination with opioids: Data from international safety surveillance.

Background: The widespread use of opioids has resulted in sharp rise of associated complications, particularly opioid-induced constipation (OIC). Opioid receptor antagonists have been proposed to treat OIC, but could precipitate rapid opioid withdrawal. As cardiovascular safety data are lacking, we assessed disproportionate reporting of adverse cardiac events associated with naloxone across large, international pharmacovigilance systems.

Catheter ablation of atrial fibrillation should be offered as primary therapy: what's your hurry?

The appropriate initial treatment of a middle-aged individual with symptomatic paroxysms of atrial fibrillation, diabetes, and hypertension should focus on eliminating the underlying causes of disease to safely reduce morbidity and prolong life. An initial strategy using ablation temporarily reduces arrhythmia symptoms and exposes the individual to potentially needless risk and repeat procedures. Randomized trials have not established the superiority of ablation to antiarrhythmic drugs with respect to prolonging life or reducing serious morbidity.

Arrhythmia associated with buprenorphine and methadone reported to the Food and Drug Administration.

Aim: To assess the relative frequency of reporting of adverse events involving ventricular arrhythmia, cardiac arrest, corrected QT interval (QTc) prolongation or torsade de pointes to the US Food and Drug Administration (FDA) between buprenorphine and methadone.

Design: Retrospective pharmacoepidemiological study.

Setting: Adverse drug events reported spontaneously to the FDA between 1969 and June 2011 originating in 196 countries (71% events from the United States).

QT interval screening in methadone maintenance treatment: report of a SAMHSA expert panel.

In an effort to enhance patient safety in opioid treatment programs, the Substance Abuse and Mental Health Saervices Administration convened a multi-disciplinary Expert Panel on the Cardiac Effects of Methadone. Panel members (Appendix A) reviewed the literature, regulatory actions, professional guidances, and opioid treatment program experiences regarding adverse cardiac events associated with methadone. The Panel concluded that, to the extent possible, every opioid treatment program should have a universal Cardiac Risk Management Plan (incorporating clinical assessment, electrocardiogram assessment, risk stratification, and prevention of drug interactions) for all patients and should strongly consider patient-specific risk minimization strategies (such as careful patient monitoring, obtaining electrocardiograms as indicated by a particular patient's risk profile, and adjusting the methadone dose as needed) for patients with identified risk factors for adverse cardiac events.

Elevated B-type natriuretic peptide is associated with increased in-hospital mortality or cardiac arrest in patients undergoing implantable cardioverter-defibrillator implantation.

Background: The implantable cardioverter-defibrillator (ICD) is the most effective treatment for preventing arrhythmic deaths in patients with heart failure, but periprocedural complications, including in-hospital mortality or cardiac arrest, may occur, and little is known about risk factors. We asked whether elevated B-type natriuretic peptide (BNP) level is associated with increased risk of in-hospital mortality or cardiac arrest in patients undergoing ICD implantation.

Methods And Results: From the National Cardiovascular Data Registry ICD Registry, we identified 53 198 patients who received ICD implants and underwent preoperative BNP measurement from 2006 to 2008.

QTc interval screening in methadone treatment.

Description: An independent panel developed cardiac safety recommendations for physicians prescribing methadone.

Methods: Expert panel members reviewed and discussed the following sources regarding methadone: pertinent English-language literature identified from MEDLINE and EMBASE searches (1966 to June 2008), national substance abuse guidelines from the United States and other countries, information from regulatory authorities, and physician awareness of adverse cardiac effects. RECOMMENDATION 1 (DISCLOSURE): Clinicians should inform patients of arrhythmia risk when they prescribe methadone.

Coronary artery aneurysm and thrombosis following chronic ephedra use.

Ephedra, also known as Ma Huang, was commonly used to enhance athletic performance, "fat burning", and weight loss before its removal from the United States in April 2004 due to acute adverse health reactions including lethal arrhythmias, stroke, vasoconstriction, and myocardial infarction. We report the case of a 29-year-old patient with acute myocardial infarction, secondary to coronary artery aneurysms and thrombosis who reported use of Ma Huang, Xenadrine(r)RFA, and Hydroxycut at recommended dosages for a combined total of approximately 2 years. Other causes of coronary artery aneurysm and hypercoagulability were ruled out.

QT-interval effects of methadone, levomethadyl, and buprenorphine in a randomized trial.

Background: Levomethadyl acetate, methadone hydrochloride, and buprenorphine hydrochloride are equally effective treatments for opioid dependence. Each blocks the human ether-a-go-go-related gene (hERG)-associated channel in vitro and represents a risk for QT prolongation. To compare the effects of 3 known hERG-associated channel blockers on the corrected QT (QTc), we conducted a randomized, controlled trial of opioid-addicted subjects.

Gender differences in Na/Ca exchanger current and beta-adrenergic responsiveness in heart failure in pig myocytes.

Clinical trials suggest females experience less heart failure (HF) progression, mortality, and arrhythmia frequency. HF increases Na/Ca exchanger (NCX) expression and activity contributing to both depressed contractility and ventricular arrhythmias, but whether gender modifies this effect is unknown. Left ventricular myocytes were isolated from control and from tachycardic pacing-induced failing swine hearts of both sexes.

Muscarinic modulation of the sodium-calcium exchanger in heart failure.

Background: The Na-Ca exchanger (NCX) is a critical calcium efflux pathway in excitable cells, but little is known regarding its autonomic regulation.

Methods And Results: We investigated beta-adrenergic receptor and muscarinic receptor regulation of the cardiac NCX in control and heart failure (HF) conditions in atrially paced pigs. NCX current in myocytes from control swine hearts was significantly increased by isoproterenol, and this response was reversed by concurrent muscarinic receptor stimulation with the addition of carbachol, demonstrating "accentuated antagonism.

Intravenous cocaine and QT variability.

Background: Dynamic instability in cardiac repolarization may contribute to drug-induced arrhythmogenesis. We hypothesized that intravenous cocaine would significantly destabilize repolarization as measured by QT variability.

Methods And Results: Twenty-nine cocaine-experienced volunteers not seeking treatment for cocaine addiction received randomized, sequential intravenous infusions of placebo or cocaine (20 and 40 mg).

Ciprofloxacin-induced torsade de pointes.

We report a rare case of torsade de pointes, a polymorphic ventricular tachycardia associated with QT interval prolongation, caused by intravenous ciprofloxacin given for pneumonia in a 22-year-old healthy Marine. Although the risk for quinolone-associated torsade de pointes appears to be low, caution is still warranted when given in the presence of pre-existing QT prolongation.