ABSTRACT

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.

What Is New?

The maximum Z score on echocardiography one week after diagnosis was the strongest of 29 variables for predicting coronary artery abnormalities (CAA) in patients with Kawasaki disease.

Even the most sensitive models had a suboptimal ability to predict CAA development and reduce the need for imaging studies, suggesting they have limited utility in clinical decision-making.

What Are the Clinical Implications?

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

There was no external funding for this study.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Institutional review board of Tokyo Metropolitan Children?s Medical Center (No. 2024b-12)

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Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

Anonymized individual participant data are kept confidential and will not be made available.

Non-standard Abbreviations and AcronymsKDKawasaki diseaseCAAcoronary artery abnormalityPEACOCKthe Prospective Study on Efficacy of Acute Treatment in a Multicenter Cohort of Children with Kawasaki DiseasePost-RAISEthe Prospective Observational study on STRAtified treatment with Immunoglobulin plus Steroid Efficacy for Kawasaki diseaseIVIGintravenous immunoglobulinIVMPintravenous methylprednisolone pulse therapyRCAproximal right coronary arteryLADproximal left anterior descending arteryCRPC-reactive proteinROCreceiver operating characteristicAUCarea under the curvePPVpositive predictive valueNPVnegative predictive value