Cardiovascular Status of Children 5 Years After Kawasaki Disease (CAVASAKI)

The aim of present study is to determine cardiovascular status of children who had KD in past and to identify possible biochemical markers of cardiovascular damage in those patients.

In this cross-sectional study children with history of KD will be examined 5 years after receiving intravenous immunoglobulin treatment (IVIG) and compared to healthy controls in terms of: serum levels of endothelial injury markers (circulating endothelial cells, galectin-3, soluble VCAM), peripheral blood pressure, central blood pressure, arterial stiffness parameters (measured by applanation tonometry), carotid intima media thickness (cIMT), capillaroscopy and echocardiography.

Study Overview

• Status: Completed
• Conditions: Kawasaki Disease; Vasculitis, Systemic

Detailed Description

All participants will be examined in Medical University Warsaw Children's Hospital.

Children with history of KD will be recruited from 2 paediatric hospitals in Warsaw and via advertisement by Polish support group for parents of children with KD in social media. Diagnosis of KD will be verified according to current American Heart Association (AHA) guidelines.

All children after KD will be examined 5 years after IVIG treatment exact to 2 months.

CAA presence at the time of KD diagnosis will be determined on the basis of medical records, after specialist consultation, in accordance to AHA definition. Worst-ever echocardiographic picture of coronary arteries will be considered in analysis.

Healthy age- and sex-matched controls (HC) will be recruited from KD patients' siblings.

Informed consent will be obtained from the parents of all patients and all HC.

Assessment of cardiovascular status

All children included in the study will undergo following tests:

1. Laboratory tests

   Blood samples will be drawn after over-night fasting. A) 1.6 ml of blood will be collected in vacutainer tube with ethylenediaminetetraacetic acid (EDTA), B) 4.9 ml of blood will be collected in vacutainer tube with clot-activator, without separation gel (serum tube).

   Routine laboratory techniques will be used to measure lipid profile, glucose and complete blood count. 1 ml of whole blood will be used for circulating endothelial cells (CEC) isolation. CEC will be identified with CD146-immunomagnetic bead extraction based on an international consensus standardised protocol. 3 ml of blood will be centrifuged at room temperature within 2 h of collection and serum will be stored in separate tubes at -70°C until analyzed. Endothelial injury markers: galectin-3 and soluble VCAM levels will be measured using standardized ELISA assays.

2. Echocardiography

   Echocardiography (ECHO) will be performed with Philips Epiq 7 ultrasound equipment with appropriate transducers by a single specialist supervised by an experienced paediatric echocardiographer. All the standard anatomic and physiological imaging will be done. Multiple imaging planes and transducer positions will be used for optimal visualization of the coronary arteries in all major coronary segments - main stem of left coronary artery, anterior interventricular branch, circumflex branch and right coronary artery will be measured according to AHA guidelines - internal vessel diameter will be assessed from inner edge to inner edge of vessel. The number and location of aneurysms and the presence or absence of intraluminal thrombi and stenotic lesions will be evaluated.

   Another evaluation will include assessment of the left ventricular form and function (ejection fraction measured by Teicholz and Simpson's method, end-systolic and end-diastolic volumes, regional wall motion estimated by M-Mode and speckle tracking modes, evaluation of diastolic function in Tissue Doppler Imaging, both systolic and diastolic function measured as myocardial performance index - i.e. Tei index), aortic root imaging (possible dilatation), valvular function (especially mitral and aortic regurgitation assessed in pulsed and color doppler), presence of pericardial effusion. All of the parameters will be calculated as Z-scores assessed by the health professionals Cardio Z mobile application developed by the experienced Paediatric Cardiology Team at Evelina Children's Hospital in London.

3. Carotid intima media thickness (cIMT)

   cIMT will be evaluated in all subjects by a single experienced specialist using 13-megahertz (MHz) linear transducer, Aloka Prosound Alpha 6, Hitachi Aloka Medical, Mitaka, Japan.

   cIMT will be defined as the mean distance from the leading edge of the lumen-intima interface to the leading edge of the media adventitia interface of the far wall, approximately 1 cm proximal to the carotid bulb. Six determinations of cIMT [mm], three on the left and three on the right side, will be obtained and averaged.

4. Pulse Wave Analysis (PWA) and Pulse Wave Velocity (PWV)

Arterial pulse waveform and aortal pulse wave velocity will be evaluated by the same investigator using a Sphygmocor device, AtCor Medical Pty Ltd., Sydney, Australia. All pulse wave and velocity measurements will be performed in the sitting position in a quiet, temperature-controlled room (20 ± 5°C) after a 5 min rest.

Peripheral pressure waveforms will be recorded from the radial artery at the right wrist, using applanation tonometry. After 20 sequential waveforms had been acquired, a validated generalized transfer function will be used to generate the corresponding central aortic pressure waveform.

All examiners will be unaware of patients' clinical details.

• Study Type: Observational
• Enrollment (Actual): 61

Contacts and Locations

Study Locations

• Poland
  • Warsaw, Poland, 02-091
    • Medical University of Warsaw Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 15 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Children 5 years after Kawasaki Disease will be recruited from 2 Warsaw hospitals and via advertisment by Polish support group for parents of children with KD in social media

Description

Inclusion Criteria:

• history of KD treated with intravenous immunoglobulin (IVIG)

Exclusion Criteria:

• any significant comorbidities,
• body mass index (BMI) value > 1 standard deviation (SD) for age and gender,
• height < 120 cm at the time of cardiovascular assessment.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Kawasaki Disease (KD); Children 5 years after Kawasaki Disease
Healthy controls (HC); Age- and sexmatched healthy siblings of children after Kawasaki Disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CEC in children 5 years after KD	comparison of CEC number in KD and HC groups	5 years
Arterial stiffness in children 5 years after KD	comparison of pulse wave velocity Z-score in KD and HC groups	5 years
Central blood pressure in children 5 years after KD	comparison of central blood pressure values in KD and HC groups	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricle size in children 5 years after KD	comparison of left ventricle mass index in KD and HC groups	5 years
Diastolic function of the left ventricle in children 5 years after KD	comparison of E/A ratio in KD and HC groups	5 years
cIMT in children 5 years after KD	comparison of cIMT thickness in KD and HC groups	5 years
Capillaroscopy in children 5 years after KD	comparison of capillary characteristics (normal / not-normal) in KD and HC groups	5 years
Endocan in children 5 years after KD	comparison of endocan serum concentration in KD and HC groups	5 years
Thrombomodulin in children 5 years after KD	comparison of thrombomodulin serum concentration in KD and HC groups	5 years
VEGF in children 5 years after KD	comparison of VEGF serum concentration in KD and HC groups	5 years
Soluble E-selectin in children 5 years after KD	comparison of soluble E-selectin serum concentration in KD and HC groups	5 years

Collaborators and Investigators

• Sponsor: Medical University of Warsaw
• Investigators: Study Chair: Ernest Kuchar, Professor, Medical University of Warsaw

Publications and helpful links

General Publications

• McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, Baker AL, Jackson MA, Takahashi M, Shah PB, Kobayashi T, Wu MH, Saji TT, Pahl E; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; and Council on Epidemiology and Prevention. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation. 2017 Apr 25;135(17):e927-e999. doi: 10.1161/CIR.0000000000000484. Epub 2017 Mar 29.
• Dietz SM, Tacke CE, Hutten BA, Kuijpers TW. Peripheral Endothelial (Dys)Function, Arterial Stiffness and Carotid Intima-Media Thickness in Patients after Kawasaki Disease: A Systematic Review and Meta-Analyses. PLoS One. 2015 Jul 10;10(7):e0130913. doi: 10.1371/journal.pone.0130913. eCollection 2015.
• Shah V, Christov G, Mukasa T, Brogan KS, Wade A, Eleftheriou D, Levin M, Tulloh RM, Almeida B, Dillon MJ, Marek J, Klein N, Brogan PA. Cardiovascular status after Kawasaki disease in the UK. Heart. 2015 Oct;101(20):1646-55. doi: 10.1136/heartjnl-2015-307734. Epub 2015 Aug 27.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Actual): September 28, 2023
• Study Completion (Actual): September 28, 2023

Study Registration Dates

• First Submitted: November 16, 2018
• First Submitted That Met QC Criteria: November 20, 2018
• First Posted (Actual): November 21, 2018

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: arterial stiffness; PWV; cIMT; galectin-3; kawasaki
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Skin Diseases; Lymphatic Diseases; Skin Diseases, Vascular; Vasculitis; Skin and Connective Tissue Diseases; Hemic and Lymphatic Diseases; Mucocutaneous Lymph Node Syndrome; Systemic Vasculitis
• Other Study ID Numbers: CAVASAKI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No