The association between pro-arrhythmic agents and aortic stenosis in young adults: is it sufficient to clarify the sudden unexpected deaths?

Abstract

Most young patients with mild-to-moderate aortic stenosis show no symptoms, and sudden death appears only occasionally. We hypothesised that malignant ventricular arrhythmias could be responsible for the high incidence of sudden death in such patients. If multiple factors such as asymptomatic aortic stenosis in association with arrhythmia-provoking agents are involved, could it be sufficient to account for sudden unexpected death? In this study, eight cases of sudden death in young adults, with ages ranging from 22 to 36 years, who had never reported any symptoms that could be related to aortic stenosis, were investigated. Full autopsies were performed, and congenital aortic stenosis in all eight cases was confirmed. DNA testing for channelopathies was negative. Comprehensive toxicological analyses found an electrolyte imbalance, or non-toxic concentrations of amitriptyline, terfenadine, caffeine, and ethanol. Collectively, these results suggest that congenital asymptomatic aortic stenosis without cardiac hypertrophy in young adults is not sufficient to cause sudden death merely on its own; rather, an additional provoking factor is necessary. According to our findings, the provoking factor may be a state of physical or emotional stress, a state of electrolyte imbalance, or even taking a therapeutic dose of a particular drug.

High-Degree Atrioventricular Block and Torsades De Pointes in Severe Aortic Stenosis Treated With Transcatheter Aortic Valve Replacement

“…Chronic AV block leads to electrical remodeling, which heightens this dispersion, creating a substrate for reentrant circuits and increasing the risk of TdP [ 11 , 12 ]. This arrhythmic complication illustrates the interplay between structural cardiac abnormalities and arrhythmogenic risks, with sudden cardiac death in severe AS patients often attributed to ventricular arrhythmias, including TdP and ventricular fibrillation [ 13 , 14 ].…”

Potential Role of Life Stress in Unexplained Sudden Cardiac Arrest

“… 18 , 19 , 20 , 21 Temporal relationships between SCD and acutely stressful events, such as extreme threats to personal safety or hearing of a loved one’s death, have also been reported. 22 Phobic anxiety has been linked to CHD and SCD in men and women, and additional psychosocial factors such as distress, anxiety, depression, and life dissatisfaction have been connected with increased risk for SCD and stroke. 9 , 11 , 12 …”