Effect of junctional reflux on the Venous Clinical Severity Score in patients with insufficiency of the great saphenous vein (JURY study)

Introduction, Objectives, and/or Purpose: Endovenous ablation provides relief for patients with significantly symptomatic venous insufficiency (SVI) who have not improved with conservative therapy. However, variability in treatment coverage creates healthcare inequity as patients without saphenofemoral junction (SFJ) reflux may not receive covered care. Patients with SVI with manifestations of varicose veins and/or edema (C2 and C3) often have pathologic reflux in the GSV with concomitant reflux in the SFJ, but this is not universally the case. Despite the variability in the anatomic pathology in patients with similar clinical profiles warranting therapy, it became a requirement to have concomitant reflux as it was thought that SFJ reflux caused progressive loss of distal valve function through transmission of venous hypertension, often referred to as the antegrade theory of reflux. Multiple contemporary clinical and basic science studies have shown that superficial valvular dysfunction can also result from degradative venous wall pathology. Taking this into account, requiring SFJ reflux for treatment of patients with pathologic refluxing the GSV and SVI is not justified. The objective of our study was to show that there is no significant difference in modified VCSS scores of patients who are scheduled for treatment of the GSV in those with GSV reflux and SFJ reflux or GSV reflux alone. If this is proven true, it would support coverage for treatment of patients with SVI with GSV reflux alone.

Methods: We performed an IRB approved cross-sectional study of patients undergoing GSV ablation at 10 US centers. Inclusion criteria: 18-80 years of age; reflux in the GSV (by ultrasound >= 2 contiguous segments above-the-knee) with/without reflux at the SFJ; candidate for treatment of the GSV by treating physician; C2 or C3. Exclusion criteria: history of DVT; prior vein ablation on the index lower extremity; concomitant obstruction of the ilio-caval system; ESRD, hepatic disease, or CHF requiring prior hospitalization. The primary outcome measure was the difference in modified VCSS scores between two groups of patients--those with GSV and SFJ reflux vs those with GSV reflux alone. Comparison of characteristics of the two groups was performed using Pearson’s Chi-Square or Fisher’s Exact test for categorical data, and Student’s t tests or Wilcoxon Rank Sum tests for continuous data. All statistical analyses were two-tailed. A p-value of < 0.05 was used to denote significance.

Results: A total of 352 patients were enrolled in the study across all 10 sites. The patients’ ablation procedures were performed between January 1, 2015 and December 31, 2022. Within the study cohort, 64.2% (n=226) had junctional reflux and 35.8% (n=126) did not have junctional reflux.
The mean age of the patients was 53.9 (SD) years. There was no difference in age between the two groups (p=0.184). The population was composed largely of women, 74.2% (n=262). The sex distribution did not differ by group (p=0.842). White patients comprised 85.8% (n=302) of the cohort; 13.6% (n=48) were non-white. Distribution by race did not differ by reflux group (p=0.548). Among the patients with junctional reflux 93.3% (n=209) were not Hispanic or Latino compared to 75.6% (n=93) patients without junctional reflux (p < 0.001). There was no difference in BMI between patients with vs. those without SFJ reflux, (28.1 vs. 27.9 kg/m2, p< 0.10). The mean VCSS scores of patients with vs. without SFJ reflux also did not differ significantly (6.4 vs. 6.6 respectively, p< 0.40). The scores for individual VCSS questions were generally similarly distributed between groups, or followed no specific pattern of distribution The two exceptions were: a larger proportion of patients with SFJ reflux scored higher for varicose veins, while a larger proportion of patients without SFJ reflux scored higher for pain.
In the entire cohort, junctional reflux was not a significant predictor of VCSS score in crude unadjusted analyses (±SE 0.21±0.26, p=0.42) or in analyses adjusted for age, sex, race, ethnicity, and BMI (0.35±0.28, p=0.20). In crude and in our final adjusted analyses, using 1 and +1 as equivalence boundaries, the VCSS scores in patients with and without SFJ reflux were found to be equivalent. In subset analyses of our cohort, SFJ reflux was not a significant predictor of VCSS score in patients with C class 2 disease (-0.55±0.33, p=0.10). After adjusting for age, sex, race, ethnicity, and BMI, and using the same -1 and +1 as equivalence boundaries, the VCSS scores were equivalent between C2 patients with and without SFJ reflux. (Figure 1)
In another subset analysis, SFJ reflux was a predictor of VCSS score in patients with C class 3 disease (-1.27±0.40, p< 0.002). In an adjusted analysis, using -1 and +1 as equivalence boundaries, the VCSS scores of C3 patients with SFJ reflux were not equivalent to those without reflux, and were, in fact lower than those without SFJ reflux.

Conclusion(s): Restricting treatment coverage to patients who have symptomatic venous insufficiency with GSV reflux to only those who have both GSV reflux and SFJ reflux creates health inequity and is not supported by modern science. The purpose of our study was to show that there is no difference in VCSS scores in patients with GSV and SFJ reflux and GSV reflux alone. The patients in this study represent a typical venous practice. The results of this multi-center study demonstrate that VCSS scores are equivalent in patients with GSV reflux with and without SFJ reflux in both crude and adjusted analysis of the entire cohort and the subset analysis in patients with C2 disease. Interestingly, in patients with C 3 disease, VCSS scores on patients with SFJ reflux were significantly lower than those without junctional reflux. Our findings suggest that absence of junctional reflux alone should not change the treatment paradigm in these patients as patients with GSV reflux alone had equivalent VCSS scores. In conclusion, patients with GSV reflux alone who meet clinical criteria for treatment should have equivalent treatment coverage to those with GSV and SFJ reflux. Our future work will examine treatment efficacy in both groups.