The risk of sudden death from tobacco cigarette (TC) smoking is largely independent of smoking burden, and reverts to that of a non-smoker soon after smoking cessation. These observations have led to the hypothesis that smoking-related sudden death is a direct toxic effect of constituent(s) in TC smoke, rather than a consequence of progressive coronary artery disease. Although controversial, electronic cigarettes (ECs) are perceived by many as a safer alternative to lethal TCs. Toxic constituents in EC emissions are orders of magnitude lower than in TC smoke that is, except for nicotine; comparable plasma nicotine levels are achievable in EC users and TC smokers.
Mechanisms of sudden death from smoking TCs are uncertain, but TCs are known to increase adrenaline levels and to change how electrical impulses are conducted in the heart – both risk factors for ventricular arrhythmias. Importantly, in single heart cells, nicotine has been shown to directly alter the electrical impulses in a way that could potentially lead to abnormal heart rhythms. These changes can be detected on the ECG in humans by measuring a segment called the "QT interval." TC smokers are reported to have prolongation of the QT interval on the ECG, indicative of abnormal electrical conduction, and a risk factor for sudden death. In studies in mice, exposure to emissions from ECs have also been reported to significantly increase the QT interval. Interestingly, in this rodent model, QT prolongation was triggered by the solvents in EC emissions, in the absence of nicotine. It is unknown if chronic EC users, like chronic TC smokers, have abnormal electrical conduction. Further, if present, it is unknown if abnormal electrical conduction is attributable to the nicotine, or the non-nicotine constituents in EC emissions. Our central hypothesis is that EC use is associated with abnormal electrical conduction in the heart detectable on the ECG, and that this effect is mediated by the nicotine, not non-nicotine constituents in EC emissions. This hypothesis will be tested in humans using a rigorous crossover design, including ECs with nicotine and without nicotine, and the nicotine inhaler.
EC-mediated QT prolongation in humans, if present, is a potential game changer. It would be expected to significantly influence regulations of ECs, and to alter the public's perception that ECs are harmless. |
