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