Version July 2025
INTRODUCTION —
Kawasaki disease (KD; previously called mucocutaneous lymph node syndrome) is one of the most common forms of systemic vasculitis in children. The acute illness is self-limited and is characterized by high fever; nonexudative conjunctivitis; inflammation of the oral mucosa; rash; cervical adenopathy; and findings in the extremities, including swollen hands and feet, red palms and soles, and, later, subungual peeling (table 1).
Children with KD are at risk for serious cardiovascular sequelae, particularly coronary artery abnormalities (CAAs), which can lead to myocardial ischemia, infarction, arrhythmia, and sudden death. The risk of developing CAAs is highest among children with KD who are not treated early in the disease with high-dose intravenous immune globulin (IVIG). Thus, initial management of patients with KD is focused on early diagnosis and timely treatment with IVIG. (See "Kawasaki disease: Initial treatment and prognosis", section on 'Intravenous immune globulin'.)
The management and prognosis of cardiac sequelae of KD, including CAAs, will be reviewed here. Other aspects of KD are discussed in greater detail separately:
●(See "Cardiovascular sequelae of Kawasaki disease: Clinical features and evaluation".)
●(See "Kawasaki disease: Pathogenesis, epidemiology, and etiology".)
●(See "Kawasaki disease: Clinical features and diagnosis".)
●(See "Kawasaki disease: Initial treatment and prognosis".)
MANAGEMENT —
Management of patients with KD and coronary artery abnormalities (CAAs) is aimed at preventing and treating coronary artery thrombosis. There are no available randomized trials of antithrombotic therapy in children with KD and CAAs. Management is based largely upon adult data for secondary prevention of atherosclerotic coronary artery disease (CAD) [1]. (See "Aspirin for the secondary prevention of atherosclerotic cardiovascular disease" and "Prevention of cardiovascular disease events in those with established disease (secondary prevention)".)
The management approach described in the following sections is generally consistent with the 2017 guidelines of the American Heart Association [2].
Antithrombotic therapy
Risk stratification — Risk stratification is based principally on the echocardiographic coronary artery luminal dimensions (table 2).
Additional features that may increase the long-term risk of myocardial ischemia include [2]:
●Long length and distal location of aneurysms
●Large total number of aneurysms
●Multiple branches affected
●Luminal irregularities
●Vessel wall abnormalities (calcification, luminal myofibroblastic proliferation)
●Functional abnormalities (impaired vasodilation, impaired flow reserve)
●Absence or poor quality of collateral vessels
●Previous revascularization performed
●Previous coronary artery thrombosis
●Previous myocardial infarction
●Ventricular dysfunction
Risk-based approach to antithrombotic therapy — During the acute phase of illness, patients with KD are generally treated with aspirin at moderate doses (30 to 50 mg/kg per day in four divided doses) for its antipyretic effect, provided there are no contraindications. This is discussed separately. (See "Kawasaki disease: Initial treatment and prognosis", section on 'Aspirin'.)
Once the patient has been afebrile for 24 to 48 hours, we suggest transitioning from moderate- to low-dose aspirin (3 to 5 mg/kg per day) to reduce the risk of coronary artery thrombosis. Low-dose aspirin is continued for a minimum of four to six weeks following the acute phase treatment, at which time it can be determined if CAAs have developed. If CAAs have not developed by four to six weeks, aspirin is discontinued. For patients with CAAs, subsequent antithrombotic therapy depends chiefly on the size and persistence of CAAs (algorithm 1), as discussed in the following sections.
For children who continue on aspirin therapy, long-term use of ibuprofen and other nonsteroidal cyclooxygenase inhibitors may be harmful and should be avoided [2].
All children with KD should have general counseling regarding healthy lifestyle and activity at primary care visits. It is also reasonable for the primary care provider to assess usual risk factors for atherosclerosis at least one year from the episode of acute KD. (See 'Counseling and screening for risk factors' below.)
No coronary involvement — Patients with no coronary involvement (Z-score always <2 and no more than a 0.9 decrease in Z-score during follow-up) can discontinue aspirin therapy after four to six weeks. No further medical therapy is necessary, and long-term follow-up with a pediatric cardiologist is generally not indicated. The primary care provider should provide general counseling regarding healthy lifestyle and physical activity promotion. (See 'Long-term follow-up' below.)
Dilation only — Patients with dilation only (Z-score ≥2 to <2.5 or if initially <2, a ≥1 decrease in Z-score during follow-up) can discontinue aspirin therapy after four to six weeks. No further medical therapy is necessary. If luminal dimensions have returned to normal, long-term follow-up with a pediatric cardiologist is generally not indicated. If dilation persists, patients are followed to 12 months and then every two to five years. (See 'Long-term follow-up' below.)
Small aneurysms — For patients with small aneurysms (Z-score ≥2.5 to <5), we suggest continuing low-dose aspirin (3 to 5 mg/kg per day). Other antiplatelet agents (eg, clopidogrel) are reasonable alternatives for patients who are intolerant to aspirin. If the aneurysm regresses to a normal size or to dilation only, aspirin can be discontinued. Long-term follow-up is as described below. (See 'Long-term follow-up' below.)
Medium aneurysms — For patients with medium-size aneurysms (Z-score ≥5 to <10, with absolute dimension <8 mm), we suggest continuing low-dose aspirin (3 to 5 mg/kg per day). We typically continue aspirin even if the aneurysm remodels to normal or dilation only, unless the patient experiences or is at risk for adverse effects from aspirin therapy.
In select high-risk patients with persistent medium-sized aneurysms, dual antiplatelet therapy (eg, with addition of clopidogrel [0.2 to 1 mg/kg per day]) may be considered. Data are limited to guide this practice. We base the decision to use dual antiplatelet therapy on the size of the aneurysm (eg, Z-scores 7.5 to <10). Other experts may consider additional risk factors. (See 'Risk stratification' above.)
Additional medical therapy is generally not necessary, although some experts may also use statins in this setting. Long-term follow-up is as described below. (See 'Long-term follow-up' below.)
Large and giant aneurysms — For patients with large and giant aneurysms (Z-score ≥10 or absolute dimension ≥8 mm), we suggest treating with both low-dose aspirin and an anticoagulant. Either a direct oral anticoagulant (DOAC; eg, apixaban, dabigatran, edoxaban, rivaroxaban) or vitamin K antagonist (eg, warfarin, with a target international normalized ratio of 2.0 to 3.0) are typically used in this setting [3-5]. Low molecular weight heparin (LMWH [eg, enoxaparin]) can also be used for this purpose [6,7]; however, it requires injections and therefore is a less attractive option for long-term therapy. Dosing guidance for these agents is provided separately. (See "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome", section on 'Anticoagulant agents'.)
If the CAA regresses to a small or medium size, the anticoagulant agent can be discontinued. If the CAA remodels to medium size, aspirin alone or dual antiplatelet therapy (eg, aspirin plus clopidogrel) is used instead of aspirin plus an anticoagulant.
Observational data suggest that combined therapy with an anticoagulant plus aspirin may be more effective than aspirin alone [7-9]. In a meta-analysis of six retrospective studies in patients with giant CAAs, combined therapy with systemic anticoagulation (chiefly warfarin) plus aspirin was associated with lower rates of myocardial infarction (odds ratio 0.27, 95% CI 0.11-0.63) and death (odds ratio 0.18, 95% CI 0.02-0.29) compared with aspirin alone [8].
There are limited data on the use of DOACs in this setting and none of the available DOAC agents are specifically approved for this indication. The clinical trials that established the efficacy and safety of these agents in pediatric patients included few patients with KD. However, as experience with using DOACs in pediatric patients continues to grow, these agents are increasingly being used as first-line agents. Compared with LMWH, DOACs have the advantage of not requiring subcutaneous injection, and compared with warfarin, they have the advantages of a more predictable dose response and less need for laboratory monitoring. The available evidence suggests that DOACs have similar efficacy compared with LMWH and warfarin without increased bleeding risk. These data are described separately. (See "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome", section on 'Direct oral anticoagulants'.)
In a clinical trial investigating the efficacy and safety of the DOAC edoxaban compared with either warfarin or LMWH in 167 children with various types of cardiac disease (including 37 patients with KD), there were no thromboembolic events and no major bleeding episodes in either treatment group during the three-month trial period [10]. During the open-label extension following the trial, two patients with KD developed coronary thromboses with myocardial infarction while receiving edoxaban. A similar trial investigated the efficacy and safety of apixaban in pediatric patients with cardiac disease; the results are not yet available [11].
Special considerations regarding antithrombotic therapy in select patients with large and giant CAAs include the following:
●High-risk patients – Patients with giant CAAs who have had a recent coronary artery thrombosis are at high risk of myocardial infarction and may warrant more intensive antithrombotic therapy. In such patients, treatment with "triple therapy" (ie, low-dose aspirin plus a second antiplatelet agent [eg, clopidogrel] plus systemic anticoagulation) may be considered. The risks of coronary thrombosis and occlusion must be weighed against the risks of bleeding, and the trade-offs should be periodically reassessed.
●Adolescent females who are sexually active or pregnant – Adolescent females with CAAs should receive reproductive counseling during adolescence. (See "Contraception: Overview of issues specific to adolescents".)
If pregnancy occurs, anticoagulation is provided, similar to guidelines for obstetric patients with prosthetic heart valves. (See "Management of antithrombotic therapy for a prosthetic heart valve during pregnancy".)
Outcomes of pregnancy in individuals with CAAs have been reported in a small case series [12].
Patients treated with combined aspirin plus anticoagulant therapy require close monitoring since they are at high risk of both thrombosis and bleeding (sometimes in the same patient) [3]. Frequent evaluation with echocardiography and electrocardiography (ECG) should be performed in patients with giant aneurysms. Symptoms of angina or palpitations with exercise, worsening of ventricular function, or a change in ECG should raise suspicion for coronary thrombosis. (See 'Long-term follow-up' below.)
Statins and other medical therapy
●Statin therapy – In our practice, we routinely screen for dyslipidemia in all children with KD-related CAAs and initiate statin therapy if warranted based upon the low-density lipoprotein cholesterol (LDL-C) level. Of note, KD-associated CAAs are considered a "high-risk" condition for the purposes of pediatric cardiovascular disease prevention, though it is uncertain whether these lesions truly predispose to atherosclerotic changes. Nevertheless, the threshold for initiating statin therapy and the target once on statin therapy are lower in patients with KD-related CAAs compared with the general pediatric population, as summarized in the figure (algorithm 2) and discussed in detail separately. (See "Dyslipidemia in children and adolescents: Management", section on 'Risk-based management approach'.)
In addition, some experts treat all children with KD-related CAAs with statin therapy regardless of LDL-C levels. This practice is based on the premise that statin therapy may have beneficial non-lipid-lowering (pleiotropic) effects, although data to support this approach are limited. (See "Mechanisms of benefit of lipid-lowering drugs in patients with coronary heart disease".)
●Additional medical therapy following myocardial infarction (MI) – For patients who experience an acute MI, ongoing medical therapy after the MI generally includes the following components, in accordance with standard therapy following MI in adult patients. Each of these is discussed in greater detail separately:
•Ongoing antithrombotic therapy (see 'Antithrombotic therapy' above)
•A beta blocker (see "Acute myocardial infarction: Role of beta blocker therapy")
•A renin-angiotensin-aldosterone system (RAAS) inhibitor (ie, an angiotensin-converting enzyme [ACE] inhibitor or angiotensin II receptor blocker [ARB]) (see "Angiotensin converting enzyme inhibitors and receptor blockers in acute myocardial infarction: Recommendations for use")
•A mineralocorticoid receptor antagonist (MRA), if the patient has reduced ventricular function (see "Management and prognosis of asymptomatic left ventricular systolic dysfunction", section on 'History of myocardial infarction')
•A statin (see "Low-density lipoprotein-cholesterol (LDL-C) lowering after an acute coronary syndrome")
Management of KD-related ischemic heart disease — Ischemic heart disease, including acute MI, is the principal cause of KD-related mortality. This complication occurs most commonly in patients with large or giant CAAs; ischemic events are uncommon in children with medium CAAs and exceedingly rare in children with small CAAs [13-15]. As discussed below, all children with persistent KD-related CAAs should have ongoing monitoring for ischemia with echocardiography and ECG, with the most intense monitoring during the first few months after the initial illness [1]. (See 'Long-term follow-up' below.)
Because MI is rare in patients with KD, principles of treatment are derived from those used in the adult population with atherosclerotic coronary artery disease (CAD) [1]. (See "Overview of the acute management of ST-elevation myocardial infarction" and "Overview of the acute management of non-ST-elevation acute coronary syndromes".)
It may not be possible to apply all aspects of adult practice when managing children with KD-related MI due to limitations related to the size of the child and/or the available resources at the treating hospital. We advise a practical approach to management [16].
Anticipatory measures — A key step in managing children with large or giant CAAs is anticipating the potential for coronary events. General anticipatory measures include:
●Parents/caregivers should be trained in cardiopulmonary resuscitation and taught to recognize signs and symptoms of MI that are specific to the age of the child.
●A written emergency action plan should be provided, which can be given to medical providers, caregivers, and schools.
●Because MI is such a rare event in the pediatric population, pediatric facilities caring for children with KD should work with colleagues in adult cardiology to develop procedures that can be executed quickly and to advise on acute care of ischemic complications.
Management of acute MI — The management of children with acute MI varies depending upon the child's age, medical comorbidities, resources and expertise at the treating hospital, and the type of MI (ST-elevation myocardial infarction [STEMI] versus non-ST-elevation myocardial infarction [non-STEMI]). STEMI involves complete coronary occlusion with myocardial injury and necrosis. In non-STEMI, myocardial blood flow is inadequate for myocardial oxygen demand, resulting in injury but less myocardial necrosis than in STEMI.
Management of STEMI focuses on restoring coronary blood flow with percutaneous coronary intervention (PCI), if available, or thrombolysis.
●PCI (preferred intervention, if possible) – Immediate PCI is the procedure of choice for patients presenting with STEMI attributable to a thrombotic occlusion of a coronary artery, who are beyond the acute/subacute phase of the illness, are large enough for use of adult-sized catheters, and can be transferred promptly (within 90 minutes) to a cardiac catheterization laboratory with staff experienced in performing PCI [17-19]. (See "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy", section on 'PCI is immediately available'.)
Prior to undergoing PCI, an oral P2Y12 inhibitor (eg, clopidogrel, ticagrelor, prasugrel) is administered. Unfractionated heparin is administered once vascular access has been established. For patients with an especially large thrombus burden (eg, giant coronary aneurysm), the IIb/IIIa receptor antagonist eptifibatide may be administered first as an intravenous (IV) bolus and then by IV infusion for 12 hours. (See "Acute ST-elevation myocardial infarction: Initial antiplatelet therapy", section on 'Primary PCI' and "Acute ST-elevation myocardial infarction: Management of anticoagulation", section on 'Primary percutaneous coronary intervention'.)
Thrombus aspiration carries risk of stroke and is not recommended. (See "Suboptimal reperfusion after primary percutaneous coronary intervention in acute ST-elevation myocardial infarction", section on 'Thrombectomy'.)
●Thrombolysis (if PCI is not possible) – Thrombolytic therapy is the alternative to PCI for children with STEMI presenting within 90 minutes if PCI is unavailable or if the child is too small for use of adult-sized catheters. (See "Acute ST-elevation myocardial infarction: Management of fibrinolysis".)
In most case reports describing fibrinolysis in patients with KD-related STEMI, alteplase was the fibrinolytic agent used [20,21]; experience using other agents (eg, reteplase, tenecteplase) is limited to studies in adult patients with STEMI.
An example of a fibrinolytic regimen includes:
•Alteplase, using either a standard-dose regimen (0.3 to 0.5 mg/kg per hour IV for six hours) or a low-dose regimen (0.03 to 0.10 mg/kg per hour IV for 6 to 12 hours; maximum dose 2 mg per hour, plus
•IV heparin infusion (administered in a separate line from the alteplase; initial dose 10 units/kg per hour, adjusted to maintain therapeutic antifactor Xa level and/or activated partial thromboplastin time) plus
•Low-dose aspirin (3 to 5 mg/kg per day)
To reduce the risk of bleeding complications, the patient's fibrinogen level should be measured before starting the infusion and every four to six hours during the infusion. Fresh frozen plasma should be administered to maintain fibrinogen >100 mg/dL. In addition, we measure antithrombin levels prior to starting the infusion and administer antithrombin concentrate if the level is low.
At the end of the 6 to 12-hour infusion, echocardiography is performed to reassess the thrombus, and alteplase may be continued for longer if the thrombus has not resolved.
In patients with a particularly large thrombus burden and high risk of occlusion, treatment with a combination of alteplase (0.25 mg/kg per hour IV for 6 hours) together with the platelet glycoprotein IIb/IIIA inhibitor eptifibitide (given as an initial IV bolus of 180 mcg/kg, followed by an IV infusion of 2 mcg/kg per minute for 12 hours) may be considered.
Additional components of ongoing medical therapy after MI are summarized above. (See 'Statins and other medical therapy' above.)
Revascularization in patients with stable CAD — In patients with clinical signs of coronary ischemia, including evidence of reversible ischemia on stress testing, we suggest coronary artery revascularization, either by PCI or coronary artery bypass grafting (CABG) procedure. The goals of coronary revascularization are to relieve symptoms of angina and reduce the risk of myocardial infarction or sudden death [22]. The decision to perform a coronary revascularization procedure in a patient with KD is based on expert consensus, indirect evidence from adults with atherosclerotic CAD, and observational data in patients with KD [23-26]. There have been tremendous advances in the field of adult CAD, which have clarified the indications for revascularization and merits of PCI versus CABG; these advances provide guiding principles for revascularization. The adult trial data are described separately. (See "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention".)
The 2017 American Heart Association guidelines include recommendations for modes of revascularization in KD based upon first principles from managing adults with CAD, together with limited experience in patients with KD [2]:
●CABG is preferred to PCI in KD patients with left main CAD, multivessel CAD with reduced left ventricular function, and multivessel CAD with lesions not amenable to PCI
●CABG is preferred to PCI in older children and adults with KD and multivessel involvement
●CABG should be performed with bilateral internal thoracic arterial grafts where possible
●PCI is preferred in patients with single-vessel or focal multivessel disease amenable to PCI
●Rotational ablation and stents should be used in PCI of calcified lesions
●Multivessel PCI is reasonable for KD patients with focal lesions amenable to PCI
●Use of drug-eluting stents during PCI is reasonable for KD patients who do not require long-term anticoagulation
●Use of drug-eluting stents during PCI may be considered for KD patients who require anticoagulation, provided that the bleeding risk of the patient is acceptable
●Use of intravascular ultrasound is reasonably indicated during PCI in KD patients to ensure adequate stent sizing and deployment
●Multivessel PCI may be considered for patients who are acceptable CABG candidates but prefer to avoid CABG, provided that the risks and benefits of both approaches are discussed with and understood by the patient
●Stand-alone balloon angioplasty should not be used for PCI in KD patients with coronary obstructions
The Research Committee of the Japanese Ministry of Health, Labour and Welfare recommends PCI for patients with the following findings [27]:
●PCI is recommended for patients with ischemic symptoms, reversible ischemia on stress testing, and/or ≥75 percent stenosis of the left anterior descending coronary artery.
●CABG is recommended over PCI for patients with severe left ventricular dysfunction or coronary lesions with multiple, ostial, or long-segment coronary artery stenosis.
When the decision is made to perform PCI in a child or adolescent with KD-related CAAs, the procedure should be performed by an adult interventional cardiologist, relying on support from pediatric specialists in smaller children. Interventional catheterization procedures used in patients with KD are similar to those used in adults. However, because affected vessels become calcified, rotational ablation and stent placement are generally preferred to percutaneous transluminal coronary angioplasty after a few years have passed since disease onset.
Surgical revascularization is most often performed in children who have symptoms of angina; significant ischemic burden based on myocardial perfusion imaging, stress testing, or invasive coronary function testing (eg, fractional flow reserve [FFR]); or clinically relevant obstruction that is believed to put them at high risk for myocardial infarction. CABG is only performed when the heart tissue to be supplied is viable and the artery beyond the planned graft site is not stenotic. In the contemporary era, almost all grafts are derived from systemic arteries (ie, internal mammary or radial artery) rather than saphenous veins because these are able to grow in size as the child matures [23-25]. Grafts have better long-term patency when performed in the older child, but subsequent use of PCI can extend graft longevity and children as young as one year of age have undergone surgical revascularization. In a single-center experience, 25-year survival after CABG procedure was 95 percent but only 60 percent of patients had escaped reoperation or PCI by this time [25].
There are no randomized trials assessing the relative merits of PCI versus CABG procedure in patients with KD. A retrospective Japanese survey suggested that patients who underwent PCI as a first revascularization procedure, compared with those whose first procedure was CABG, had similar rates of mortality and acute MI [28]. However, the PCI group was more likely to undergo repeat revascularization procedures. The reintervention rate was especially high in patients whose CABG procedures were performed in the absence of ischemic findings, presumably because competitive flow caused graft failure.
Role of cardiac transplantation — Cardiac transplantation is reserved for patients with end-stage ischemic cardiomyopathy who are not candidates for coronary revascularization procedures [29]. (See "Heart transplantation in adults: Indications and contraindications".)
LONG-TERM FOLLOW-UP
Frequency of follow-up
●Patients with coronary artery abnormalities (CAAs) – Follow-up evaluation for patients with KD-related CAAs generally includes an interval history, physical examination, electrocardiogram (ECG), and echocardiography. The frequency and type of follow-up assessments and counseling are based upon the patient's coronary artery status of the patient, as summarized in the table (table 3) [2].
Assessment for inducible myocardial ischemia may be appropriate, depending on the size of the CAA and presence of coronary stenosis. Noninvasive tests to assess for inducible myocardial ischemia include stress echocardiography, stress ECG, stress magnetic resonance imaging (MRI), nuclear medicine perfusion imaging, or stress-positron emission tomography (PET) scan. Additionally, follow-up angiography (with computed tomography, MRI, or invasive catheterization) may be considered for some patients, particularly if there is evidence of inducible ischemia. When cardiac catheterization is performed, coronary angiography should be accompanied by tests of coronary function (eg, fractional flow reserve) to assess the significance of stenotic lesions. Additional details regarding these tests are provided in a separate topic review. (See "Cardiovascular sequelae of Kawasaki disease: Clinical features and evaluation", section on 'Stress testing for inducible ischemia' and "Cardiovascular sequelae of Kawasaki disease: Clinical features and evaluation", section on 'Coronary angiography' and "Clinical use of coronary artery pressure flow measurements", section on 'Fractional flow reserve'.)
●Patients without CAAs – Patients without CAAs during the first month after KD onset and who lack lingering or recurrent signs or symptoms of cardiac disease can be discharged from cardiology follow-up [30,31]. This is based on the observation that the risk of future CAAs is exceedingly low in patients without evidence of CAA by approximately one month after disease onset [30,31]. The available data also suggest that such individuals are at low risk of premature atherosclerotic CAD in adulthood [32]. Nevertheless, we agree with the American Heart Association guidelines, which emphasize that such patients should receive routine preventive cardiology counseling at visits with their primary care providers. The optimal follow-up for these patients continue to be debated [33,34].
Counseling and screening for risk factors — All patients with KD and their parents/caregivers should be counseled on risk factors for atherosclerotic coronary artery disease (CAD), regardless of severity of coronary involvement in the acute phase of their illness. Screening and counseling regarding the risk of atherosclerotic CAD should involve all of the following:
●Assessment of cardiovascular risk factors – Thresholds for treatment of risk factors (eg, hypertension, hypercholesterolemia), which are lower than for the general pediatric population, have been proposed in accordance with severity of coronary involvement (algorithm 2). As patients with persistent aneurysms approach adulthood, we believe that they should be treated according to adult guidelines for secondary prevention of cardiovascular disease. (See "Overview of pediatric risk factors for premature atherosclerotic cardiovascular disease (ASCVD)" and "Prevention of cardiovascular disease events in those with established disease (secondary prevention)".)
●Lipid screening – Patients >2 years old without persistent CAAs should undergo lipid screening one year after the acute phase of KD. If screening results are normal, it is reasonable to repeat lipid screening at ages 10 and 20 years. For patients with persistent aneurysms, we suggest annual lipid screening. (See 'Statins and other medical therapy' above.)
The approach to lipid screening in children, including the evaluation and management of abnormal lipid values, is discussed separately. (See "Dyslipidemia in children and adolescents: Definition, screening, and diagnosis", section on 'Approach to screening'.)
●Promoting a healthy lifestyle – We stress the importance of a heart-healthy diet, regular exercise, and avoidance of nicotine exposure, including secondhand exposure. (See "Pediatric prevention of adult cardiovascular disease: Promoting a healthy lifestyle and identifying at-risk children".)
Participation in competitive sports — All patients with KD should avoid a sedentary lifestyle, and counseling should proactively address the importance of regular aerobic exercise. In those with coronary aneurysms and/or stenosis, recommendations regarding participation in competitive or high-intensity sports are guided by testing for inducible myocardial ischemia and exercise-induced arrhythmia, as well as risk of bleeding on anticoagulant therapy [35].
In general, we follow the 2015 American Heart Association and American College of Cardiology guidelines for sports participation in patients with CAD, including KD [35]:
●Patients who never had CAAs and those with dilation only that subsequently regressed to normal who do not have evidence of exercise-induced ischemia or arrhythmia can and are encouraged to resume participation in all competitive sports after symptoms have resolved, generally at approximately six to eight weeks after illness onset.
●In patients with aneurysms, exercise recommendations are guided by findings on stress testing with myocardial perfusion imaging and evaluation of left ventricular function:
•Patients who have had a recent myocardial infarction or revascularization procedure are restricted from competitive sports until their recovery is complete, at which time, exercise and myocardial function are reevaluated. If left ventricular ejection fraction is normal and exercise testing reveals no reversible ischemia or arrhythmia, participation in class IA and IB sports (figure 1) is permitted. (See "Athletes: Overview of sudden cardiac death risk and sport participation", section on 'Coronary artery disease'.)
•Collision sports should be avoided in patients receiving antiplatelet or antithrombotic therapy.
•Patients with small to moderate CAAs without exercise-induced ischemia or arrhythmias may participate in low- to moderate-intensity competitive sports (classes IA, IB, IIA, and IIB) (figure 1).
•Patients with one or more large CAAs should undergo annual stress testing, and activity should be guided by results.
Immunizations — Patients with KD should receive all routine childhood vaccinations. Annual influenza vaccination is especially imperative in patients with KD on chronic aspirin therapy because of the association of aspirin therapy and influenza with Reye syndrome. Other antiplatelet agents (eg, clopidogrel) should be temporarily substituted for aspirin during episodes of influenza or chicken pox. (See "Standard immunizations for children and adolescents: Overview", section on 'Routine schedule' and "Seasonal influenza in children: Prevention with vaccines".)
PROGNOSIS —
For patients with KD and coronary artery abnormalities (CAAs), the prognosis depends upon the size of the aneurysm. Small and medium aneurysms generally have a favorable prognosis, with a low risk of myocardial ischemic events and/or mortality [36-38]. In contrast, large and giant aneurysms (ie, those with a Z-score ≥10 or an internal diameter >8 mm) have a high risk of morbidity and mortality [36,38-40]. Approximately 20 to 50 percent of such aneurysms become obstructed, increasing the risk of myocardial infarction, arrhythmias, or sudden death [36,38-41]. Patients with CAAs with maximum Z-score ≥20 are at particularly high risk or morbidity and mortality [40]. (See "Cardiovascular sequelae of Kawasaki disease: Clinical features and evaluation", section on 'Long-term complications'.)
Among patients who develop aneurysms, mortality is highest between 15 and 45 days after onset of KD [42]. Because coronary artery thrombosis is the leading cause of death in KD, antithrombotic medications form the cornerstone of therapy for patients with aneurysms [2]. (See 'Risk-based approach to antithrombotic therapy' above.)
In a study that reported outcomes among 1651 patients with CAAs, the CAA had regressed to normal diameter by 10 years after disease onset in 99 percent of small CAAs, 92 percent of medium CAAs, and 57 percent of large CAAs [40]. No cardiac complications were reported for patients with small CAAs. Only one patient with medium CAAs experienced cardiac complications (chronic ischemia resulting in heart failure and death; this patient had CAAs in all four coronary artery branches with maximal Z-score of 8.5). Among patients with large CAAs, the 10-year risk of coronary artery thrombosis was 18 percent, the risk of acute myocardial infarction (AMI) was 5 percent, and the risk of heart transplantation or death from cardiac causes was 2 percent. The risk of complications was highest among patients with maximum Z-score ≥20, complex coronary architecture, and/or aneurysms involving multiple coronaries.
Similar findings were noted in a retrospective study of 1073 patients with KD followed at a single institution from 1980 to 2012 [41]. In long-term follow-up (median 6.7 years), myocardial ischemia, AMI, or death occurred in 13 patients (48 percent) with giant aneurysms, one patient (2 percent) with a medium aneurysm, and no patients with small aneurysms. Of the patients who developed AMI, 67 percent occurred within the first year of KD onset.
Among patients with giant aneurysms, 30-year survival rates are 85 to 90 percent [22,43,44]. Survival is better among patients with unilateral giant aneurysms compared with bilateral (96 versus 87 percent, respectively) [44]. Most fatalities occur in the first year after disease onset. Survivors commonly experience cardiovascular events (eg, AMI, syncope, arrhythmias) and/or require coronary artery interventions (eg, percutaneous coronary catheter intervention, coronary artery bypass grafting [CABG]). In one study from Japan, 30-year cardiac event-free survival was 36 percent (21 percent in patients with bilateral giant aneurysms, 59 percent in those with unilateral) [44]. CABG was performed in 69 percent of patients with bilateral giant aneurysms and 20 percent of those with unilateral aneurysms. In another Japanese series of 60 patients who experienced myocardial infarction due to KD, the survival rate was 63 percent at 30 years. Ventricular tachycardia was increasingly common with time, with >70 percent of patients affected by 25 years [45]. Survival was highly related to ejection fraction, with worse prognosis for those with ejection fraction ≤45 percent.
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Kawasaki disease" and "Society guideline links: Lipid disorders and atherosclerosis in children".)
INFORMATION FOR PATIENTS —
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Kawasaki disease (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Risk stratification – Management of patients with Kawasaki disease (KD) and coronary artery abnormalities (CAAs) is aimed at preventing and treating coronary artery thrombosis. Risk stratification is based upon worst and current echocardiographic coronary artery luminal dimensions (table 2), as well as advanced imaging and medical history. (See 'Risk stratification' above.)
●Risk-based approach to antithrombotic therapy – In the acute phase of illness, patients with KD are generally treated with moderate-dose aspirin as an antipyretic if there are no contraindications, as discussed separately. (See "Kawasaki disease: Initial treatment and prognosis".)
After the patient has been afebrile for 24 to 48 hours, we suggest transitioning to low-dose aspirin (Grade 2C). Aspirin is given at a dose of 3 to 5 mg/kg per day for a minimum of four to six weeks, at which time, it can be determined if CAAs have developed. Other antiplatelet agents (eg, clopidogrel) are reasonable alternatives for patients who are intolerant to aspirin. (See 'Risk-based approach to antithrombotic therapy' above.)
Additional treatment depends chiefly on the size and persistence of CAAs (algorithm 1):
•No coronary involvement – If CAAs have not developed after four to six weeks, aspirin is discontinued. (See 'No coronary involvement' above.)
•Dilation only – Patients with dilation only (Z-score ≥2 to <2.5 or if initially <2, a ≥1 decrease in Z-score during follow-up) can discontinue aspirin therapy after four to six weeks. (See 'Dilation only' above.)
•Small aneurysms – For patients with small aneurysms (Z-score ≥2.5 to <5), we suggest long-term low-dose aspirin (Grade 2C). If the aneurysm regresses to a normal size or to dilation only, aspirin can be discontinued. (See 'Small aneurysms' above.)
•Medium aneurysms – For patients with medium aneurysms (Z-score ≥5 to <10, with absolute dimension <8 mm), we suggest long-term low-dose aspirin (Grade 2C). We typically continue aspirin even if the aneurysm remodels to normal or dilation only, unless the patient experiences or is at risk for adverse effects from aspirin therapy. In select high-risk patients with persistent medium-sized aneurysms, dual antiplatelet therapy (eg, with addition of clopidogrel 0.2 to 1 mg/kg per day) may be considered. (See 'Medium aneurysms' above.)
•Large and giant aneurysms – For patients with large and giant aneurysms (Z-score ≥10 or absolute dimension ≥8 mm), we suggest long-term systemic anticoagulation with either a direct oral anticoagulant (eg, apixaban, rivaroxaban) or vitamin K antagonist (eg, warfarin) in addition to low-dose aspirin (Grade 2C). If the aneurysm regresses to a small or medium size, anticoagulant therapy can be discontinued, but low-dose aspirin is continued. (See 'Large and giant aneurysms' above.)
●Avoid other nonsteroidal anti-inflammatory drugs (NSAIDs) while on aspirin therapy – For patients with CAAs who continue on aspirin therapy, long-term use of ibuprofen and other NSAIDs may be harmful and should generally be avoided. (See "Nonselective NSAIDs: Overview of adverse effects".)
●Management of acute myocardial infarction (MI) – Patients who suffer acute MI require urgent therapy for reperfusion and revascularization. The choice of therapeutic intervention depends upon multiple factors, including the patient's age and size, type of MI (ST-elevation myocardial infarction [STEMI] versus non-ST-elevation myocardial infarction [non-STEMI]), timing of presentation, and the available staffing and experience in the cardiac catheterization laboratory (see 'Management of acute MI' above):
•For patients with STEMI who are large enough in size, have availability of appropriate catheterization laboratory staff, and in whom cardiac catheterization can be performed in a timely fashion, we suggest immediate percutaneous coronary intervention (PCI) rather than fibrinolysis (Grade 2C). (See 'Management of acute MI' above and "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy", section on 'PCI is immediately available'.)
•For patients with STEMI who are too small or do not have access to prompt cardiac catheterization, we suggest fibrinolysis with alteplase (Grade 2C). An example of a fibrinolytic regimen is provided in the text above. (See 'Management of acute MI' above and "Acute ST-elevation myocardial infarction: Management of fibrinolysis".)
●Long-term follow-up – The long-term follow-up care of patients with KD is based on the coronary artery status and includes assessment of other cardiovascular risk factors, screening for dyslipidemia, promoting a heart-healthy diet, and exercise recommendations (table 3). In patients with CAAs, assessment for inducible myocardial ischemia (with stress echocardiography, stress electrocardiography (ECG), stress magnetic resonance imaging [MRI], nuclear medicine perfusion imaging, or stress-positron emission tomography [PET]) may be appropriate depending on the size of the CAA and presence of coronary stenosis. (See 'Long-term follow-up' above and "Cardiovascular sequelae of Kawasaki disease: Clinical features and evaluation", section on 'Stress testing for inducible ischemia'.)
Patients with evidence of reversible ischemia on noninvasive stress testing should undergo further evaluation with cardiac catheterization. Decisions regarding coronary artery revascularization in such patients are individualized and made in collaboration with a multidisciplinary care team (including pediatric cardiologists, adult cardiologist, and cardiac surgeons) and the patient and their parents/caregivers. (See 'Revascularization in patients with stable CAD' above.)
●Prognosis – For patients with KD and CAAs, the risks of serious morbidity and mortality are directly related to maximum aneurysm size. Patients who had small and medium aneurysms in the acute phase generally have a favorable prognosis, with a low risk of myocardial ischemic events and/or mortality. In contrast, patients with large and giant aneurysms (ie, Z-scores ≥10 or an internal diameter >8 mm) have a higher risk of complications including myocardial infarction, arrhythmias, or sudden death. These risks are highest in patients with CAAs with maximum Z-score ≥20. (See 'Prognosis' above.)
