Short-term follow-up of Quality-of-Life in interventionally treated patients with post-thrombotic syndrome after deep venous occlusion

Abstract

Introduction

Treatment of deep venous occlusive disease is gaining popularity, although the results and outcomes of various techniques are yet to be fully studied. Quality-of-Life (QoL) improvement is a valid and important outcome in medicine, but no specific QoL instruments for deep venous pathology exist up until now. We assessed the short term QoL effects of treated patients with post thrombotic syndrome after deep venous occlusion.

Materials and methods

Patients with proven venous occlusive disease referred to the outpatient clinic of our department of Venous Surgery in the Maastricht University Medical Centre were included. After inclusion, patients were treated by PTA and stenting and when indicated an endophlebectomy was performed and an AV fistula was made. QoL was assessed with the disease specific VEINES-QOL/Sym and the generic SF-36 questionnaires preoperatively at baseline and postoperatively at 3 and 12 months.

Results

61 patients completed the 3 month follow-up period and 28 patients the 12 month follow-up period.

VEINES-QOL and Sym scores improved after 3 months: 17.5 points for QOL (p = < 0.001) and 21.4 points for Sym (p = < 0.001)) and after 12 months 18.8 points for QOL (p = 0.004) and 21.3 points for Sym (p = 0.003)). The SF-36 scores improved significantly in the domains “physical functioning”, “role physical” and “bodily pain”.

Conclusions

Treating deep venous occlusive disease leads to short-term improvement of both disease specific QoL as well as generic QoL scores. Larger long-term follow-up studies are needed to corroborate these results.

Keywords

Quality of Life post thrombotic syndrome deep venous occlusion PTA venous stent MUMC Maastricht

Introduction

Treatment methods in venous disease have always traditionally focused on the superficial veins of the lower limbs. With the advent of modern imaging techniques such as duplex ultrasound (DUS), computer tomography and magnetic resonance imaging of the venous system (MRV) much has changed in our understanding of the venous system and the various underlying diseases leading to reflux, deep venous insufficiency and superficial pathology such as varicose veins and skin changes.¹

Investigation of the deep venous system and the effects of deep venous thrombosis (DVT) have shown that a large percentage of deep venous disease is treatable, despite of what one used to think in earlier days. Widespread diseases such as the post thrombotic syndrome (PTS) and venous ulceration are more and more found to be caused by occlusions and outflow obstructions of the deep venous system and/or the iliac and caval tracts.^1,2 Roughly half of the patients with a DVT develops PTS within 1 year.³ PTS limbs have more than a threefold risk on developing reflux and venous obstructive disease.⁴

Venous occlusions are often the result of a previous DVT, which leaves the vein wall scarred, shrunken and damaged.⁵ In a small percentage of cases the occlusion of the iliac veins is iatrogenic, e.g. after placement of intravenous lines or previous surgeries. Also certain anatomic variations such as the May-Thurner syndrome can lead to venous obstruction on its own or cause deep venous thrombosis in the lower limbs.⁶

New techniques and materials have improved the chances of treating complex deep venous occlusive disease considerably. This is mainly because stent manufacturers have successfully developed dedicated venous stents and a new generation of thrombolysis and thrombectomy devices have matured over the last years, improving their efficacy and ease of use.^2,7

Deep venous occlusion has a significant negative impact on quality of life (QoL).^8,9 The direct economic effects are reflected in high health-care costs and the indirect effects are reflected in an increase of work absenteeism.¹⁰ The subsequent events resulting from DVT, such as pulmonary embolism (PE) and PTS, will further decrease QoL and increase the economic burden even more.¹⁰

Up until now QoL in venous occlusion patients has not been studied properly in a longitudinal way. Instruments measuring QoL are often not specific enough for these patients. In our view the VEINES-QOL/Sym instrument can be used in this manner (for the time being), provided it is adapted to measure clinical change in (interventionally treated) patients. We studied the VEINES-QOL/Sym results in a group of these patients before the intervention, as well 3 and 12 months post-interventionally.

Table 1.

follow-up schedule of measurements during one year.

	T0 (baseline)	6 weeks	T3 months	T6 months	T12 months
VEINES-QOL	Yes	No	Yes	No	Yes
VEINES-Sym	Yes	No	Yes	No	Yes
SF-36	Yes	No	Yes	No	Yes
C(EAP)	Yes	Yes	Yes	Yes	Yes
VCSS score	Yes	Yes	Yes	Yes	Yes
Villalta scale	Yes	Yes	Yes	Yes	Yes
DUS	Yes	Yes	Yes	Yes	Yes
MRV	Yes	No	No	No	No
4-way X-stent	No	No	Yes	No	No

Definition of population

In this observational prospective cohort study, we included patients who were referred to our department of Venous Surgery in the Maastricht University Medical Centre between April 1, 2009, and January 23, 2013. These patients all had chronic complaints of severe venous symptoms (CEAP scores C4-6) or venous claudication combined with signs of deep venous occlusion.

Table 2.

Overall VEINES-QOL and Sym scores (disease specific) and results of paired t-test analysis at baseline (T0), after 3 months (T3) and after one year (T12).

		T0	T3	p-value* (trend)	p-value** (group)	T12	p-value▴ (trend)	p-value▾ (group)
VEINES-QOL	mean (std. dev)	50.3 (20.6)	67.8 (23.1)	<0.001	0.009	69.1 (24.2)	0.004	0.081
	n	60	60	59		33	32
VEINES-Sym	mean (std. dev)	46.9 (22.4)	68.3 (24.5)	<0.001	0.139	68.2 (26.2)	0.003	0.032
	n	60	58	58		33	32

p-value of paired T-test (T0-T3)

p-value of group difference in trends (T0-T3) by repeated measures ANOVA

▴

p-value of paired T-test (T0-T12)

▾

p-value of group difference in trends (T0-T12) by repeated measures ANOVA

In order to assess eligibility for inclusion patients were analyzed with duplex ultrasound (DUS) imaging and magnetic resonance venography (MRV). The scanning protocols and equipment have been described previously.^11,12 When a chronic iliac vein obstruction was suspected, we specifically looked for the location and extent of obstruction to plan our interventional approach. We also evaluated the patency of the common femoral vein, identified the presence of collateral pathways or external compression, or both, and the outflow through the inferior vena cava. Evident external compression of the left common iliac vein with clear diameter reduction on MRV and DUS was considered a May-Thurner syndrome in patients with accompanying clinical signs.

Table 3.

Overall SF-36 QoL scores (generic) and results of paired t-test analysis at baseline (T0), after 3 months (T3) and after one year (T12).

		T0	T3	p-value* (trend)	p-value** (group)	T12	p-value▴ (trend)	p-value▾ (group)
SF-36
Physical Functioning	mean (std. dev)	60.1 (25.1)	72.9 (23.8)	<0.001	0.299	75.5 (23.9)	0.015	0.800
	n	61	61	61		33	33
Role-Physical	mean (std. dev)	49.7 (31.7)	63 (33.1)	0.010	0.474	67.8 (28.8)	0.058	0.638
	n	60	61	60		33	33
Bodily Pain	mean (std. dev)	55.5 (24.6)	67.9 (29)	0.002	0.191	66.7 (26.6)	0.110	0.214
	n	61	60	60		33	33
General Health	mean (std. dev)	55.5 (20.3)	60.6 (23.1)	0.072	0.832	60 (21.5)	0.210	0.778
	n	61	61	61		33	33
Vitality	mean (std. dev)	54 (20.6)	57.9 (23.2)	0.187	0.442	57.2 (21.1)	0.668	0.648
	n	61	60	60		33	33
Social Functioning	mean (std. dev)	67 (26.8)	71.5 (27.7)	0.159	0.483	76.9 (30.3)	0.357	0.681
	n	61	60	60		33	33
Role-Emotional	mean (std. dev)	71.6 (30.1)	77.8 (28)	0.153	0.051	75.6 (29.1)	0.504	0.098
	n	59	61	59		33	32
Mental Health	mean (std. dev)	68.9 (18.4)	72.7 (19.3)	0.150	0.033	60 (21.5)	0.611	0.184
	n	61	60	60		33	33

p-value of paired T-test (T0-T3)

p-value of group difference in trends (T0-T3) by repeated measures ANOVA

▴

p-value of paired T-test (T0-T12)

▾

p-value of group difference in trends (T0-T12) by repeated measures ANOVA

Bold values are considered statistically significant.

Material and methods

Quality-of-Life

Generic QoL was assessed with the SF-36v2 (Short-Form 36)¹³. The RAND SF-36 is a generic Quality of Life instrument which consist of 36 items, divided over eight dimensions of health: physical functioning, social functioning, role limitations (physical problems), role limitations (emotional problems), pain, mental health, vitality and general health perception. Each dimension has a theoretical score between 0–100 (higher is more favorable for the patient), which reflects the health perception for that dimension.¹⁴ Disease specific QoL was assessed with the VEINES-QOL/Sym. The VEINES-QOL/Sym consists of 25 items, of which 10 items are symptom related, 9 items assess limitations in daily activities, 1 item assesses changes over the past year and 5 items cover psychological impact of venous disease. All items are measured on 2 to 7 point Likert scales of intensity, frequency or agreement. Two scales are calculated from the completed questionnaire: the VEINES-QOL (25 items) score, which measures the overall QoL of venous disease patients and the VEINES-Sym (10 items) score, which measures their symptom severity.¹⁵ Both scales theoretically lie between 0 and 100 (VAS scale). A higher score means a higher QoL.

Clinical and radiological examination

All patients underwent a clinical examination, the VCSS score was assessed, the C of the CEAP classification was scored and the Villalta scale was used to score the severity of (any) post-thrombotic syndrome.

Radiological work-up included magnetic resonance venography (MRV) and a duplex ultrasound (DUS) exam in order to identify the extend of the pathology. DUS was also used for follow-up after treatment. After 3 months a 4-way X-ray image of the stented trajectory was made.

Type of diagnosis and treatment

The patients in this study were assigned to one of 3 categories after inclusion and completion of the diagnostic workup:

Post-thrombotic syndrome, treated by PTA and stenting. (PTS)

Extended post-thrombotic syndrome with complex pathology, treated by hybrid procedures: PTA and stenting, endophlebectomy and AV fistula. (EPTS)

May-Thurner syndrome, treated by PTA and stenting. (MTS)

Depending on the findings during the diagnostic workup and the selected treatment, as described above, the procedure took place in a dedicated intervention room at the radiology department or in a dedicated vascular surgical suite with fluoroscopic assistance, allowing for a combined approach of endophlebectomy of the common femoral vein, with the creation of an arteriovenous fistula (AVF), and recanalizing the iliac obstruction. After dilatation, one or more self-expendable stents, sized from 14–60 to 100 mm up to 26–80 mm, including Sinus-XL or Sinus Venous (Optimed, Ettlingen, Germany), Wallstent (Boston Scientific, Natick, MA), Zilver Vena (Cook Corp), and Andrastent XL (Bioassist, Albuquerque, NM), were deployed at the predilated site. Venograms above, below, and at the level of the obstruction were repeated to assess the results. During a number of procedures, an endophlebectomy (ie, surgical desobstruction) was performed in which the post-thrombotic vein was longitudinally opened, intraluminal scar tissue was carefully removed, and the venotomy was closed with or without a patch, depending on the lumen size. This was done in patients in whom pre- or perioperative inflow into the stent was deemed insufficient and was accompanied by the creation of an AVF between the common femoral vein and femoral artery to ensure a further improved inflow into the stented tract. DUS imaging was performed the day after the procedure to assess the venous outflow and stent patency. Patients were usually discharged after 2 days when a percutaneous intervention was performed and after 5 days when a combined surgical approach was followed.

Table 4

VEINES-QOL and Sym scores (disease specific) per patient category.

		T0	T3	p-value* (group)	T12	p-value** (group)
VEINES-QOL				0.009		0.081
PTS	mean (std. dev)	49.1 (21.6)	64.9 (21.6)		63.1 (23)
	n	30	30		15
EPTS	mean (std. dev)	52.8 (14.6)	50.2 (21.9)		56.5 (17.4)
	n	9	9		6
MTS	mean (std. dev)	49.7 (22.9)	79.5 (18.6)		91.5 (6.8)
	n	13	13		5
VEINES-Sym				0.139		0.032
PTS	mean (std. dev)	43.8 (23.9)	65.9 (25.8)		61.4 (26.7)
	n	29	29		15
EPTS	mean (std. dev)	54.6 (18.0)	57.6 (26.5)		58.5 (28.4)
	n	9	9		6
MTS	mean (std. dev)	44.9 (20.0)	78.3 (20)		89.3 (6.7)
	n	13	13		5

p-value of group difference in trends (T0-T3) by repeated measures ANOVA

p-value of group difference in trends (T0-T12) by repeated measures ANOVA

Follow-up study

Standardized follow-up was planned for each patient at 6 weeks, 3 months, 6 months, and 1 year. See Table 1 for the follow-up schedule.

Statistics

Metric data are represented by means and standard deviations, if normally distributed. If not, lowest and highest scores are also given. Normality of statistical distributions is measured by the Shapiro-Wilk test. The VEINES-QOL tests have been transformed to VAS (0–100) scales with corresponding linear transformations, if items are dichotomous or polytomous. Both VEINES-QOL overall results and VEINES-Sym results are given at baseline (T0), at three months post-operatively (T3) and at 12 months post-operatively (T12). Correspondingly, the eight SF-36 scales are also given at the same follow-up moments.

Data-analysis starts with paired t-tests and Wilcoxon signed-rank tests. Next, repeated measures ANOVA is done with both T0 to T3 months analysis for the larger group of patients and a T0-T3-T12 longitudinal analysis for a subset of the group with one-year results in the follow-up. To gauge the effects of intervention type the within-patients ANOVA was specified as a between-patient factor. A p-value of less than 0.05 was assumed to be statistically significant. All data-analysis was performed with SPSS-pc version 21.

Results

This study includes 61 patients with 2 consecutive measurements (T0 and T3) and 28 with 3 consecutive measurements (T0, T3 and T12). These patients are a selection of the in total 219 patients we treated interventionally during the analysed period. Mean age was 44 years. (std. dev. 14.7, range 18–73) The male/female distribution was 12/49. The males had a non significant higher mean age (51.1 (std. dev. 13.8)) than the females (42.4 (std. dev 14.6)) (p = .070).

32 (59%) patients were assigned to the PTS group, 9 (17%) to the EPTS group and 13 (24%) to the MTS group. 7 (12%) patients had to be excluded from the results because of treatment deviation.

When compared to baseline (T0) the overall group shows a significant increase in both VEINES-QOL and Sym scores at 3 months (17.5 for QOL (p < 0.001) and 21.4 for Sym (p < 0.001)) as well after 12 months. (18.8 for QOL (p = 0.004) and 21.3 for Sym (p = 0.003) (Table 2 and Figure 1)). A change of 13 or more on a VAS scale is generally known to be clinically significant.¹⁶

The SF-36 QoL questionnaire showed statistical significant change in three of the eight domains: physical functioning (12.8 at 3 months (p < 0.001) and 15.4 at 12 months (p = 0.015)), role-physical (13.3 at 3 months (p = 0.010)) and bodily pain (12.4 at 3 months (p = 0.002) (Table 3)).

Figure 1.

VEINES-QOL/Sym scores (disease specific) for the complete cohort at T0, T3 and T12.

The VEINES-QOL/Sym scores turn out to be different between the 3 defined patient groups. The patients in the MTS group show the largest improvement both in QOL (29.8 at 3 months (p = 0.009), 41.8 at 12 months (p = 0.081)) as well as in the Sym scores (33.4 at 3 months (p = 0.139), 44.4 at 12 months (p = 0.032)). The EPTS group showed practically no improvement, (QOL -2.6 at 3 months and 3.7 at 12 months, Sym 3 at 3 months and 3.9 at 12 months) (Table 4 and Figure 2).

Conclusions

Treating deep venous occlusive disease improves both disease specific QoL as well 3 of the scales of the SF-36. The greatest QoL increases seem to be linked to pain-relief and improved physical functioning. Treatment of deep venous occlusion caused by the May-Thurner syndrome shows the greatest short-term improvement. Larger long-term follow-up studies are needed to corroborate these results.

Figure 2.

VEINES-QOL/Sym scores (disease specific) per patient group at T0, T3 and T12.

Discussion

Up until now there is no gold standard for classifying deep venous occlusive disease.⁶ This makes it difficult to perform a valid follow-up of the results of deep venous treatments. Validated Quality of Life (QoL) instruments^9,17 are available which, theoretically measure the patient’s view on the impact of deep venous disease. For the time being treatment evaluation based on QoL measurements can be a valid quid pro quo to assess the success and/or failure of treatment. Clinical follow-up with duplex ultrasound and other imaging modalities show only the anatomical and/or physiological effects of treatment, which do not necessarily correlate with the patient-experienced results, as shown in this series.

The effects of the interventions in this study on QoL are promising, even with the relatively small number of patients included. The lack of improvement shown in the complex EPTS group can, besides the small number of patients, be explained by the extent of the pathology and the relatively invasive nature of the treatment, which includes surgical endophlebectomy and the creation of AV fistula. Recovery from this procedure is slower and puts more strain on the patients, leading to only minor - or no improvement on both the symptomatic as well on the QoL scores. We also occlude most AV fistula after 3 months, which very well might influence the QoL scoring as well. In this group of patients venous claudication is one of the main disabling problems these patients encounter and this problem is not assessed in the used QoL questionnaires. We added specific venous claudication questions to our standard intake forms in order to see if this will significantly influence outcomes in the future.

Another point of consideration is the fact that the natural properties of the veins in the legs might never return after years of distension and increased pressure. Even after successfully restoring the venous outflow and relieving the venous hypertension, it might take months, even years to regain their shape and physical properties. This process can best be compared to the abdomen of a pregnant woman in the first months after delivery, when the abdominal wall is recovering and regaining it’s original shape. This delayed, if at all, recovery from venous hypertension and an insufficient outflow can very well influence the QoL outcomes for the PTS and EPTS groups.

The relative large QoL increase for the MTS group can be explained by the fact that these patients usually have less severe PTS, less venous claudication and far less permanent vein wall damage in the legs. This results in faster recovery when compared to the PTS and EPTS groups.

Generic QoL improvements in the physical functioning and bodily pain domains can also be explained by the nature of deep venous occlusive disease, where venous outflow is obstructed and leads to increased pressure in the venous system of the lower limbs, which in term leads to varicose veins, pain, heaviness, restless legs and on the long term causes skin changes, ulcers and decreased physical functioning. When the occlusion is treated these symptoms will subside and improve, leading to a QoL increase for the mentioned health domains.

Further study is needed with larger numbers of patients, especially on the long term effects of complex deep venous treatments which include surgical desobstruction. We hypothesize that the described QoL improvements will persist and even improve further, because of the physiological and histological effects of removing the occlusion(s), which in our clinical experience need 6 to 12 months to manifest completely. Although depending on the cause of the original occlusion, recurrence of the complaints and the resulting decrease in QoL is unlikely in most cases. Even when the primary treatment fails, good clinical results are achieved with secondary treatments.⁷

The currently available QoL instruments are suboptimal for use in complex deep venous disease, because most of them are created for a specific disease or purpose, mostly focused on the effects of superficial venous incompetence in the lower limbs. They are not optimized for assessing the true QoL effects of pathology like e.g. the May-Thurner syndrome, deep venous obstruction of the iliac tract and pelvic congestion syndrome. The symptoms and subjects covered by most questionnaires are not specific enough for the above-mentioned pathology. The need for new and improved QoL instruments, which cover the whole spectrum of venous disease, especially including venous claudication, is thus clear, but such an instrument has yet to be constructed.

Further evolution and development of treatment modalities for deep venous occlusive disease will lead to a wider adoption of these techniques, further increasing our knowledge and experience. Because of the small number of centers adequately equipped to diagnose deep venous pathology and subsequently perform the correct treatment it is favorable to centralize treatments and perform collaborative gathering of research data with a small number of dedicated institutions. Only then will it be possible to truly estimate the treatment effects and measure reliable outcomes in terms of economic impact, QoL and overall patient-health.

Footnotes

Declaration of interest

All the authors have no conflict of interest and nothing to disclose.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors

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