Kawasaki disease medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arzu Kalayci, M.D. [2] Dildar Hussain, MBBS [3]

Treatment

Medical Therapy

Intravenous Immunoglobulin (IVIG) and aspirin are indicated in the treatment of Kawasaki Disease. It is imperative that treatment be started as soon as the diagnosis is made to prevent damage to the coronary arteries. Except for Kawasaki disease and a couple of other indications, aspirin is otherwise normally not recommended for children due to its association with Reye's syndrome. Children with Kawasaki disease should be hospitalized.

• 1. Initial treatment

• Preferred regimen: IVIG 2 g/kg single infusion within the first 7-10 days of illness AND Aspirin 80-100 mg/kg/day qid , reduce the aspirin dose after the child has been afebrile for 48 to 72 hours, then begin low-dose aspirin (3 to 5 mg/kg/day) and maintain it until the patient shows no evidence of coronary changes by 6 to 8 weeks after the onset of illness
• Note (1): Other clinicians continue highdose aspirin until day 14 of illness and 48 to 72 hours after fever cessation
• Note (2): For children who develop coronary abnormalities, aspirin may be continued indefinitely

• 2. Treatment of Patients Who Failed to Respond to Initial Therapy (persistent or recrudescent fever ≥ 36 hours after completion of the initial IVIG infusion)

• Preferred regimen: IVIG 2 g/kg q24h for 1-3 days OR Methylprednisolone 30 mg/kg IV for 2-3 hours q24h for 1-3 days

AHA Scientific Statement on Kawasaki Disease

Recommendations for Initial Treatment With Intravenous Immunoglobulin (IVIG) and Asetil Salisilat Acid (ASA)

Class I

"1. Patients with complete KD criteria and those who meet the algorithm criteria for incomplete KD should be treated with high-dose IVIG (2 g/kg given as a single intravenous infusion) within 10 days of illness onset but as soon as possible after diagnosis.(Level of Evidence: A) "

Class IIa

"1. It is reasonable to administer IVIG to children presenting after the 10th day of illness (ie, in whom the diagnosis was missed earlier) if they have either persistent fever without other explanation or coronary artery abnormalities together with ongoing systemic inflammation, as manifested by elevation of ESR or CRP (CRP >3.0 mg/dL). (Level of Evidence: B) "

"2. Administration of moderate-(30–50mg·kg−1·d−1) to high-dose (80–100 mg·kg−¹·d−¹) ASA is reasonable until the patient is afebrile, although there is no evidence that it reduces coronary artery aneurysms. (Level of Evidence: C) "

Class III

"1. IVIG generally should not be administered to patients beyond the tenth day of illness in the absence of fever, significant elevation of inflammatory markers, or coronary artery abnormalities . (Level of Evidence: C) "

"2. The ESR is accelerated by IVIG therapy and therefore should not be used to assess response to IVIG therapy. A persistently high ESR alone should not be interpreted as a sign of IVIG resistance. (Level of Evidence: C) "

Recommendations for Adjunctive Therapies for Primary Treatment

Class IIb

"1. Administration of a longer course of corticosteroids (eg, tapering over 2–3 weeks), together with IVIG 2 g/kg and ASA, may be considered for treatment of high-risk patients with acute KD, when such high risk can be identified in patients before initiation of treatment. (Level of Evidence: B) "

Class III

"1. Single-dose pulse methylprednisolone should not be administered with IVIG as routine primary therapy for patients with Kawasaki Disease. (Level of Evidence: B) "

Recommendations for Additional Therapy in the IVIG-Resistant Patient

Class IIa

"1. It is reasonable to administer a second dose of IVIG (2 g/kg) to patients with persistent or recrudescent fever at least 36 hours after the end of the first IVIG infusion. (Level of Evidence: B) "

Class IIb

"1. Administration of high-dose pulse steroids (usually methylprednisolone 20–30 mg/kg intravenously for 3 days, with or without a subsequent course and taper of oral prednisone) may be considered as an alternative to a second infusion of IVIG or for retreatment of patients with KD who have had recurrent or recrudescent fever after additional IVIG. (Level of Evidence: B) "

"2. Administration of a longer (eg, 2–3 weeks) tapering course of prednisolone or prednisone, together with IVIG 2 g/kg and ASA, may be considered in the retreatment of patients with KD who have had recurrent or recrudescent fever after initial IVIG treatment. (Level of Evidence: B) "

"3. Administration of infliximab (5 mg/kg) may be considered as an alternative to a second infusion of IVIG or corticosteroids for IVIG-resistant patients. (Level of Evidence: C) "

"4. Administration of cyclosporine may be considered in patients with refractory KD in whom a second IVIG infusion, infliximab, or a course of steroids has failed. (Level of Evidence: C) "

"5. Administration of immunomodulatory monoclonal antibody therapy (except TNF-α block- ers), cytotoxic agents, or (rarely) plasma exchange may be considered in highly refractory patients who have failed to respond to a second infusion of IVIG, an extended course of steroids, or infliximab. (Level of Evidence: C) "

Recommendations for Treatment of Coronary Artery Thrombosis

Class I

"1. Coronary artery thrombosis with actual or impending occlusion of the arterial lumen should be treated with thrombolytic therapy or, in patients of sufficient size, by mechanical restoration of coronary artery blood flow at cardiac catheterization.(Level of Evidence: C) "

"2. Thrombolytic agents should be administered together with low-dose ASA and low-dose heparin, with careful monitoring for bleeding.(Level of Evidence: C) "

Class IIb

"1. Treatment of coronary artery thrombosis with substantial thrombus burden and high risk of occlusion with a combination of reduced-dose thrombolytic therapy and abciximab may be considered. (Level of Evidence: C) "

Recommendations for Risk Stratification of Coronary Artery Abnormalities

Class IIa

"1. It is reasonable to use echocardiographic coronary artery luminal dimensions converted to BSA-adjusted Z scores to determine risk stratification. (Level of Evidence: B) "

"2. It is reasonable to incorporate both maximal and current coronary artery involvement in risk stratification. (Level of Evidence: C) "

"3. It is reasonable to incorporate the presence of additional features other than coronary artery luminal dimensions into decisions regarding risk stratification. (Level of Evidence: C) "

No Involvement (Z Score Always <2)

Class IIa

Frequency of cardiology assessment (to include history and physical examination, echocardiography, electrocardiography)

"1. It is reasonable to discharge patients from cardiology care at 4 to 6 weeks after KD onset, although ongoing follow-up to 12 months may be considered. Ongoing cardiology follow-up is not indicated. Patients and families should be advised to remember that having had KD is part of the patient’s permanent medical history (Level of Evidence: C)"

Type and frequency of additional cardiology assessment (other cardiology testing)

Class IIa

"1. It is reasonable that no additional cardiology assessment be performed. (Level of Evidence: C)"

Cardiovascular risk factor assessment and management

Class IIa

"1. It is reasonable to provide general counseling regarding healthy lifestyle and activity promotion at every visit; this may be provided by the primary care provider. (Level of Evidence: C)"

"2. It is reasonable to assess blood pressure, fast- ing lipid profile, body mass index (and plot), waist circumference, dietary and activity assessment, and smoking at least once and ideally at least 1 year from the episode of acute KD; this may be performed by the primary care provider. (Level of Evidence: C)"

Medical therapy (β-blockers, angiotensin-converting enzyme inhibitor [ACEI], statin)

Class III

"1. No additional medical therapy should be given. (Level of Evidence: C) "

Thromboprophylaxis

Class IIa

"1. It is reasonable to give low-dose ASA for up to 4 to 6 weeks after the episode of acute KD, which should be discontinued thereafter. (Level of Evidence: C) "

Physical activity

Class IIa

"1. It is reasonable to provide physical activity counseling at every visit with no restrictions or precautions at any time. (Level of Evidence: B)"

Reproductive counselling

Class IIa

"1. It is reasonable to provide age-appropriate counseling regarding contraception and pregnancy without modification. (Level of Evidence: B) "

Dilation Only (Z Score ≥2 but <2.5, or a Decrease in Z Score During Follow-up ≥1)

Class IIa

Frequency of cardiology assessment (to include history and physical examination, echocardiography, electrocardiography)

"1. If luminal dimensions have returned to normal by 4 to 6 weeks after KD onset, it is reasonable to discharge the patient from cardiology care, although ongoing follow-up to 12 months may be considered. (Level of Evidence: B) ". (Level of Evidence: C) "

"2. If dilation remains present at 4 to 6 weeks after KD onset, then it is reasonable to continue follow-up to 12 months. If the luminal dimensions return to normal before then, it is reasonable to discharge the patient from ongoing cardiology care. (Level of Evidence: B) ". (Level of Evidence: C) "

"3. Resolution is expected within 1 year. If dilation persists at 1 year, consider whether this represents a dominant branch. If this is a probable explanation, then it is reasonable to discharge the patient from ongoing cardiology care, although ongoing follow-up every 2 to 5 years may be considered. Patients and families should be advised to remember that having had KD is part of the patient’s permanent medical history. (Level of Evidence: C) ". (Level of Evidence: C) "

Type and frequency of additional cardiology assessment (other cardiology testing)

Class IIa

"1. It is reasonable that no additional cardiology assessment be performed. (Level of Evidence: B) ". (Level of Evidence: C) "

Cardiovascular risk factor assessment and management

Class IIa

"1. It is reasonable to provide general counseling regarding healthy lifestyle and activity promotion at every visit; this may be provided by the primary care provider. (Level of Evidence: C) ". (Level of Evidence: C) "

"2. It is reasonable to assess blood pressure, fasting lipid profile, body mass index (and plot), waist circumference, dietary and activity assessment, and smoking at least once and ideally at least 1 year from the episode of acute KD; this may be performed by the primary care provider. (Level of Evidence: C) ". (Level of Evidence: C) "

Medical therapy (β-blockers, ACEI, statin)

Class III

"1. No additional medical therapy should be given. (Level of Evidence: C) "

Thromboprophylaxis

Class IIa

"1. It is reasonable to give low-dose ASA until 4 to 6 weeks after the acute episode, which should be discontinued thereafter. (Level of Evidence: C) "

Physical activity

Class IIa

"1. It is reasonable to provide physical activity counseling at every visit with no restrictions or precautions at any time. (Level of Evidence: B) "

Reproductive counseling

Class IIa

"1. It is reasonable to provide age-appropriate counseling regarding contraception and pregnancy without modification. (Level of Evidence: B) "

Small Aneurysms (Z Scoren ≥2 but <5)

Current or Persistent Small Aneurysms

Frequency of cardiology assessment (to include history and physical examination, echocardiography, electrocardiography)

Class IIa

"1. Patients should be seen at 4 to 6 weeks after the acute KD episode, then it is reasonable to assess after 6 months and 1 year. Ongoing follow-up assessment every year thereafter is reasonable (Level of Evidence: B) "

Type and frequency of additional cardiology assessment (other cardiology testing)

Class IIa

"1. It is reasonable to assess for inducible myocardial ischemia (stress echocardiography, stress with magnetic resonance imaging [MRI], stress nuclear medicine [NM], positron emission tomography [PET]) every 2 to 3 years or if the patient has symptoms suggestive of ischemia or signs suggestive of ventricular dysfunction (Level of Evidence: B) "

Class IIb

"2. Further imaging with angiography (CT, MRI, invasive) may be considered for periodic surveillance every 3 to 5 years (Level of Evidence: C) "

Cardiovascular risk factor assessment and management

Class IIa

"1.It is reasonable to provide general counseling regarding healthy lifestyle and activity promotion at every visit; this may additionally be provided by the primary care provider (Level of Evidence: C) "

"2. It is reasonable to assess blood pressure, fasting lipid profile, body mass index (and plot), waist circumference, dietary and activity assessment, and smoking at least once and ideally at least 1 year from the episode of acute KD; this may be performed by the primary care provider. It is reasonable to obtain a follow-up fasting lipid profile as per the Expert Panel guidelines (Level of Evidence: C) "

Medical therapy (β-blockers, ACEI, statin)

Class IIb

"1. Empirical statin therapy for non–lipid-lowering (pleiotropic) effects may be considered (Level of Evidence: C) "

Class III

"1. Empirical treatment with β-blockers is not indicated (Level of Evidence: C) "

Thromboprophylaxis

Class I

"1. Patients should be treated with low-dose ASA (Level of Evidence: C) "

Class IIa

"1. Use of an alternative antiplatelet agent (eg, a thienopyridine such as clopidogrel) instead of ASA is reasonable if the patient is intolerant or resistant to ASA (Level of Evidence: C) "

Class III

"1. Anticoagulation or treatment with dual-antiplatelet therapy is not indicated (Level of Evidence: C) "

Physical activity

Class IIa

"1. It is reasonable to provide physical activity counseling at every visit with no restrictions or precautions at any time (Level of Evidence: C) "

Reproductive counseling

Class IIa

"1. It is reasonable to provide age-appropriate counseling regarding contraception and pregnancy without modification. (Level of Evidence: B) "

Regression to Normal Z Score or Dilation Only

Frequency of cardiology assessment (to include history and physical examination, echocardiography, electrocardiography)

Class IIa

"1. It is reasonable to assess every 1 to 3 years. It is reasonable not to perform echocardiogra- phy unless there is evidence for inducible myocardial ischemia or the patient has symptoms suggestive of ischemia or signs suggestive of ventricular dysfunction. (Level of Evidence: B) "

Type and frequency of additional cardiology assessment (other cardiology testing)

Class IIa

"1. It is reasonable to assess for inducible myocardial ischemia (stress echocardiography, stress with MRI, stress NM perfusion imaging, PET) every 3 to 5 years or if the patient has symptoms suggestive of ischemia or signs suggestive of ventricular dysfunction. (Level of Evidence: B) "

Class IIb

"1. Further imaging with angiography (CT, MRI, invasive) may be considered only if there is evidence for inducible myocardial ischemia or ventricular dysfunction. (Level of Evidence: C) "

Cardiovascular risk factor assessment and management

Class IIa

"1. It is reasonable to provide general counseling regarding healthy lifestyle and activity promotion at every visit; this may additionally be provided by the primary care provider.(Level of Evidence: C) "

"2. It is reasonable to assess blood pressure, fasting lipid profile, body mass index (and plot), waist circumference, dietary and activity assessment, and smoking every 2 years; this may be performed by the primary care provider. It is reasonable to obtain a follow- up fasting lipid profile. (Level of Evidence: C) "

Medical therapy (β-blockers, ACEI, statin)

Class IIb

"1. Empirical statin therapy for non–lipid-lowering (pleiotropic) effects may be considered.(Level of Evidence: C) "

Class III

"1. Empirical treatment with β-blockers is not indicated.(Level of Evidence: C) "

Thromboprophylaxis

Class IIb

"1. Ongoing treatment with low-dose ASA may be considered, although it is reasonable to discontinue.(Level of Evidence: C) "

Class IIa

"1. Use of an alternative antiplatelet agent (eg, a thienopyridine such as clopidogrel) instead of ASA is reasonable if the patient is intol- erant or resistant to ASA.(Level of Evidence: C) "

Physical activity

Class IIa

"1. It is reasonable to provide physical activity counseling at every visit with no restrictions or precautions at any time .(Level of Evidence: C) "

Reproductive counselling

Class IIa

"1. It is reasonable to provide age-appropriate counseling regarding contraception and pregnancy without modification.(Level of Evidence: B) "

Medium Aneurysms (Z Score ≥5 to <10, With an Absolute Luminal Dimension <8 mm)

Current or Persistent Medium Aneurysms

Frequency of cardiology assessment (to include history and physical examination, echocardiography, electrocardiography)

Class IIa

Patients should be seen at 4 to 6 weeks after the acute KD episode; then it is reasonable to assess after 3 months, 6 months, and 1 year. Ongoing follow-up assessment every 6 to 12 months thereafter is reasonable

Type and frequency of additional cardiology assessment (other cardiology testing)

Class IIa

"1. It is reasonable to assess for inducible myo- cardial ischemia (stress echocardiography, stress with MRI, stress NM perfusion imaging, PET) every 1 to 3 years or if the patient has symptoms suggestive of ischemia or signs suggestive of ventricular dysfunction.(Level of Evidence: B) "

Class IIb

"1. Further imaging with angiography (CT, MRI, invasive) may be considered for periodic sur- veillance every 2 to 5 years.(Level of Evidence: C) "

Cardiovascular risk factor assessment and management

Class IIa

"1. It is reasonable to provide general counseling regarding healthy lifestyle and activity promotion at every visit; this may additionally be provided by the primary care provider.(Level of Evidence: C) "

"2. It is reasonable to assess blood pressure, fasting lipid profile, body mass index (and plot), waist circumference, dietary and activity assessment, and smoking at least once and ideally at least 1 year from the episode of acute KD; this may be performed by the primary care provider. It is reasonable to obtain a follow-up fasting lipid profile.(Level of Evidence: C) "

Medical therapy (β-blockers, ACEI, statin)

Class IIb

"1. Empirical statin therapy for non–lipid-lowering (pleiotropic) effects may be considered.(Level of Evidence: C) "

Class III

"1. Empirical treatment with β-blockers is not indicated.(Level of Evidence: C) "

Thromboprophylaxis

Class I

"1. Patients should be treated with low-dose ASA.(Level of Evidence: C) "

Class IIa

"1. Use of an alternative antiplatelet agent (eg, a thienopyridine such as clopidogrel) instead of ASA is reasonable if the patient is intoler- ant or resistant to ASA.(Level of Evidence: C) "

Class IIb

"1. Additional patient and coronary artery characteristics may be considered in decision making regarding intensification of thromboprophylaxis.(Level of Evidence: C) "

"2. Dual-antiplatelet therapy with an additional antiplatelet agent (eg, a thienopyridine such as clopidogrel) may be considered.(Level of Evidence: C) "

Class III

"1. Use of anticoagulation (warfarin, LMWH) is not indicated.(Level of Evidence: C) "

Physical activity

Class I

"1. For patients taking dual-antiplatelet therapy, activities involving a risk of bodily contact, trauma, or injury should be restricted or modified.(Level of Evidence: B) "

Class IIa

"1. It is reasonable to provide physical activity counseling at every visit without restrictions or precautions. Participation in competitive sports or high-intensity activities should be guided by results from testing for inducible myocardial ischemia or exercise-induced arrhythmias.(Level of Evidence: C) "

Reproductive counselling

Class IIa

"1. It is reasonable to discourage use of oral contraceptive drugs that increase thrombosis risk, to recommend that pregnancy be supervised by a multidisciplinary team including a cardiologist, and to alter thromboprophylaxis management during pregnancy and delivery.(Level of Evidence: B) "

Regression to Small Aneurysms

Frequency of cardiology assessment (to include history and physical examination, echocardiography, electrocardiography)

Class IIa

"1. Ongoing follow-up assessment every year is reasonable.(Level of Evidence: B) "

Type and frequency of additional cardiology assessment (other cardiology testing)

Class IIa

"1. It is reasonable to assess for inducible myocardial ischemia (stress echocardiography, stress with MRI, stress NM perfusion imaging, PET) every 2 to 3 years or if the patient has symptoms suggestive of ischemia or signs suggestive of ventricular dysfunction.(Level of Evidence: B) "

Class IIb

"1. Further imaging with angiography (CT, MRI, invasive) may be considered for periodic surveillance every 3 to 5 years.(Level of Evidence: C) "

Cardiovascular risk factor assessment and management

Class IIa

"1. It is reasonable to provide general counseling regarding healthy lifestyle and activity promotion at every visit; this may additionally be provided by the primary care provider.(Level of Evidence: C) "

"2. It is reasonable to assess blood pressure, fasting lipid profile, body mass index (and plot), waist circumference, dietary and activ- ity assessment, and smoking every year; this may be performed by the primary care provider. It is reasonable to obtain a follow- up fasting lipid profile.(Level of Evidence: C) "

Medical therapy (β-blockers, ACEI, statin)

Class IIb

"1. Empirical statin therapy for non–lipid-lowering (pleiotropic) effects may be considered.(Level of Evidence: C) "

Class III

"1. Empirical treatment with β-blockers is not indicated.(Level of Evidence: C) "

Thromboprophylaxis

Class I

"1. Patients should be treated with low-dose ASA.(Level of Evidence: C) "

Class IIa

"1. Use of an alternative antiplatelet agent (eg, a thienopyridine such as clopidogrel) instead of ASA is reasonable if the patient is intolerant or resistant to ASA.(Level of Evidence: C) "

Class IIb

"1. Dual-antiplatelet therapy with an additional antiplatelet agent (eg, a thienopyridine such as clopidogrel) may be considered.(Level of Evidence: C) "

"2. Additional patient and coronary artery characteristics may be considered in decision making regarding intensification or discontinuation of thromboprophylaxis.(Level of Evidence: C) "

Class III

"1. Use of anticoagulation is not indicated.(Level of Evidence: C) "

Physical activity

Class I

"1. For patients taking dual-antiplatelet therapy, activities involving a risk of bodily contact, trauma, or injury should be restricted or modified.(Level of Evidence: B) "

Class IIa

"1. It is reasonable to provide physical activity counseling at every visit without restrictions or precautions. Participation in competitive sports or high-intensity activities should be guided by results from testing for inducible myocardial ischemia or exercise-induced arrhythmias.(Level of Evidence: C) "

Reproductive counselling

Class IIa

"1. It is reasonable to discourage use of oral contraceptive drugs that increase thrombo- sis risk, to recommend that pregnancy be supervised by a multidisciplinary team includ- ing a cardiologist, and to alter thromboprophylaxis management during pregnancy and delivery.(Level of Evidence: B) "

Regression to Normal Z Score or Dilation Only

Frequency of cardiology assessment (to include history and physical examination, echocardiography, electrocardiography)

Class IIb

"1. Ongoing follow-up assessment every 1 to 2 years is reasonable. Not performing routine 2D echocardiography may be considered unless there is evidence for inducible myocardial ischemia or the patient has symptoms suggestive of ischemia or signs suggestive of ventricular dysfunction (Level of Evidence: B) "

Type and frequency of additional cardiology assessment (other cardiology testing)

Class IIa

"1. It is reasonable to assess for inducible myocardial ischemia (stress echocardiography, stress with MRI, stress NM perfusion imaging, PET) every 2 to 4 years or if the patient has symptoms suggestive of ischemia or signs suggestive of ventricular dysfunction.(Level of Evidence: B) "

"2. It is reasonable to perform no further imaging with angiography (CT, MRI, invasive) in the absence of evidence of inducible myocardial ischemia. (Level of Evidence: C) "

Cardiovascular risk factor assessment and management

Class IIa

"1. It is reasonable to provide general counseling regarding healthy lifestyle and activity promotion at every visit; this may additionally be provided by the primary care provider.(Level of Evidence: C) "

"2. It is reasonable to assess blood pressure, fasting lipid profile, body mass index (and plot), waist circumference, dietary and activ- ity assessment, and smoking every 2 years; this may be performed by the primary care provider. It is reasonable to obtain a follow- up fasting lipid profile.(Level of Evidence: C) "

Medical therapy (β-blockers, statin)

Class IIb

"1. Empirical statin therapy for non–lipid-lowering (pleiotropic) effects may be considered.(Level of Evidence: C) "

Class III

"1. Empirical treatment with β-blockers is not indicated.(Level of Evidence: C) "

Thromboprophylaxis

Class IIa

"1. It is reasonable to continue treatment with low-dose ASA.(Level of Evidence: C) "

"2. Use of an alternative antiplatelet agent (eg, a thienopyridine such as clopidogrel) instead of ASA is reasonable if the patient is intolerant or resistant to ASA.(Level of Evidence: C) "

Class IIb

"1. Use of an additional antiplatelet agent (eg, a thienopyridine such as clopidogrel) is not recommended except in the presence of inducible myocardial ischemia.(Level of Evidence: C) "

"2. Additional patient and coronary artery characteristics may be considered in decision making regarding intensification or discontinuation of thromboprophylaxis.(Level of Evidence: C) "

Class III

"1. Use of anticoagulation (warfarin/LMWH) is not indicated.(Level of Evidence: C) "

Physical activity

Class IIa

"1. It is reasonable to provide physical activity counseling at every visit without restrictions or precautions. Participation in competitive sports or high-intensity activities should be guided by results from testing for inducible myocardial ischemia or exercise-induced arrhythmias.(Level of Evidence: C) "

Reproductive counselling

Class IIa

"1. It is reasonable to provide age-appropriate counseling regarding contraception and pregnancy without modification.(Level of Evidence: B) "

Large and Giant Aneurysms (Z Score ≥10 or Absolute Dimension ≥8 mm)

Frequency of cardiology assessment (to include history and physical examination, echocardiography, electrocardiography)

Class IIa

"1. It is reasonable to assess patients at 1, 2, 3, 6, 9, and 12 months after the episode of acute KD in the first year and every 3 to 6 months thereafter.(Level of Evidence: C) "

Type and frequency of additional cardiology assess- ment (other cardiology testing)

Class IIa

"1. It is reasonable to assess for inducible myocardial ischemia (stress echocardiography, stress with MRI, stress NM perfusion imaging, PET) every 6 to 12 months or if the patient has symptoms suggestive of ischemia or signs suggestive of ventricular dysfunction.(Level of Evidence: B) "

Class IIb

"1. Further imaging with angiography (CT, MRI, invasive) may be considered for diagnostic and prognostic purposes during the first year and may be considered for periodic surveillance every 1 to 5 years thereafter.(Level of Evidence: C) "

Cardiovascular risk factor assessment and management

Class IIa

"1. It is reasonable to provide general counseling regarding healthy lifestyle and activity promotion at every visit; this may additionally be provided by the primary care provider.(Level of Evidence: C) "

Class IIa

"1. It is reasonable to assess blood pressure, body mass index (and plot), waist circumference, dietary and activity assessment, and smoking every 6 to 12 months; this may be performed by the primary care provider. It is reasonable to obtain a fasting lipid profile during follow- up.(Level of Evidence: C) "

Medical therapy (β-blockers, ACEI, statin)

Class IIb

"1. Empirical statin therapy for non–lipid-lowering (pleiotropic) effects may be considered.(Level of Evidence: C) "

"2. Empirical treatment with β-blockers may be considered .(Level of Evidence: C) "

Thromboprophylaxis

Class I

"1. Patients should be treated with low-dose ASA.(Level of Evidence: C) "

Class IIa

"1. Use of an alternative antiplatelet agent (eg, a thienopyridine such as clopidogrel) instead of ASA is reasonable if the patient is intolerant or resistant to ASA.(Level of Evidence: C) "

"2. Use of warfarin to achieve a target international normalized ratio of 2 to 3 is reasonable.(Level of Evidence: B) "

"3. Use of LMWH to achieve target anti-factor Xa levels of 0.5 to 1.0 U/mL is reasonable as an alternative to warfarin.(Level of Evidence: C) "

Class IIb

"1. Use of an additional antiplatelet agent (eg, a thienopyridine such as clopidogrel) may be considered together with ASA and warfarin/ LMWH (triple therapy) for thromboprophylaxis in the setting of very extensive or distal coronary artery aneurysms, or if there is a history of coronary artery thrombosis.(Level of Evidence: C) "

"2. Additional patient and coronary artery characteristics (Table 9) may be considered in decision making regarding adjustments to strategy for thromboprophylaxis.(Level of Evidence: C) "

Physical activity

Class I

"1. Activities involving a risk of bodily contact, trauma, or injury should be restricted or modified if the patient is on dual-antiplatelet or anticoagulation therapy.(Level of Evidence: B) "

Class IIa

"1. It is reasonable to provide physical activity counseling at every visit without restrictions or precautions. Participation in competitive sports or high intensity activities should be guided by results from testing for inducible myocardial ischemia or exercise-induced arrhythmias.(Level of Evidence: C) "

Reproductive counselling

Class IIa

"1. It is reasonable to discourage use of oral contraceptive drugs that increase thrombosis risk, to recommend that pregnancy be super- vised by a multidisciplinary team including a cardiologist, and to alter thromboprophylaxis management during pregnancy and delivery.(Level of Evidence: B) "

Regression to Medium Aneurysms

Frequency of cardiology assessment (to include history and physical examination, echocardiography, electrocardiography)

Class IIa

"1. It is reasonable to assess the patient every 6 to 12 months.(Level of Evidence: C) "

Type and frequency of additional cardiology assessment (other cardiology testing)

Class IIa

"1. It is reasonable to assess for inducible myocardial ischemia (stress echocardiography, stress with MRI, stress NM perfusion imaging, PET) every year or if the patient has symptoms suggestive of ischemia or signs suggestive of ventricular dysfunction.(Level of Evidence: B) "

Class IIb

"1. Further imaging with angiography (CT, MRI, invasive) may be considered for periodic surveillance every 2 to 5 years.(Level of Evidence: C) "

Cardiovascular risk factor assessment and management

Class IIa

"1. It is reasonable to provide general counseling regarding healthy lifestyle and activity promotion at every visit; this may additionally be provided by the primary care provider.(Level of Evidence: C) "

"2. It is reasonable to assess blood pressure, body mass index (and plot), waist circumference, dietary and activity assessment, and smoking every year; this may be performed by the primary care provider. It is reason- able to obtain a follow-up fasting lipid profile.(Level of Evidence: C) "

Medical therapy (β-blockers, ACEI, statin)

Class IIb

"1. Empirical statin therapy for non–lipid-lowering (pleiotropic) effects may be considered.(Level of Evidence: C) "

"2. Empirical treatment with β-blockers may be considered.(Level of Evidence: C) "

Thromboprophylaxis

Class I

"1. Patients should be treated with low-dose ASA.(Level of Evidence: C) "

Class IIa

"1. Use of an alternative antiplatelet agent (eg, a thienopyridine such as clopidogrel) instead of ASA is reasonable if the patient is intolerant or resistant to ASA.(Level of Evidence: C) "

"2. Discontinuation of anticoagulation (warfarin/ LMWH) and substitution with an additional antiplatelet agent (eg, a thienopyridine such as clopidogrel) is reasonable.(Level of Evidence: C) "

Class IIb

"1. Additional patient and coronary artery characteristics may be considered in decision making regarding adjustments to strategy for thromboprophylaxis.(Level of Evidence: C) "

Class III

"1. Use of anticoagulation (warfarin, LMWH) is not indicated.(Level of Evidence: C) "

Physical activity

Class I

"1. Activities involving a risk of bodily contact, trauma, or injury should be restricted or modified for patients on dual-antiplatelet or anticoagulation therapy.(Level of Evidence: B) "

Class IIa

"1. It is reasonable to provide physical activity counseling at every visit without restrictions or precautions. Participation in competitive sports or high-intensity activities should be guided by results from testing for inducible myocardial ischemia or exercise-induced arrhythmias.(Level of Evidence: C) "

Reproductive counselling

Class IIa

"1. It is reasonable to discourage use of oral contraceptive drugs that increase thrombosis risk, to recommend that pregnancy be super- vised by a multidisciplinary team including a cardiologist, and to alter thromboprophylaxis management during pregnancy and delivery.(Level of Evidence: B) "

Regression to Small Aneurysms

Frequency of cardiology assessment (to include history and physical examination, echocardiography, electrocardiography)

Class IIa

"1. It is reasonable to assess the patient every 6 to 12 months.(Level of Evidence: C) "

Type and frequency of additional cardiology assessment (other cardiology testing)

Class IIa

"1. It is reasonable to assess for inducible myocardial ischemia (stress echocardiography, stress with MRI, stress NM perfusion imaging, PET) every 1 to 2 years or if the patient has symptoms suggestive of ischemia or signs suggestive of ventricular dysfunction.(Level of Evidence: B) "

Class IIb

"1. Further imaging with angiography (CT, MRI, invasive) may be considered for periodic surveillance every 2 to 5 years.(Level of Evidence: C) "

Cardiovascular risk factor assessment and management

Class IIa

"1. It is reasonable to provide general counseling regarding healthy lifestyle and activity promotion at every visit; this may additionally be provided by the primary care provider.(Level of Evidence: C) "

"2. It is reasonable to assess blood pressure, body mass index (and plot), waist circumference, dietary and activity assessment, and smoking every year; this may be performed by the primary care provider. It is reason- able to obtain a follow-up fasting lipid profile.(Level of Evidence: C) "

Medical therapy (β-blockers, ACEI, statin)

Class IIb

"1. Empirical statin therapy for non–lipid-lowering (pleiotropic) effects may be considered.(Level of Evidence: C) "

"2. Empirical treatment with β-blockers may be considered.(Level of Evidence: C) "

"3. Discontinuation of additional medical therapy may be considered.(Level of Evidence: C) "

Thromboprophylaxis

Class I

"1. Patients should be treated with low-dose ASA.(Level of Evidence: C) "

Class IIa

"1. Use of an alternative antiplatelet agent (eg, a thienopyridine such as clopidogrel) instead of ASA is reasonable if the patient is intolerant or resistant to ASA.(Level of Evidence: C) "

Class IIb

"1. Additional patient and coronary artery char- acteristics may be considered in decision making regarding adjustments to strategy for thromboprophylaxis.(Level of Evidence: C) "

Class III

"1. Anticoagulation or dual-antiplatelet therapy is not indicated.(Level of Evidence: C) "

Physical activity

Class I

"1. For patients on anticoagulation or dual-antiplatelet therapy, activities involving a risk of bodily contact, trauma, or injury should be restricted or modified.(Level of Evidence: B) "

Class IIa

"1. It is reasonable to provide physical activity counseling at every visit without restrictions or precautions. Participation in competitive sports or high-intensity activities should be guided by results from testing for inducible myocardial ischemia or exercise-induced arrhythmias.(Level of Evidence: C) "

Reproductive counselling

Class IIa

"1. It is reasonable to provide age-appropriate counseling regarding contraception. It is reasonable to recommend that pregnancy be supervised by a multidisciplinary team including a cardiologist and to alter thromboprophylaxis management during pregnancy and delivery.(Level of Evidence: B) "

Regression to Normal Z Score or Dilation Only

Frequency of cardiology assessment (to include history and physical examination, echocardiography, electrocardiography)

Class IIa

"1. It is reasonable to assess the patient every 1 to 2 years. Not performing routine 2D echocardiography may be considered unless there is evidence for inducible myocardial ischemia or the patient has symptoms suggestive of ischemia or signs suggestive of ventricular dysfunction.(Level of Evidence: C) "

Type and frequency of additional cardiology assessment (other cardiology testing)

Class IIa

"1. It is reasonable to assess for inducible myocardial ischemia (stress echocardiography, stress with MRI, stress NM perfusion imaging, PET) every 2 to 5 years or if the patient has symptoms suggestive of ischemia or signs suggestive of ventricular dysfunction.(Level of Evidence: B) "

Cardiovascular risk factor assessment and management

Class IIa

"1. It is reasonable to provide general counseling regarding healthy lifestyle and activity promotion at every visit; this may additionally be provided by the primary care provider.(Level of Evidence: C) "

"2. It is reasonable to assess blood pressure, body mass index (and plot), waist circumference, dietary and activity assessment, and smoking every 2 years; this may be performed by the primary care provider. It is reasonable to obtain a follow-up fasting lipid profile as per the Expert Panel guidelines.(Level of Evidence: C) "

Medical therapy (β-blockers, ACEI, statin)

Class IIb

"1. Empirical statin therapy for non–lipid-lowering (pleiotropic) effects may be considered.(Level of Evidence: C) "

Class III

"1. Empirical treatment with β-blockers is not indicated.(Level of Evidence: C) "

Thromboprophylaxis

Class IIa

"1. It is reasonable to continue treatment with low-dose ASA.(Level of Evidence: C) "

"2. Use of an alternative antiplatelet agent (eg, a thienopyridine such as clopidogrel) instead of ASA is reasonable if the patient is intol- erant or resistant to ASA.(Level of Evidence: C) "

Class IIb

"1. Additional patient and coronary artery characteristics may be considered in decision making regarding intensification or discontinuation of thromboprophylaxis.(Level of Evidence: C) "

Class III

"1. Use of anticoagulation (warfarin/LMWH) or dual-antiplatelet therapy is not indicated.(Level of Evidence: C) "

Physical activity

Class I

"1. For patients on anticoagulation or dual-anti- platelet therapy, activities involving a risk of bodily contact, trauma, or injury should be restricted or modified.(Level of Evidence: B) "

Class IIa

"1. It is reasonable to provide physical activity counseling at every visit without restrictions or precautions. Participation in competitive sports or high-intensity activities should be guided by results from testing for inducible myocardial ischemia or exercise-induced arrhythmias.(Level of Evidence: C) "

Reproductive counselling

Class IIa

"1. It is reasonable to provide age-appropriate counseling regarding contraception. It is reasonable to recommend that pregnancy be supervised by a multidisciplinary team including a cardiologist and to alter thrombo- prophylaxis management during pregnancy and delivery.(Level of Evidence: B) "

Recommendations for Testing for Inducible Ischemia

Class IIa

"1. It is reasonable to use stress echocardiography or CMRI, NM MPI, or PET for assessment of inducible myocardial ischemia. Note: The general principle is to minimize risk to the patient, particularly cumulative radiation dose, and this should guide selection of testing modality based on patient and institutional characteristics(Level of Evidence: B) "

Class III

"1. Exercise treadmill electrocardiographic testing alone should not be used for assessment for inducible myocardial ischemia.(Level of Evidence: C) "

Recommendation for Assessment of Patients With Inducible Myocardial Ischemia

Class I

"1. Patients with evidence of inducible myocardial ischemia on testing should undergo invasive coronary angiography.(Level of Evidence: B) "

Recommendations for Indications for Mechanical Revascularization

Class I

"1. Adult patients with remote history of KD presenting with STEMI should be referred emergently for coronary angiography for determination of best means of flow restoration in the culprit artery.(Level of Evidence: C) "

"2. Revascularization should be performed in KD patients with stable angina and high-risk coronary anatomy including left main CAD, multi- vessel coronary disease with reduction in LV function, multivessel coronary disease with diabetes mellitus, or high-risk noninvasive ischemia testing.(Level of Evidence: C) "

"3. Revascularization should be performed for patients with non–ST-segment elevation and coronary anatomy amenable to revascularization on coronary angiography.(Level of Evidence: C) "

Class IIa

"1. Revascularization for patients with stable angina and symptoms refractory to maximal medical therapy is reasonable. (Level of Evidence: C) "

Class IIb

"1. Revascularization for KD patients with silent ischemia and ischemia involving >10% of LV mass may be considered. (Level of Evidence: C) "

Class III

"1. Revascularization should be avoided in KD patients in the acute/subacute phase of the illness with STEMI attributable to acute thrombotic occlusion of an aneurysm.(Level of Evidence: C) "

Recommendations for Modes of Revascularization

Class I

"1. CABG is preferred to PCI in KD patients with left main CAD, multivessel CAD with reduced LV function, multivessel CAD with lesions not amenable to PCI, and multivessel CAD in diabetic patients.(Level of Evidence: B) "

"2. CABG is preferred to PCI in older children and adults with KD and multivessel involvement .(Level of Evidence: C) "

"3. CABG should be performed with bilateral internal thoracic arterial grafts where possible.(Level of Evidence: B) "

"4. PCI is preferred in patients with single-vessel or focal multivessel disease amenable to PCI.(Level of Evidence: C) "

"5. RA and stents should be used in PCI of calcified lesions.(Level of Evidence: C) "

Class IIa

"1. The use of multivessel PCI is reasonable for KD patients with focal lesions amenable to PCI. (Level of Evidence: C) "

"2. The use of DESs during PCI is reasonable for KD patients who do not require long- term anticoagulation. (Level of Evidence: C) "

"3. The use of IVUS is reasonably indicated during PCI in KD patients to ensure adequate stent sizing and deployment. (Level of Evidence: C) "

Class IIb

"1. Multivessel PCI may be considered for patients who are acceptable CABG candidates but prefer to avoid CABG, provided the risks and benefits of both approaches are discussed with and understood by the patient. (Level of Evidence: C) "

"2. The use of DESs during PCI may be considered for KD patients who require anti- coagulation, provided the bleeding risk of the patient is acceptable. (Level of Evidence: C) "

Class III

"1. Stand-alone balloon angioplasty should not be used for PCI in KD patients with coronary obstructions.(Level of Evidence: C) "

Recommendation for Cardiac Transplantation

Class IIa

"1. The use of multivessel PCI is reasonable for KD patients with focal lesions amenable to PCI. (Level of Evidence: C) "