SHA24/091001

Management of Kawasaki disease with established coronary involvement

Khalfan Al Senaidi, MD,FAAP,FRCPC Pediatric Cardiologist, Sultan Qaboos University Hospital, Oman Saudi Heart Association conference February/16/2013

Question ď Ž

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Under what circumstances should a transient childhood illness be considered a lifelong potential cardiac risk factor?

Do all patients who have had KD require special follow-up, intermittent cardiac testing, and preventive measures?

If not, which patients are at significant risk for late coronary events to justify being placed in a high-risk category?

Background Most common cause of acquired heart disease

among children Japan in 1967 by Kawasaki Peak incidence between 1 - 2 years 80 % of patients are younger than 5 years Recurrence 3 – 3.6 %

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Pediatrics

2001

Cases of Kawasaki syndrome per 100 000 children younger than 5 years

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Pediatr Res 2 0 0 3 ; 5 3 : 1 5 3 –8 7

Pathogenesis  Etiology is unknown, autoimmune, genetic,

environmental  Acute phase: generalized microvasculitis, first 10 days after the onset of the fever,  Subacute

(10 -30 days):  15 % to 20 % coronary artery aneurysms  High mortality and long term morbidity 5

Pediatrics 2 0 0 4

Coronary aneurysms Proximal segments, fusiform , saccular,

cylindrical or beads on strings appearance Proximal LAD, proximal RCA, LMCA, LCX Late changes: (after 40 days) : MI healing and fibrosis  marked intimal thinking, calcification,  thrombus formation and stenosis 

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Clinical manifestation

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Clinical manifestation

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Incomplete Kawasaki

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AHA Circulation 2004

Risk factors for coronary aneurysms         10

Duration of fever ( > 14 days) Persistent fever after IVIG Anemia Leukocytosis Increased CRP Low albumin Age < 1 year Male American Heart Association ; 1 9 9 3

Coronary aneurysms Diagnosis  Aneurysms occur 10 to 30 days, rare < 10 days  Echocardiography remains the test of

choice  Measurement from inner edge to inner edge with exclusion of branching points  Multiple views should be taken  Baseline, 2 weeks, 6- 8 weeks  Some suggest at 6 – 12 months F/U  More frequent if complications 11

Pediatrics 2 0 0 4 ;1 1 4 ;1 7 0 8 - 1 7 3 3

Coronary aneurysm Echo

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Giant aneurysm

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Coronary aneurysm

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Pediatrics 2 0 0 4

Coronary artery aneurysms classification  AHA classification:

Small, < 5 mm  Medium 5 – 8 mm  Giant > 8 mm  Japanese Ministry of Health criteria:  > 3 mm in children < 5 years of age  > 4 mm in children ≥ 5 years of age  or size ≥ 1.5 times that of adjacent segment 

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AHA . 1 9 9 4 , Ministry of Health and Welfare ; 1 9 8 4

Coronary artery aneurysms Based BSA and Z scores  Japan Ministry of Health criteria  Underdiagnosed

and underestimated the true prevalence of coronary artery dilation  Therefore the measurements should be adjusted for body surface area  Z scores available but only for the LMCA, proximal LAD, RCA  So ≥ 1.5 times criteria could be used 16

J Pediatr . 1 9 9 8 , Circulation 2 0 0 7

Coronary artery aneurysms Z scores 

Provide more accurate assessment of the size of the proximal RCA, LAD

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Z score ≥ 2.5 -3 SD in one segment expected to occur in 0.6-0.1% of population

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LMCA has variation

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Jane et al Circulation 2 0 0 4

Other imaging modalities RT 3D echocardiography ,superior to 2D  Gadolium enhanced MRA and multislice spiral CT has being shown to be useful in detection of coronary aneurysm  Benefits of scar detection, stenosis assessment and 

simultaneous perfusion, function and viability evaluation

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Pediatr Radio 2 0 0 6 , J cardiovasc Mag Res 2 0 0 6

MRA

J Am Coll Cardio

Spiral CT

Regression of coronary aneurysms  Angiographic resolution in 50 to 67% in 1 to 2

years after the onset of the disease  Myointimal proliferation  Factors:  Smaller aneurysms, Age less than 1 year  Female  Fusiform rather than saccular  Located in distal segments 20

Circulation . 1987

Effect of Immunoglobulin on coronary aneurysms Standard therapy for many years  A generalized anti-inflammatory  IVIG 2g/kg as single dose has the greatest efficacy  Aneurysms to < 5 % if given ≤ 7 to 10 days, giant aneurysms < 1%  Reduction mortality from 1% to 0.1%  Rx < day 5 of illness appears no more likely to prevent cardiac sequelae 

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J Pediatr . 1 9 9 7

Dose response effect Immunoglobulin ď Ž

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Met analysis, 1629 patients U.S and Japan randomized controlled studies

Masaru et al J pediatrics 1997

Effect of Aspirin on coronary aneurysms  Anti-inflammatory , at high doses  afebrile in 48 to 72 hrs most centers  Antiplatelet, at low doses

6 -8 weeks and re assess  It does not appear to lower the frequency of the development of coronary abnormalities 

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Cochrane review 2 0 0 6

Fatal complication

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Bruckheimer, E. Circulation. 1998

Coronary artery aneurysm stenosis  Prevalence continue to rise almost linearly over

time  Worst prognosis occurs in giant aneurysm 

(50% chance mean f/u 8 years)

 Thrombus promoted by sluggish flow and

stenosis at proximal and distal ends  MI is principal cause of death in Kawasaki disease  Highest risk first year of onset of the disease 25

Ped cardiology 2 0 0 5 , Chin Med J ( Engl ). 2 0 0 2

Coronary artery aneurysm Thrombosis  Thrombosis once initiated may

progress rapidly  Different mechanism to adult MI  No randomized, controlled trials children  Streptokinase, urokinase, and tissue plasminoge activator  Mechanical restoration angioplasty or stent placement

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Pediatr Res . 2003;53:153–157

Giant coronary aneurysm Aspirin vs Warfarin       27

Retrospective study of 68 pts, 1974 - 2004 Group 1, 19 patients, aspirin and warfarin Group 2, 49 patients, aspirin Incident of MI : Group 1 5% vs 29 % Sudden death: Non in group 1 Group 2 : 14 % Sugahara et al Pediatric cardiology 2008

Catheter intervention for coronary aneurysms  Research Committee of the Japanese Ministry

of Health; presenting with ischemic symptoms  without ischemic symptoms but with reversible ischemia on stress test  without ischemia but with >75% stenosis in the LAD 

 Contraindicated if multiple, ostial or long

segment 28

Pediatr Int . 2 0 0 1 ;4 3 :5 5 8 –5 6 2

Interventional catheterization 

Balloon angioplasty : As long as < 2 years from diagnosis, due to dense fibrosis and calcifications  Rotational ablation if can not balloon < 10 atm (risk of new aneurysm 16 % ) 

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Stents: Older children with mild calcifications ( > 13y)  Localized lesions 

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Pediatr Int . 2001;43:558–562

Surgical management indications for bypass surgery in Kawasaki disease is still being debated  General agreement for indications:  Specific

Severe obstruction > 2 major coronary arteries  Severe obstruction of LMCA  Severe obstruction of LAD 

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AHA 2 0 0 4

Surgical options for coronary aneurysms Excision or plication unsuccessful  Arterial versus venous grafts ?  Questionnaire, 323 centers, Japan 

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Etsuko et al Circulation 2 0 0 4

Surgical interventions for coronary aneurysms

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Etsuko et al Circulation

Cardiac transplantation 

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A small number of patients with Kawasaki disease have undergone cardiac transplantation (13) Severe myocardial dysfunction Severe ventricular arrhythmias Severe coronary arterial lesions Almost half of the transplant patients had undergone previous bypass grafting procedures

Paul A et al Pediatrics 1997

Other long term issues     

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Early atherosclerotic changes Reduced vascular vasodilation when challenged Altered lipid metabolism Progressive dilation of the aortic root These issues are regardless of history of aneurysms

Newburger et al Circulation 1991

AHA Scientific Statement

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І) No coronary artery changes   

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No aspirin or restriction of activity beyond 1st 6-8 w No invasive testing Cardiovascular risk assessment and counseling every 5 years intervals

П) Transient ectasia disappear first 1st 6- 8 W  No aspirin or restriction of activity beyond 1st 6-8 W  No invasive testing  Cardiovascular risk assessment and counseling every 3-5 years intervals American Heart Association Circulation 2004

Risk stratification 

Ш) 1 small-medium aneurysm

Low dose aspirin 3-5 mg/kg at least till regression  Activity guided by stress testing, perfusion scan every 2 years  Contact sports discouraged while on antiplatelet  Follow up every year: echo, ECG  Angiography if noninvasive tests suggest ischemia 

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AHA 2 0 0 4

Risk stratification 

IV) ≥ 1 large or giant or multiple or complex

with no obstruction Long term antiplatelet therapy and warfarin ( INR 2-2.5) or LMWH  Contact sports discouraged  Annual stress testing, perfusion scan  Follow up every 6 months : Echo, ECG  First angiography 6-12 month or sooner if indicated 

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AHA 2 0 0 4

Risk stratification 

V) Coronary artery obstruction

Long term antiplatelet therapy and warfarin ( INR 2-2.5) or LMWH  Consider B blockers to reduce myocardial O2 consumption  Contact sports discouraged  Annual stress testing, perfusion scan  Follow up every 6 months : echo, ECG  Angiography recommended to address therapeutic options 

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AHA 2 0 0 4

Conclusion 

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KD a leading cause of acquired heart disease in children Often a diagnostic challenge Recent newer imaging modalities may help in management and follow up of aneurysms Follow up and management dependent on risk Long term consequence are still not fully known

Thank you for your attention