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Cardiovascular sequelae of Kawasaki disease: Management and prognosis

Cardiovascular sequelae of Kawasaki disease: Management and prognosis
Authors:
Jane W Newburger, MD, MPH
Sarah D de Ferranti, MD, MPH
David R Fulton, MD
Section Editor:
John K Triedman, MD
Deputy Editor:
Carrie Armsby, MD, MPH
Literature review current through: Nov 2022. | This topic last updated: Feb 10, 2022.

INTRODUCTION — Kawasaki disease (KD; also called mucocutaneous lymph node syndrome) is a vasculitis of unknown etiology that generally occurs in infancy and childhood. 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. (See "Kawasaki disease: Clinical features and diagnosis" and "Kawasaki disease: Epidemiology and etiology".)

Children with KD are at risk for serious cardiovascular sequelae, particularly coronary artery abnormalities (CAAs), which can lead to myocardial ischemia, infarction, 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 treatment with IVIG. (See "Kawasaki disease: Initial treatment and prognosis".)

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: 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 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) or at very high risk".)

The management approach described in the following sections is generally consistent with the 2017 guidelines of the American Heart Association [2].

Risk stratification of coronary artery abnormalities — Risk stratification is based principally on the echocardiographic coronary artery luminal dimensions (table 1).

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

Antithrombotic therapy — In 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, if there are no contraindications. However, it does not reduce the incidence of coronary aneurysms. (See "Kawasaki disease: Initial treatment and prognosis", section on 'Aspirin'.)

To reduce the risk of coronary thrombosis, low-dose aspirin (3 to 5 mg/kg per day) is continued for a minimum of four to six weeks following the acute phase treatment, at which time, it can be determined if coronary abnormalities have developed. The transition from moderate- to low-dose aspirin is typically made once the patient has been afebrile for 24 to 48 hours. By four to six weeks, if CAAs have not developed, aspirin is discontinued. For patients with CAAs who continue on aspirin therapy, long-term use of ibuprofen and other nonsteroidal cyclooxygenase inhibitors may be harmful and should be avoided [2,3].

All children 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.)

Additional treatment depends chiefly on the size and persistence of CAAs (algorithm 1), as discussed in the following sections.

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. Additional medical therapy is generally not necessary. Some experts use statins in this setting for the theoretical benefit of its 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".)

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 of coronary artery abnormalities' 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 adding an anticoagulant such as low molecular weight heparin (LMWH [eg, enoxaparin]) or vitamin K antagonist (eg, warfarin, with a target international normalized ratio of 2.0 to 3.0) to low-dose aspirin. Dosing and monitoring of anticoagulant agents are discussed separately. (See "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome", section on 'Low molecular weight heparin' and "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome", section on 'Vitamin K antagonists'.)

Data on the use of direct oral anticoagulants (DOACs) in children with KD are limited. Clinical trials evaluating the DOACs apixaban and edoxaban in this setting are ongoing [4,5]. Until additional data are available, use of DOACs in pediatric patients with KD is generally limited to the setting of a clinical trial. Use of DOACs in children with venous thromboembolism is discussed separately. (See "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome", section on 'Direct oral anticoagulants'.)

Observational data suggest that combined therapy with an anticoagulant plus aspirin may be more effective than aspirin alone [6,7]. If the CAA regresses to a small or medium size, systemic anticoagulation can be discontinued. If the CAA remodels to medium size, dual antiplatelet therapy (eg, aspirin plus clopidogrel) or aspirin alone is used instead of aspirin plus an anticoagulant.

Special considerations regarding antithrombotic therapy in select patients with large and giant CAAs include the following:

Infants – In infants, anticoagulation treatment should be based on the criterion of Z-score ≥10 rather than maximum internal diameter of ≥8 mm [8]. LMWH is preferred over warfarin because of its predictable anticoagulant response. (See "Neonatal thrombosis: Management and outcome", section on 'Anticoagulant agents' and "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome", section on 'Anticoagulant agents'.)

High-risk – 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: Issues specific to adolescents".)

If pregnancy occurs, anticoagulation is provided, similar to guidelines for obstetric patients with prosthetic heart valves. Outcomes of pregnancy in women with CAAs in a small series appear to be excellent [9]. (See "Management of antithrombotic therapy for a prosthetic heart valve during pregnancy".)

Patients treated with both aspirin and warfarin require close monitoring since they are at high risk of both thrombosis and bleeding (sometimes in the same patient) [10]. Frequent evaluation with echocardiography and electrocardiography (ECG) should be performed in patients with giant aneurysms. A worsening of ventricular function or a change in ECG should raise suspicion for coronary thrombosis. (See 'Long-term follow-up' below.)

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 infraction (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 [6]. In a retrospective study of patients with giant CAAs, there was no difference in the frequency of thrombotic coronary artery occlusions between LMWH and warfarin therapy [11]. Severe bleeding was more frequently observed in patients treated with warfarin, and minor bleeding was more frequent in patients treated with LMWH.

Myocardial infarction and coronary thrombosis — Myocardial infarction is the principal cause of KD mortality and occurs most frequently among patients with giant CAAs [12]. As discussed below, ongoing monitoring with echocardiography and ECG is recommended, with the most intense monitoring in the first few months after the initial illness [1]. (See 'Long-term follow-up' below.)

Because myocardial infarction is rare in patients with KD, principles of treatment are derived from those used in the adult population with atherosclerotic 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".)

We have treated children with coronary thrombosis as follows:

For patients who present with an ST-elevation myocardial infarction attributable to a thrombotic occlusion of a coronary artery, who are beyond the acute/subacute phase of the illness, who are large enough for use of adult-sized catheters, and who can be transferred promptly (within 90 minutes) to a cardiac catheterization laboratory with staff experienced in performing percutaneous coronary intervention (PCI), immediate angiography with mechanical restoration of myocardial blood flow is the procedure of choice. (See "Primary percutaneous coronary intervention in acute ST-elevation myocardial infarction: Periprocedural management".)

For children in the acute/subacute phase of illness or those who are not candidates for mechanical restoration of flow in the cardiac catheterization laboratory, we administer systemic recombinant tissue plasminogen activator (alteplase 0.5 mg/kg per hour intravenously for six hours), low-dose aspirin (3 to 5 mg/kg per day), and heparin (initial dosing at 10 units/kg per hour, which is adjusted to a targeted anti-factor Xa level and/or activated partial thromboplastin time). Echocardiographic imaging then is performed to reassess the thrombus, and alteplase may be continued for longer if the thrombus has not resolved. (See "Acute ST-elevation myocardial infarction: The use of fibrinolytic therapy".)

In some patients with a particularly large thrombus burden and high risk of occlusion, treatment with a combination of alteplase (0.25 mg/kg intravenously per hour), together with abciximab (platelet glycoprotein IIb/IIIA inhibitor, as an initial bolus of 0.25 mg/kg over 30 minutes, followed by an infusion of 0.125 micrograms/kg per minute for 12 hours) may be considered.

When echocardiographic surveillance during the acute or subacute phase of disease reveals a new mural, nonocclusive thrombus, administration of abciximab together with low-dose heparin (10 units/kg per hour) to prevent clot extension is reasonable.

Following acute myocardial infarction (AMI), we may treat patients with beta blockers, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, and aldosterone blockers in addition to their antithrombotic regimen, in accordance with standard therapy after myocardial infarction in adults. (See "Overview of the nonacute management of ST-elevation myocardial infarction", section on 'Further medical therapy'.)

Coronary revascularization procedures — 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 [13]. The decision to perform a coronary revascularization procedure in a patient with KD is based on consensus of experts, indirect evidence from adults with atherosclerotic CAD, and observational data in patients with KD [14-17].

There are no randomized clinical trials assessing the relative merits of PCI versus CABG procedure in KD. A retrospective Japanese survey suggested that patients who undergo PCI as a first revascularization procedure, compared with those whose first procedure is surgical, had similar rates of mortality and AMI. However, the PCI group was more likely to undergo repeat revascularization procedures [18]. 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.

The Research Committee of the Japanese Ministry of Health, Labour and Welfare recommends PCI for patients with the following findings [19]:

Ischemic symptoms

Reversible ischemia on stress testing

≥75 percent stenosis of the left anterior descending coronary artery

Performance of PCI in the child or adolescent after KD should be done 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.

The 2017 American Heart Association guidelines include recommendations for modes of revascularization in KD based upon first principles from adult coronary heart disease, together with experience in 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

Standalone balloon angioplasty should not be used for PCI in KD patients with coronary obstructions

The Japanese committee recommends CABG procedure rather than PCI for patients with the following findings [19]:

Severe left ventricular dysfunction

Coronary lesions with multiple, ostial, or long-segment coronary artery stenosis

Surgical revascularization is most often performed in children who have symptoms of angina, have important ischemic burden on myocardial perfusion imaging or stress testing, or have clinically relevant obstruction that is believed to put them at high risk for myocardial infarction. CABG procedures are only performed when the myocardium to be supplied is viable and the artery beyond the planned graft site is not stenotic [20]. 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 [14-16]. 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 [16].

Cardiac transplantation — Cardiac transplantation is reserved for patients with end-stage ischemic cardiomyopathy who are not candidates for coronary revascularization procedures [21]. (See "Heart transplantation in adults: Indications and contraindications".)

LONG-TERM FOLLOW-UP

Frequency of follow-up — Follow-up evaluation for patients with KD and coronary artery abnormalities (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 coronary artery status of the patient, as summarized in the table (table 2) [2].

Assessment for inducible myocardial ischemia may be appropriate, depending on the size of the CAA and presence of coronary stenosis. Assessing for inducible myocardial ischemia can be performed with stress echocardiography, stress ECG, stress magnetic resonance imaging (MRI), and/or nuclear medicine perfusion imaging. 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. The details of these tests are discussed 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'.)

Counseling and screening for risk factors — All patients with KD and their families 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 risk factors for development of atherosclerosis and early cardiovascular disease in childhood" and "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

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. 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 smoking including passive smoking. (See "Pediatric prevention of adult cardiovascular disease: Promoting a healthy lifestyle and identifying at-risk children".)

Patients who do not have CAAs in the first month after KD onset and who do not have lingering or recurrent signs or symptoms can be discharged from cardiology follow-up [22,23]. 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 [22,23]. The available data also suggest that such individuals are at low risk of adult CAD [24]. However, 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 provider. The optimal frequency and intensity of follow-up for these patients continue to be debated [25,26]. With continued surveillance, the long-term repercussions of KD into advanced age, including its effects on risks of coronary artery, valvular, and myocardial disease, will be more fully elucidated.

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 [27].

In general, we follow the 2015 American Heart Association and American College of Cardiology guidelines for sports participation in patients with CAD, including KD [27]:

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' and "Cardiac rehabilitation: Indications, efficacy, and safety in patients with coronary heart 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 [28-30]. 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 [28,30-32]. Approximately 20 to 50 percent of such aneurysms become obstructed, increasing the risk of myocardial infarction, arrhythmias, or sudden death [28,30-33]. Patients with CAAs with maximum Z-score ≥20 are at particularly high risk or morbidity and mortality [32]. (See 'Myocardial infarction and coronary thrombosis' above and "Cardiovascular sequelae of Kawasaki disease: Clinical features and evaluation", section on 'Myocardial infarction'.)

Among patients who develop aneurysms, mortality is highest between 15 and 45 days after onset of KD [12]. 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 '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 [32]. 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 [33]. 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 [13,34,35]. Survival is better among patients with unilateral giant aneurysms compared with bilateral (96 versus 87 percent, respectively) [35]. 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) [35]. 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 [36]. 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

Rationale for antithrombotic therapy – Management of patients with Kawasaki disease (KD) and coronary artery abnormalities (CAAs) is aimed at preventing and treating coronary artery thrombosis. Management is based largely upon adult data for secondary prevention of coronary artery disease (CAD). (See 'Management' above and "Aspirin for the secondary prevention of atherosclerotic cardiovascular disease" and "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

Risk stratification – Risk stratification is based principally on the echocardiographic coronary artery luminal dimensions (table 1). (See 'Risk stratification of coronary artery abnormalities' above.)

Risk-based approach to antithrombotic therapy – In the acute phase of illness, patients with KD are generally treated with moderate-dose aspirin 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 '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 low molecular weight heparin (LMWH; eg, enoxaparin) 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 antiinflammatory 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 myocardial infarction – Patients who suffer acute myocardial infarction (AMI) require urgent therapy for reperfusion and revascularization. The choice of therapeutic intervention depends on the size of the patient and the timing of AMI relative to the phase of illness (see 'Myocardial infarction and coronary thrombosis' above):

For patients who are beyond the acute/subacute phase of the illness and who are large enough for use of adult-sized catheters, we suggest immediate coronary angiography with mechanical restoration of myocardial blood flow (Grade 2C)

In smaller patients and those in the acute/subacute phase of illness, we suggest systemic recombinant tissue plasminogen activator (alteplase 0.5 mg/kg per hour intravenously for six hours) in conjunction with aspirin and heparin (Grade 2C)

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 2). In patients with CAAs, assessment for inducible myocardial ischemia (with stress echocardiography, stress electrocardiography (ECG), stress magnetic resonance imaging [MRI], and/or nuclear medicine perfusion imaging) 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'.)

In patients with evidence of reversible ischemia on stress testing, we suggest that coronary artery revascularization intervention be performed (Grade 2C). (See 'Coronary revascularization procedures' above.)

Prognosis – For patients with KD and CAAs, the risks of serious morbidity and mortality are directly related to maximum aneurysm size. Small and medium aneurysms 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.)

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Topic 114918 Version 10.0

References