Relationship between clinical severity and hemodynamic impact of great saphenous vein incompetence using strain gauge plethysmography and duplex ultrasound

Abstract

Objectives

To evaluate the relation of quantitative Duplex ultrasound (DUS) and strain gauge plethysmography (SGP) parameters with clinical severity and quality of life in patients with superficial venous incompetence.

Methods

DUS volume flow and distal SGP refilling times (T₅₀ and T₉₀) were evaluated in 152 patients (164 Limbs) with superficial incompetence. Clinical severity and quality of life were evaluated with C of the CEAP classification, venous clinical severity score (VCSS), Aberdeen varicose vein questionnaire (AVVQ), and EuroQol 5D-3L.

Results

Higher DUS volume flow was associated with higher C in CEAP scores. Volume flow was also related to T₅₀ and T₉₀. Shorter T₅₀ and T₉₀ were associated with higher C in CEAP and VCSS. T₅₀ was also associated with EQ-5DVAS. Reflux extension to the foot wase associated with shorter T₅₀ and T₉₀ and higher DUS volume flow.

Conclusions

DUS volume flow and SGP refilling times are related with clinical severity and provide quantitative information regarding venous function in patients with superficial incompetence.

Keywords

Venous incompetence duplex ultrasound plethysmography

Introduction

Chronic venous incompetence is a common condition with severe impact on quality of life (QoL) even in early disease stages.^1–3 Reflux time (RT) derived by duplex ultrasound (DUS) is recommended by the European guidelines for diagnosis of venous incompetence.⁴ RT is useful for identifying venous reflux but does not show the extent of reflux and has poor relation to disease severity.⁵ One problem with RT is that the quantity of reflux will differ if the velocity or the size of the vein is different, and RT may primarily be regarded as a qualitative variable.⁶ Other DUS derived flow parameters, for example, peak reflux flow, volume flow, recirculation index, and reflux volume may provide quantitative evaluations of reflux but has not been implemented widely.^5,7–10

Indirect quantification of venous reflux is often estimated by different plethysmographic techniques, which have been suggested to provide information of whole limb venous hemodynamics.^4,11,12 The venous filling index (VFI), derived from air plethysmography, is probably the most studied parameter.^5,13,14 VFI can be used as a discriminative value in identifying significant reflux and has been linked to clinical severity.¹³ We have developed a new method of distal strain gauge plethysmography (SGP) with standardized selective superficial occlusion.^15-17 By using the method, we have shown that it is possible to predict the hemodynamic outcome after intervention in patients with great saphenous vein (GSV) incompetence.¹⁵ Nevertheless, it remains unclear to which extent the derived SGP parameters relate to clinical severity. Thus, in an attempt to quantify superficial venous incompetence we have developed a protocol that contains DUS measurements of reflux volume flow after automatic calf cuff inflation/deflation and distal SGP measurements with selective superficial occlusion.¹⁵ The aim of this study was twofold. First, to examine the relationship between distal SGP measurements and DUS derived volume flow in patients with great saphenous vein (GSV) incompetence. Second, to evaluate the relation of DUS and SGP parameters with clinical data including the C part of the CEAP classification, venous clinical severity score (VCSS) Aberdeen varicose vein questionnaire (AVVQ) and EuroQol 5D-3L.^18–21 We hypothesized that quantitative measurements from DUS and SGP were associated with clinical severity.

Material and methods

152 patients (164 limbs) with GSV incompetence selected for treatment at our clinic were recruited between September 2014 and February 2021. They were referred to our polyclinics in Linköping and Norrköping, Sweden. Inclusion criteria were Great saphenous vein (GSV) incompetence (C in CEAP, C2–C6).¹⁸ Exclusion criteria were incompetent tributaries near the saphenofemoral junction, incompetence in small saphenous vein (SSV) and/or incompetence in deep veins. All patients were examined according to C in CEAP¹⁸ and Venous Clinical Severity Score (VCSS),¹⁹ disease specific and generic QoL questionnaires were completed (Aberdeen Varicose Vein Questionnaire (AVVQ) and EuroQol 5D-3L (EQ-5D)).^20,21 DUS and SGP where then performed by biomedical scientists at the Department of Clinical Physiology, Linköping, Sweden. Ethics committee approval were received from the regional ethics committee (DNR 2011/48,431, 2020/05,676), written informed consent was obtained from participating patients.

SGP with selective superficial occlusion

Distal SGP with selective occlusion of the superficial veins allows a hemodynamic evaluation of the superficial and deep veins separated from each other.¹⁷ The protocol has been validated by ascending phlebology and has previously described in detail.^15–17 Briefly, compression cuffs were applied just over the malleoli and below the tibial condyles to facilitate superficial venous occlusion and a strain gauge was placed around the forefoot to measure changes in volume (Figure 1). In order to activate the calf muscle pump and foot pump, patients performed 20 knee bends at 1 sec intervals after which they remained still until a new steady state volume was achieved. The time in seconds for 50% (T₅₀) and 90% (T₉₀) of the venous volume to be refilled was evaluated. The procedure was repeated with individualized inflated cuff pressures to achieve superficial occlusion (Figure 2). The pressure equations for superficial occlusion have previously been described in detail.^15,16.

(i) ankle pressure = hydrostatic column (cm x 0.76) + (30 cm x 0.76) + 30 mmHg.

(ii) calf pressure = hydrostatic column (cm x 0.76) + (30 cm x 0.76) + 60 mmHg.

Figure 1.

Illustration of methodological set up with calf cuff, ankle cuff, and strain gauge for distal SGP. As noted it is possible to use a strain gauge on the calf as well.

Figure 2.

Schematic illustration from original SGP recording performed with and without superficial occlusion in a patient with GSV incompetence. T50 and T90 increased significantly after superficial occlusion.

The hydrostatic column represents the distance between heart level and the respective cuff. A hydrostatic column of 30 cm is then added (converted to mm Hg) because the original experiments were conducted in the supine position with a measuring point 30 cm above heart level. Finally, ankle/calf pressures of 30/60 mmHg occlude the superficial but not the deep venous system.¹⁷ A conversion factor from cmH2O to mmHg of 0.76 was used.

Based on previous determinations, the methodological error of SGP measurements were set to 5 s for T₅₀ and 14 s for T₉₀, that is, values above these were used to indicate that a change in refilling times between two measurements probably reflected a true alteration.^15,16 All data were recorded, stored, and analyzed using PeriVasc software (Ekman Biomedical Data AB, Gothenburg, Sweden).

Duplex ultrasound (DUS)

DUS examinations were performed with ACUSON S2000 system (Siemens Medical Solutions, Malvern, PA, USA) and GE Logic E10 US system (LOGIQ E9 XDclear 2.0 General Electric Medical Systems US, Wauwatosa, WI, USA) with 9 and 18 MHz transducers. The 9 MHz transducer was used for assessment of reflux. Both the 18 and 9 MHz transducer were used to exclude wall changes in the superficial and deep veins. Presence of normal phasic flow during breathing in the common femoral vein was mandatory in order to exclude significant central obstruction. Diameter measurements were performed in the proximal part of GSV. The examination followed a standardized protocol to assess reflux in superficial, perforator, and deep veins. A standardized cuff unit (Ekman Biochemical Data AB, Gothenburg, Sweden) inflated to 100 mmHg was used for distal compression and rapid release. GSV incompetence was quantified as reflux volume flow (ml/min). Reflux volume flow was derived from the time average velocity (TAV, m/s), measured during one sec covering the period with the highest flow rate after release of distal compression, and the cross-sectional area of the vessel which was considered to be circular (A = πr²). Thus, reflux volume flow (ml/min) was calculated according to the following: reflux volume flow (ml/min) = TAV (m/s) x A (cm²) x 60. Based on previous studies²² GSV incompetence was defined as severe (>100 mL/minute and/or a maximal flow velocity of >30 cm/second), moderate (30–100 mL/minute and/or <30 cm/second) or mild (<30 mL/minute).

QoL measurements

To review quality of life disease specific Venous Clinical Severity Score (VCSS) and Aberdeen Varicose Vein Questionnaire (AVVQ) were used in combination with the generic instrument EQ 5D-3L.^19–21

Statistics

Values are expressed as median and percentiles unless otherwise stated. Non-parametric tests were used. Correlations were calculated using Spearman’s rho. Correlations were generally considered weak if rho ≤0.4, moderate if 0.4 < rho <0.7, and strong if rho >0.7.²³ Mann–Whitney U test was used to compare groups and Wilcoxon signed-ranks test to compare individual paired data. Statistical analyses were carried out using SPSS 27.0 for windows (IBM, Armonk, NY, USA). p-values <0.05 were considered significant.

Results

152 patients (164 limbs) were evaluated for this study. Included patients and demographical data are presented in Table 1. Details of the anatomical distribution of the reflux are presented in Table 2. One limb has had previous phlebectomies. All limbs showed normal phasic flow and normal breathing curve in the common femoral vein before treatment.

Table 1.

Demographical data.

Patients (n. bilateral)	152 (12)
Limbs	164
Sex (F/M)	91/73
Mean age, y, (range)	51 (20–82)
Mean diameter at proximal thigh (range)	7.36 (3.50–16.00)
C in CEAP (limbs)
C2	25
C3	61
C4	48
C5	24
C6	6

Table 2.

Anatomical distribution of reflux.

	Limbs	Percent
GSV	9	5
GSV+Tributaries	100	61
GSV+Tributaries+Perforator	49	30
GSV+Perforator	6	4
Total	164	100
Extension of great saphenous vein reflux from saphenofemoral junction
Knee	84	51
Mid-calf	36	22
Foot	44	27
Total	164	100

GSV (incompetent Great saphenous Vein); Tributaries (Incompetent Tributary veins originating from GSV); Perforator (Incompetent perforating vein).

DUS and clinical severity

The GSV diameter and DUS derived volume flow were assessed in relation to clinical severity and quality of life. GSV diameter correlated with DUS volume flow (rho = 0.58, p < 0.001). C of CEAP demonstrated a weak correlation with volume flow (rho = 0.20, p = 0.009) but not with GSV diameter (rho = 0.12, p = 0.12). VCSS, EQ-5DIndex, EQ-5DVAS and AVVQ, showed no correlation with volume flow (rho = 0.13, p = 0.10; rho = −0.01, p = 0.93; rho = 0.05, p = 0.57; rho = −0.05, p = 0.57) or GSV diameter (r = 0.12, p = 0.13; rho = −0.06, p = 0.44; rho = 0.04, p = 0.67; rho = −0.04, p = 0.59) (Table 3). Patients were stratified into two groups based on C of CEAP; group 1 (C2–C3) and group 2, (C4–C6). Significant group difference was found for volume flow (ml/min); median (25th–75th percentile) 231 (169–368) vs. 320 (201–642) p = 0.012 (Mann–Whitney U) (Figure 3). No group difference was found for GSV diameter (mm); median (25th–75th percentile) 7.2 (6.0–8.2) vs. 7.2 (6.1–8.8) p = 0.25.

Table 3.

Correlations.

	DUS				Plethysmography
	GSV diameter (mm)		Max reflux (ml/min)		T₅₀ (sec)		T₉₀ (sec)
	rho	p	rho	p	rho	p	rho	p
CEAP	0.12	0.12	0.20	0.009*	−0.34	<0.001*	−0.29	<0.001*
VCSS	0.12	0.13	0.13	0.10	−0.23	0.003*	−0.28	<0.001*
AVVQ	−0.04	0.59	−0.05	0.57	−0.09	0.28	−0.07	0.39
EQ-5DIndex	−0.06	0.44	−0.01	0.93	−0.07	0.37	−0.12	0.15
EQ-5DVAS	0.04	0.67	0.05	0.57	−0.19	0.024*	−0.16	0.06

Figure 3.

Comparison of duplex volume flow (ml/min) between limbs with C in CEAP 2–3 vs 4–6.

SGP and clinical severity

T₅₀ and T₉₀ were also evaluated in relation to clinical severity and quality of life. Both parameters showed a weak correlation with C in CEAP (T₅₀, rho = −0.34, p < 0.001; T₉₀, rho = −0.29, p < 0.001) and VCSS (T₅₀, rho = −0.23, p = 0.003; T₉₀, rho = −0.28, p < 0.001). EQ-5DVAS correlated weakly with T₅₀ but not T₉₀ (T₅₀, rho = −0.19 p = 0.024; T₉₀, rho = −0.16, p = 0.06). EQ-5DIndex and AVVQ showed no correlations with SGP (T₅₀, rho = −0.07, p = 0.37; T₉₀, rho = −0.12, p = 0.15), (T₅₀, rho = −0.09 p = 0.28; T₉₀, rho = −0.07, p = 0.39) (Table 3). Patients classified as C4–C6 showed significantly shorter T₅₀ and T₉₀ compared to patients with C2–C3; T₅₀ (sec) median (25th–75th percentile) 5 (3–10) vs. 10 (5–19) p < 0.001; T₉₀ (sec) median (25th–75th percentile) 22 (12–40) vs. 35 (23–50) p < 0.001 (Mann–Whitney U) (Figures 4 and 5).

Figure 4.

Comparison of strain gauge plethysmography T50 (Time in seconds to 50% of the venous volume to be refilled) between limbs with C in CEAP 2–3 vs 4–6.

Figure 5.

Comparison of strain gauge plethysmography T90 (Time in seconds to 90% of the venous volume to be refilled) between limbs with C in CEAP 2–3 vs 4–6.

DUS and SGP parameters

Shorter refilling times during SGP were weakly associated with higher DUS volume flow (T₅₀, rho = −0.29 p < 0.001; T₉₀, rho = −0.25, p = 0.001). GSV diameter showed no correlation with T₅₀ or T₉₀ (T₅₀, rho = −0.14, p = 0.07; T₉₀, rho = −0.08, p = 0.32).

Anatomical extent of reflux

Anatomical extent was classified by DUS as GSV reflux to the knee, mid-calf or foot. Patients with GSV reflux to the foot demonstrated shorter T₅₀ and T₉₀ without superficial occlusion as well as higher DUS volume flow compared to patients with reflux to the knee or mid-calf (Table 4). No differences were found in delta T₅₀ or T₉₀, i.e., the difference between SGP with and without superficial occlusion (Table 4). A borderline significant difference was seen between reflux length and VCSS (p = 0.05). AVVQ (p = 0.99), EQ-5DIndex (p = 0.51) and EQ-5DVAS (p = 0.40) were not related to reflux length. Patients with reflux to the foot were more frequently classified as C4–6 compared to patients with mid-calf reflux (p = 0.02). No differences in C group (C2–C3 and C4–C6) were seen between patients with reflux to the knee and mid-calf (p = 0.35).

Table 4.

Duplex ultrasound, strain gauge plethysmography and anatomical extent of reflux.

Parameters	Anatomical extent of GSV reflux			p-value
	Knee	Mid-calf	Foot
GSV diameter, mm	6.8 (6.0–8.3)	7.1 (5.8–8.4)	7.9 (6.4–9.2)	0.063
DUS volume flow, ml/min	250 (145–380)	260 (193–383)	370 (224–746)*†	0.002
T₅₀ baseline, sec	8 (5–15)	10 (5–16)	4 (3–9)*†	<0.001
T₅₀ occlusion, sec	29 (23–38)	25 (19–37)	24 (17–35)	0.057
Delta T₅₀, sec	20 (10–24)	16 (8–25)	19 (11–28)	0.44
T₉₀ baseline, sec	32 (20–48)	33 (19–51)	18 (12–35)*†	0.001
T₉₀ occlusion, sec	64 (50–82)	65 (43–86)	51 (41–72)*	0.038
Delta T₉₀, sec	28 (15–48)	29 (10–42)	29 (16–45)	0.80

. †

* p < 0.05 Foot vs Knee, *† p < 0.05 Foot vs Mid-calf

Data are expressed as median (25th–75th percentile). All data were analyzed by Kruskal–Wallis with post hoc analysis (Mann-Whitney U). GSV, Great saphenous Vein; DUS, Duplex ultrasound.

Discussion

This study aimed to assess quantitative measurements of DUS derived volume flow and distal SGP measurements of refilling times with clinical data including the C part of the CEAP classification, venous clinical severity score (VCSS), Aberdeen varicose vein questionnaire (AVVQ), and EuroQol 5D-3L. Both DUS volume flow and distal SGP refiling times were weakly associated with the clinical severity but DUS to a lesser extent. Higher DUS volume flow demonstrated a significant but weak correlation to shorter SGP refilling times.

Current guidelines recommends DUS assessment of retrograde flow in diagnosing superficial venous incompetence using reflux time (RT) with a cut of value of >0.5 sec⁴ This suggested reference value may primarily be viewed as a qualitative parameter, that is, to establish the presence or absence of reflux, and RT has been shown to have poor correlation with clinical parameters.⁵ DUS derived volume flow was assessed in this study and we found a significant, but weak, correlation with C in CEAP. Patients with C4–C6 disease demonstrated higher volume flow compared to those with C2–C3 disease. This is in line with earlier studies who found higher volume flow and peak reflux velocity in patients with more severe disease based on C of the CEAP classification.^5,8 Higher volume flow was also associated with lower refilling times measured using SGP, which seems to indicate that volume flow is related to reduced venous drainage. No correlations were detected with health related quality of life measurements. Correlating haemodynamic parameters with clinical severity and quality of life has proven to be difficult and this is probable due to several reasons. It is not always easy to know if symptoms are mostly derived from venous or non-venous origin.²⁴ Further, there seem to be a quite large variability of perceived symptoms across the C of CEAP, and pain as well as the extent of varicose veins may not be a feature of late disease with skin changes.^10,24,25 High observer variability in the completion of the questionnaire may also contribute.¹⁰ It should be noted that the duration of the disease probably plays an important role.²⁶ Based on present and previous data indicating a weak correlation with clinical signs, one can argue that it may be even more important to have quantitative data describing venous drainage. A quantitative parameter of venous function could serve as an objective reference value and thus make it easier for the treating physician to navigate between the multifactorial natures of symptom in the lower limbs. Thus, it seems important to move from the current procedure with a mainly qualitative assessment to quantitative estimates of venous reflux that could help quantify the amount of reflux in a particular patient. It should be noticed that our evaluation of volume flow was conducted at a single point in proximal GSV and does not take into account whether the reflux is segmental or axial. This may account for some of the detected overlap between different C classes in CEAP. Other measurements such as total reflux volume²⁷ and recirculation index,²⁶ which includes antegrade flow assessment, have also been proposed and further research to find the most suitable parameter is warranted.¹⁰

One limitation with DUS is that it does not provide a global assessment of venous function. Plethysmographic methods are often used to determine whole limb venous hemodynamics^15,28,29 and venous filling index (VFI), derived from air plethysmography, is the most studied parameter.^10,13,28,30 VFI is generally regarded as the best determinant for venous disease, a higher VFI has been associated to higher C classes and VCSS scores, although there seems to be a significant individual overlap.¹³ Distal SGP was used in this study to evaluate whole limb hemodynamics and both T₅₀ and T₉₀ showed a significant, but weak, correlation with C in CEAP, VCSS, and T₅₀ with EQ-5DVAS. We also found that patients with more advanced disease (C4–C6) demonstrated a significantly lower T₅₀ and T₉₀ compared to patients with C2–3 disease. This correlation is consistent with earlier work using air plethysmography and VFI.^5,8,13 As with other plethysmographic parameters we observed a overlap between individuals in different C classes, however this was less apparent in T₅₀ compared to T₉₀.

In accordance with previous studies, patients with axial reflux were more frequently classified as C4–C6 in CEAP.^31,32 These patients also demonstrated shorter T₅₀ and T₉₀ as well as higher DUS volume flow compared to patients with reflux to the knee or mid-calf. However, no significant differences in VCSS, AVVQ, EQ-5DIndex, or EQ-5DVAS were found in respect to reflux length. This further exemplifies the difficulty of estimating clinical severity but it also highlights the need for objective reference values. For example, in patients with unfavorable outcome after intervention an objective numerical value may help to determine if any venous pathology persists. In such cases, it is important to quantify venous function in both the preoperative and the postoperative phase. Plethysmography, and some DUS parameters,¹⁰ allows these types of measurements. Nonetheless, an advantage with our method is the additional information derived from delta T₅₀ and T₉₀. We have shown that refilling times are comparable between preoperative examinations with superficial occlusion and postoperative examinations without superficial occlusion in patients with GSV incompetence, that is, it seems possible to predict the hemodynamic outcome after intervention.¹⁵ In this study, delta values were similar for patients with reflux to the knee, mid-calf and foot, which indicate a comparable improvement in venous hemodynamics after superficial intervention regardless of reflux length.

Limitations

Both DUS and SGP evaluations are user-dependent and susceptible for methodological errors. However, DUS examinations were conducted following a strict protocol to minimize inter-observer error in the measurements. The coefficient of variation for T₅₀ and T₉₀ are 16% and 18%, which seems acceptable.¹⁵ It should be noted that although our model with standardized superficial occlusion has been validated by ascending phlebography, incomplete occlusion might occur in patients with severe obesity or severe skin changes.¹⁵ SGP refilling times depend not only on the severity of reflux but also on the venous reservoir that has to be filled after exercise, as well as the degree of which the reservoir has been emptied during exercise. SGP measurements of volume changes require a cylindrical shape of the evaluated object. Based on this, no quantitative volume measurement was possible on the foot. Thus, incorporating volume measurements may provide a more comprehensive overview and is recommended in future studies. Finally, the duration of the disease is most likely a significant factor when evaluating the relation between hemodynamically parameters and clinical severity. Unfortunately, this study do not have data regarding the duration of the disease but following studies ought to consider the factor of time as a covariant.

Conclusion

Both volume flow derived from DUS and refilling times derived from distal SGP were markers for clinical severity in patients with superficial incompetence. The current golden standard of using DUS reflux time, a qualitative parameter, ought to be revisited and it is suggested that venous reflux should be evaluated with appropriate quantitative tests.

Footnotes

Acknowledgements

We thank Mikael Ekman for technical support.

Author’s note

Clinicaltials.gov: Lower Limb Venous Insufficiency and the Effect of Radiofrequency Treatment versus Open Surgery. Nr: NCT02397226.

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) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was supported by grants from Linköping University Hospital Research Fund (RÖ-857151, RÖ-760041, RÖ-653211, RÖ-559511), Linköping, Sweden. ALF Grants, Region Östergötland (ALF Grants, RÖ-700491, RÖ-794311, RÖ-900741, R), Linköping, Sweden.

Ethical approval

The study was approved by the regional ethical review board in Linköping (DNR2011/484-31, 2020-05676), Sweden and written informed consent was provided by each participant.

Guarantor

POE Nelzén

Contributorship

POE Nelzén and H Zachrisson were involved in patient recruitment and/or protocol development. POE Nelzén wrote the first draft of the manuscript. POE Nelzén, J Skoog, and H Zachrisson were involved in data analysis. All authors reviewed and edited the article and approved the final version of the article.

ORCID iDs

P Oskar E Nelzén

Johan Skoog

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