Thrombotic Risk Stratification of Coronary Aneurysms in Kawasaki Disease Patients: The Study of Morphology and Hemodynamics
Kawasaki disease (KD), a systemic vasculitis predominantly affecting children, can lead to the development of coronary artery aneurysms (CAAs) as a critical complication. These aneurysms predispose patients to thrombotic events, resulting in myocardial ischemia, infarction, and sudden death. Current clinical management relies heavily on anticoagulation therapy, yet there remains a pressing need for precise risk stratification tools to guide treatment decisions. This study addresses this gap by integrating morphological and hemodynamic parameters to develop a thrombotic risk scoring system for CAAs in KD patients.
Study Design and Methodology
The retrospective observational study analyzed 48 CAAs from 29 KD patients who underwent coronary computed tomography angiography (CTA) at West China Hospital. Aneurysms were categorized into high-risk (n=18, with thrombosis) and low-risk (n=30, without thrombosis) groups based on CTA findings. Patient-specific 3D coronary models were reconstructed from CTA images using SimVascular, an open-source software. Computational fluid dynamics (CFD) simulations were performed to assess hemodynamic parameters, incorporating physiological boundary conditions such as Windkessel RCR models for aortic outlets and lumped parameter networks for coronary outlets. The meshed models contained approximately 1.5 million tetrahedral elements to ensure computational accuracy.
Thirty-five morphological and hemodynamic parameters were evaluated. Morphological parameters included clinical diameter (Dclin), maximum diameter (Dmax), aneurysm length (Length), maximum cross-sectional area (Amax), surface area (SA), volume (V), undulation index (UI), and ratios such as RD/d (aneurysm-to-distal diameter ratio). Hemodynamic parameters focused on wall shear stress (WSS)-related metrics: time-averaged WSS (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), endothelial cell activation potential (ECAP), and normalized TAWSS (NTAWSS). Additional metrics quantified the percentage of aneurysm surface area exposed to abnormal hemodynamic thresholds (e.g., TAWSS 4, ECAP >0.05).
Key Findings: Morphological Risk Factors
Univariate analysis revealed significant morphological differences between high- and low-risk aneurysms. High-risk aneurysms exhibited larger dimensions, including Dclin (11.34 ± 4.10 mm vs. 6.70 ± 2.09 mm, P=0.0001), Dmax (12.00 ± 4.17 mm vs. 7.23 ± 2.33 mm, P=0.0001), Amax (78.82 ± 57.83 mm² vs. 31.14 ± 21.26 mm², P=0.0005), and V (1,485.00 ± 1,369.72 mm³ vs. 416.47 ± 408.70 mm³, P=0.0018). The undulation index (UI), reflecting geometric complexity, was markedly higher in high-risk aneurysms (1.39 ± 0.26 vs. 1.12 ± 0.14, P<0.0001). Multidimensional parameters like UI and V demonstrated stronger discriminatory power than unidimensional metrics.
Multivariate logistic regression identified Dmax as the most significant independent morphological predictor of thrombosis (P=0.0039). A cutoff value of 8.2 mm for Dmax yielded an area under the receiver operating characteristic curve (AUC) of 0.878 (95% CI: 0.756–0.954), with 83.33% sensitivity and 80.00% specificity. This aligns with clinical observations that larger aneurysms are prone to stasis and thrombus formation.
Hemodynamic Risk Factors
Hemodynamic analysis highlighted distinct flow patterns between groups. High-risk aneurysms exhibited larger regions of low TAWSS, elevated OSI, prolonged RRT, and higher ECAP values, indicating disturbed flow conducive to thrombosis. Key findings included:
- TAWSS: Average TAWSS was significantly lower in high-risk aneurysms (3.25 ± 1.58 dyne/cm² vs. 6.15 ± 2.71 dyne/cm², P<0.0001). The percentage of aneurysm area with TAWSS <4 dyne/cm² (A(TAWSS<4)%) was markedly higher in the high-risk group (72.25 ± 22.46% vs. 32.13 ± 27.08%, P<0.0001).
- OSI: Elevated OSI values (0.09 ± 0.04 vs. 0.06 ± 0.03, P=0.0089) indicated oscillatory flow in high-risk aneurysms.
- RRT and ECAP: Prolonged RRT (4.47 ± 2.10 vs. 3.15 ± 1.50, P=0.0297) and higher ECAP (68.74 ± 17.55% vs. 50.53 ± 19.67%, P=0.0073) suggested increased blood stagnation and endothelial activation.
Multivariate analysis identified four independent hemodynamic predictors: TAWSSaverage (P=0.0457), OSIaverage (P=0.0853), ECAPaverage (P=0.0147), and A(RRT>4)% (P=0.0478). The combined hemodynamic risk score (HRS) achieved an AUC of 0.897 (95% CI: 0.783–0.964), outperforming individual parameters.
Integrated Risk Stratification System
The study developed a Combined Risk Score (CRS) integrating Dmax and four hemodynamic parameters. Each parameter was assigned a binary risk value (0 or 1) based on cutoff thresholds:
- Dmax >8.2 mm
- TAWSSaverage <4.35 dyne/cm²
- OSIaverage >0.05
- ECAPaverage >63.51%
- A(RRT>4)% >9.31%
The CRS ranged from 0 to 5, with scores >2 indicating high thrombotic risk. The CRS demonstrated superior diagnostic accuracy (AUC=0.941, 95% CI: 0.844–0.986) compared to morphology-only (AUC=0.878) or hemodynamics-only (AUC=0.897) models. At the optimal cutoff of CRS >2, sensitivity was 94.44%, and specificity was 86.67%, highlighting its potential as a clinical decision-making tool.
Clinical Implications and Future Directions
This study underscores the synergistic value of combining morphological and hemodynamic assessments for thrombotic risk stratification. While Dmax remains a practical clinical marker, hemodynamic parameters provide deeper insights into flow disturbances that precede thrombosis. For instance, low TAWSS and high OSI reflect endothelial dysfunction and platelet activation, while elevated ECAP and RRT indicate regions of blood stagnation.
The proposed CRS could guide personalized anticoagulation strategies. Patients with CRS ≤2 may require less aggressive therapy, reducing bleeding risks, while those with CRS >2 may benefit from intensified monitoring and treatment. However, the study’s retrospective design and small sample size (n=48 aneurysms) necessitate validation in larger cohorts. Future work should incorporate advanced CFD refinements, such as non-Newtonian blood models and vessel wall elasticity, to enhance simulation accuracy. Longitudinal studies linking CRS to clinical outcomes (e.g., infarction rates) will further validate its prognostic utility.
Conclusion
This study establishes a novel framework for thrombotic risk assessment in KD-related CAAs by integrating morphological and hemodynamic biomarkers. The CRS, leveraging Dmax, TAWSS, OSI, ECAP, and RRT, offers a robust tool for identifying high-risk patients requiring proactive management. By elucidating the interplay between aneurysm geometry and flow dynamics, this work advances the pathophysiological understanding of CAA thrombosis and paves the way for precision medicine in KD care.
doi.org/10.1097/CM9.0000000000001931
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