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Original Research: TOBACCO |

Chronic and Acute Effects of Smoking on Left and Right Ventricular Relaxation in Young Healthy Smokers* FREE TO VIEW

Barbara Lichodziejewska, MD, PhD; Katarzyna Kurnicka, MD; Katarzyna Grudzka, MD; Jerzy Małysz, MD; Michał Ciurzyński, MD, PhD; Danuta Liszewska-Pfejfer, MD, PhD
Author and Funding Information

*From the Department of Internal Medicine and Cardiology, Institute of Dentistry, Warsaw Medical University, Warsaw, Poland.

Correspondence to: Barbara Lichodziejewska, MD, PhD, Department of Internal Medicine and Cardiology, Institute of Dentistry, Warsaw Medical University, 02–005 Warsaw, Lindleya 4, Poland; e-mail: barlicho@wp.pl



Chest. 2007;131(4):1142-1148. doi:10.1378/chest.06-2056
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Published online

Background: Left ventricular (LV) diastolic dysfunction has been observed in cigarette smokers with coronary artery disease. The aim of the study was to assess LV and right ventricular (RV) diastolic function in healthy, young, and slim smokers before and after smoking one cigarette.

Material and methods: The participants were 66 healthy volunteers (age < 40 years; body mass index < 25 kg/m2): 33 smokers (study group [HS]) and 33 nonsmokers (control group). Echocardiographic examination was done in the HS before smoking one cigarette (HS-1) and after smoking one cigarette (HS-2). To assess diastolic function of LV and RV mitral valve flow (MVF), pulmonary venous flow (PVF) and tricuspid valve flow (TVF) were evaluated.

Results: MVF early to late phase ratio (E/A) was significantly lower in HS-1 and HS-2 than in the control group. The PVF systolic to diastolic phase ratio (S/D) was significantly higher in HS-1 and HS-2 than in the control group. These changes suggest LV diastolic function impairment in the HS, but the MVF pattern remained within the normal range. PVF S/D showed systolic dominance (S/D > 1) typical for impaired LV relaxation and abnormal for this age group. TVF E/A was significantly lower in HS-2 than in HS-1 and control subjects and suggests RV diastolic dysfunction.

Conclusions: The following conclusion are made: (1) MVF and PVF demonstrate LV relaxation impairment in healthy smokers before and after smoking one cigarette; (2) the assessment of PVF is a good method reflecting LV diastolic function changes, even when MVF remains normal; and (3) TVF shows RV relaxation impairment after smoking one cigarette in healthy smokers.

Figures in this Article

Impairment of relaxation, the early phase of ventricular diastole, is the first stage of diastolic dysfunction. Left ventricular (LV) diastolic function can be determined by Doppler echocardiography-derived mitral valve flow (MVF) velocities.14 The addition of a pulmonary venous flow (PVF) pattern enables more accurate assessment of LV diastolic function1,56 The role of the right ventricle in hemodynamic function of the heart is now emphasized. Right ventricular (RV) diastolic function can be assessed by recording the tricuspid valve flow (TVF) pattern, but the studies on this subject are sparse.710 In the last decade, the myocardial performance index (MPI) has been described as a good marker of ventricular global—systolic and diastolic—function.1112 Impaired LV diastolic function usually precedes systolic dysfunction13 and may cause clinical signs of congestive heart failure.3,14Cigarette smoking is one of the major risk factors for cardiovascular disease. In smokers with coronary artery disease, abnormalities of LV diastolic function were detected.1516 The impairment of LV relaxation observed in healthy smokers was shown in some studies. Most of the researchers1719 assessed LV diastolic function by evaluation of MVF. The aim of our study was to examine the LV diastolic function by assessing MVF and PVF, LV MPI, and also diastolic and global RV function in young healthy smokers before and after smoking one cigarette. LV diastolic function may be impaired by obesity,17 and the Doppler patterns of diastolic filling are strongly dependent on age2021; therefore, the authors conducted the study on young (age ≤ 40 years) participants with normal body mass index (BMI). The focus of interest was if smoking impaired the LV and RV function even in healthy, young, and slim persons.

Participants

The inclusion criteria were age < 40 years, BMI < 25 kg/m2, normal BP, and normal parameters of echocardiographic examination (wall thickness, left and right chamber size, valvular function, and left and right ventricular systolic function). All the participants were healthy volunteers with normal results of routine physical examination, chest radiography, standard resting ECG, and routine laboratory tests. The inclusion criteria for smokers were additionally smoking > 10 cigarettes per day over the last 5 years. The study group (HS) consisted of 33 healthy smokers (19 women, age 22 to 40 years) who smoked 10 to 25 cigarettes per day for 6 to 20 years. The control group included 33 healthy nonsmokers (16 women, age 20 to 40 years).

Study Protocol

In all participants, echocardiographic examination in the left lateral position, and heart rate and BP measurements after 10 min of rest were performed. In the HS, the first examination was done after a 2-h nonsmoking period (HS before smoking one cigarette [HS-1]); the second examination was done immediately after smoking one cigarette containing 0.9 mg of nicotine (HS after smoking one cigarette [HS-2]). The duration of the second examination was 9 to 14 min. All participants gave written consent before inclusion in the study. The protocol was approved by the Bioethical Committee of Warsaw Medical University.

Methods

Echocardiography was performed with a Hewlett-Packard SONOS 2000 (Andover, MA) imaging system. Transducer frequency was 2 MHz. Recording and calculations were performed according to the standards and recommendation of the American Society of Echocardiography.22

Echocardiographic studies were recorded on videotape. In LV and RV filling, end-expiratory beats were measured and a mean of three cycles was used for calculations. The analysis of echocardiograms was performed by two independent observers.

LV Diastolic Function Assessment

From the apical four-chamber view, the transmitral flow at the level of the leaflet tips was obtained and following parameters were defined: the maximal velocity (centimeters per second) of MVF early phase (E) and the maximal velocity of MVF late phase (A), the MVF E/A ratio, and deceleration time (DT; milliseconds) of MVF E. From the apical five-chamber view, the simultaneous recording of the aortic and mitral flows was evaluated and the isovolumetric relaxation time (IVRT; milliseconds) was measured.1,23 From the apical four-chamber view, PVF was revealed by placing the pulsed-wave Doppler sample volume approximately 1 cm into the right upper pulmonary vein.1 The following parameters were defined: the maximal velocity of PVF systolic phase (S), the maximal velocity of PVF diastolic phase (D), the PVF S/D ratio, and the maximal velocity of atrial reversal flow.1,23 Technically sufficient for calculations, Doppler spectrum of atrial reversal flow was detected in 82% of participants. Normal values for persons < 40 years old according to previously reported data4,6,21,24 were as follows: E/A > 1, DT < 180 ms, IVRT < 75 ms, S/D < 1, and atrial reversal flow < 0.35 cm/s as reflecting normal atrial pressure. Impaired relaxation was defined by the diminution of E/A, prolongation of DT and IVRT, and S/D elevation (Fig 1 ).

Global LV Function Assessment

LV MPI, defined as the sum of LV isovolumetric contraction and relaxation times (milliseconds) divided by the LV ejection time (milliseconds), was calculated according to the method described by Tei et al,11 with normal values of 0.39 ± 0.05 (mean ± SD) [Fig 2 ].

RV Diastolic Function Assessment

From the apical four-chamber view, transtricuspid flow was obtained and the following parameters were measured: maximal velocity of TVF E, and the maximal velocity of TVF A. The TVF E/A ratio > 1 was considered as the normal value.7,10,23 Because the Doppler spectral envelopes of transtricuspid flow could not be well defined,23 and the measurements of IVRT and TVF E DT could be not precise, the authors decided not to include these data in the study.

From subcostal view, the right superior hepatic vein was visualized and the hepatic vein flow was revealed by placing the pulsed-wave Doppler sample volume approximately 1 to 2 cm from the junction with the inferior vena cava.23 Good visualization of hepatic vein flow pattern is difficult23 and was possible in only 53% of examined group. The maximal velocity of hepatic vein flow S, D, and the S/D ratio were defined.

Global RV Function Assessment

RV MPI was calculated according to Tei et al12 with normal values of 0.28 ± 0.04.

Statistical Analysis

Parametric data were analyzed using the Smirnov-Koumogorov test if data had a normal distribution. The parameters were compared using paired and unpaired Student t tests. Pearson correlation coefficients were calculated to determine the strength of linear relationships of variables of Doppler echocardiographic parameters with independent variables such as duration of smoking and number of cigarettes per day. Comparisons between nonparametric data were evaluated by the χ2 test with the Yates correction when appropriate. A p value < 0.05 was considered statistically significant for all tests. The interobserver variability was 5.8 ± 3.2, and intraobserver variability was 2.6 ± 2.4.

Table 1 shows the characteristics of the study population. The parameters of the physical examination and velocity time integral (VTI) of the pulmonary valve and aortic valve flows reflecting RV and LV stroke volumes25 are shown in Table 2 . Only heart rate showed significant difference and was higher in HS-2 than in HS-1 and the control group.

The parameters of LV function are shown in Table 3 . MVF E was not significantly lower in HS-1 and HS-2 than in the control group, while MVF A was higher in HS-2 than in HS-1, and higher in HS-1 than in the control group. Subsequently, the MVF E/A ratio (Fig 3 ) was lower in HS-1 and HS-2 than in the control group. PVF S was higher in HS-1 and HS-2 than in the control group, and PVF D tended to be nonsignificantly lower in HS-1 and HS-2 than in the control group; therefore, PVF S/D ratio (Fig 4 ) was higher in HS-1 and HS-2 than in the control group. Also, MVF E DT was longer in HS-1 and HS-2 than in the control group. These changes suggest the impairment of LV diastolic function in smokers. The PVF S/D ratio showed positive correlation in HS-2 with the duration of smoking in years (r = 0.47; p < 0.03).

The parameters of RV function are shown in Table 4 . TVF E did not differ significantly between groups. However, TVF A was higher in HS-2 than in HS-1 and in HS-1 than in the control group; so the TVF E/A ratio was lower in HS II than in HS-1 and HS-1 than in the control group. The changes suggest the impairment of RV diastolic function after smoking a cigarette.

The effects of chronic cigarette smoking are well established. Smoking causes endothelial dysfunction, coronary atherosclerosis, higher heart rate, elevated BP, and may lead to increased myocardial oxygen consumption.15,2627 The raise in systemic vascular resistance was observed even in otherwise healthy young smokers.28Acute inhalation of nicotine temporarily decreases nitrate, nitrite, and serum antioxidant concentrations in the plasma29and is associated with accelerated heart rate and higher BP. The increase of arterial stiffness was also reported.30Smoking also causes an increase in coronary resistance, a reduction in the coronary blood flow and the coronary flow reserve, and the possibility of the coronary spasm in patients with coronary artery disease.3132

Abnormalities of diastolic filling play an important role in the clinical status and prognosis of patients with most heart diseases.1 Changes in LV diastolic filling after acute administration of nicotine in patients with coronary artery disease were described by some authors. Störk et al16 examined 28 patients aged 38 to 70 years. After smoking one cigarette containing 0.9 mg of nicotine, the significant decrease of E/A ratio and IVRT prolongation was observed. Kyriakides et al15 investigated 20 smokers with coronary artery disease compared to 20 healthy smokers. After acute administration of 1.35 mg of nicotine, there was no change in IVRT, DT, and A velocity, and a significant decrease of E velocity in the coronary artery disease group. In healthy smokers, the authors noticed no changes in any Doppler echocardiographic filling parameter.

The findings of these studies suggest that the decrease of coronary blood flow, which is a direct effect of smoking,32 causes an imbalance between myocardial oxygen demand and supply for the energy-consuming process of myocardial repolarization, and thus impairs LV diastolic function.16 A similar mechanism may be responsible for chronic and acute effects of smoking on LV diastolic function in healthy persons.

Reports on LV diastolic function in healthy smokers are sparse. Voutilainen et al17noticed no significant difference between smokers and nonsmokers in a rather nonuniform group of 93 healthy persons aged 11 to 91 years. Störk et al18assessed LV diastolic filling parameters in a group of 22 healthy subjects, and demonstrated a decrease of E-wave and increase of A-wave velocities and velocity time integrals, and also an increase of IVRT duration. Alam et al19 studied transmitral velocities, the mitral annular velocities determined by Doppler tissue imaging, and PVF velocities before and after smoking one cigarette containing 1.1 mg of nicotine in a group of 36 healthy persons (13 smokers, 23 nonsmokers; mean age, 38 years). There was no change in PVF, but the changes of mitral Doppler and tissue Doppler imaging showed the impairment of LV diastolic relaxation. The present study revealed prolonged E DT, higher A wave and lower E/A ratio in MVF, and higher S wave and lower S/D ratio in PVF in healthy young smokers in comparison to nonsmokers. These changes, more pronounced after acute inhalation of nicotine, suggest dysfunction of early phase of LV diastole.

Reports1819 mentioned above show the impairment of LV diastolic relaxation by the assessment of transmitral flow or mitral annulus velocities. Doppler PVF pattern also has been used as complementary information to the analysis of left-sided heart filling pressures.33 The present study demonstrated a high usefulness of the assessment of PVF for reflecting early, nonsymptomatic stages of impaired LV relaxation. Many investigators5,33 have shown that transthoracic pulmonary venous recordings appear to be accurate enough to be used in clinical practice. In experienced echocardiography laboratories, pulmonary venous systolic and diastolic flow can be successfully estimated in most cases.33 Atrial reversal flow is more difficult to assess.1,5 In the present study, we were able to obtain systolic and diastolic pulmonary inflow in all persons and atrial reversal flow in 82%. The determination of PVF could be important in different clinical situations, especially in patients with normal or pseudonormal mitral patterns, for it reflects not only LV but also left atrial filling pressures.1,3435

Most of the researchers1518 examined groups of smokers at various ages. Age is the most powerful determinant of the Doppler filling indexes.20 In the present survey, a group of young persons aged < 40 years was investigated. In this age group, a domination of early diastolic filling is normal for mitral inflow profile. In smokers before and after acute consumption of nicotine, the MVF E/A velocity ratio was significantly lower, but it remained within normal ranges. Additionally, it should be taken into account that MVF A-wave elevation observed in HS-2 could be caused by heart rate acceleration.3637 The assessment of PVF, independent on the heart rate6 and reflecting left atrial pressure, relaxation, and compliance,38 gave us more precise information on these persons. In smokers, the S/D velocity ratio was significantly higher than in nonsmokers, and it even raises after smoking a cigarette. In this investigated group of young participants, the PVF profile with a dominant systolic inflow was typical for impaired relaxation in smokers, whereas in nonsmokers the PVF profile remained normal with domination of diastolic filling.

The results of the present study suggest that the PVF parameters are especially sensitive markers in detection of early subclinical LV diastolic dysfunction, even when MVF parameters remain normal. It was not a major dysfunction but a bend from a normal state that did not cause any clinical symptoms of heart failure. Therefore, none of the studied smokers met the criteria of a major diastolic dysfunction presented in the report of the European Study Group on Diastolic Heart Failure.39

The usefulness of PVF assessment for demonstration of mild stages of LV relaxation impairment was reported previously.35,4041 This is in contrast to findings by Alam et al,19 who did not describe any changes in PVF after smoking a cigarette. The possible explanation may be the fact that the group examined19 included both smokers and nonsmokers.

The left and right ventricles influence the performance of each other.7,9 Additionally, smoking could impair the energy-consuming process of diastolic relaxation of the right ventricle. Thus, in smokers the changes of Doppler-derived diastolic patterns of the right-sided heart could occur. To our knowledge, there are no previous investigations of this subject. In the present study, the assessment of transtricuspid inflow, although the values remained within the normal range, revealed an impairment of RV relaxation in smokers after acute consumption of nicotine.

The role of assessment of the MPI of the left and right ventricles is now emphasized. These complex measurements express not only diastolic but also systolic function of the ventricles. Abnormal values were observed in patients with dilated cardiomyopathy, myocardial infarction, congestive heart failure, and pulmonary hypertension.1112,4246 The lack of changes in the present study suggests that the mild LV and RV diastolic dysfunction demonstrated by MVF E/A and PVF S/D variations in young healthy smokers does not impair global function of ventricles.

Conclusions are as follows: (1) changes of MVF and PVF demonstrate impairment of LV relaxation in healthy smokers before and after smoking one cigarette; (2) assessment of PVF is a good method to reflect changes of LV diastolic function, even when MVF remain normal; and (3) changes of TVF indicate that in healthy smokers acute consumption of nicotine causes impairment of RV relaxation.

Abbreviations: A = late phase; BMI = body mass index; D = maximal velocity of pulmonary venous flow diastolic phase; DT = deceleration time of early phase of mitral or tricuspid valve flow; E = early phase; E/A = early to late phase ratio; HS = study group; HS-1 = study group before smoking one cigarette; HS-2 = study group after smoking one cigarette; IVRT = isovolumetric relaxation time; LV = left ventricular; MPI = myocardial performance index; MVF = mitral valve flow; PVF = pulmonary venous flow; RV = right ventricular; S = maximal velocity of pulmonary venous flow systolic phase; S/D = systolic to diastolic phase ratio; TVF = tricuspid valve flow; VTI = velocity time integral

The work was performed at the Department of Internal Medicine and Cardiology, Institute of Dentistry, Warsaw Medical University, Warsaw, Poland.

The authors have no conflicts of interest to disclose.

Figure Jump LinkFigure 1. The parameters of Doppler MVF and PVF. Impairment of relaxation is reflected in MVF by decreased velocity of E, increased velocity of A, and longer duration of times: IVRT and DT and in PVF by increased velocity of S and decreased velocity of D. Atrial reversal flow (Ar) velocity reflects atrial pressure. AoVF = aortic valve flow.Grahic Jump Location
Figure Jump LinkFigure 2. The calculation of MPI, defined as the sum of LV isovolumetric contraction and relaxation times divided by the LV ejection time. IVCT = isovolumetric contraction time; ET = ejection time. See Figure 1 legend for expansion of abbreviation.Grahic Jump Location
Table Graphic Jump Location
Table 1. Group Characteristics*
* 

Data are presented as mean ± SD unless otherwise indicated. NS = not significant.

Table Graphic Jump Location
Table 2. Parameters of Physical Examination and Systolic Function of Ventricles*
* 

Data are presented as mean ± SD. See Table 1 for expansion of abbreviation.

Table Graphic Jump Location
Table 3. Echocardiographic Parameters of LV Diastolic and Global Function*
* 

Data are presented as mean ± SD. See Table 1 for expansion of abbreviation.

Figure Jump LinkFigure 3. MVF E/A ratio in examined groups. The broken line indicates the lower limit of normal range for persons < 40 years old. Values are mean ± SD.Grahic Jump Location
Figure Jump LinkFigure 4. PVF S/D ratio in examined groups. The broken line indicates the upper limit of normal range for persons < 40 years old. Values are mean ± SD.Grahic Jump Location
Table Graphic Jump Location
Table 4. Echocardiographic Parameters of RV Diastolic and Global Function*
* 

Data are presented as mean ± SD. HVF = hepatic vein flow. See Table 1 for expansion of abbreviation.

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Figures

Figure Jump LinkFigure 1. The parameters of Doppler MVF and PVF. Impairment of relaxation is reflected in MVF by decreased velocity of E, increased velocity of A, and longer duration of times: IVRT and DT and in PVF by increased velocity of S and decreased velocity of D. Atrial reversal flow (Ar) velocity reflects atrial pressure. AoVF = aortic valve flow.Grahic Jump Location
Figure Jump LinkFigure 2. The calculation of MPI, defined as the sum of LV isovolumetric contraction and relaxation times divided by the LV ejection time. IVCT = isovolumetric contraction time; ET = ejection time. See Figure 1 legend for expansion of abbreviation.Grahic Jump Location
Figure Jump LinkFigure 3. MVF E/A ratio in examined groups. The broken line indicates the lower limit of normal range for persons < 40 years old. Values are mean ± SD.Grahic Jump Location
Figure Jump LinkFigure 4. PVF S/D ratio in examined groups. The broken line indicates the upper limit of normal range for persons < 40 years old. Values are mean ± SD.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Group Characteristics*
* 

Data are presented as mean ± SD unless otherwise indicated. NS = not significant.

Table Graphic Jump Location
Table 2. Parameters of Physical Examination and Systolic Function of Ventricles*
* 

Data are presented as mean ± SD. See Table 1 for expansion of abbreviation.

Table Graphic Jump Location
Table 3. Echocardiographic Parameters of LV Diastolic and Global Function*
* 

Data are presented as mean ± SD. See Table 1 for expansion of abbreviation.

Table Graphic Jump Location
Table 4. Echocardiographic Parameters of RV Diastolic and Global Function*
* 

Data are presented as mean ± SD. HVF = hepatic vein flow. See Table 1 for expansion of abbreviation.

References

Rakowski, H, Appleton, C, Chan, K-L, et al (1996) Canadian consensus recommendations for the measurement and reporting of diastolic dysfunctions by echocardiography.J Am Soc Echocardiogr9,736-760. [PubMed] [CrossRef]
 
Oh, JK, Appleton, P, Hatle, LK, et al The noninvasive assessment of left ventricular diastolic function with two-dimensional and Doppler echocardiography.J Am Soc Echocardiogr1997;10,246-270. [PubMed]
 
Appleton, CP, Hatle, LK, Popp, RL Relation of transmitral flow velocity patterns to left ventricular diastolic function: new insights from a combined hemodynamic and Doppler echocardiographic study.J Am Coll Cardiol1988;12,426-440. [PubMed]
 
Appleton, CP, Hatle, LK The natural history of left ventricular filling abnormalities: assessment by two-dimensional and Doppler echocardiography.Echocardiography1992;9,437-457
 
Klein, AL, Tajik, AJ Doppler assessment of pulmonary venous flow in healthy subjects and patients with heart disease.J Am Soc Echocardiogr1991;4,379-392. [PubMed]
 
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