Influence of Timing of Stenting on Condition of Venous Valves of Lower Extremities, Frequency and Severity of Development of Post-Thrombotic Disease

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LIST OF ABBREVIATIONS

DVT — deep vein thrombosis

LE — lower extremities

PTD— post-thrombotic disease

SCDT — selective catheter-directed thrombolysis

US — ultraviolet examination

INTRODUCTION

The main chronic complication of acute deep vein thrombosis (DVT) of the lower extremities (LE) is post-thrombotic disease (PTD) [1]. Even early identified and timely treated DVT of LE almost always leads to the irreversible alterations of the venous wall and of valve structures. PTD is manifested by edema and heaviness in the extremity, trophic disorders alternated with venous claudication. Clinical manifestations of PTD are most pronounced in the development of post-thrombotic valvular incompetence leading to vertical venous reflux and chronic venous hypertension.

The severity of PTD is usually determined on the Villalta scale [2]. The most severe types of PTD develop after iliofemoral thrombosis, which is also an important predictor of recurrent DVT [3–7]. The iliofemoral DVT accounts for about 20% of all DVT of LE with development of symptomatic PTD in 66% of cases and venous trophic ulcers in 10%–15% [8]. Along with life style modification, elastic compression stockings and phlebotropicagents are widely used in treatment of PTD [9, 10]. A promising surgical direction in the treatment of DVT is catheter-directed thrombolysis, which at different times can be supplemented with stenting of the iliac veins, which reduces the risk of developing severe PTD [11–14].

The aim of this study to evaluate the effect of the timing of stenting on the condition of the valve apparatus, the frequency and severity of the development of post-thrombotic disease in patients With acute deep vein thrombosis of the lower extremities.

MATERIALS AND METHODS

The study was of prospective intervention design. For the primary analysis, 65 patients with proximal venous thrombosis were selected. Later, 7 patients refused to participate in the study. During history taking, 9 patients were excluded because of non-correspondence to inclusion criteria. In result, 49 patients were included in the study (Figure 1).

 

Fig. 1. Block-diagram of the study. Note: US — ultrasound examination.

 

Inclusion criteria: acute proximal DVT of LE identified by US, edema and pain in the affected extremity, age of thrombosis up to 14 days, age of patent ≥ 18 years, signing of the informed consent to participate in the study.

Non-inclusion criteria: a history of allergic reaction to an iodine contrast agent, recent surgical interventions, pregnancy, pulmonary embolism, chronic renal failure, pastDVT of LE, body mass index ≥ 35 kg/m², trophic venous ulcers, documented cancer process, high risks of bleeding on the HAS-BLED scale, a history of stroke, impossibility to come to follow-up examinations.

Study groups. After inclusion in the study, the patient underwent a selective catheter-directed thrombolysis (SCDT). After completion of the thrombolysis, early (up to 7 days) or delayed stenting (7–30 days) was conducted.

Assessment criteria. The frequency of detection and severity of symptoms of PTD were assessed on the Villalta scale at 3, 6 and 12 months. The condition of the valves of the femoral and popliteal veins was assessed at 12 months. The valves were assessed using a scoring system, in which, in case of absence of reflux in the studied segment, a point was added, and if reflux was detected, no point was added. The maximum scorewas 2.

Ethics. The study was approved by the Local Ethics Committee at Clinical Hospital No. 1 of Administrative Department of the President of the Russian Federation (Protocol No. 3/d of November 30, 2021).

Statistical analysis. Comparison of shares in the groups was carried out using the chi-square test (χ2). Comparisons of Villalta scores were assessed using Mann–Whitney test. The severity of PTD depending on the state of the valve apparatus was compared using Kruskal–Wallis test. The influence of the chosen treatment strategy on the condition of the valvular apparatus was assessed using Mann–Whitney test.

RESULTS

The frequency of development of PTD and severity of its symptoms throughout a year after acute DVT of LE and the conducted treatment are presented in Table 1. The average scores on the Villalta scale are presented in Figure 2.

 

Table 1. Frequency of Development and Severity of Symptoms (n (%)) of Post-Thrombotic Disease at 3 Months, 6 Months and 12 Months

Assessment Time	Severity of Symptoms on Villalta Scale	Delayed stenting	Early stenting	p
n		24	25
3 Months	Absent	5 (20)	12 (50)	0.052
	Mild	19 (76)	12 (50)
	Moderate	1 (4)	0
	Severe	0	0
6 Months	Absent	0	6 (25)	0.001
	Mild	12 (48)	15 (63)
	Moderate	13 (52)	3 (13)
	Severe	0	0
12 Months	Absent	0	6 (25)	0.0005
	Mild	10 (40)	15 (62.5)
	Moderate	13 (52)	3 (12.5)
	Severe	2 (8)	0

 

Fig. 2. Average score on the Villalta scale in the groups at 3 months (А), 6 months (B) и 12 (C) months of follow-up.

 

The analysis of the state of the valves after treatment revealed that in the early stenting group, by the end of the observation period (12 months), 18 patients (75%) had intact valves in at least one segment. Differences in the scoring (Me (Q1–Q3)) of the valve conditionshowed that it wasstatistically significantly better in this group 1.0 (1.0–2.0) versus 1.0 (0–1.0), p = 0.0005.

Also, in the early stenting group, in 6 (25%) patients, the valves of both the femoral and popliteal segments remained intact. In the delayed stenting group, reflux was recorded in the valves of the femoral and popliteal segment in 12 (48%) patients, reflux in one of the segments was recorded in 4 (16%) and 9 (36%) patients. There were no patients with intact valves of both segments after delayed stenting.

When analyzing the incidence and severity of PTD symptoms at 12 months, in 6 (13%) patients, the valvular apparatus of both segments functioned, PTD symptoms were absent. In 25 (51%) patients, in the absence of reflux in at least one valve segment, mild PTD developed. Sixteen (32%) and 2 (4%) patients developed moderate and severe PTD, which was associated with reflux in both segments. When analyzing the dependence of factors, statistically significant differences were found (p < 0.001).

DISCUSSION

As a result of study, it was found that early stenting permits to reduce the rate of occurrence and severity of PTD symptoms, among other things, due to preservation of the valvular apparatus of the lower extremities. Delayed stenting was associated with the development of valvular reflux in the femoral and popliteal segments, which, in turn,was associated with increase in the frequency of severe and moderate PTD.

 

Table 2. Ultraviolet Examination Results of Lower Extremity Veins at 12 Months Depending on Severity of Post-Thrombotic Disease

Symptoms of Post-Thrombotic Disease	n	Ultraviolet Examination Results, points		p
		Me	Q1–Q3
Absent	6	2.0	2.0–2.0	< 0.001
Mild	25	1.0	1.0–2.0	0.0001
Moderate	16	0.0	0.0–1.0	0.004
Severe	2	0.0	0.0–0.0	0.008

 

The highest quality evidence base regarding PTD in patients who have suffered acute DVT of LE was obtained in two multicenter randomized controlled trials: CaVenT and ATTRACT.

The CaVenT study showed improvement of the patency of the iliofemoral segment (65.9% vs. 47.4%) and lower frequency of development of PTD (41.1% versus 55.6%) in application of SCDL in comparison with patients who received only conservative therapy. These results persisted for 24 months after treatment and remained such within 5 years of follow-up [13]. However, SCDT did not improve the quality of life in the long term [14]. On the other hand, in ATTRACT sub analysis of iliofemoral thrombosis, there were no differences in the frequency of development of PTD in the 6–24-month period between the groups with isolated anticoagulant therapy or SCDT. Analysis of the additional evaluation criteria showed the advantages of SCDT: in the SCDTgroup, fewer cases of moderate and severe PTD were recorded (18% and 28%, p = 0.021; 9% and 15%; p = 0.048, respectively). Besides, SCDT led to a significant reduction of pain and edema of LE within 30 days, reduction of severity of PTD and significant improvement of the quality of life [15].

CaVenT and ATTRACT studies were criticized for a low frequency of stent implantation, which was not an obligatory part of the study protocol. Only 16.7% and 28.0% of patients in the comparison groups (39.0% with proximal DVT) had stents implanted.

Studies on the influence of the state of the valves on the development of PTD were carried out as early as in 1979 by K C Shull and A N Nicolaides, and in 1995 B E Johnson demonstrated that the development ofvalvular incompetenceof the LE in a severe form observed in most cases, contributes to the development of PTD [16, 17]. Despite a relatively long time of studying the problem, the influence of endovascular treatment methods and the timing of their implementation on the condition of the valves has not yet been assessed. We have shown that the earlystenting has undoubted advantages over delayed stenting in patients after catheter-directed thrombolysis for proximal venous thrombosis [18, 19].

Limitations. The study has a non-randomized design and a small sample size.

CONCLUSION

Early stenting after selective catheter-directed thrombolysis in patients with iliofemoral deep vein thrombosis permits to reduce the frequency of development and severity of manifestations of post-thrombotic disease. Selective catheter-directed thrombolysiswith early elimination of residual obstruction helps preserve the valvular apparatus of the lower extremities in at least one segment, which contributes to reduction of the frequency and severity of the post-thrombotic disease.

ADDITIONALLY

Funding. This study was not supported by any external sources of funding.

Conflict of interests. The authors declare no conflicts of interests.

Contribution of authors: V. V. Boyarintsev, V. E. Barinov, I. A. Zolotukhin, S. V. Zhuravlev — development of the concept and formulation of the research topic, scientific guidance on the design and content of the article; E. V. Barinov, M. B. Bazarova — writing the text, conducting statistical analysis, formulating conclusions; A. S. Pankov — editing. The authors confirm the correspondence of their authorship to the ICMJE International Criteria. All authors made a substantial contribution to the conception of the work, acquisition, analysis, interpretation of data for the work, drafting and revising the work, final approval of the version to be published and agree to be accountable for all aspects of the work.

Финансирование. Авторы заявляют об отсутствии внешнего финансирования при проведении исследования.

Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов.

Вклад авторов: Бояринцев В. В., Баринов В. Е., Золотухин И. А., Журавлев С. В. — разработка концепции и формулирование темы исследования, научное руководство по оформлению и содержанию статьи; Баринов Е. В., Базарова М. Б. — написание текста, проведение статистического анализа, формулирование выводов; Панков А. С. — редактирование текста. Авторы подтверждают соответствие своего авторства международным критериям ICMJE (все авторы внесли существенный вклад в разработку концепции, проведение исследования и подготовку статьи, прочли и одобрили финальную версию перед публикацией).

About the authors

Valeriy V. Boyarintsev

Central State Medical Academy of Department of Presidential Affairs

Email: wpx@mail.ru
ORCID iD: 0000-0001-9707-3262
SPIN-code: 2491-7199

MD, Dr. Sci. (Med.), Professor

Russian Federation, Moscow

Evgeniy V. Barinov

Central State Medical Academy of Department of Presidential Affairs; Clinical Hospital No. 1 (Volynskaya) of the Presidential Administration of the Russian Federation

Author for correspondence.
Email: dr.ev.barinov@gmail.com
ORCID iD: 0009-0005-2311-0637
SPIN-code: 9423-3640
Russian Federation, Moscow; Moscow

Aleksey S. Pankov

Clinical Hospital No. 1 (Volynskaya) of the Presidential Administration of the Russian Federation

Email: pancaver2004@mail.ru
ORCID iD: 0000-0001-8616-0678
SPIN-code: 4830-3377

MD, Cand. Sci. (Med.)

Russian Federation, Moscow

Victor E. Barinov

Central State Medical Academy of Department of Presidential Affairs; Clinical Hospital No. 1 (Volynskaya) of the Presidential Administration of the Russian Federation

Email: vicbarin@mail.ru
ORCID iD: 0000-0002-0434-2484
SPIN-code: 1981-6745

MD, Dr. Sci. (Med.), Associate Professor

Russian Federation, Moscow; Moscow

Mekhridzhamal B. Bazarova

Central State Medical Academy of Department of Presidential Affairs; Clinical Hospital No. 1 (Volynskaya) of the Presidential Administration of the Russian Federation

Email: mehri.68@mail.ru
ORCID iD: 0009-0008-5882-8122
SPIN-code: 3212-6536

MD, Cand. Sci. (Med.)

Russian Federation, Moscow; Moscow

Sergey V. Zhuravlev

Central State Medical Academy of Department of Presidential Affairs; Clinical Hospital No. 1 (Volynskaya) of the Presidential Administration of the Russian Federation

Email: volynka@volynka.ru
ORCID iD: 0000-0003-4335-0329
SPIN-code: 9046-6156

MD, Cand. Sci. (Med.)

Russian Federation, Moscow; Moscow

Igor' A. Zolotukhin

N. I. Pirogov Russian National Research Medical University

Email: zoloto70@bk.ru
ORCID iD: 0000-0002-6563-0471
SPIN-code: 3426-2981

MD, Dr. Sci. (Med.), Professor

Russian Federation, Moscow

References

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