This Provisional PDF corresponds to the article as it appeared upon acceptance. Fully formatted
PDF and full text (HTML) versions will be made available soon.
Acute effects of using an electronic nicotine-delivery device (electronic
cigarette) on myocardial function: comparison with the effects of regular
BMC Cardiovascular Disorders 2014, 14:78doi:10.1186/1471-2261-14-78
Konstantinos E Farsalinos (email@example.com)
Dimitris Tsiapras (firstname.lastname@example.org)
Stamatis Kyrzopoulos (email@example.com)
Maria Savvopoulou (firstname.lastname@example.org)
Vassilis Voudris (email@example.com)
26 July 2013
21 June 2014
23 June 2014
Like all articles in BMC journals, this peer-reviewed article can be downloaded, printed and
distributed freely for any purposes (see copyright notice below).
Articles in BMC journals are listed in PubMed and archived at PubMed Central.
For information about publishing your research in BMC journals or any BioMed Central journal, go to
BMC Cardiovascular Disorders
© 2014 Farsalinos et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
Acute effects of using an electronic nicotine-delivery
device (electronic cigarette) on myocardial function:
comparison with the effects of regular cigarettes
Konstantinos E Farsalinos1*
* Corresponding author
1 Department of Cardiology, Onassis Cardiac Surgery Center, Sygrou 356,
Kallithea 17674, Greece
Electronic cigarettes have been developed and marketed in recent years as smoking
substitutes. However, no studies have evaluated their effects on the cardiovascular system.
The purpose of this study was to examine the immediate effects of electronic cigarette use on
left ventricular (LV) function, compared to the well-documented acute adverse effects of
Echocardiographic examinations were performed in 36 healthy heavy smokers (SM, age 36 ±
5 years) before and after smoking 1 cigarette and in 40 electronic cigarette users (ECIG, age
35 ± 5 years) before and after using the device with “medium-strength” nicotine
concentration (11 mg/ml) for 7 minutes. Mitral flow diastolic velocities (E, A), their ratio
(E/A), deceleration time (DT), isovolumetric relaxation time (IVRT) and corrected-to-heart
rate IVRT (IVRTc) were measured. Mitral annulus systolic (Sm), and diastolic (Em, Am)
velocities were estimated. Myocardial performance index was calculated from Doppler flow
(MPI) and tissue Doppler (MPIt). Longitudinal deformation measurements of global strain
(GS), systolic (SRs) and diastolic (SRe, SRa) strain rate were also performed.
Baseline measurements were similar in both groups. In SM, IVRT and IVRTc were
prolonged, Em and SRe were decreased, and both MPI and MPIt were elevated after
smoking. In ECIG, no differences were observed after device use. Comparing after-use
measurements, ECIG had higher Em (P = 0.032) and SRe (P = 0.022), and lower IVRTc (P =
0.011), MPI (P = 0.001) and MPIt (P = 0.019). The observed differences were significant
even after adjusting for changes in heart rate and blood pressure.
Although acute smoking causes a delay in myocardial relaxation, electronic cigarette use has
no immediate effects. Electronic cigarettes’ role in tobacco harm reduction should be studied
intensively in order to determine whether switching to electronic cigarette use may have
long-term beneficial effects on smokers’ health.
Current Controlled Trials ISRCTN16974547
Electronic cigarette, Smoking, Myocardial function, Diastolic function, Tobacco harm
Smoking is a major risk factor for cardiovascular disease [1,2]. Although several
pharmaceutical products are available for smoking cessation, long term quit-rates are
relatively low . Therefore, tobacco harm reduction strategy and products have been
developed, with the main goal to reduce the amount of harmful substances administered to
the human body.
Electronic cigarettes have been introduced to the market in recent years as an alternative-to-
smoking habit. They consist of a battery-part, a cartridge containing liquid and an electrical
resistance that is heated by activation of the battery and evaporates the liquid. The liquid
usually contains glycerol, propylene glycol, water, nicotine and a variety of flavours that the
user can choose. By using this device, nicotine is delivered to the upper and lower respiratory
tract without any combustion involved. Millions of people are using electronic cigarettes
worldwide; however, lack of clinical research has raised global debate, controversy and
serious public health concerns .
Several studies have shown that, even in healthy smokers, acute smoking inhalation has
significant adverse effects on left ventricular (LV) myocardial function that can be detected
by echocardiography [5-7]. No study has ever evaluated the effects of electronic cigarette use
on cardiac function; thus, the purpose of the current study was to investigate the acute effects
of using an electronic cigarette ad lib for 7 minutes on haemodynamic parameters and
myocardial function, compared to the effects of smoking a tobacco cigarette.
The study sample consisted of consecutive healthy subjects visiting our hospital for routine
examinations that volunteered to participate. All participants were asymptomatic, had normal
physical examination and resting electrocardiogram and were not taking any medications.
Smokers (group SM) were included if they were smoking for at least 5 years and were
consuming at least 15 cigarettes per day. The reason for including only heavy smokers was
that a study examining the characteristics of electronic cigarette consumers showed that most
electronic cigarette users were formerly heavy smokers . Electronic cigarette users (group
ECIG) were included if they had quit smoking and were using electronic cigarettes with
nicotine-containing liquid for at least 1 month, according to self-report. To avoid potential
compensatory effects from using lower nicotine-containing liquid, participants were included
if they were daily consumers of similar “strength” liquids (9-12 mg/ml nicotine
concentration) to that used in the study (11 mg/ml). Exclusion criteria were: presence of any
major risk factor for cardiovascular disease (i.e. diabetes, hypertension, hyperlipidemia and
family history of premature coronary artery disease), history of endocrine disorders, body-
mass index > 30 kg/m2 and more than occasional alcohol intake. Additional exclusion criteria
were derived from the echocardiography studies: elevated LV mass index (>115 g/m2 for
males and > 95 g/m2 for females), abnormal LV function (LV ejection fraction < 55%) and
more than mild valve regurgitation.
In total, 81 subjects were eligible to participate. Three smokers did not present for the
scheduled evaluation. One electronic cigarette user was excluded because of moderate aortic
regurgitation and ascending aorta dilatation due to bicuspid aortic valve. One smoker was
excluded due to mildly depressed ejection fraction and hypokinesia of LV lateral wall. The
final study sample consisted of 76 subjects, 40 electronic cigarette users (3 females) and 36
smokers (3 females). Written informed consent was obtained from all subjects for
participation in the study, and the protocol was approved by the ethics committee of Onassis
Cardiac Surgery Center.
All smokers were asked to use one commercially-available tobacco cigarette of the same
nicotine (1.0 mg), tar (10 mg) and carbon monoxide (10 mg) yields. Electronic cigarette users
were asked to use a commercially-available device with liquid containing 11 mg/ml nicotine
concentration. The device used was an eGo-T battery (Nobacco, Athens, Greece) with an
eGo-C atomiser (Alter Ego, Athens, Greece). It is considered a “second-generation” device.
Unlike cigarette-like devices which consist of a small battery and a polyfil-containing
atomiser (commonly called “cartomiser”), the electronic cigarette used in this study is a
multi-piece system (Figure 1). It consists of a 650mAh rechargeable lithium battery,
delivering 3.5 volts to the atomiser (measured by a volt-meter), and an atomiser consisting of
4 parts: the tank which stores the liquid (capacity of approximately 1.1 ml), the atomiser
body, the atomiser head which includes the resistance, and the atomiser cap. It is a manually-
activated device, by pressing a button; it does not produce any vapour when not activated by
Figure 1 Electronic cigarette device and liquid used in the study.
The electronic cigarette liquid used in the study contained 11 mg/ml nicotine and is
considered “medium strength” according to manufacturer’s report (USA Mix Med, formerly
known as MLB-Med, Nobacco, Athens, Greece). It is sold in 20 ml bottles. It was the only
liquid tested by an independent laboratory (National Center for Scientific Research
“Demokritos”, mass spectrometry and dioxin analysis laboratory) at the time of study
initiation . According to the laboratory report, the contents were: propylene glycol (α -
propylene glycol or 1,2-propanediol) in a concentration > 60%, linalool (3,7-dimethylocta-
1,6-dien-3-ol) in a concentration < 5%, nicotine (<10%), tobacco essence (<5%), and methyl
vanillin (4-hydroxy-3-methoxybenzaldehyde) at < 1%. No tobacco-specific nitrosamines or
polycyclic aromatic hydrocarbons were detected.
For every participant, a new cartridge and atomiser head was used. One of the researchers
filled the cartridge with 1 ml of liquid; subsequently it was positioned in the atomiser and the
participant started using it. The battery was fully charged before being used by each subject.
Participants presented to the echocardiographic laboratory after fasting and refraining from
alcohol and caffeine consumption for 4 hours; they were also asked to refrain from smoking
and electronic cigarette use for 4 hours before the study.
Participants were allowed to rest for 5 minutes before initiating the echocardiographic
examination. A baseline echocardiographic examination was performed in smokers, who
were then transferred to a room next to the echocardiography laboratory and smoked 1
tobacco cigarette. For electronic cigarette users, after the baseline echocardiogram they were
asked to use the electronic cigarette device ad lib for 7 minutes in another room which was
not used by smokers, to avoid environmental exposure to smoke. Subsequently, all
participants returned to the echocardiography laboratory and, after 5 minutes of rest, a second
echocardiogram was performed in both groups.
Heart rate and BP were measured before and during each echocardiographic examination.
The Brinkman index was calculated (product of number of cigarettes smoked daily and years
of smoking) according to participants’ self-report. Echocardiograms were performed using a
commercially available system (Vivid 7, GE Vingmed, Horten, Norway). Studies were
digitally recorded on hard disk for offline analysis using dedicated software (Echopac, GE
Medical Systems, Horten, Norway) by a single, blinded to the protocol, experienced
echocardiographer. Reported values represent the average of 3 consecutive beats.
Two-dimensional echocardiographic measurements
The echocardiographic examinations were performed according to recent guidelines . LV
dimensions, septal and posterior wall thickness were measured from standard 2-dimensional
images at parasternal long-axis view. LV mass was indexed to body-surface area. Ejection
fraction was evaluated from the apical four and two-chamber views using the Simpson’s rule
. Left atrial (LA) antero-posterior diameter was also measured.
Doppler flow and tissue Doppler velocity measurements
From transmitral flow measurements, peak early (E) and late (A) velocities, their ratio (E/A)
and E wave deceleration time (DT) were estimated. Ejection time was estimated by recording
LV outflow tract velocity. By simultaneously recording aortic and mitral flows using
continuous-wave Doppler the isovolumetric relaxation time (IVRT) was measured, and was
then corrected to heart rate by dividing it with the square root of R-R interval (IVRTc).
Pulsed-wave Doppler tissue velocities were measured by placing a 1.5 mm sample volume at
the lateral, septal, anterior and inferior insertion sites of the mitral leaflets. Systolic (Sm),
early diastolic (Em) and late diastolic (Am) peak velocities were measured and averaged
from the 4 sites. The ratio of early-to-late annular velocity (Em/Am) and early mitral flow to
early diastolic mitral annular velocity (E/Em) were also determined.
Myocardial performance index was measured by two methods (Figure 2): using Doppler flow
velocity measurements as described by Tei et al.  (MPI) and using pulsed-wave tissue
Doppler measurements of mitral annulus velocities (MPIt) .
Figure 2 Myocardial performance index, measured by two methods: (1) Doppler flow
velocity measurements of mitral inflow and left ventricular outflow tract; the index was
derived by the formula: MPI = (a-b)/b, and (2) Pulsed-wave tissue Doppler
measurements of mitral annulus velocity; the index was derived from the formula:
MPIt = (a’-b’)/b’.
To check for reproducibility of measurements, the intraobserver mean percent error (the
absolute difference between two measurements divided by their mean) was calculated from
10 randomly selected studies 15 days later, analyzed by the same blinded echocardiographer
who performed all measurements. The results were 5.1 ± 2.9% for IVRT, 3.5 ± 2.5% for
MPI, 3.6 ± 2.2% for MPIt and 2.6 ± 1.9% for Em.
Longitudinal deformation measurements
Longitudinal deformation measurements were performed by analyzing two-dimensional
echocardiographic images using the method of speckle tracking echocardiography . End-
diastole was defined as the peak of the R wave on the electrocardiographic trace; end-systole
(aortic valve closure) was defined from pulsed-wave Doppler tracing at the LV outflow tract
as the end of systolic forward flow. Subjects with inadequate tracking of more than one LV
segment in each view were excluded from the analysis. By averaging segmental values in all
views, end-systolic global strain (GS) was measured. Global peak longitudinal systolic (SRs),
early diastolic (SRe) and late diastolic (SRa) strain rate were measured. The intraobserver
mean percent error of longitudinal deformation measurements in our laboratory was 3.1 ±
1.5% for GS, 3.6 ± 1.8% for SRs, 3.9 ± 1.9% for SRe and 3.6 ± 2.0% for SRa.
The Kolmogorov-Smirnov tests were applied to assess the normality of data; all parameters
were normally distributed except from daily cigarette consumption. Continuous variables
were expressed as mean ± SD or median (interquartile range). Categorical variables were
expressed as number (percentage). Inter-group comparisons of baseline characteristics data
were made by unpaired Student’s t-test and Mann–Whitney test; Fisher’s exact test was used
for categorical variables.
Repeated measurements analysis of variance (ANOVA) was used in order to evaluate
changes in parameters before and after smoking one cigarette or using the electronic cigarette
device (before-use and after-use measurements). Changes in echocardiographic and
deformation parameters that were significantly different between the two study groups from
analysis of variance were further analyzed using linear regression analyses, in order to find if
the effect of smoking was significant after adjusting for changes in heart rate and systolic BP.
For every parameter, a different linear regression analysis was performed. Change (∆) in
parameter was the dependent variable; group (SM vs. ECIG) and change in heart rate and
systolic BP were the independent variables. All P values reported are two-tailed. Statistical
significance was set at 0.05 and analyses were conducted using SPSS statistical software
(version 18.0, SPSS Inc., Chicago, USA).
A repeated measures ANOVA power analysis was conducted. For this design, 76 participants
(40 in the smokers group and 36 in the electronic cigarette users group) achieved a power of
0.90 for the between-subjects main effect at an effect size of 0.30; a power of 0.90 for the
within-subjects main effect at an effect size of 0.15; and a power of 0.90 for the interaction
effect at an effect size of 0.15.
Both groups had similar baseline characteristics (Table 1). Electronic cigarette users had quit
smoking for 97 ± 50 days and were using electronic cigarettes for 100 ± 49 days. They had
higher lifetime smoking exposure, with Brinkman index 33% higher compared to smokers,
due to higher daily cigarette consumption when they were smokers.
Table 1 Baseline characteristics of the study population
Males n (%)
Body mass index (kg/m2)
Body surface area (m2)
Smoking duration (years)
Cigarette consumption (n/d)b
Electronic cigarette use durationd
Systolic BP (mmHg)
Diastolic BP (mmHg)
Heart rate (beats/m)
Total cholesterol (mmol/l)
LDL cholesterol (mmol/l)
HDL cholesterol (mmol/l)
Ejection fraction (%)
LA diameter (mm)
LV mass index (g/m2)
BP, blood pressure, LVEDV, left ventricular end-diastolic volume; LVESV, left ventricular end-systolic
volume; LDL, low-density lipoprotein; HDL, high-density lipoprotein; LA, left atrium.
a Fisher’s exact test; bValues expressed as median (interquartile range); cMann-Whitney test; dDuration
expressed in months.
Smokers (n = 36) Electronic cigarette users (n = 40) P-value
36 ± 5
24.8 ± 2.3 25.3 ± 2.4
2.03 ± 0.15 2.00 ± 0.18
16 ± 5
20 (20–26) 30 (20–35)
371 ± 132 493 ± 228
123.0 ± 9.8 123.9 ± 8.6
75.8 ± 5.6 75.6 ± 6.1
67.5 ± 7.9 67.1 ± 10.3
8308 ± 1235 8312 ± 1363
4.51 ± 0.34 4.44 ± 0.35
4.85 ± 0.21 4.77 ± 0.30
2.99 ± 0.23 2.91 ± 0.26
1.38 ± 0.15 1.38 ± 0.18
1.05 ± 0.14 1.04 ± 0.18
63 ± 5
35 ± 4
64 ± 10
35 ± 5
17 ± 5
6 ± 4
62 ± 4
34 ± 3
65 ± 13
Changes in haemodynamic, Doppler echocardiography and longitudinal deformation
measurements for the study groups are presented in Tables 2 and 3. Baseline measurements
were similar between groups for all parameters.
Table 2 Haemodynamic and Doppler flow measurements in electronic cigarette users
(ECIG, n = 40) and smokers (SM, n = 36), before and after device and cigarette use
Systolic BP (mmHg)
ECIG 123.9 ± 8.6 124.6 ± 9.9
SM 123.0 ± 9.8 129.6 ± 9.2
Diastolic BP (mmHg)
ECIG 75.6 ± 6.1 78.5 ± 5.9
SM 75.8 ± 5.6 80.2 ± 5.8
Heart rate (beats/m)
ECIG 67.1 ± 10.3 67.5 ± 10.6
SM 67.5 ± 7.9 73.5 ± 6.8
ECIG 8312 ± 1363 8397 ± 1462
SM 8308 ± 1235 9556 ± 1084
ECIG 70.1 ± 12.5 71.4 ± 13.2
SM 72.9 ± 8.5 72.2 ± 10.2
ECIG 51.1 ± 10.2 52.7 ± 9.8
SM 50.4 ± 8.8 53.3 ± 9.1
ECIG 1.41 ± 0.29 1.37 ± 0.26
SM 1.49 ± 0.32 1.39 ± 0.30
ECIG 173 ± 11
SM 170 ± 16
ECIG 74.6 ± 9.5 73.6 ± 9.9
SM 73.0 ± 8.7 77.7 ± 13.5
ECIG 78.9 ± 11.8 77.7 ± 11.6
SM 77.3 ± 10.1 86.1 ± 16.4
0.7 ± 4.6
6.6 ± 5.2
3.0 ± 3.6
4.4 ± 3.3
0.4 ± 4.8
5.9 ± 4.7
84 ± 708
1248 ± 840
1.2 ± 5.0
−0.6 ± 6.1
1.6 ± 5.6
2.9 ± 5.7
−0.03 ± 0.14
−0.10 ± 0.16
1 ± 8
3 ± 10
−1.0 ± 5.7
5.6 ± 9.2
−1.2 ± 6.9
10.4 ± 10.1
174 ± 14
172 ± 16
BP, blood pressure; E, mitral flow early diastolic velocity; A, mitral flow late diastolic velocity; DT,
deceleration time of early mitral flow; IVRT, isovolumetric relaxation time; IVRTc, IVRT corrected to heart
rate; MPI, myocardial performance index estimated by Doppler flow echocardiography.
a P-value for time effect.
b Repeated measurements ANOVA. Effects reported are significant differences between the two groups in the
degree of change in each particular variable.
c P-value for group effect.
0.39 ± 0.07
0.40 ± 0.05
0.38 ± 0.06
0.43 ± 0.06
−0.01 ± 0.04
0.03 ± 0.04
Table 3 Tissue Doppler velocity and longitudinal deformation measurements in
electronic cigarette users (ECIG, n = 40) and smokers (SM, n = 36), before and after
device and cigarette use respectively*
ECIG 9.7 ± 1.6 9.9 ± 1.6
SM 9.7 ± 1.4 9.7 ± 1.5
P-valuec 0.896 0.723
ECIG 12.7 ± 1.9 12.9 ± 2.1
SM 12.8 ± 2.1 11.9 ± 1.5
P-valuec 0.892 0.032
ECIG 9.7 ± 1.7 9.9 ± 1.6
SM 9.3 ± 1.2 9.4 ± 1.3
P-valuec 0.212 0.099
ECIG 1.34 ± 0.29 1.33 ± 0.28
SM 1.40 ± 0.28 1.30 ± 0.24
P-valuec 0.408 0.655
ECIG 5.60 ± 1.04 5.61 ± 1.11
SM 5.83 ± 0.95 6.10 ± 0.98
P-valuec 0.311 0.044
ECIG 0.48 ± 0.08 0.47 ± 0.09
SM 0.49 ± 0.06 0.52 ± 0.07
P-valuec 0.654 0.019
ECIG −21.1 ± 1.9 −21.5 ± 1.6
SM −21.0 ± 2.6 −20.7 ± 3.1
P-valuec 0.769 0.192
ECIG −1.13 ± 0.10 −1.14 ± 0.11
SM −1.08 ± 0.13 −1.10 ± 0.13
P-valuec 0.059 0.115
ECIG 1.47 ± 0.25 1.49 ± 0.23
SM 1.43 ± 0.25 1.35 ± 0.24
0.2 ± 0.7
−0.8 ± 1.1
0.2 ± 0.7
−0.7 ± 1.4
0.2 ± 0.8
0.1 ± 0.6
−0.01 ± 0.13
−0.08 ± 0.13
0.01 ± 0.47
0.29 ± 0.74
−0.01 ± 0.04
0.03 ± 0.05
−0.4 ± 1.2
0.2 ± 1.7
−0.01 ± 0.07
−0.2 ± 0.1
0.01 ± 0.08
−0.08 ± 0.12
*Longitudinal deformation measurements were performed in 37 electronic cigarette users and 34 smokers.
Sm, mitral annulus systolic velocity; Em, mitral annulus early diastolic velocity; Am, mitral annulus late
diastolic velocity; MPIt, myocardial performance index estimated by tissue Doppler echocardiography; GS,
global longitudinal strain; SRs, peak systolic strain rate; SRe, peak early diastolic strain rate; SRa, peak late
diastolic strain rate.
a P-value for time effect.
b Repeated measurements ANOVA. Effects reported are significant differences between the two groups in the
degree of change in each particular variable.
c P-value for group effect.
0.88 ± 0.20
0.86 ± 0.14
0.89 ± 0.18
0.88 ± 0.14
0.01 ± 0.08
0.03 ± 0.09
After-use values of systolic BP, heart rate and pressure-rate product were elevated in the SM
group but not in the ECIG group (Table 2). The overall change from baseline was
significantly different between the two groups. In contrast, diastolic BP increased equally in
From Doppler flow echocardiographic measurements (Table 2), E velocity and DT remained
unchanged after use in both groups. A velocity was increased and E/A was decreased in SM,
but the overall change was not significantly different between the two groups (P = 0.317 and
P = 0.053, respectively). IVRT, IVRTc and MPI were increased after smoking one cigarette
in the SM group, and the degree of change was significantly different between the two study
groups (P = 0.001, P < 0.001 and P = 0.001 respectively). The after-use levels of IVRTc and
MPI were greater in SM compared to ECIG, as was shown by the between-groups analysis.
Concerning Doppler tissue velocity measurements (Table 3), Sm and Am remained
unchanged after use in both groups. However, Em was significantly reduced in SM group
after smoking. It was lower when compared to ECIG after using the device, and the degree of
change was significantly different between the two groups (P < 0.001). Em/Am was reduced
and E/Em was increased in SM, but the difference of the overall change between the two
groups was statistically significant for Em/Am only (P = 0.011). MPIt increased after
smoking in SM; the degree of change was significantly different between the two groups (P <
0.001), with after-use levels being significantly higher in SM compared to ECIG (P = 0.019).
Longitudinal deformation measurements (Table 3) were feasible in 37 electronic cigarette
users and 34 smokers. No difference in GS, SRs and SRa was observed in ECIG and SM
after use. However, SRe was significantly reduced in SM post-smoking, with the degree of
change being statistically significant between groups (P < 0.001).
The results of multiple linear regression analyses are displayed in Table 4. Even after
adjusting for changes in systolic BP and heart rate, changes in IVRT, IVRTc, MPI, Em, MPIt
and SRe were significantly higher in SM group.
Table 4 Results from linear regression analyses for the effect of group (smokers vs.
electronic cigarette users) on changes (∆) of Doppler echocardiography measurements,
after adjusting for changes in systolic blood pressure and heart rate
*Regression coefficient for the comparison of SM group to ECIG group, adjusted for changes in
systolic blood pressure and heart rate.
This is the first study to examine the acute effects of electronic cigarette use on myocardial
function. No adverse effects on LV myocardial function were observed after using electronic
cigarette with nicotine-containing liquid for 7 minutes. On the contrary, significant changes
in diastolic function parameters were found after smoking 1 tobacco cigarette.
The acute adverse effects of smoking on myocardial relaxation were originally observed in
coronary artery disease patients , with acute impairment of coronary vasomotion
implicated as the main cause . Such effects on diastolic function are also detected in
healthy smokers [5-7] Cigarette smoke contains significant amounts of free radicals,
promoting oxidative stress and inflammation  At the cellular level, decreased function of
myocardial mitochondria  and DNA damage  has been observed. These mechanisms
may be implicated in delaying myocardial relaxation from acute use and promoting
atherosclerosis and cardiovascular disease from chronic use. In this study, several parameters
commonly used for evaluating diastolic function  and longitudinal deformation
measurements which are considered more sensitive in detecting pathology  were
significantly altered after smoking inhalation.
Electronic cigarettes were invented in 2003, but awareness and use has significantly
increased over the past 3 years . They do not contain tobacco and their use does not
involve combustion. However, lack of research on their health effects has generated
significant controversy over their safety. FDA and WHO issued public statements in 2009,
expressing concern and recommending that electronic cigarette use should be avoided. WHO
has specifically asked for studies to be performed before regulation or even ban is imposed.
Cahn and Siegel summarized the results of 16 studies evaluating the chemical composition of
liquids used for electronic cigarettes . Nitrosamines were found in only two of the
studies, at levels similar to those present in nicotine patch; a recent review indicated that the
levels of nitrosamines in electronic cigarettes were up to 1800 times lower compared to
tobacco cigarettes . The main constituents, besides nicotine, were propylene glycol and
glycerine, which are also present in tobacco cigarettes; however, the combustion process
from smoking leads to production of acrolein, acetaldehyde and formaldehyde, which
promote oxidative stress and have cardiotoxic properties . In electronic cigarettes, such
chemicals may be formed from the heating process during liquid evaporation; however, the
levels found were lower compared to tobacco cigarettes by orders of magnitude . This
may explain the results from laboratory studies, in which electronic cigarette vapour was
significantly less cytotoxic compared to cigarette smoke on cultured cells [26,27].
Cardiotoxic substances like nitrosamines, heavy metals and polycyclic aromatic
hydrocarbons were not detected in the liquid used in this study . These parameters may
explain the differences in diastolic function observed between smokers and electronic
cigarette users after smoking and device use. Moreover, a study evaluating the effects of
smoking compared to nicotine delivered by gum showed that nicotine alone did not cause
acute changes in diastolic function . It seems that nicotine absorption rate is lower from
electronic compared to tobacco cigarette use , even when using new-generation devices
; the difference in haemodynamic response between the two groups may be attributed to
this. However, haemodynamic parameters cannot explain the differences in diastolic function
parameters, since linear regression analyses revealed that changes in Doppler and
deformation parameters were associated with cigarette smoking even after adjusting for
changes in systolic BP and heart rate.
From a public health perspective, epidemiological studies have shown that tobacco harm
reduction strategy and products may be promising regarding cardiovascular disease risk
reduction . Electronic cigarettes are unique since they are the only products that do not
contain tobacco, while they mimic the act of smoking and provide motor and sensory
stimulation. Thus, they may deal with both the chemical (nicotine delivery) and behavioural
components of cigarette addiction  and studies indicate that they may be effective in
promoting smoking cessation [32,33]. This study provides the first clinical evidence that
electronic cigarettes have less acute adverse effects on myocardial function when compared
to tobacco cigarettes.
Some limitations apply to this study. A small sample size was studied, and examination
focused only on immediate effects. The results do not indicate that electronic cigarettes are
absolutely safe for the cardiovascular system. Other parameters known to be adversely
affected by acute smoking, such as coronary microvascular and endothelial function or
vascular distensibility, were not examined. Moreover, the parameters examined are affected
mainly by heart rate changes. Although heart rate was not included as a covariate in the
repeated-measures ANOVA, the linear regression analysis showed that changes in diastolic
function were significantly different between groups independently of the changes in heart
rate and systolic BP. This can be explained by the small difference in post-use heart rate
between groups of only 6 beats per minute. Studies on long-term effects are necessary;
however, more time of use is needed before any such studies are published since electronic
cigarettes were introduced to the market in recent years and there is a substantial delay
between smoking initiation and development of clinically-evident disease. We asked subjects
to use the electronic cigarette for 7 minutes. It is unknown whether more time of use could
have had a different impact. However, timing was based on the approximate time of smoking
1 regular cigarette; in fact, it took smokers 5 minutes to smoke one cigarette while electronic
cigarette users were asked to use the device for a longer time. Additionally, experienced users
were examined, who use the device more intensively than novice users . Unfortunately,
there are no other means of comparing electronic with tobacco cigarette use. Although
plasma nicotine levels were not measured, the haemodynamic response observed suggests
that the nicotine delivery rate from electronic cigarettes is lower and slower compared to
tobacco cigarettes. This has been validated by studies performed recently [30,35]. The results
of this study are not necessarily applicable to all liquids available in the market. If non-
pharmaceutical grade nicotine is used, several tobacco impurities may be present and inhaled
by the user. The same applies for other liquid constituents . Finally, although all subjects
were considered healthy based on history taking, clinical examination, resting ECG and
echocardiogram, it cannot be excluded that some subjects may suffer from subclinical
coronary artery disease. However, there was no indication to perform any additional
examinations in the study population.
Although acute smoking inhalation caused a delay in LV myocardial relaxation in smokers,
electronic cigarette use was found to have no such immediate effects in daily users of the
device. This short-term beneficial profile of electronic cigarette compared to smoking,
although not conclusive about its overall health-effects as a tobacco harm reduction product,
provides the first evidence about the cardiovascular effects of this device. Since awareness
and use of electronic cigarettes are continuously rising, more studies are urgently needed,
focusing on the pathophysiological mechanisms of disease where smoking is implicated and
ultimately on long-term effects. Such studies will provide additional scientific data to public
health authorities so that they decide on the regulatory status of this product.
After this study was completed, the authors have performed studies using funds provided to
the institution by e-cigarette companies.
KF was responsible for study conception and design. KF, DT and MS were responsible for
data collection. SK was responsible for off-line measurements of echocardiographic
parameters. KF, DT and VV were responsible for statistical analysis and interpretation. KF,
DT and VV drafted the manuscript. All authors read and approved the manuscript.
This research received no specific grant from any funding agency in the public, commercial,
or not-for-profit sectors.
1. Ockene IS, Miller NH: Cigarette smoking, cardiovascular disease, and stroke: a
statement for healthcare professionals from the American Heart Association.
Circulation 1997, 96(9):3243–3247.
2. Merry AH, Boer JM, Schouten LJ, Feskens EJ, Verschuren WM, Gorgels AP, van den
Brandt PA: Smoking, alcohol consumption, physical activity, and family history and the
risks of acute myocardial infarction and unstable angina pectoris: a prospective cohort
study. BMC Cardiovasc Disord 2011, 11:13.
3. Rigotti NA, Pipe AL, Benowitz NL, Arteaga C, Garza D, Tonstad S: Efficacy and safety
of varenicline for smoking cessation in patients with cardiovascular disease: a
randomized trial. Circulation 2010, 121(2):221–229.
4. Cobb NK, Byron MJ, Abrams DB, Shields PG: Novel nicotine delivery systems and
public health: the rise of the “e-cigarette”. Am J Public Health 2010, 100(12):2340–2342.
5. Lichodziejewska B, Kurnicka K, Grudzka K, Malysz J, Ciurzynski M, Liszewska-Pfejfer
D: Chronic and acute effects of smoking on left and right ventricular relaxation in
young healthy smokers. Chest 2007, 131(4):1142–1148.
6. Karakaya O, Barutcu I, Esen AM, Kaya D, Turkmen M, Melek M, Onrat E, Esen OB,
Celik A, Kilit C, Saglam M, Kirma C: Acute smoking-induced alterations in Doppler
echocardiographic measurements in chronic smokers. Tex Heart Inst J 2006, 33(2):134–
7. Farsalinos K, Tsiapras D, Kyrzopoulos S, Voudris V: Acute and chronic effects of
smoking on myocardial function in healthy heavy smokers: a study of Doppler flow,
Doppler tissue velocity, and two-dimensional speckle tracking echocardiography.
Echocardiography 2013, 30(3):285–292.
8. Farsalinos KE, Romagna G, Tsiapras D, Kyrzopoulos S, Voudris V: Evaluating nicotine
levels selection and patterns of electronic cigarette use in a group of "vapers" who had
achieved complete substitution of smoking. Subst Abuse 2013, 7:139–146.
9. Leontiadis L: Results of Chemical Analyses in NOBACCO Electronic Cigarette Refills.
Athens: Mass Spectrometry and Dioxin Analysis Laboratory, National Centre for Scientific
Research “Demokritos”; 2009. accessed 11 December 2012.
10. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH,
Roman MJ, Seward J, Shanewise J, Solomon S, Spencer KT, St John Sutton M, Stewart W,
American Society of Echocardiography's Nomenclature and Standards Committee; Task
Force on Chamber Quantification; American College of Cardiology Echocardiography
Committee; American Heart Association; European Association of Echocardiography,
European Society of Cardiology: Recommendations for chamber quantification. Eur J
Echocardiogr 2006, 7(2):79–108.
11. Tei C, Ling LH, Hodge DO, Bailey KR, Oh JK, Rodeheffer RJ, Tajik AJ, Seward JB:
New index of combined systolic and diastolic myocardial performance: a simple and
reproducible measure of cardiac function: a study in normals and dilated
cardiomyopathy. J Cardiol 1995, 26(6):357–366.
12. Gaibazzi N, Petrucci N, Ziacchi V: Left ventricle myocardial performance index
derived either by conventional method or mitral annulus tissue-Doppler: a comparison
study in healthy subjects and subjects with heart failure. J Am Soc Echocardiogr 2005,
13. Amundsen BH, Helle-Valle T, Edvardsen T, Torp H, Crosby J, Lyseggen E, Støylen A,
Ihlen H, Lima JA, Smiseth OA, Slørdahl SA: Noninvasive myocardial strain measurement
by speckle tracking echocardiography: validation against sonomicrometry and tagged
magnetic resonance imaging. J Am Coll Cardiol 2006, 47(4):789–793.
14. Kyriakides ZS, Kremastinos DT, Rentoukas E, Mavrogheni S, Kremastinos DI,
Toutouzas P: Acute effects of cigarette smoking on left ventricular diastolic function. Eur
Heart J 1992, 13(6):743–748.
15. Deanfield JE, Shea MJ, Wilson RA, Horlock P, de Landsheere CM, Selwyn AP: Direct
effects of smoking on the heart: Silent ischemic disturbances of coronary flow. Am J
Cardiol 1986, 57(13):1005–1009.
16. Ambrose JA, Barua RS: The pathophysiology of cigarette smoking and
cardiovascular disease: an update. J Am Coll Cardiol 2004, 43(10):1731–1737.
17. Gvozdjáková A, Bada V, Sány L, Kucharská J, Krutý F, Bozek P, Trstanský L, Gvozdják
J: Smoke cardiomyopathy: disturbance of oxidative processes in myocardial
mitochondria. Cardiovasc Res 1984, 18(4):229–232.
18. Izzotti A, D'Agostini F, Balansky R, Degan P, Pennisi TM, Steele VE, De Flora S:
Exposure of mice to cigarette smoke and/or light causes DNA alterations in heart and
aorta. Mutat Res 2008, 644(1–2):38–42.
19. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, Waggoner AD,
Flachskampf FA, Pellikka PA, Evangelisa A: Recommendations for the evaluation of left
ventricular diastolic function by echocardiography. Eur J Echocardiogr 2009, 10(2):165–
20. Korinek J, Wang J, Sengupta PP, Miyazaki C, Kjaergaard J, McMahon E, Abraham TP,
Belohlavek M: Two-dimensional strain–a Doppler-independent ultrasound method for
quantitation of regional deformation: validation in vitro and in vivo. J Am Soc
Echocardiogr 2005, 18(12):1247–1253.
21. Pearson JL, Richardson A, Niaura RS, Vallone DM, Abrams DB: E-cigarette awareness,
use, and harm perceptions in US adults. Am J Public Health 2012, 102(9):1758–1766.
22. Cahn Z, Siegel M: Electronic cigarettes as a harm reduction strategy for tobacco
control: a step forward of a repeat of past mistakes? J Public Health Policy 2011,
23. Farsalinos KE, Polosa R: Safety evaluation and risk assessment of electronic
cigarettes as tobacco cigarette substitutes: a systematic review. Ther Adv Drug Safety
24. Luo J, Hill BG, Gu Y, Cai J, Srivastava S, Bhatnagar A, Prabhu SD: Mechanisms of
acrolein-induced myocardial dysfunction: implications for environmental and
endogenous aldehyde exposure. Am J Physiol Heart Circ Physiol 2007, 293(6):H3673–
25. Goniewicz ML, Knysak J, Gawron M, Kosmider L, Sobczak A, Kurek J, Prokopowicz A,
Jablonska-Czapla M, Rosik-Dulewska C, Havel C, Jacob P III, Benowitz N: Levels of
selected carcinogens and toxicants in vapour from electronic cigarettes. Tob Control
?:?. Mar 6. [Epub ahead of print].
26. Romagna G, Allifranchini E, Bocchietto E, Todeschi S, Esposito M, Farsalinos KE:
Cytotoxicity evaluation of electronic cigarette vapor extract on cultured mammalian
fibroblasts (ClearStream-LIFE): comparison with tobacco cigarette smoke extract.
Inhal Toxicol 2013, 25(6):354–361.
27. Farsalinos KE, Romagna G, Allifranchini E, Ripamonti E, Bocchietto E, Todeschi S,
Tsiapras D, Kyrzopoulos S, Voudris V: Comparison of the cytotoxic potential of cigarette
smoke and electronic cigarette vapour extract on cultured myocardial cells. Int J
Environ Res Public Health 2013, 10(10):5146–5162.
28. Gembala MI, Ghanem F, Mann CA, Sorrell VL: Acute changes in left ventricular
diastolic function: cigarette smoking versus nicotine gum. Clin Cardiol 2006, 29(2):61–
29. Bullen C, McRobbie H, Thornley S, Glover M, Lin R, Laugesen M: Effects of an
electronic nicotine delivery device (e cigarette) on desire to smoke and withdrawal, user
preferences and nicotine delivery: randomised cross-over trial. Tob Control 2010,
30. Farsalinos KE, Spyrou A, Tsimopoulou K, Stefopoulos C, Romagna G, Voudris V:
Nicotine absorption from electronic cigarette use: comparison between first and new-
generation devices. Sci Rep 2014, 4:4133.
31. Janzon E, Hedblad B: Swedish snuff and incidence of cardiovascular disease: a
population-based cohort study. BMC Cardiovasc Disord 2009, 9:21.
32. Siegel MB, Tanwar KL, Wood KS: Electronic cigarettes as smoking-cessation tool:
results of an online survey. Am J Prev Med 2011, 40(4):472–475.
33. Caponnetto P, Campagna D, Cibella F, Morjaria JB, Caruso M, Russo C, Polosa R:
Efficiency and safety of an electronic cigarette (ECLAT) as tobacco cigarettes
substitute: a prospective 12-month randomized control design study. PLoS One 2013,
34. McQueen A, Tower S, Sumner W: Interviews with "vapers": implications for future
research with electronic cigarettes. Nicotine Tob Res 2011, 13(9):860–867.
35. Dawkins L, Corcoran O: Acute electronic cigarette use: nicotine delivery and
subjective effects in regular users. Psychopharmacology (Berl) 2014, 231(2):401–407.
Figure 2 Download full-text