Predicting coronary artery abnormalities in Kawasaki disease: Model development and external validation

Background

Kawasaki disease (KD) is an acute, pediatric vasculitis associated with coronary artery abnormality (CAA) development. Echocardiography at month 1 post-diagnosis remains the standard for CAA surveillance despite limitations, including patient distress and increased healthcare burden. With declining CAA incidence due to improved treatment, the need for routine follow-up imaging is being reconsidered. This study aimed to develop and externally validate models for predicting CAA development and guide the need for echocardiography.

Methods

This study used two prospective multicenter Japanese registries: PEACOCK for model development and internal validation, and Post-RAISE for external validation. The primary outcome was CAA at the month 1 follow-up, defined as a maximum coronary artery Z score (Zmax) ≥ 2. Twenty-nine clinical, laboratory, echocardiographic, and treatment-related variables obtained within one week of diagnosis were selected as predictors. The models included simple models using the previous Zmax as a single predictor, logistic regression models, and machine learning models (LightGBM and XGBoost). Their discrimination, calibration, and clinical utility were assessed.

Results

After excluding patients without outcome data, 4,973 and 2,438 patients from PEACOCK and Post-RAISE, respectively, were included. The CAA incidence at month 1 was 5.5% and 6.8% for the respective group. For external validation, a simple model using the Zmax at week 1 produced an area under the curve of 0.79, which failed to improve by more than 0.02 after other variables were added or more complex models were used. Even the best-performing models with a highly sensitive threshold failed to reduce the need for echocardiography at month 1 by more than 30% while maintaining the number of undiagnosed CAA cases to less than ten. The predictive performance declined considerably when the Zmax was omitted from the multivariable models.

Conclusions

The Zmax at week 1 was the strongest predictor of CAA at month 1 post-diagnosis. Even advanced models incorporating additional variables failed to achieve a clinically acceptable trade-off between reducing the need for echocardiography and reducing the number of undiagnosed CAA cases. Until superior predictors are identified, echocardiography at month 1 should remain the standard practice.

Clinical Perspective