EXPRESS: Impact of Methamphetamine Route of Administration on Cardiac Function.

BACKGROUND: Methamphetamine use is an increasingly detrimental public health crisis linked to significant cardiovascular harm, particularly methamphetamine-associated cardiomyopathy (MACM), which impairs left ventricular ejection fraction (LVEF). Despite well-documented cardiotoxic effects of methamphetamine, the impact of the route of administration (ROA) on LVEF remains underexplored. OBJECTIVE: This review examines how various ROAs of methamphetamine affect LVEF. It aims to inform clinical decision-making and support the development of pragmatic, risk-reduction interventions in addiction medicine and emergency settings. METHODS: We conducted a narrative review of peer-reviewed literature, prioritizing studies from the last 15 years while including seminal earlier work as well. Eligible studies examined methamphetamine use with reported LVEF or cardiac outcomes stratified by ROA. We included human and animal studies across diverse settings and excluded editorials, non-cardiac-focused papers, and studies involving exclusively people <18 years or pregnant individuals. RESULTS/FINDINGS: Our review of 57 papers showed that ROA may impact methamphetamine cardiotoxicity. IV use is linked to abrupt hemodynamic stress, including rapid volume shifts, along with embolic risk and severe LVEF decline. Smoking leads to repeated dosing, oxidative stress, production of harmful pyrolytic intermediates and pulmonary vascular injury. Intranasal use causes systemic vasospasm, while oral ingestion results in prolonged exposure and cumulative myocardial stress. However, direct, comparative clinical data on ROA and LVEF remain sparse and confounded by factors such as polysubstance use, homelessness, and underreporting. CONCLUSION: ROA may significantly modulate the impact of methamphetamine on LVEF. Future larger-scale, longitudinal studies are critical to clarify this relationship and guide targeted interventions.