Lower extremity CVI is a prevalent condition in vascular surgery, with stenosis or obstruction of the iliac vein and/or inferior vena cava frequently significant contributors to its onset2,3,6. The American Venous Forum proposed the CEAP classification in 1993, which was subsequently revised in 2020, based on the clinical manifestations (C), aetiology (E), anatomy (A), and pathophysiology (P) of patients with lower extremity CVI7. Notably, the clinical classification is highly important in assessing CVI7,8. Within the CEAP classification, C0 corresponds to patients devoid of visible or palpable signs of venous disease and thus are frequently overlooked by clinicians. Further subdivision of C0 includes those without lower limb symptoms (C0a) and those presenting with symptoms (C0s)7. Currently, there is still controversy surrounding the selection of patients for endovascular treatment of NIVLs. Most scholars agree that patients with moderate to severe symptoms and those unresponsive to conservative treatment may opt for endovascular therapy. Therefore, in this study, nonvascular disease patients (C0a) composed the control group, while patients exhibiting lower extremity CVI (C0s-6) composed the experimental group, further subdivided based on the severity of clinical symptoms. Haemodynamic simulation, a noninvasive method, is then employed to analyse the local haemodynamic and morphological characteristics of the iliac and inferior vena cava veins, assessing the impact of NIVLs on iliac vein haemodynamics9. Although intravascular ultrasound is currently an important diagnostic and therapeutic tool, it is undeniably an invasive procedure, whereas the noninvasive nature of haemodynamic simulation offers distinct advantages9.Figure 1Pressure of the bilateral iliac veins and inferior vena cava (IVC) in 24 subjects. The pressure at the caudal end of the stenotic segment of the left common iliac vein (LCIV) gradually increases with increasing clinical classification, with the most substantial increase observed in Group C subjects (red area). Conversely, the pressure at the cranial end of the stenotic segment of the LCIV significantly decreases, even dropping below the pressure level at the IVC (blue area), with increasing clinical classification. A1-A8: Group A, control group (C0a); B1-B8: Group B, mild group (C0s and C1-2); C1-C8: Group C, moderate to severe group (C3-6).Haemodynamic simulation is a pivotal tool for revealing the intricacies of blood flow within the circulatory system. In recent years, a large number of studies have conducted research on haemodynamic simulations, with a plethora of sophisticated haemodynamic models emerging to accurately replicate various blood flow phenomena within the human body10,11,12,13. These models offer invaluable assistance in the diagnosis and treatment of cardiovascular diseases. The advent of individualized modelling, leveraging imaging data to construct precise three-dimensional (3D) models of vascular systems, has revolutionized haemodynamic research14,15,16. By observing haemodynamic alterations at the local and systemic levels, individualized modelling enables a comprehensive understanding of disease pathogenesis, progression, and treatment efficacy. CFD, a cornerstone in haemodynamic simulation, is widely employed in the construction of human vascular models and subsequent haemodynamic investigations14,17. In this study, CFD was used to simulate the local haemodynamics of left NVILs, allowing an assessment of its impact on changes in lower extremity CVI symptoms.The findings of this study indicated a significant increase in pressure at the caudal end of the stenotic LCIV segment, accompanied by increased blood flow velocity, greater TAWSS, and shorter RRT within the stenotic segment, aligning closely with those of a previous report18. Moreover, the results of this study revealed a correlation between these haemodynamic changes and the severity of the clinical symptoms of CVI. The substantial pressure difference at both ends of the stenotic LCIV segment may induce severe haemodynamic disturbances, potentially resulting in local venous vessel wall damage, exacerbating venous stenosis, and precipitating venous hypertension at the caudal end of the stenotic segment. Such effects could contribute to the progression of lower extremity CVI and potentially predispose the individual to lower extremity deep vein thrombosis2,9,18,19. Notably, this study also revealed a decrease in pressure at the cranial end of the stenotic LCIV segment, occasionally dropping below the pressure within the IVC. This phenomenon could be attributed to the Bernoulli effect in fluid dynamics. Given the nonslip rigid wall setting of the vascular wall in this study, adherence to the Bernoulli principle was ensured.In this study, ∆P and ∆V were significantly correlated with the clinical classification, underscoring their potential as objective indicators for guiding clinical surgery. Substantial differences in ∆P and ∆V were observed between the experimental group and the control group, as well as between the moderate to severe group (C3-6) and the mild group (C0s-2). Conversely, the differences between the mild group and the control group (C0a) were not significant. These findings suggest that ∆P and ∆V may serve as indirect indicators of the degree of LCIV stenosis, offering valuable guidance for clinical decision-making. Notably, advances in vascular ultrasound technology have made it possible to accurately measure blood flow velocity and offered hope that vascular pressure can also be evaluated through vascular ultrasound examination in the foreseeable future20. The eventual accessibility of both the ∆P and ∆V through noninvasive means could significantly improve clinical practice, allowing improved patient care and treatment strategies.The unique local anatomy of the left iliac vein results in distinct challenges, including compression by the right iliac artery and lumbar vertebral bodies and the potential formation of fibrous bands within stenotic vein segments17. Consequently, the cross-sectional area of the stenotic segment often assumes an irregular shape. Traditional methods, such as calculating the stenosis rate based on vessel diameter, may inadequately reflect the impact of vascular lesions on haemodynamics. Therefore, in this study, 3D modelling of the iliac vein allowed the use of the cross-sectional area to calculate the stenosis rate, which served as an evaluation index. This approach effectively circumvents errors stemming from irregular cross-sectional areas of venous vessels. Presently, most imaging devices support automatic measurement of vessel cross-sectional area, which could reduce the impact of human measurement errors when utilizing the cross-sectional area stenosis rate as a diagnostic criterion. A previous study indicated a high incidence of NVILs in asymptomatic individuals; approximately 66% of population had an LCIV compression stenosis rate exceeding 25%, with an overall average of 35.5%21. Consistent with these findings, in this study, varying degrees of compression stenosis were identified in the LCIV of asymptomatic subjects within the control group, with a cross-sectional area stenosis rate of 15.8% ± 6.9%. Discrepancies in the stenosis rate may have arisen from differences in the calculation methods, which could also account for the absence of clinically relevant symptoms in the LCIV stenosis population. Moreover, this study revealed a significant correlation between the cross-sectional area stenosis rate of the stenotic LCIV segment and the clinical classification. Distinct thresholds were observed between the control group and the mild group and between the mild group and the moderate to severe group (24.3% and 44.2%, respectively). These findings suggest that the cross-sectional area stenosis rate of the stenotic LCIV segment quantitatively corresponds with the severity of symptoms in patients with lower extremity CVI, offering another promising, objective indicator for guiding treatment decisions.Figure 2Analysis of the correlations between haemodynamic indicators and clinical classification. (A) Pressure at the caudal end of the stenotic segment of the left common iliac vein (LCIV) (P1); (B) Pressure at the cranial end of the stenotic LCIV segment (P2); (C) Pressure difference between the two ends of the stenotic LCIV segment (∆P, ∆P = P1–P2); (D) Blood flow velocity in the stenotic LCIV segment (V1); (E) Blood flow velocity at the confluence of the left internal and external iliac vein (V2); (F) Blood flow velocity difference between the stenotic segment of the LCIV and the caudal end (∆V, ∆V = V1–V2); (G) Time-averaged wall shear stress (TAWSS) in the stenotic LCIV segment; (H) Relative residence time (RRT) in the stenotic LCIV segment. (A) Control group (C0a); (B) Mild group (C0s and C1-2); (C) Moderate to severe group (C3-6). For each group, n = 8.Several scholars have suggested that the confluence angle of the bilateral iliac vein could impact the wall shear stress within the stenotic iliac vein segment and the pressure difference around it18,19. Similarly, our investigation revealed a potential correlation between the confluence angle of the bilateral iliac vein and the clinical classification. However, statistical analysis revealed no significant differences, which might be attributed to the selection and grouping of the study subjects as well as the relatively small sample size in this study.Moreover, our study revealed a positive correlation between the length of the stenotic LCIV segment and the clinical classification, in line with fluid physics principles. This suggests that as the length of the stenotic LCIV segment increases, so does the severity of blood flow disturbance, while the shear and friction forces on the vascular wall also increase. Consequently, this leads to more profound vascular damage and elevated vascular pressure. Hence, standardized measurement of the length of the stenotic LCIV segment could serve as a crucial factor in the treatment decision-making process for NVIL patients.Importantly, while CFD based on mathematical models offers valuable insights, it is inherently limited in the ability to fully replicate the intricate haemodynamics and pathological variability of the cardiovascular system. Unlike those of the arterial vessels, venous vessel walls are thin and flexible and are influenced by respiratory movements, thus increasing the complexity of modelling efforts. Therefore, the outcomes derived from CFD should be regarded as references rather than exact replicas of physiological processes. Due to stringent inclusion criteria and the stratification of subjects based on clinical classification of CVI, subjects in the moderate to severe group were relatively scarce, resulting in only 24 subjects being included in this study. Nonetheless, rigorous numerical simulations have clearly demonstrated the significance of CFD in assessing left NIVLs. Moreover, the collateral circulation of the iliac veins in NIVL patients exhibits considerable diversity and complexity, varying significantly among patients. Due to sample size limitations, this study did not conduct subset analysis of collateral circulation. Currently, artificial intelligence technology is advancing rapidly. We anticipate that artificial intelligence will soon integrate seamlessly with 3D vascular model construction and haemodynamic simulation, alleviating the burden of human modelling. The more precise models, algorithms, and larger-scale studies can provide more accurate clinical information for the diagnosis and treatment of NVILs.
Table 3 Values of morphological indicators.In conclusion, haemodynamic analysis provided crucial insights into the haemodynamic changes occurring within the stenotic segment of the LCIV and its surrounding vasculature. These changes include venous hypertension at the caudal end of the stenotic LCIV segment, high blood flow velocity, an elevated TAWSS, and reduced RRT within the stenosis segment, all of which are indicative of lower extremity CVI progression. Moreover, indicators such as the ∆P, ∆V, and cross-sectional area stenosis rate exhibited positive correlations with the clinical classification, serving as direct or indirect indicators of the severity of LCIV stenosis. Additionally, the length of the stenotic segment correlated positively with the clinical classification. These objective, quantitative measures provide valuable means for assessing the severity of the condition of patients with NIVLs, aiding clinical diagnosis and optimizing treatment planning.Figure 3Analysis of the correlations between morphological indicators and clinical classification. (A) Minimum cross-sectional area of the stenotic segment of the left common iliac vein (LCIV) (S1); (B) Cross-sectional area of the caudal end of the stenotic LCIV segment (S2); (C) Cross-sectional area stenosis rate = (1–S1/S2) × 100%; (D) Cross-sectional area of the confluence of the bilateral common iliac veins (S3); E: Ratio of S1 to S3; F: Bifurcation angle at the confluence of the centrelines of the bilateral common iliac veins (θ); (G) Length of the stenotic LCIV segment (L1); (H) Distance from the narrowest point of the LCIV to the confluence point of the centrelines of the bilateral common iliac veins (L2). (A) Control group (C0a); (B) Mild group (C0s and C1-2); (C) Moderate to severe group (C3-6). For each group, n = 8.
Haemodynamic study of left nonthrombotic iliac vein lesions: a preliminary report
