Relation between clinical findings and diagnostic parameters in patients undergoing superficial venous intervention for symptomatic chronic venous disease due to isolated venous reflux

Abstract

Objective

Although a multitude of techniques exist for the treatment of superficial venous reflux in symptomatic patients with chronic venous disease (CVD), metrics used to determine and quantify superficial reflux and thereby assess the need for intervention remain unclear. This study explores this topic by evaluating duplex ultrasound (DUS) and air plethysmography (APG) metrics in terms of their relation to clinical parameters in the setting of isolated lower extremity venous reflux.

Methods

Analysis of retrospectively collected data of patients who underwent successful endovenous laser ablation of superficial venous reflux with/without stab phlebectomies for symptomatic CVD from venous reflux was carried out to determine predictors of initial clinical presentation and outcomes after successful intervention. Characteristics evaluated included the Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) clinical class, venous clinical severity score (VCSS), grade of swelling (GOS), and visual analog scale pain; DUS characteristics included superficial vein diameter, total reflux volume in the limb, and venous segmental disease score (VSDS). APG metrics included venous volume (VV) and venous filling index, in addition to calf pump function metrics (ejection fraction [EF] and residual volume fraction). Bivariate correlation analysis, paired/unpaired t tests, and regression analysis were used to evaluate the data.

Results

There were 131 patients (134 limbs) with a median age of 61 (25-87) years, of whom 96 were women and 35 men. The median body mass index was 28.3 (18-57). There were 44 limbs in the C2 class, 38 limbs in the C3 class, 42 limbs in the C4 class, 2 limbs in the C5 class, and 8 limbs in the C6 class. All limbs had superficial reflux, including 80 with superficial reflux in the great saphenous vein (GSV) alone, and 54 had reflux in both GSV and small saphenous vein (SSV). There were no limbs with isolated reflux in the SSV. A total of 57 limbs had additional reflux in the deep veins (30 axial deep venous reflux). There were 21 limbs with reflux in the perforator veins. All limbs underwent successful ablation of the GSV, whereas 120 underwent additional stab phlebectomies at the same time, 1 limb had additional sclerotherapy (also at the time of the index procedure), and 5 limbs underwent treatment of the SSV. The median follow-up was 188 days. The correlation between DUS metrics (GSV diameter and total reflux volume) and clinical parameters (CEAP clinical class, VCSS, GOS, and visual analog scale pain score) was weak (r = 0.1-0.3; P > .05), although VSDS had a moderate correlation (r = 0.4; P = .004) with VCSS. A weak correlation was also noted between the clinical parameters and APG metrics (venous filling index, EF, residual volume fraction), except VV, which had a moderate correlation (r = 0.4; P < .001). At baseline, while VSDS was found to be a significant predictor for CEAP clinical class (hazard ratio [HR] = 8.1; P = .005) and VCSS (HR = 5.3, P = .03), VV was noted to be a significant predictor for GOS (HR =17; P < .001). After successful superficial venous intervention, there was improvement in clinical, DUS (VSDS), and APG metrics. VSDS was again a significant predictor of improvement in VCSS (HR = 9.3; P = .003), whereas both VV (HR = 5.5, P = .02) and EF (HR = 6.2; P = .01) were significant predictors for improvement in GOS after intervention.

Conclusions

In symptomatic patients with CVD from isolated venous reflux, initial clinical presentation and improvement after successful superficial venous intervention can be predicted by DUS (VSDS) and APG (VV and EF) metrics. After such intervention, there is improvement in clinical, DUS, and APG metrics.

Article Highlights.

• •Type of Research: Single-center, retrospective cohort study
• •Key Findings: In 134 limbs with chronic venous disease from isolated venous reflux, baseline clinical metrics including Clinical, Etiology, Anatomy, and Pathophysiology clinical class, venous clinical severity score, grade of swelling, and visual analog scale pain score had mostly weak correlations (r < 0.3) with duplex ultrasound metrics (superficial vein diameter, total reflux volume, and venous segmental disease score) and air plethysmography measures (reflux [venous volume and venous filling index] and calf pump function [ejection fraction and residual volume fraction]). Improvement in these metrics was noted after successful superficial venous intervention.
• •Take Home Message: In patients with chronic venous disease from isolated venous reflux, the venous segmental disease score is a significant predictor of the Clinical, Etiology, Anatomy and Pathophysiology clinical class and venous clinical severity score, whereas venous volume is a significant predictor of grade of swelling both at baseline and after superficial venous intervention.

Vein ablation technologies have progressed significantly in the last two decades, with a variety of thermal and nonthermal technologies currently existing.¹ However, even with this profusion of technology, the basic question of how much the nature and extent of venous reflux contributes to symptom development and the role of calf pump dysfunction remains to be elucidated. Although studies have noted the important role the calf pump plays in the development of reflux,2, 3, 4 given that the dermal venous plexus communicates directly with the superficial venous system, disease development (skin changes/ulceration) can potentially occur even in the presence of a normal calf pump. In addition, although studies have evaluated the role of the vein diameter,^5,6 patterns of reflux,⁷ reflux volume,⁶ and, in some cases, their impact on clinical (including the Clinical, Etiology, Anatomy, and Pathophysiology [CEAP] clinical class or venous clinical severity score [VCSS]) and hemodynamic parameters, the outcomes have been variable. Although varying degrees of correlation have been noted between the aforementioned variables and CEAP,^5,8 air plethysmography (APG)-derived hemodynamic metrics,^5,7 and VCSS,^9,10 no such correlation was noted with quality of life measures.^9,10 In addition, the predictive ability of these parameters taken together of both the initial clinical presentation and outcomes after intervention has not been explored. Evaluating patterns of venous reflux (superficial/perforator/deep/combined) alongside volume of reflux and status of calf pump can not only be helpful in predicting initial clinical presentation in patients with venous reflux without obstruction but also be helpful in prognosticating outcomes after the management of superficial venous disease. This study explores the relation between clinical parameters, duplex ultrasound (DUS) metrics, and APG measures in terms of the ability of DUS and APG to predict baseline clinical presentation and improvement after superficial venous intervention in patients with symptomatic isolated venous reflux.

Methods

Study design

This is a single-center, retrospective cohort study. Franciscan Missionaries of Our Lady University institutional review board approval was obtained for the dissemination of deidentified patient data. Patient consent was obtained for all tests and procedures.

Setting

The RANE Center is a tertiary center for the management of venous and lymphatic disorders.

Participants

Symptomatic patients with chronic venous disease (CEAP clinical class 2-6) due to venous reflux (superficial/perforator/deep/combination) and who underwent successful superficial vein ablation with/without additional stab phlebectomies/sclerotherapy formed the study cohort. Limbs that had deep venous obstruction were excluded. If multiple superficial veins had reflux, ablation of more than one vein was left to the discretion of the provider. Ablation of any pathologic perforator vein(s) was also left to the providers' discretion. Successful ablation was defined as complete occlusion of the treated segment on DUS at postprocedure follow-up.

Venous intervention and follow-up

All patients underwent vein ablation via endovenous laser ablation (EVLT) of the great saphenous vein (GSV) with or without ablation of the small saphenous vein (SSV) between 2016 and 2022. A 1470-nm Spectranetics laser catheter (CVX-300; Philips) was used for the procedure with 75 to 100 J of energy per cm. If they had symptomatic venous varicosities, they underwent stab phlebectomies or sclerotherapy as well in the same session. Follow-up was at 6 weeks and 6 months after the procedure and included a DUS, APG evaluation, and clinic visit. Further follow-up was dictated by the presence of residual/recurrent symptoms/signs. Reintervention, either ablation or repeat stab phlebectomies, was pursued in the setting of recurrence of quality-of-life impairing clinical manifestations.

Measurements

Clinical metrics evaluated included the CEAP clinical class, VCSS (0-27 [30 – 3 for compression stockings]), grade of swelling (GOS: 0-4), and visual analog scale pain score (VAS: 0-10). The GOS was categorized as 0: no swelling, 1: pitting, nonobvious swelling, 2: visible ankle swelling, 3: gross swelling involving the leg up to the knee, and 4: gross swelling involving the entire leg, including the thigh. Although the CEAP clinical class was generally assessed only initially, the remaining metrics were all appraised at every clinic follow-up visit. The last follow-up response available was used in postoperative outcome analysis. DUS characteristics evaluated included nature of reflux (superficial/perforator/deep/combination), vein diameter (mm), and total reflux volume (TRV) in the limb (cc). The vein diameter used was the smallest diameter along the length of the refluxing vein. Reflux volume (cc) was computed as follows:

$$\text{Reflux}\text{volume}=A\left(\mathrm{\pi }{r}^2\right)\times v\times t$$

A = area of the vein at the site of reflux, where the vein has the smallest diameter, v = velocity of the refluxing blood at that site, and t = duration of reflux.

TRV was the sum of the reflux volume across both the deep and superficial veins in a given limb. The venous segmental disease score (VSDS) was also assessed using the reflux criteria of the score.¹¹ APG characteristics evaluated included reflux (venous volume [VV] and venous filling index [VFI]) and calf pump function (ejection fraction [EF] and residual volume fraction [RVF]). These metrics were obtained using the technique described by Christopoulos et al.¹² The success of endovenous ablation was assessed via DUS at follow-up.

Statistical analysis

Statistical analysis was performed using SPSS version 28 (IBM). Comparisons were made at baseline and after intervention using bivariate correlation analysis, paired/unpaired t tests, and regression analysis. A P value of ≤.05 was considered significant.

Results

There were 131 patients (134 limbs) with a median age of 61 (25-87) years, of whom there were 96 women and 35 men. The median body mass index was 28.3 (18-57). There were 44 limbs in the C2 class, 38 limbs in the C3 class, 42 limbs in the C4 class, 2 limbs in the C5 class, and 8 limbs in the C6 class. All limbs had superficial reflux, including 80 with superficial reflux in the entire (above and below knee) GSV alone and 54 had reflux in both GSV (entire) and SSV. There were no limbs with isolated reflux in the SSV. A total of 57 limbs had additional reflux in the deep veins. Of these, 30 had axial reflux and the remaining segmental reflux. The distribution of this deep venous reflux included 21 limbs with reflux in the common femoral vein, 33 with reflux in the femoral vein, 3 with reflux in the profunda femoris vein, 51 with reflux in the popliteal vein, 24 with reflux in the gastrocnemius vein, and 21 with reflux in the posterior tibial vein. There were also 21 limbs with reflux in the perforator veins. There were 52 limbs with reflux in the GSV only (group I), 28 limbs with reflux in the GSV and deep veins (group II), 24 limbs with reflux in the GSV and SSV (group III), and 30 limbs with reflux in the GSV, SSV, and deep veins (group IV). All limbs underwent successful ablation of the GSV, whereas 120 underwent additional stab phlebectomies, 1 limb had additional sclerotherapy, and 5 limbs underwent ablation of the refluxing SSV as well. There were no interventions on refluxing perforator veins. The median follow-up was 188 (22-708) days. Baseline characteristics are considered in Table I. Baseline APG and reflux characteristics are considered in Table II and subgroup characteristics in Table III.

Table I.

Breakdown of baseline characteristics of the study cohort (n = 134 limbs; 131 patients)

Variable	Value
Age, years, median (range)	61 (25-87)
Male:female	35:96
Left:right	59:75
GSV-only reflux	80 limbs
GSV + SSV reflux	54 limbs
Superficial + deep reflux	57 limbs
BMI, median (range)	28.3 (13.3-56.8)
CEAP clinical class, No. (%)
C2	44 (33)
C3	38 (28)
C4	42 (31.5)
C5	2 (1.5)
C6	8 (6)

BMI, Body mass index; CEAP, Clinical, Etiology, Anatomy, and Pathophysiology classification; GSV, Great saphenous vein; SSV, small saphenous vein.

Table II.

Baseline clinical, duplex ultrasound (DUS), and air plethysmography (APG) characteristics (study cohort: n = 134 limbs; 131 patients)

Clinical, median (range)
VCSS	7.2 (3-19)
GOS	1.1 (0-3)
VAS pain score	4 (0-9)
DUS, median (range)
GSV diameter, mm	7 (3-15)
SSV diameter, mm	4 (3-10)
Total reflux volume, cc	77 (2-442)
VSDS	2.5 (1.5-8.5)
APG, median (range)
VV, cc	224 (19-243)
VFI, cc/s	3.2 (0.6-12)
EF, %	50 (10-97)
RVF, %	38 (5-97)

EF, Ejection fraction; GOS, grade of swelling; GSV, great saphenous vein; RVF, residual volume fraction; SSV, small saphenous vein; VAS, visual analog scale; VCSS, venous clinical severity score; VFI, venous filling index; VSDS, venous segmental disease score; VV, venous volume.

Table III.

Breakdown of subgroup baseline characteristics of the study cohort

Parameters	Reflux characteristics
	GSV only	GSV + DVR	GSV + SSV	GSV + SSV + DVR
CEAP, class	3	4	3	3
VCSS, mean ± SD	5.5 ± 2.4	9.3 ± 4.7	7.5 ± 2.5	8.6 ± 5
GOS, mean ± SD	0.8 ± 0.8	1.3 ± 0.8	1.6 ± 1.2	1.0 ± 1.0
VAS pain score, mean ± SD	3.4 ± 2.5	3.7 ± 2.9	3.4 ± 2.8	3.1 ± 2.7
TRV, cc, mean ± SD	57 ± 66	131 ± 106	67 ± 91	108 ± 81

CEAP, Clinical, Etiology, Anatomy, and Pathophysiology classification; DVR, deep venous reflux; GOS, grade of swelling; GSV, great saphenous vein; SD, standard deviation; SSV, small saphenous vein; TRV, total reflux volume; VAS, visual analog scale; VCSS, venous clinical severity score.

Correlation between parameters used to assess initial clinical presentation

Clinical parameters evaluated included CEAP clinical class, VCSS, GOS, and VAS pain score. When evaluated among themselves, for the entire cohort, there is a strong correlation between the CEAP clinical class and VCSS (r = 0.83; P < .001), whereas there is a moderate correlation between the CEAP clinical class and GOS (r = 0.61; P < .001). The correlation between the CEAP clinical class and VAS pain score was weak (r = 0.18; P = .05). The correlation between VCSS and GOS was moderate (r = 0.63; P < .001), whereas the correlation between VCSS and VAS pain score was negligible (r = 0.02; P = .8). The correlation between GOS and VAS pain score was also negligible (r = 0.04; P = .66).

Relation of diagnostic parameters to initial clinical presentation

The correlation between the clinical parameters and DUS metrics (GSV diameter and TRV) was mostly weak (0.1-0.3; P > .05), although VSDS had a moderate correlation (0.4; P = .004) with VCSS and a strong correlation (0.8) with GOS, which was, however, not significant (P = .42). A weak correlation was also noted between the clinical parameters and APG metrics (VFI, EF, and RVF), except VV, which had a moderate correlation with GOS (r = 0.4; P < .001). These findings are considered in Table IV. These correlations did not change significantly when the four groups (groups I-IV) were analyzed individually. On multivariable regression analysis among all DUS and APG measures, VSDS was found to be a significant predictor for the CEAP clinical class (hazard ratio [HR] = 8.1, P = .005) and VCSS (HR = 5.3, P = .03), whereas VV was noted to be a significant predictor for GOS (HR =17, P < .001). There were no DUS or APG measures that were statistically significant predictors for the VAS pain score. These findings are noted in Table V. Again, these findings did not change when these groups were individually analyzed.

Table IV.

Baseline clinical, duplex ultrasound (DUS), and air plethysmography (APG) correlations

Clinical correlations
	CEAP	VCSS	GOS	VAS pain score
CEAP	1	0.8 (P < .001)	0.6 (P < .001)	0.2 (P = .05)
VCSS	0.8 (P < .001)	1	0.6 (P < .001)	0.3 (P = .03)
GOS	0.6 (P < .001)	0.6 (P < .001)	1	0.04 (P = .66)
VAS pain score	0.2 (P = .05)	0.3 (P = .03)	0.04 (P = .66)	1

DUS and clinical correlations
	CEAP	VCSS	GOS	VAS pain score
GSV diameter	0.8 (P = .19)	0.3 (P = .63)	0.2 (P = .02)	0.1 (P = .42)
Total reflux volume	0.2 (P = .03)	0.2 (P = .14)	0.1 (P = .52)	0.2 (P = .82)
VSDS	0.2 (P = .02)	0.4 (P = .004)	0.8 (P = .42)	0.4 (P = .69)

APG and clinical correlations
	CEAP	VCSS	GOS	VAS pain score
VV	0.2 (P = .04)	0.1 (P = .62)	0.4 (P < .001)	0.2 (P = .10)
VFI	0.2 (P = .09)	0.2 (P = .24)	0.3 (P < .001)	0.1 (P = .21)
EF	0.01 (P = .95)	0.2 (P = .34)	0.1 (P = .54)	0.1 (P = .22)
RVF	0.02 (P = .79)	0.01 (P = .9)	0.02 (P = .84)	0.01 (P = .89)

DUS and APG correlations
	VV	VFI	EF	RVF
GSV diameter	0.2 (P = .03)	0.4 (P < .001)	0.03 (P = .72)	0.01 (P = .95)
Total reflux volume	0.3 (P < .001)	0.3 (P = .002)	0.1 (P = .9)	0.2 (P = .03)
VSDS	0.2 (P = .02)	0.2 (P = .008)	0.1 (P = .49)	0.1 (P = .13)

DUS correlations
	GSV diameter	Total reflux volume	VSDS
GSV diameter	1	–	0.1 (P = .38)
Total reflux volume	–	1	0.3 (P < .001)
VSDS	0.1 (P = .38)	0.3 (P < .001)	1

CEAP, Clinical, Etiology, Anatomy, and Pathophysiology classification; EF, ejection fraction; GOS, grade of swelling; GSV, great saphenous vein; RVF, residual volume fraction; VAS, visual analog scale; VCSS, venous clinical severity score; VFI, venous filling index; VSDS, venous segmental disease score; VV, venous volume.

Table V.

Impact of duplex ultrasound (DUS) and air plethysmography (APG) measures on baseline clinical parameters

	Unstandardized β (B)	SE (B)	Standardized β (β)	Test statistic	P
CEAP
GSV diameter	0.046	0.046	0.115	1.013	.31
Total reflux volume	0.000	0.001	0.058	0.523	.60
VSDS	0.170	0.060	0.277	2.853	.01
VV	0.004	0.003	0.155	1.306	.19
VFI	–0.071	0.063	–0.144	–1.127	.26
EF	0.002	0.007	0.028	0.225	.82
RVF	0.002	0.006	0.037	0.273	.79
VCSS
GSV diameter	0.547	0.294	0.329	1.862	.07
Total reflux volume	–0.007	0.011	–0.155	–0.617	.54
VSDS	0.884	0.383	0.435	2.307	.03
VV	0.025	0.020	0.285	1.260	.22
VFI	–0.606	0.427	–0.306	–1.418	.17
EF	0.055	0.043	0.257	1.271	.21
RVF	0.028	0.047	0.168	0.589	.56
GOS
GSV diameter	0.073	0.046	0.189	1.609	.11
Total reflux volume	–0.001	0.001	–0.208	–1.839	.07
VSDS	0.073	0.053	0.133	1.367	.18
VV	0.011	0.003	0.514	4.170	<.001
VFI	–0.003	0.058	–0.008	–0.058	.95
EF	0.002	0.006	0.033	0.276	.78
RVF	–0.008	0.006	–0.187	–1.438	.15
VAS pain score
GSV diameter	0.070	0.111	0.077	0.630	.53
Total reflux volume	0.000	0.002	–0.014	–0.112	.91
VSDS	–0.064	0.144	–0.047	–0.448	.66
VV	–0.007	0.007	–0.122	–0.956	.34
VFI	–0.122	0.149	–0.113	–0.819	.42
EF	0.027	0.017	0.212	1.632	.11
RVF	0.028	0.015	0.262	1.830	.07

CEAP, Clinical, Etiology, Anatomy, and Pathophysiology classification; EF, ejection fraction; GOS, grade of swelling; GSV, great saphenous vein; RVF, residual volume fraction; SE, standard error; VAS, visual analog scale; VCSS, venous clinical severity score; VFI, venous filling index; VSDS, venous segmental disease score; VV, venous volume.

Outcomes after successful venous intervention

After intervention, clinical parameters demonstrated improvement, with the median VCSS decreasing from 7.7 to 2.9 (P < .001), the median GOS improving from 1.1 to 0.24 (P < .001), and the median VAS pain score improving from 3.4 to 0.3 (P < .001). Ulcers healed in 6 of 8 limbs (75%). Two ulcers developed over the course of the follow-up, both in C4 limbs. With regard to deep venous reflux, improvement in deep reflux volume after treatment was greater in segments above the knee (33%) compared with improvement at (25%) or below the knee (25%). From a DUS standpoint, the median VSDS improved from 3.2 to 1.8 (P < .001). APG metrics also showed improvement, with the median VV improving from 111 cc to 91.5 cc (P < .001) and the median VFI from 3.7 to 1.8 (P < .001). The median EF also improved from 51% to 59% (P < .001). The RVF dropped from 40% to 29% (P < .001). Tables VI and VII depict improvements after ablation, with the latter table depicting improvement in clinical parameters across the 4 subgroups after ablation.

Table VI.

Improvement in clinical, duplex ultrasound (DUS), and air plethysmography (APG) variables after superficial intervention

Pre- and postintervention comparisons
	Baseline	Postintervention	Change	P
VCSS	7.7	2.9	4.8	<.001
GOS	1.1	0.2	0.9	<.001
VAS pain score	3.4	0.3	3.1	<.001
VSDS	3.2	1.8	1.4	<.001
VV, cc	111	92	19	<.001
VFI	3.7	1.8	1.9	<.001
EF, %	51	59	8	<.001
RVF, %	40	29	11	<.001

EF, Ejection fraction; GOS, grade of swelling; RVF, residual volume fraction; VAS, visual analog scale; VCSS, venous clinical severity score; VFI, venous filling index; VSDS, venous segmental disease score; VV, venous volume.

Table VII.

Breakdown of improvement in variables after intervention across the 4 subgroups

Subgroup postintervention characteristics
Parameters	Reflux characteristics
	GSV only	GSV + DVR	GSV + SSV	GSV + SSV + DVR
VCSS, mean ± SD	–3.7 ± 1.7a	–5.5 ± 3.6a	–4.6 ± 1.7a	–6.3 ± 3.1a
GOS, mean ± SD	–0.6 ± 1.0a	–1.0 ± 0.6a	–1.2 ± 1.2a	–0.7 ± 0.9a
VAS pain score, mean ± SD	–3.1 ± 2.2a	–3.4 ± 2.5a	–3.2 ± 2.6a	–2.6 ± 2.3a

DVR, Deep venous reflux; GOS, grade of swelling; GSV, great saphenous vein; SD, standard deviation; SSV, small saphenous vein; VAS, visual analog scale; VCSS, venous clinical severity score.

^aStatistically significant (based on the paired t test).

Predictors of clinical improvement after successful ablation

After ablation, of all the DUS and APG measures, VSDS was the only significant predictor of improvement in VCSS (HR = 9.3, P = .003). When broken down, for a baseline VSDS <2, the mean improvement in VCSS was 3 (range 1-6), for a VSDS of 2 to 2.9, the mean improvement in VCSS was 4 (range 0-9), for a VSDS of 3 to 3.9, the mean VCSS improvement was 5 (range 5-6), for a VSDS of 4 to 5, the mean VCSS improvement was 4 (range 3-10), and for a VSDS >5, the VCSS improvement was 7 (range 3-14). Both VV (Hazard ratio [HR] = 5.5, P = .02) and EF (HR = 6.2, P = .01) were significant predictors for improvement in GOS. There were no significant predictors for improvement in the VAS pain score. The data are presented in Table VIII. These findings held when the four groups were analyzed individually.

Table VIII.

Impact of change in the duplex ultrasound (DUS) and air plethysmography (APG) variables after intervention on follow-up clinical parameters

	Unstandardized β (B)	SE (B)	Standardized β (β)	Test statistic	P
VCSS
VSDS	0.480	0.158	0.268	3.043	.003
VV	–0.004	0.008	–0.058	–0.491	.62
VFI	–0.108	0.132	–0.083	–0.817	.42
EF	–0.007	0.010	–0.064	–0.721	.47
RVF	0.007	0.012	0.060	0.579	.56
GOS
VSDS	0.028	0.052	0.047	0.541	.59
VV	0.006	0.003	0.276	2.344	.02
VFI	–0.003	0.042	–0.007	–0.067	.95
EF	–0.008	0.003	–0.221	–2.497	.01
RVF	–0.001	0.004	–0.032	–0.313	.75
VAS pain score
VSDS	0.157	0.136	0.105	1.154	.25
VV	–0.001	0.007	–0.017	––0.141	.89
VFI	–0.073	0.111	–0.069	–0.658	.51
EF	0.001	0.009	0.008	0.092	.94
RVF	0.002	0.010	0.023	0.215	.83

EF, Ejection fraction; GOS, grade of swelling; RVF, residual volume fraction; SE, standard error; VAS, visual analog scale; VCSS, venous clinical severity score; VFI, venous filling index; VSDS, venous segmental disease score; VV, venous volume.

Calf pump status

From a calf pump failure standpoint, at baseline, 49% of limbs had an EF <50%, and 31% of limbs had an RVF of ≥50%. Twenty-nine percent of limbs had both an EF <50% and an RVF >50%. After successful EVLT, while only 47% of limbs with EF <50% improved to ≥50%, 97% of limbs with RVF ≥50% improved to <50%. Improvements in EF and RVF after ablation are presented in Table VI.

Discussion

In symptomatic patients with CVD due to isolated venous reflux, metrics used to assess and quantify superficial reflux to determine the need for treatment and outcomes after treatment remain uncertain. This study has sought to explore this aspect by evaluating clinical, DUS, and APG parameters and their relation to one another.

Clinical parameters used to assess initial presentation

From a clinic metric standpoint, while GOS and VAS pain evaluate different aspects of the symptom complex of CVD, VCSS is a composite representation of pain and swelling, among other variables. Although VCSS had a strong correlation with GOS, it had only a negligible correlation with VAS pain score. This is true for the CEAP clinical class as well, which demonstrates a moderate correlation with GOS, while only having a weak correlation with VAS pain score. This difference is likely due to the low pain scores in this cohort (median VAS pain score of 3.4), with the other (nonpain) components of the VCSS contributing to the final VCSS.

Diagnostic parameters and clinical presentation

When these clinical metrics were evaluated against DUS variables, the correlations between clinical metrics (CEAP clinical class, VCSS, GOS, and VAS pain score) and DUS variables (GSV diameter and TRV) were mostly weak (r = 0.1-0.3; P > .05). VSDS, however, had a moderate correlation (r = 0.4; P = .004) with VCSS and a strong correlation (0.8) with GOS, which was, however, not significant (P = .42). A similar finding was noted when clinical metrics were evaluated against APG variables, with only a weak correlation noted between the clinical parameters and APG metrics (VFI, EF, and RVF) except for VV and GOS. So overall, correlation is weak for the variables DUS and APG apart from VSDS and VV. While it would have been intuitive to think that superficial vein diameter or quantum of reflux, as assessed by TRV, would have a moderate to strong correlation with clinical presentation, this does not appear to be the case.

When the ability of the DUS and APG variables to predict initial clinical presentation was evaluated, while VSDS was found to be a significant predictor for the CEAP clinical class (HR = 2.9, P = .005) and VCSS (HR = 2.3, P = .03), VV was noted to be a significant predictor for GOS (HR = 4.1, P < .001). There were no DUS or APG measures that were statistically significant predictors for the VAS pain score. Overall, it appears that from a DUS standpoint, VSDS, by giving a comprehensive evaluation of reflux in the leg, appears to be a better metric than vein diameter or volume of reflux in predicting initial clinical presentation, given that both CEAP clinical class and VCSS give a comprehensive assessment of the limb. From a pure limb edema standpoint, VV, as would be expected, is able to predict the GOS. VV represents the entire limb volume, including any changes in interstitial fluid volume and not just venous volume, as the name suggests. Given the important role lymphatics play in the drainage of interstitial fluid in the lower extremity, VV likely represents the status of both the venous and lymphatic systems of the affected extremity.

Predictors of clinical improvement after successful superficial venous treatment

After intervention, as expected, there was a statistically significant improvement in VCSS, GOS, and VAS pain scores across the study cohort. When DUS and APG measures were evaluated for their ability to assess such clinical improvement, VSDS improvement was again a significant predictor of improvement in VCSS (HR = 3, P = .003), whereas both VV (HR = 2.3, P = .02) and EF (HR = 2.3, P = .01) were significant predictors for improvement in GOS. Here again, there were no significant predictors for improvement in the VAS pain score. Abolishment of superficial venous reflux should lead to improved VSDS and VCSS, as well, given the construct of these scores. However, one would have expected a reduction in VV to be a predictor for improvement in VCSS as it has been with GOS, but this was not found to be the case. Improvement (reduction) in VV does not translate into improvement in VCSS, likely due to the construct of the latter. However, VV is a predictor for improvement in GOS, given that they both are measures of overall edema in the limb, and any mitigation of such edema by EVLT and stab phlebectomies should result in improvement in VV and GOS. Similarly, an improvement in the EF leads to reduced limb edema and improvement in GOS. This, however, does not apply to reductions in VFI or RVF; neither measure was found to be predictive of improvement in GOS.

Role of calf pump function

Calf pump dysfunction has been variously defined, including using either a cutoff for EF or a cutoff for RVF.^4,13,14 Forty-nine percent of limbs in the study had an EF of <50%, whereas 31% of limbs had an RVF of ≥50%, with 29% of limbs having both an EF <50% and an RVF >50%. After successful treatment, a greater percentage of limbs showed improvement in RVF (97%) compared with EF (47%). Despite this, there was an improvement in clinical metrics across the cohort. Neither EF nor RVF was a predictor of initial presentation, including CEAP, VCSS, GOS, or VAS pain score. Improvement in EF, however, was a significant predictor (HR = 2.3, P = .01) for improvement in GOS. These results highlight the relative lack of applicability of calf pump function metrics to predict the initial presentation of CVD due to superficial venous reflux and venous varicosities.

Metrics that impact superficial venous disease

Clinical measures, including VCSS, GOS, and VAS pain score, can capture clinical manifestations of CVD from superficial venous reflux and venous varicosities, such that changes with treatment can be assessed through these variables. Except for the VAS pain score, both VCSS and GOS have a good correlation with the CEAP clinical class. The only DUS variable in this study that is able to predict initial clinical presentation (VCSS and GOS) is VSDS, whereas VV is the only APG variable that is able to predict GOS. From an improvement in clinical outcomes from a post-treatment standpoint, VSDS and VV are measures that can again predict improvement. These findings did not change when individual subgroups were analyzed. Factors that predict clinical manifestations in this setting are complex and go beyond TRV. The latter parameter incorporates both vein diameter and reflux (velocity and duration of reflux), and so should have been a predictor of clinical manifestations, but this was not found in this study. This goes against other studies that have used maximum reflux velocity and similar parameters to predict outcome.15, 16, 17 This study differs in having used the smallest vein diameter and time-averaged duration of reflux, and also in having used reflux volume, a combination of diameter and velocity, as opposed to one or the other. Reflux in the gastrocnemius and posterior tibial veins was also assessed, segments that are not typically assessed in other studies. Our findings indicate that the distribution of reflux (VSDS) matters more than the quantum of reflux (vein diameter and reflux volume). So, the greater the initial VSDS, the worse the initial presentation (CEAP and VCSS) and greater the improvement in the VCSS after treatment. Superficial vein diameter and TRV are unable to predict initial presentation or improvement. In essence, while using DUS, computing VSDS, and when using APG, assessing VV and EF, likely represent the best metrics.

The study has many limitations, including a relatively small sample size and the absence of data regarding quality-of-life metrics. Although the Chronic Venous Insufficiency Questionnaire 20 scores were assessed for this cohort of patients, unfortunately, both pre- and post-Chronic Venous Insufficiency Questionnaire 20 scores were available only for a very limited number of patients and hence were not included in the analysis. Comprehensive data on the use of compression and its compliance were also not available in this patient cohort. These limitations are likely to impact the results of the study.

Conclusions

In patients with chronic venous disease due to isolated venous reflux, initial clinical presentation (CEAP, VCSS, and GOS) and improvement (VCSS and GOS) after successful treatment can be predicted through the use of VSDS from DUS and VV from APG. After such treatment, improvement in clinical (VCSS, GOS, and VAS pain score), duplex ultrasound (VSDS), and air plethysmography metrics (VV, VFI, EF, and RVF) can be expected. Further corroboration is warranted.

Author contributions

Conception and design: AJ

Analysis and interpretation: AJ, JO, MD

Data collection: AJ, JO, MD

Writing the article: AJ, JO, MD

Critical revision of the article: AJ

Final approval of the article: AJ, JO, MD

Statistical analysis: Not applicable

Obtained funding: Not applicable

Overall responsibility: AJ

Funding

None.

Disclosures

None.