Exp Mol Pathol. 2026 Jul 15;147:105068. doi: 10.1016/j.yexmp.2026.105068. Online ahead of print.
ABSTRACT
Sudden cardiac death (SCD) in individuals ≤35 years remains a major challenge for cardiology and forensic medicine, often affecting subjects without prior symptoms. At the same time, the consumption of energy drinks (EDs) and the medical or non-medical use of cognitive enhancers or "smart drugs" (SDs), including methylphenidate, amphetamine derivatives, and modafinil, has increased markedly among adolescents, students, and athletes. This review integrates mechanistic, clinical, epidemiological, and forensic evidence to clarify the role of EDs and SDs as arrhythmogenic triggers, identify at-risk populations, and outline diagnostic and regulatory implications. ED formulations consistently produce measurable cardiovascular effects. Experimental whole-heart models show that caffeine-taurine combinations shorten action potential duration and effective refractory period, facilitating re-entry. Clinical and forensic case reports describe SCD or near-fatal arrhythmias shortly after ED intake, particularly in individuals later diagnosed with long-QT syndrome, catecholaminergic polymorphic ventricular tachycardia, or other inherited channelopathies, supporting a trigger-on-substrate mechanism. Prescription SDs increase sympathetic tone, myocardial oxygen demand, and autonomic stress, especially under dehydration, sleep deprivation, strenuous exercise, or polysubstance use. Although population-level risk is low, adults with hypertension or occult cardiac disease and young individuals with latent genetic substrates exhibit substantially increased vulnerability. Stimulants seldom act as sole causes of SCD but can significantly lower the arrhythmic threshold in susceptible individuals, particularly under physiological or environmental stress. Integrating clinical screening, rigorous forensic investigation, including molecular autopsy, and improved regulatory measures are essential to reduce preventable stimulant-associated cardiac deaths while preserving legitimate therapeutic use.
PMID:42456408 | DOI:10.1016/j.yexmp.2026.105068