The following are key points to remember from this state-of-the-art review on cardiovascular complications of opioid use:

1. 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 to the status of a “fifth vital sign” boosted widespread prescribing for chronic, noncancer pain.
2. This, coupled with rising misuse, initiated a surge in unintentional deaths, increased drug-associated acute coronary syndrome (ACS), and endocarditis. Cardiovascular complications of opioids are now a major public health concern worldwide.
3. Opioid toxicity is primarily mediated via potent µ-receptor agonism resulting in ventilatory depression. However, both overdose and opioid withdrawal can trigger major adverse cardiovascular events resulting from hemodynamic, vascular, and proarrhythmic/electrophysiological consequences.
4. Although natural opioid analogues are devoid of repolarization effects, synthetic agents may be proarrhythmic. The US Center for Substance Abuse Treatment recommends QTc interval screening in methadone treatment.
5. Specifically, although natural opioids cause ventilatory depression, synthetic opioids exhibit additional influences on conduction, repolarization, and arrhythmia risk in susceptible individuals. Electrocardiogram (ECG) screening is recommended in a collaborative guideline from the Heart Rhythm Society and American Pain Association for chronic pain populations.
6. Opioids exhibit a myriad of cardiovascular complications including hypotension, bradycardia, peripheral vasodilatory flushing, and syncope. By contrast, opioid withdrawal triggers hypertension, tachycardia, stress cardiomyopathy, and potentially ACS.
7. Risk mitigation strategies are needed to address ventilatory depression, ventricular arrhythmia, and the rising incidence of endocarditis.
8. Cardiovascular specialists should be prudent regarding the quantity of opioid prescribed for post-procedure patients and should avoid chronic prescribing.
9. Early recognition of the signs of dependency and withdrawal is essential to ensure prompt referral to addiction treatment resources.
10. The most important strategy for reducing the impact of opioids on mortality is vigilant prescribing practices, and to address the unmet need to promptly identify cardiovascular events in overdose, prevent endocarditis, and stratify arrhythmia risk among vulnerable patients on chronic opioid therapy.

Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Hypertension

Keywords: Acute Coronary Syndrome, Analgesics, Opioid, Arrhythmias, Cardiac, Bradycardia, Chronic Pain, Drug Overdose, Electrocardiography, Endocarditis, Heart Failure, Hemodynamics, Hypertension, Hypotension, Methadone, Opioid-Related Disorders, Pharmaceutical Preparations, Primary Prevention, Public Health, Respiratory Insufficiency, Syncope, Tachycardia, Takotsubo Cardiomyopathy, Vascular Diseases, Vital Signs

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