1. A REVI EW OF ACUTE CARDI AC ABNORMALI T I ES I N CHI LDREN WI TH KAWAS AKI DI S EAS E I N A TERTI ARY HOS PI TAL Clariss Lovelle A. Blanco, MD Maria Malaya D. Guevara, MD St. Luke’s Medical Center, QC Philippines

2. INTRODUCTION AND LITERATURE REVIEW  Kawasaki disease (KD) is the leading cause of acquired heart disease among children in developed countries 1,2  Various cardiac sequelae that account for most of the morbidity and mortality of Kawasaki disease  Myocarditis, pericardial effusions, coronary artery aneurysms or ectasia, ischemic heart disease, and even sudden death 3 1.Kliegman, R, et.al 2007, Nelson’s textbook of Pediatrics 18 th edition, Saunders Elsevier, Philadelphia, PA. 2.Kawasaki syndrome: an intriguing disease with numerous unsolved dilemmas. Falcini F, Capannini S, Rigante D. Pediatr Rheumatol Online J. 2011 JulFalcini FCapannini SRigante DPediatr Rheumatol Online J. 20;9:17. 3.Kawasaki disease: etiology, pathogenesis and treatment. Barron, K. Cleveland Clinic Journal of Medicine. 2002; 69-II:69-78.

3.  Filipino children with KD believed to be at higher risk of developing coronary artery aneurysms than other Asian and non-Asian children.  The aneurysm rate was 23.8%, 10.5% and 7.8% for Filipinos, non-Filipino Asians and all other groups, respectively. 4 4. Manzano, Elvira. “Filipino children at higher risk of severe Kawasaki disease.” Medical Tribune. MIMS Philippines., May 2011. Web. 5 December 2014

4.  Many studies done abroad have sought to identify risk factors for coronary artery lesions (CAL) secondary to KD  Conflicting results on the risk factors for CAL

5. Variability in reported clinical and laboratory findings associated with coronary artery involvement in KD. 5 5. Can coronary artery involvement in Kawasaki Disease be predicted? Ghelani S, Kwatra N, Spurney C. Diagnostics. 2013; 3, 232-243; doi:10.3390/diagnostics3020232.

6.  Local literature about KD has been scarce  Most of the few Philippine studies have had small populations with usual focus only on the disease profile  Continuous monitoring of KD is critical to gain a better understanding of the global extent of this complex disease. 7 7. Epidemiology of Kawasaki disease in Asia, Europe, and the United States. Uehara, R and Belay, E. Journal of Epidemiology. 2012; 22:2.

7. RESEARCH OBJECTIVES  GENERAL OBJECTIVE  To describe the acute cardiac abnormalities in children with Kawasaki disease at St. Luke’s Medical Center- Quezon City (SLMC-QC) and to identify a correlation of clinical and laboratory findings with these acute cardiac abnormalities

8.  SPECIFIC OBJECTIVES  To describe clinical and demographic data on cases of KD at SLMC-QC  To describe the acute cardiac abnormalities seen in children with KD at SLMC-QC

9.  To compare KD patients with or without acute cardiac involvement according to clinical and laboratory parameters such as:  Age  Sex  Presence or absence of each of the principal criteria  Atypical/incomplete presentation  Laboratory findings

10. SCOPE AND LIMITATIONS OF THE STUDY  This study is limited to cases of Kawasaki Disease in St Luke’s Medical Center, Quezon City, Philippines from January, 2004 to December, 2013  Relied heavily on the completeness and accuracy of the chart retrieval system of the hospital’s Medical Records section and on the completeness and accuracy of chart entries as well

11.  Echocardiogram findings subject to the interpretation of the pediatric cardiologist  Laboratory results were checked, compared and confirmed for accuracy with the St. Luke’s Healthcare System  Both ESR and CRP were not done in all patients

12. METHODOLOGY  Retrospective cross sectional study  Conducted at St. Luke’s Medical Center Quezon City (SLMC-QC)  Medical records of children aged 0 to 18 years old discharged from SLMC-QC from January 2004 to December 2013 with the diagnosis, “Kawasaki Disease” (ICD 10 Code M30.3)

13.  OPERATIONAL DEFINITIONS  Kawasaki disease (epidemiological case definition)  Fever  Day of illness or fever  Refractory Kawasaki disease  Acute cardiac abnormalities  Coronary artery lesions due to Kawasaki disease  CBC, ESR, CRP

14.  INCLUSION CRITERIA AND EXCLUSION CRITERIA  Medical records  Children aged 0-18 years old  Discharged from SLMC QC  January 2004 to December 2013  Diagnosis: “Kawasaki Disease”  Patients without any echocardiogram done during the admission were excluded

15.  DATA COLLECTION

16.  DESCRIPTION OF OUTCOME MEASURES  Descriptive statistics  Measures of central tendency and measures of dispersion  Ratio and proportion for the frequency distribution of each variable  Prevalence of patients with and without acute cardiac abnormalities

17.  STATISTICAL TREATMENT  Means + SD  Medians, IQR  Proportions  Two groups -- KD patients with acute cardiac abnormalities and those without were compared in terms of a set of clinical and laboratory parameters  Chi-square test or Fisher exact test to compare proportions as appropriate  Unpaired t test or Mann Whitney U test for univariable analyses  Type I error at 0.05

18. RESULTS AND DISCUSSION Table 1. Population profile Age Group (N=67)Number% <6 months46.0 6-11 months1014.9 1-5 years4465.7 6-10 years69.0 11-15 years23.0 16-18 years11.4 Age, in years, Median (IQR) 2 (1-4) Number% Sex (N=67) Male3755.2 Female3044.8

19. Table 1. Population profile, Cont’n Month of AdmissionNumber% January1014.9 February34.5 March1217.9 April710.4 May57.4 June68.9 July11.5 August46.0 September46.0 October57.5 November57.5 December57.5

20. Table 1. Population profile, Cont’n Principal Clinical Features of KD Patients (N=67) Number% Rash5683.6 Eyes5480.6 Oral5988.1 Lymph node4973.1 Extremity changes3552.2 Atypical Presentation (N = 67) 3146.3 Duration of Fever to Diagnosis or Time of Treatment with IVIG, Median (IQR) 7 (6-10)

21. Table 1. Population profile, Cont’n Laboratory Parameters in KD Patients Hematocrit (vol%), Median (IQR) 33.2 (30.5 – 35.3) WBC Count (/mm 3 ), Mean + SD 16,582 + 6,731 Platelet Count (/mm 3 ), Mean + SD 462,363 + 208,689 ESR (mm/hour), Mean + SD 71 + 30 CRP (mg/dL), Median (IQR) 48 (24-96) Number% PatientsTreatedwith IVIG (N=67) 6191.0 Refractory KD (N = 61)58.1

22. Table 2. Acute Cardiac Abnormalities in KD Patients Number% Acute Cardiac Abnormalities (N = 67) 5988.1 (+) Cardiac Exam Findings (N = 67) 3450.7 Tachycardia3146.3 Murmur34.5 Irregular heart rhythm11.5 (+) ECG Findings (N=13) 753.8 Sinus tachycardia538.5 Axis deviation215.4 LVH215.4 Non specific ST-T wave changes 215.4 Others 2 (1- Sinus pause /arrest; 1- RV conduction delay) 15.4

23. Table 2. Acute Cardiac Abnormalities in KD Patients, Cont’n Number% (+) Echocardiogram Findings (N=63) 5277.6 Pericardial effusion4059.7 Coronary artery dilatation/ ectasia 1826.9 Coronary artery aneurysm 34.5 Perivascular brightness / cuffing 69.0 Mitral regurgitation46.0 Fair to low EF46.0 LVH or enlargement34.5 Thickened mitral valve23.0 Flattened septal motion11.5

24. Table 3. Comparison of clinical and laboratory parameters between KD patients with and without acute cardiac abnormalities (p value <0.05 considered statistically significant) With Acute Cardiac Abnormaliti es Without Acute Cardiac Abnormalities p value Age, in years, Median, IQR 2.0 (1-4)1.5 (0.6-5.8)0.883 Male, %57.637.50.451 Rash, %83.187.51.000 Eyes, %81.475.00.647 Oral, %89.875.00.242 Lymphadenopathy, % 74.662.50.672 Extremity changes, % 52.550.01.000 Incomplete KD, %44.162.50.456

25. Table 3. Comparison of clinical and laboratory parameters between KD patients with and without acute cardiac abnormalities, Cont’n (p value <0.05 considered statistically significant) With Acute Cardiac Abnormaliti es Without Acute Cardiac Abnormaliti es p value Hematocrit, %, Median (IQR) 33.1 (30.2 – 35.3)34.8 (30.4 – 36.0)0.191 WBC count, /mm 3, Mean + SD 16,267 + 6,68718,868 + 7,0610.309 Platelet count, /mm 3, Mean + SD 459,052 + 209,053486,375 + 218,603 0.731 CRP, mg/dL, Median (IQR) 48 (24 – 96)24 (6-60)0.080 ESR, mm/hr, Mean + SD 70 + 3074 + 340.819

26. CONCLUSION  Kawasaki disease in the SLMC-QC experience…  86.6% of KD patients <5 years old  Peak age of incidence: 2 years old  1.2:1 male to female ratio  Peak occurrences between January to April  Most frequently observed principal clinical feature: oral mucosal changes (88.1%)  Hematocrit, WBC’s, platelets, ESR, CRP

27.  Kawasaki disease in the SLMC-QC experience (Continuation)…  46.3 % incomplete or atypical KD  Median duration of the illness to diagnosis or treatment with IVIG:7 (6-10) days  91% patients received IVIG infusion during admission  5 of 61 (8.1%) treated patients refractory to IVIG

28.  Acute cardiac abnormalities in Kawasaki disease patients are very common and mostly non- specific, seen in 59 (88.1%) of the 67 patients  50.7% with significant cardiac exam findings  Most frequently observed cardiac examination finding: Tachycardia (46.3%)

29.  Acute cardiac abnormalities (Continuation)…  77.6% with noteworthy results on echocardiogram  Most common echocardiogram finding:Pericardial effusion (59.7%)  40.4% with coronary artery lesions  7 of 13 patients(53.8%) with significant ECG findings

30.  No significant difference in the clinical and laboratory parameters between KD patients with acute cardiac abnormalities and those without  Accurate assessment for the risk of acute cardiac involvement in Kawasaki disease may be difficult

31. RECOMMENDATIONS  Long term follow-up and documentation of cardiac findings of KD patients  Determine risk factors for coronary artery lesions  Large, local prospective study of Kawasaki disease patients, with only one cardiologist interpreting the echocardiograms to confirm the Filipinos’ risk for more serious cardiac sequelae 4 4. Manzano, Elvira. “Filipino children at higher risk of severe Kawasaki disease.” Medical Tribune. MIMS Philippines., May 2011. Web. 5 December 2014

32.  Heightened awareness of KD  Keep KD in the differential diagnosis of every child with fever of at least several days’ duration, rash, and nonpurulent conjunctivitis  The American Heart Association’s 2004 guidelines on KD remains to be a helpful tool for physicians in the diagnosis and management of these patients

33.  Other problem areas that need to be addressed by future studies:  Difficulties in early identification of the atypical and incomplete cases  Coronary artery injuries in children not fulfilling the classic diagnostic criteria  Genetic predisposition to Kawasaki disease  Vascular dysfunction in patients not showing echocardiographic evidence of coronary artery abnormalities in the acute phase of Kawasaki disease  Risk of potential premature atherosclerosis. 2 2. Kawasaki syndrome: an intriguing disease with numerous unsolved dilemmas. Falcini F, Capannini S, Rigante D. Pediatr Rheumatol Online J. 2011 Jul 20;9:17.Falcini FCapannini SRigante DPediatr Rheumatol Online J.