Cardiac Doppler in patients with primary varicose veins of lower extremities

Abstract

Aim

This study examines the characteristics of cardiac Doppler in patients with primary varicose veins of lower extremities.

Material and methods

We performed retrospective descriptive statistical analysis of cardiac Doppler data of 85 patients with primary varicose veins and compared obtained parameters with normal values.

Results

Patients with primary varicose veins in comparison with normal controls have significantly lower early diastolic mitral and tricuspid inflow velocities (E wave), significantly higher late diastolic mitral and tricuspid inflow and annular velocities (A and a′ waves), significantly higher systolic mitral and tricuspid annular velocities (s′ wave), and they have normal early diastolic mitral and tricuspid annular velocities (e′ wave).

Conclusion

Cardiac Doppler in patients with primary varicose veins differs significantly from the actual normal values. Possible mechanism of this finding is compensatory increased atrial ejection fraction due to altered preload in patients with primary varicose veins.

Keywords

Duplex ultrasound physiology varicose veins venous flow

Introduction

Venous return is influenced by the interaction between a central pump (the heart), pressure gradients, the peripheral venous pump, and competent valves in patent veins.¹ Several studies suggest the relationships between varicose veins and cardiovascular conditions.^2–4 But the relationships between the cardiac hemodynamics and varicose veins remain unclear due to the lack of research works. To determine these relationships, we conducted a retrospective investigation of echocardiographic Doppler data in a cohort of patients with primary varicose veins.

Material and methods

Patient population

This retrospective study consisted of patients referred to us for treatment of varicose veins from November 2017 to January 2019. Inclusion criteria for retrospective data analysis were patients with primary varicose veins of lower extremities in clinical classes C2–C6 in the Clinical Etiological Anatomical Pathophysiological (CEAP) classification⁵ who underwent cardiac Doppler. Cardiac Doppler data were collected as a part of preoperative focused echocardiography in patients who chose general anesthesia for the treatment of varicose veins. Exclusion criteria were previously diagnosed or revealed during our echocardiographic assessment-relevant cardiac diseases that may affect the cardiac Doppler parameters.^6–8 Personal identifiers were not used in the analysis part of the evaluation.

Normal controls in our study were previously derived reference ranges for normal cardiac Doppler from the other studies. The first control subgroup included 449 healthy adult Caucasian volunteers from the NORRE Study⁶ with normal physical cardiac examination, no cardiovascular risk factor, and without a history of any cardiovascular disease.^6,9 The second control subgroup were normal population values from more than 55 studies (more than 2850 subjects) summarized in Guidelines for the Echocardiographic Assessment of the Right Heart in Adults.⁷

Ultrasound examination

Duplex ultrasound and transthoracic echocardiograms were performed in a standardized manner^1,6,7,9–12 using ultrasound scanners Philips Affiniti 50, Mindray TE7, and Toshiba Viamo to investigate the anatomy and the hemodynamic features of the venous system and of the heart and to determine the causes of latent or manifest peripheral edema in patients with varicose veins. We conducted qualitative and quantitative assessment of available mitral and tricuspid inflow and annular velocities: E-, A-, e′-, a′-, and s′-wave. Invalid Doppler echocardiograms were excluded from the further analysis.

Statistical analysis

For descriptive statistical analysis, we used R (Deducer—Java Gui for R. Version 1.7-9. R version 2.15). Continuous variables were expressed as mean and standard deviation. To compare the obtained means and standard deviations of our group with normal controls, we used case–control study design. Data of the controls were given as means and standard deviations for the first control subgroup⁶ or confidence intervals for the second control subgroup.⁷ Confidence intervals for the means of the second control subgroup were converted to standard deviations accordingly.¹³ Data of the patients with primary varicose veins were matched for age with the first control subgroup. Matching of the data with the second control subgroup was not required. Histograms were used to assess normality. Difference between our patients with primary varicose veins and normal controls was analyzed for statistical significance with unpaired t test (Welch’s—unequal variance). For the calculation of statistical tests, we used GraphPad Prism Software (Version 8.0.1). The value of p < 0.05 was considered as statistically significant.

Results

Valid information was available for 85 patients with primary varicose veins. The patients were adult Caucasian aged from 20 to 89 years (mean 54.7 years ± 14.5 SD). Fifty-three percent were females. Information about previous therapy of varicose veins was available for 81 patients. Recurrence was diagnosed in 31 (38.3%) cases. Recurrence of varicose veins included recurrent varices, residual varices, and PREVAIT (PREsence of Varices (residual or recurrent) after InTervention).¹ Data about involved side were available for all 85 patients. Forty-eight (56.5%) patients had varicose veins on both legs. Data about clinical class were available for 75 patients. Twenty-three (31%) of our patients were in C2 clinical class, 32 (43%)—C3, 9 (12%)—C4, 1(1%)—C5, and 10 (13%)—C6.

Table 1 gives characteristics and cardiac Doppler parameters of all patients with primary varicose veins. Tables 2 and 3 show the difference in means between the data of patients with primary varicose veins and normal controls from the other studies.^6,7

Table 1.

Characteristics and cardiac Doppler parameters of all patients with primary varicose veins who underwent preoperative echocardiography.

Parameter	Mean (SD)	n^a
Age	54.7 (14.5)	85
Gender: female/male	45/40	85
PW Doppler at the mitral valve
E wave velocity (cm/s)	61.0 (13.9)	85
A wave velocity (cm/s)	70.1 (19.1)	85
E/A ratio	0.9 (0.3)	85
Tissue Doppler at the mitral valve
Septal e′ wave (cm/s)	10.0 (2.9)	78
Septal a′ wave (cm/s)	11.9 (3.1)	78
Septal s′ wave (cm/s)	10.1 (2.4)	78
Lateral e′ wave (cm/s)	13.1 (3.8)	77
Lateral a′ wave (cm/s)	12.2 (3.6)	77
Lateral s′ wave (cm/s)	11.2 (2.4)	76
Septal E/e′ ratio	6.5 (2.1)	78
Lateral E/e′ ratio	5.0 (1.8)	77
PW Doppler at the tricuspid valve
E wave velocity (cm/s)	42.9 (8.3)	84
A wave velocity (cm/s)	46.3 (11.1)	84
E/A ratio	1.0 (0.3)	84
Tissue Doppler at the tricuspid valve
e′ wave (cm/s)	12.6 (3.3)	78
a′ wave (cm/s)	16.4 (4.3)	78
s′ wave (cm/s)	14.9 (3.5)	77
E/e′ ratio	3.6 (1.1)	78

PW: Pulsed wave.

^aNumber of participants (valid data).

Table 2.

Difference of cardiac Doppler parameters between the mPVV and the first control subgroup.⁶

Parameter	mPVV^a mean (SD, n^b)	Mean difference with controls^c	p
Age (years)	48.3 (10.5, n=63)	+2.5 (+5.5%)	0.1
Gender (female)	51%	−5%	0.45**
PW Doppler at the mitral valve
E wave velocity (cm/s)	62.7 (13.8, n=63)	−13.3 (−17.5%)	<0.0001*
A wave velocity (cm/s)	66.7 (17.7, n=63)	+6.7 (+11.2%)	0.006*
E/A ratio	1.0 (0.36, n=63)	−0.37 (−27%)	<0.0001*
Tissue Doppler at the mitral valve
Septal e′ wave (cm/s)	10.6 (2.9, n=57)	+0.3 (+2.9%)	0.47
Septal a′ wave (cm/s)	11.7 (2.9, n=57)	+2.3 (+24.5%)	<0.0001*
Septal s′ wave (cm/s)	10.0 (2.0, n=57)	+1.9 (+23.5%)	<0.0001*
Lateral e′ wave (cm/s)	13.9 (3.7, n=56)	+0.4 (+3.0%)	0.45
Lateral a′ wave (cm/s)	11.8 (3.8, n=56)	+2.6 (+28.3%)	<0.0001*
Lateral s′ wave (cm/s)	11.3 (2.4, n=55)	+1.5 (+15.3%)	<0.0001*
Septal E/e′ ratio	6.2 (1.8, n=57)	−1.7 (−21.5%)	<0.0001*
Lateral E/e′ ratio	4.8 (1.6, n=56)	−1.3 (−21.3%)	<0.0001*
Tissue Doppler at the tricuspid valve
e′ wave (cm/s)	12.9 (3.3, n=57)	−0.2 (−1.5%)	0.67
a′ wave (cm/s)	15.5 (3.5, n=57)	+2.4 (+18.3%)	<0.0001*
s′ wave (cm/s)	14.7 (3.1, n=56)	+1.4 (+10.5%)	<0.002*

mPVV: matched primary varicose veins group; PW: pulsed wave.

^aMatched for age group of patients with primary varicose veins.

^bNumber of participants (valid data).

^cMean difference with normal controls calculated as: mPVV mean minus control group mean.6 Results are expressed as value and percentage. Control group means were taken as 100%.

*Two-tailed p < 0.01 unpaired t test. By conventional criteria, this difference is statistically significant; **Calculated with Chi-square test.

Table 3.

Difference of PW-Doppler parameters at the tricuspid valve between the nPVV and the second control subgroup.⁷

Parameters	nPVV^a group mean (SD, n^b)	Mean difference with controls^c	p
E wave velocity (cm/s)	42.9 (8.3, n=84)	−7.1 (−20.6%)	<0.0001*
A wave velocity (cm/s)	46.3 (11.1, n=84)	+6.3 (+15.8%)	<0.0001*
E/A ratio**	1.0 (0.3, n=84)	−0.4 (−28.6%)	<0.0001*

PW: Pulsed wave; nPVV: non-matched primary varicose veins group.

^aNon-matched group of patients with primary varicose veins.

^bNumber of participants (valid data).

^cMean difference with normal controls calculated as: nPVV mean minus control group mean.⁷ Results are expressed as value and percentage. Control group means were taken as 100%.

*Two-tailed p < 0.0001 unpaired t test. By conventional criteria, this difference is extremely statistically significant; **Average E/A ratio = 1.6 in the third decade of life, decreasing by 0.1 for every subsequent decade.⁷ Based on these data, mean age of the second control subgroup was 50–60 years. This corresponds to the nPVV mean age of 54.7 years.

We found that cardiac Doppler in patients with primary varicose veins differs significantly from the normal values and has the following features:

significantly lower early diastolic mitral and tricuspid inflow velocities (E wave) that represent atrioventricular pressure gradient;¹⁰

significatly higher late diastolic mitral and tricuspid inflow and annular velocities (A and a′ waves) that represent atrial contraction, atrial fraction, and atrial ejection force;^14,15

significantly higher systolic mitral and tricuspid annular velocities (s′ wave) that represent ventricular systole;^7,11,14

normal early diastolic mitral and tricuspid annular velocities (e′ wave) that represent myocardial relaxation and filling pressure.^10,14

We also found significant correlation between cardiac Doppler and clinical class in CEAP classification in our cohort with simple statistical tests. We are planning further multiple regression analysis of the data set to confirm this finding.

Some of our patients were also assessed postoperative with cardiac Doppler. But the cohort was too small for the adequate parametric or nonparametric statistical analysis.

Discussion

We found that cardiac Doppler parameters of patients with primary varicose veins differ significantly from the normal values. This information supports the hypothesis that primary varicose veins of lower extremities are related to cardiac hemodynamics. Based on our findings, patients with primary varicose veins have increased ventricular and atrial contraction and altered atrioventricular pressure gradient. Possible mechanism of these findings is compensatory increased atrial ejection fraction^15,16 due to altered preload¹⁷—one of the potential causes of chronic peripheral venous hypertension in patients with primary varicose veins of lower extremities.

To our knowledge, this is the first study that assessed the relationships between the cardiac Doppler and varicose veins of lower extremities.

Our study has several limitations. First, this study was retrospective, single-center, and with limited number of participants for the adequate data stratification. However, standardized approach was used to collect and analyze the data. One further limitation of our study is that cardiac Doppler is influenced by many factors, such as age, gender, cardiovascular disorders, etc.^6,7,14,15 To prevent confounding due to these factors, we matched our data with normal controls where it was required. We cannot affirm that all patients in our cohort were cardiac healthy subjects. Some potential confounding due to this factor was possible in our study. But we excluded the patients with previously diagnosed or revealed during our echocardiographic assessment-relevant valvular diseases, wall motion abnormalities, and changes of heart chambers and walls.

Finally, this study shows the characteristics of cardiac Doppler in patients with primary varicose veins of lower extremities in comparison with normal controls. Based on our findings, cardiac Doppler in patients with primary varicose veins differs significantly from the actual normal values. This information supports the hypothesis that primary varicose veins of lower extremities are related to cardiac hemodynamics. Possible mechanism of this relation is compensatory increased atrial ejection fraction due to altered preload—one of the potential causes of elevated peripheral venous pressure in patients with primary varicose veins. We are planning regression analysis of the actual data set, further observational and experimental studies to explain our findings and to determine the role of cardiac hemodynamics in progression and recurrence of varicose veins.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethical approval

The study complies with the Declaration of Helsinki, and the research protocol was approved by the locally appointed ethics committee (Number: III/1/sja/ewa FF4/2019).

Guarantor

YR.

Contributorship

YR: ethical approval, data analysis, and draft of the manuscript. YR and VR: literature search and editing of the manuscript.

Acknowledgements

The authors would like to thank Dr Patricia Schaub for her assistance in this research. The authors would also like to thank Lagunita—Stanford University and especially Dr Kristin Sainani for the online learning materials (Writing in the Sciences and Statistics in Medicine).

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