Abstract Body (Do not enter title and authors here): Introduction:
Electronic cigarettes (e-cig) have been promoted as nicotine (NIC) delivery systems without the adverse effects of tobacco cigarettes; however, the increasing popularity of EC has prompted concerns about their potential cardiovascular (CV) toxicity. As e-cig are relatively new products, their long-term CV effects over the lifetime of the user remain unclear. We developed a mouse model of chronic e-cig exposure that mimics human NIC exposure levels to simulate long-term human use.

Objective:
To characterize the effects of long-term e-cig exposure on the structure, contractile function and electrophysiological function of the heart with exposures for >50% of life-span.

Methods:
C57/BL6 male mice were exposed to either air (25 mice) or aerosol from e-cig liquid containing 24 mg/ml NIC (25 mice) for 3 hours/day, 5 days/week, over 64 weeks. Blood pressure (BP) was measured by tail-cuff. Echocardiography was performed to assess the structure and function of the left ventricle (LV) and right ventricle (RV). High-resolution 3D visualization of LV and RV was also performed by cardiac CINE-MRI. Cardiac rate and electrophysiology was measured by electrocardiography (ECG).

Results:
Compared to the air control group, e-cig exposure for 64 weeks led to major changes in heart structure and function (Table 1). Marked elevations in systolic BP (SBP), diastolic BP (DBP), and mean BP (MBP) of 49%, 66%, and 63%, respectively, were observed. Echocardiography revealed concentric LV hypertrophy (LVH) with increases in both LV and RV end-diastolic and end-systolic wall thicknesses. LV mass was 43% increased. Marked RV hypertrophy (RVH) was also observed. The presence of LVH and RVH was confirmed on cardiac MRI. ECG exhibited 6% slower heart rate with e-cig exposure along with 23% prolonged PR interval and 91% increase in P wave duration. QT interval was 20% prolonged indicative of delayed ventricular depolarization and repolarization.

Conclusions:
Long term e-cig exposure caused hypertension with LV and RV hypertrophy with alterations in atrial and ventricular conduction seen. Thus, long-term e-cig use may predispose to hypertrophic heart disease and cardiac conduction abnormalities.