A REVI EW OF ACUTE CARDI ACABNORMALI 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, MDSt. Luke’s Medical Center, QCPhilippines

INTRODUCTION AND LITERATURE REVIEW

Kawasaki disease (KD) is the leading cause of acquired heart disease among children in developed countries1,2

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 death3

1. Kliegman, R, et.al 2007, Nelson’s textbook of Pediatrics 18th 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 Jul

20;9:17.3. Kawasaki disease: etiology, pathogenesis and treatment. Barron, K. Cleveland Clinic Journal of Medicine. 2002; 69-II:69-78.

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

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

Variability in reported clinical and laboratory findingsassociated 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.

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.

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

SPECIFIC OBJECTIVES

To describe clinical and demographic data on cases

of KD at SLMC-QC

To describe the acute cardiac abnormalities seen inchildren with KD at SLMC-QC

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

SCOPE AND LIMITATIONS OFTHE 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

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

METHODOLOGY

Retrospective cross sectional study

Conducted at St. Luke’s Medical Center QuezonCity (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)

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

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 duringthe admission were excluded

DATA COLLECTION

DESCRIPTION OF OUTCOME MEASURES

Descriptive statistics

Measures of central tendency and measures of dispersion

Ratio and proportion for the frequency distribution ofeach variable

Prevalence of patients with and without acute cardiac abnormalities

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 forunivariable analyses

Type I error at 0.05

RESULTS AND DISCUSSIONTable 1. Population profileAge Group (N=67) Number %

<6 months 4 6.0

6-11 months 10 14.9

1-5 years 44 65.7

6-10 years 6 9.0

11-15 years 2 3.0

16-18 years 1 1.4

Age, in years, Median(IQR)

2 (1-4)

Number %

Sex (N=67)

Male 37 55.2

Female 30 44.8

Table 1. Population profile, Cont’nMonth of Admission Number %

January 10 14.9

February 3 4.5

March 12 17.9

April 7 10.4

May 5 7.4

June 6 8.9

July 1 1.5

August 4 6.0

September 4 6.0

October 5 7.5

November 5 7.5

December 5 7.5

Table 1. Population profile, Cont’nPrincipal Clinical Features ofKD Patients (N=67)

Number %

Rash 56 83.6

Eyes 54 80.6

Oral 59 88.1

Lymph node 49 73.1

Extremity changes 35 52.2

Atypical Presentation(N = 67)

31 46.3

Duration of Fever to Diagnosisor Time of Treatment with IVIG, Median (IQR)

7 (6-10)

Table 1. Population profile, Cont’nLaboratory Parameters in KD Patients

Hematocrit (vol%),Median (IQR)

33.2 (30.5 – 35.3)

WBC Count (/mm3),Mean + SD

16,582 + 6,731

Platelet Count (/mm3),Mean + SD

462,363 + 208,689

ESR (mm/hour),Mean + SD

71 + 30

CRP (mg/dL),Median (IQR)

48 (24-96)

Number %

Patients TreatedwithIVIG (N=67)

61 91.0

Refractory KD (N = 61) 5 8.1

Table 2. Acute Cardiac Abnormalities in KD PatientsNumber %

Acute CardiacAbnormalities (N = 67)

59 88.1

(+) Cardiac ExamFindings (N = 67)

34 50.7

Tachycardia 31 46.3Murmur 3 4.5Irregular heart rhythm 1 1.5(+) ECG Findings(N=13)

7 53.8

Sinus tachycardia 5 38.5Axis deviation 2 15.4LVH 2 15.4Non specific ST-T wavechanges

2 15.4

Others 2(1- Sinus pause /arrest;

1- RV conduction delay)

15.4

Table 2. Acute Cardiac Abnormalities in KD Patients, Cont’n

Number %

(+) Echocardiogram Findings (N=63)

52 77.6

Pericardial effusion 40 59.7

Coronary artery dilatation/ ectasia

18 26.9

Coronary arteryaneurysm

3 4.5

Perivascular brightness / cuffing

6 9.0

Mitral regurgitation 4 6.0

Fair to low EF 4 6.0

LVH or enlargement 3 4.5

Thickened mitral valve 2 3.0

Flattened septal motion 1 1.5

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

Abnormalities

Without Acute

Cardiac Abnormalities

p value

Age, in years,Median, IQR

2.0 (1-4) 1.5 (0.6-5.8) 0.883

Male, % 57.6 37.5 0.451

Rash, % 83.1 87.5 1.000

Eyes, % 81.4 75.0 0.647

Oral, % 89.8 75.0 0.242

Lymphadenopathy, % 74.6 62.5 0.672

Extremity changes, % 52.5 50.0 1.000

Incomplete KD, % 44.1 62.5 0.456

Table 3. Comparison of clinical and laboratory parametersbetween KD patients with and without acute cardiac abnormalities, Cont’n(p value <0.05 considered statistically significant)

With AcuteCardiac

Abnormalities

Without AcuteCardiac

Abnormalities

p value

Hematocrit, %,Median (IQR)

33.1 (30.2 – 35.3) 34.8 (30.4 – 36.0) 0.191

WBC count, /mm3,Mean + SD

16,267 + 6,687 18,868 + 7,061 0.309

Platelet count, /mm3,Mean + SD

459,052 + 209,053 486,375 + 218,603 0.731

CRP, mg/dL,Median (IQR)

48 (24 – 96) 24 (6-60) 0.080

ESR, mm/hr,Mean + SD

70 + 30 74 + 34 0.819

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

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

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%)

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

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

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 sequelae4

4. Manzano, Elvira. “Filipino children at higher risk of severe Kawasaki disease.” Medical Tribune. MIMS Philippines., May 2011. Web. 5 December 2014

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

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.