Relationships Between Venous Reflux Patterns, Clinical Severity, and Health-related Quality of Life – a Retrospective Analysis of a Prospectively Recruited Cohort

Introduction, Objectives, and/or Purpose: Duplex ultrasound is the gold-standard imaging modality to evaluate the venous system and anatomical distribution of reflux in CVD patients. Patterns of venous reflux may be classified by the anatomical component of the CEAP classification system into combinations of deep, perforator and superficial reflux or the VEIN-TERM classification system, which divides venous reflux into axial and segmental reflux. It further subdivides axial and segmental reflux into superficial, deep, or combined (deep and/or perforator and/or superficial) reflux. However, it is currently unclear whether different anatomical reflux patterns in the anatomical CEAP and VEIN-TERM classification systems correlate with different disease severity and health-related quality of life (HRQoL) outcomes.

The overall aim of this study is to determine the relationship between clinical severity, HRQoL and different anatomical patterns of reflux. This study aims to compare the clinical severity using the mean VCSS of different reflux patterns in the VEIN-TERM and CEAP classification systems. It also aims to compare the mean HRQoL using the disease-specific Aberdeen Varicose Vein Questionnaire (AVVQ) scores of different reflux patterns in the VEIN-TERM and CEAP classification systems

Methods: A retrospective analysis of prospectively collected data from 507 symptomatic CVD patients and 105 asymptomatic controls was performed. CVD patients were recruited from the Vascular Surgery Outpatient Department at Imperial College Healthcare National Health Service Foundation Trust in the United Kingdom between 2014 to 2017. All individuals underwent duplex ultrasound assessment. Patients were stratified according to the VEIN-TERM classification (no reflux, superficial axial, deep axial, combined axial, superficial segmental, deep segmental, and combined segmental reflux), and the CEAP classification (eight reflux patterns reflecting combinations of deep and/or superficial and/or perforator reflux). The Aberdeen Varicose Vein Questionnaire (AVVQ) and EuroQol-5D-3-level (EQ-5D-3L) score were used to compare HRQoL, and the Venous Clinical Severity Score (VCSS) was used to compare clinical severity between groups. Two-tailed Kruskal-Wallis H tests with post-hoc pairwise comparisons at the 5% significance level were conducted to determine whether a significant difference in VCSS, AVVQ, and EQ-5D-3L scores existed between the reflux patterns as defined by both classification systems. Significance values were adjusted by the Bonferroni correction for multiple tests to reduce the probability of type I errors.

Results: The study cohort consisted of 507 patients and 105 asymptomatic volunteers (controls). The mean age of patients was significantly greater than the mean age of controls (54.1 years versus 36.0 years, p< 0.00001). Similar sex distribution was seen in both groups, with 61.0% (n=308) of patients and 62.9% (n=66) of controls being female (p=0.687). Most patients had C2, C3, and C4 disease (48.7%, 12.2%, and 27.0% respectively), while the majority of asymptomatic controls were classified as C0 and C1 (69.5% and 29.5% respectively) (Table 1).

Significantly greater VCSS scores were seen in the presence of most reflux patterns when compared to patients with no reflux (p < 0.001). However, the isolated deep reflux and the deep and perforator reflux group did not have a significantly different VCSS score to participants with no reflux.

Between reflux patterns, VCSS scores were only higher when comparing patients with reflux in the deep, superficial and perforator systems (pattern 8) against those with isolated superficial venous reflux (pattern 3) (6.65 ± 4.56 versus 4.66 ± 3.72, p=0.013). No other pairwise comparisons reached statistical significance (Figure 1).

All VEIN-TERM reflux patterns were associated with a significantly greater VCSS when compared to participants with no reflux (p < 0.001). Across all clinical CEAP classes, superficial axial reflux had a significantly greater VCSS than superficial segmental reflux (p < 0.001). Combined axial reflux was also associated with a higher VCSS than superficial segmental reflux (p=0.042). Deep axial reflux was associated with a higher VCSS than superficial segmental reflux, but this only trended towards significance (p=0.051) (Figure 2).

Significantly greater AVVQ scores were seen in the presence of most reflux patterns when compared to patients with no reflux (p < 0.001). However, the isolated deep reflux group did not have a significantly greater AVVQ score versus the no reflux group.

Between reflux patterns, AVVQ scores were only higher when comparing patients with reflux in the deep, superficial and perforator systems (pattern 8) against those with isolated superficial venous reflux (pattern 3) (26.2 ± 15.2 versus 17.4 ± 12.7, p< 0.001). No other pairwise comparisons reached statistical significance (Figure 3).

All VEIN-TERM reflux patterns showed significantly worse AVVQ scores when compared to participants with no reflux (p < 0.001). However, there were no significant differences in the AVVQ scores between the remaining six categories of reflux.

Conclusion(s): This study has demonstrated that most reflux patterns in both the anatomical CEAP and VEIN-TERM are associated with worse clinical severity and HRQoL versus no reflux. This study also suggests that a greater extent of reflux, in particular superficial axial and combined axial reflux in the VEIN-TERM classification, and combined deep, perforator, and superficial reflux in the anatomical CEAP classification, are significantly associated with increased clinical severity. Combined deep, perforator, and superficial reflux was also associated with a worse HRQoL. The early identification of such patient groups at risk of increased disease severity and worse quality of life may help with treatment personalisation and resource allocation towards those who may require more intensive management.