IMPORTANCE Electronic cigarettes (e-cigarettes) have gained unprecedented popularity, but virtually nothing is known about their cardiovascular risks. OBJECTIVE To test the hypothesis that an imbalance of cardiac autonomic tone and increased systemic oxidative stress and inflammation are detectable in otherwise healthy humans who habitually use e-cigarettes. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional case-control study of habitual e-cigarette users and nonuser control individuals from 2015 to 2016 at the University of California, Los Angeles. Otherwise healthy habitual e-cigarette users between the ages of 21 and 45 years meeting study criteria, including no current tobacco cigarette smoking and no known health problems or prescription medications, were eligible for enrollment. Healthy volunteers meeting these inclusion criteria who were not e-cigarette users were eligible to be enrolled as control individuals. A total of 42 participants meeting these criteria were enrolled in the study including 23 self-identified habitual e-cigarette users and 19 self-identified non–tobacco cigarette, non–e-cigarette user control participants. MAIN OUTCOMES AND MEASURES Heart rate variability components were analyzed for the high-frequency component (0.15–0.4 Hz), an indicator of vagal activity, the low-frequency component (0.04–0.15 Hz), a mixture of both vagal and sympathetic activity, and the ratio of the low frequency to high frequency, reflecting the cardiac sympathovagal balance. Three parameters of oxidative stress were measured in plasma: (1) low-density lipoprotein oxidizability, (2) high-density lipoprotein antioxidant/anti-inflammatory capacity, and (3) paraoxonase-1 activity. RESULTS Of the 42 participants, 35% were women, 35% were white, and the mean age was 27.6 years. The high-frequency component was significantly decreased in the e-cigarette users compared with nonuser control participants (mean [SEM], 46.5 [3.7] nu vs 57.8 [3.6] nu; P = .04). The low-frequency component (mean [SEM], 52.7 [4.0] nu vs 39.9 [3.8] nu; P = .03) and the low frequency to high frequency ratio (mean [SEM], 1.37 [0.19] vs 0.85 [0.18]; P = .05) were significantly increased in the e-cigarette users compared with nonuser control participants, consistent with sympathetic predominance. Low-density lipoprotein oxidizability, indicative of the susceptibility of apolipoprotein B–containing lipoproteins to oxidation, was significantly increased in e-cigarette users compared with nonuser control individuals (mean [SEM], 3801.0 [415.7] U vs 2413.3 [325.0] U; P = .01) consistent with increased oxidative stress, but differences in high-density antioxidant/anti-inflammatory capacity and paraoxonase-1 activity were not significant. CONCLUSIONS AND RELEVANCE In this study, habitual e-cigarette use was associated with a shift in cardiac autonomic balance toward sympathetic predominance and increased oxidative stress, both associated with increased cardiovascular risk.

This review summarizes the detrimental effects of cigarette and noncigarette emission exposure on autonomic function, with particular emphasis on the mechanisms of acute and chronic modulation of the sympathetic nervous system. We propose that the nicotine and fine particulate matter in tobacco smoke lead to increased sympathetic nerve activity, which becomes persistent via a positive feedback loop between sympathetic nerve activity and reactive oxidative species. Furthermore, we propose that baroreflex suppression of sympathetic activation is attenuated in habitual smokers; that is, the baroreflex plays a permissive role, allowing sympathoexcitation to occur without restraint in the setting of increased pressor response. This model is also applicable to other nontobacco cigarette emission exposures (e.g., marijuana, waterpipes [hookahs], electronic cigarettes, and even air pollution). Fortunately, emerging data suggest that baroreflex sensitivity and autonomic function may be restored after smoking cessation, providing further evidence in support of the health benefits of smoking cessation.

BackgroundChronic electronic (e) cigarette users have increased resting cardiac sympathetic nerve activity and increased susceptibility to oxidative stress. The purpose of the present study is to determine the role of nicotine versus non‐nicotine constituents in e‐cigarette emissions in causing these pathologies in otherwise healthy humans.Methods and ResultsThirty‐three healthy volunteers who were not current e‐cigarette or tobacco cigarette smokers were studied. On different days, each participant used an e‐cigarette with nicotine, an e‐cigarette without nicotine, or a sham control. Cardiac sympathetic nerve activity was determined by heart rate variability, and susceptibility to oxidative stress was determined by plasma paraoxonase activity. Following exposure to the e‐cigarette with nicotine, but not to the e‐cigarette without nicotine or the sham control, there was a significant and marked shift in cardiac sympathovagal balance towards sympathetic predominance. The decrease in high‐frequency component and the increases in the low‐frequency component and the low‐frequency to high‐frequency ratio were significantly greater following exposure to the e‐cigarette with nicotine compared with exposure to the e‐cigarette without nicotine or to sham control. Oxidative stress, as estimated by plasma paraoxonase, did not increase following any of the 3 exposures.ConclusionsThe acute sympathomimetic effect of e‐cigarettes is attributable to the inhaled nicotine, not to non‐nicotine constituents in e‐cigarette aerosol, recapitulating the same heart rate variability pattern associated with increased cardiac risk in multiple populations with and without known cardiac disease. Evidence of oxidative stress, as estimated by plasma paraoxonase activity, was not uncovered following acute e‐cigarette exposure.

The electronic cigarette (EC) is a new source of indoor airborne particles. To better understand the impacts of secondhand vaping (SHV) emissions on indoor air quality, real-time measurements of particle size distribution, particle number concentration (PNC), fine particulate matter (PM 2.5 ), CO 2 , CO, and formaldehyde were conducted before, during, and after 10 min EC-use among 13 experienced users in an 80 m 3 room. To assess particle transport in the room, multiple sampling locations were set up at 0.8, 1.5, 2.0, and 2.5 m away from the subjects. The arithmetic mean (standard deviation) of background PNC and PM 2.5 concentrations in the room were 6.39 £ 10 3 (1.58 £ 10 2 ) particles/cm 3 and 8 (1) mg/m 3 , respectively. At 0.8 m away from EC users, right after initiation of puffing, the PNC and PM 2.5 concentrations can reach a peak of »10 5 particles/cm 3 and »3 £ 10 3 mg/m 3 , respectively, and then dropped quickly to background levels within 20 s due to dilution and evaporation. At the 0.8 m sampling location, the mean PNC and PM 2.5 concentrations during puffing were 2.48 £ 10 4 (2.14 £ 10 4 ) particles/cm 3 and 188 (433) mg/m 3 , respectively. In addition, two modes of SHV particles were observed at about 15 and 85 nm. Moreover, concentrations of SHV particles were negatively correlated with the distances to EC users. At the 1.5 m location, PNC and PM 2.5 levels were 9.91 £ 10 3 (1.76 £ 10 3 ) particles/cm 3 and 19 (14) mg/m 3 , respectively. Large variations of mean PNC levels exhaled per puff were observed both within and between EC users.

Tobacco cigarette(TC) smoking has never been lower in the US, but EC vaping has reached epidemic proportions amongst our youth. Endothelial dysfunction, as measured by flow mediated vasodilation(FMD) is a predictor of future atherosclerosis and adverse cardiovascular events, and is impaired in TC smokers, but whether FMD is also reduced in EC vapers is uncertain. The aim of this study in otherwise healthy young people was to compare the effects of acute and chronic TC smoking and EC vaping on FMD. FMD was compared in 47 non-smokers(NS), 49 chronic EC-vapers and 40 chronic TC-smokers at baseline, and then after EC-vapers(n=31) and non-smokers(n= 47) acutely used an EC-with-nicotine(ECN), EC-without-nicotine(EC0), and nicotine inhaler(NI) at ~4week intervals, and after TC-smokers(n=33) acutely smoked a TC, compared to sham-control. Baseline FMD was not different among the groups (NS:7.7±4.5%∆ vs EC:6.6±3.6%∆ vs TC:7.9±3.7%∆, p=0.35), even when compared by group and sex. Acute TC smoking vs control impaired FMD(FMD pre/post smoking: -2.52±0.92%∆ vs 0.65±0.93%∆, p=0.02). Although the increase in plasma nicotine was similar, acute EC vaping did not impair FMD. In otherwise healthy young people who regularly smoke TCs or ECs, impaired FMD was not present. However, FMD was significantly impaired after smoking one TC, but not after vaping an equivalent "dose"(estimated plasma nicotine) of an EC, consistent with the notion that non-nicotine constituents in TC smoke mediate the impairment. Although it is reassuring that acute EC-vaping did not acutely impair FMD, it would be dangerous and premature to conclude that ECs do not lead to atherosclerosis.

Abnormal ventricular repolarization, as indicated by prolonged Tpeak-end (Tp-e), is associated with increased sudden death risk. Baseline ECG indexes of repolarization, Tp-e, Tp-e/QT, and Tp-e/QTc, were not different among tobacco cigarette (TC) smokers, electronic cigarette (EC) users, and nonsmokers at baseline, but when TC smokers smoked one TC, all parameters were prolonged. Using an electronic cigarette with nicotine, but not without nicotine, increased the Tp-e/QT. Smoking induces changes in ECG indexes of ventricular repolarization associated with increased sudden death risk.

The “Splenocardiac Axis” describes an inflammatory signaling network underlying acute cardiac ischemia, characterized by sympathetic nerve stimulation of hematopoietic tissues, such as the bone marrow and spleen, which then release proinflammatory monocytes that populate atherosclerotic plaques, thereby promoting ischemic heart disease. Electronic (e) cigarettes, like tobacco cigarettes trigger sympathetic nerve activation, but virtually nothing is known about their influence on hematopoietic and vascular tissues and cardiovascular risks. The objective of this study was to determine if the Splenocardiac Axis is activated in young adults who habitually use either tobacco or e‐cigarettes. In otherwise healthy humans who habitually use tobacco cigarettes or e‐cigarettes (not both), we used 18F‐flurorodeoxyglucose positron emission tomography/computer tomography (FDG‐PET/CT) to test the hypothesis that tobacco or e‐cigarettes increased metabolic activity of the hematopoietic and vascular tissues. FDG uptake in the spleen increased from nonuser controls (1.62 ± 0.07), to the e‐cigarette users (1.73 ± 0.04), and was highest in tobacco cigarette smokers (1.82 ± 0.09; monotone P = 0.05). Similarly, FDG uptake in the aorta increased from the nonuser controls (1.87 ± 0.07) to the e‐cigarette users (1.98 ± 0.07), and was highest in tobacco cigarette smokers (2.10 ± 0.07; monotone P = 0.04). FDG uptake in the skeletal muscle, which served as a control tissue, was not different between the groups. In conclusion, these findings are consistent with activation of the Splenocardiac Axis by emissions from tobacco cigarettes and e‐cigarettes. This activation suggests a mechanism by which tobacco cigarettes, and potentially e‐cigarettes, may lead to increased risk of future cardiovascular events.

Background: Since its introduction in 1967, neuromodulation through spinal cord stimulation (SCS) or dorsal root ganglion stimulation (DRGs) has advanced significantly in both the technology and indications for use. There are now over 14,000 SCS implants performed worldwide every year. This review focuses on mechanisms behind the loss of efficacy in neuromodulation and current data on salvage therapy, defined as the conversion of a neuromodulation device to an alternative SCS or DRG stimulation, in the event of loss of efficacy or failure of a trial. Study Design: A narrative review of clinical studies regarding habituation, explant data, and salvage therapy with SCS. Methods: Available literature was reviewed on spinal cord stimulation technology and salvage therapy. Data sources included relevant literature identified through searches of PubMed, MEDLINE/OVID, SCOPUS, and manual searches of the bibliographies of known primary and review articles. Outcome Measures: The primary outcome measures were to understand the mechanisms of loss of efficacy, provide a review of explants due to failure in treatment, and summarize the data on current salvage therapy in SCS. Results: A total of eight studies and four abstracts/poster presentations were identified and reviewed. Of the eight studies, only one was a randomized controlled trial. Conclusions: There is limited evidence for the appropriate treatment alternatives, but from data currently available the conversion from conventional tonic stimulation to burst, high frequency (10 kHz), multiple wave forms, and/or DRGs may be appropriate in select patients and will require further research to determine the most appropriate first line salvage in the context of the underlying pain pathology.