What are the long-term effects of Kawasaki disease and how can they be managed?

Long-Term Effects of Kawasaki Disease

The most critical long-term effect of Kawasaki disease is coronary artery damage, which occurs in 15-25% of untreated patients and 5% of treated patients, with myocardial infarction from thrombotic occlusion being the principal cause of death. 1

Coronary Artery Complications

Aneurysm Evolution and Outcomes

Approximately 50-67% of coronary artery aneurysms show angiographic regression within 1-2 years, but this apparent resolution is deceptive—these vessels remain structurally and functionally abnormal. 1

• Regressed aneurysms demonstrate persistent fibrous intimal thickening, abnormal vasoreactivity to vasodilators, and endothelial dysfunction despite normal-appearing lumen diameter on angiography. 1
• Intravascular ultrasound reveals marked myointimal thickening even in angiographically "normal" vessels. 1
• Smaller aneurysms, fusiform morphology (versus saccular), distal location, and age <1 year at onset predict higher likelihood of regression. 1

Progressive Stenotic Disease

The 50% of aneurysms that do not regress face progressive complications, with stenotic lesions developing from myointimal proliferation that continues to worsen almost linearly over time. 1

• Giant aneurysms (≥8 mm diameter) carry the worst prognosis, with thrombosis promoted by sluggish blood flow and stenotic lesions at aneurysm margins. 1
• The highest risk of myocardial infarction occurs in the first year after disease onset, particularly with obstruction of the left main coronary artery or both the right coronary artery and left anterior descending artery. 1

Extracardiac Vascular Involvement

Aneurysms can develop in non-coronary arteries including subclavian, brachial, axillary, iliac, femoral vessels, and occasionally the abdominal aorta and renal arteries. 1

• The American Heart Association recommends abdominal aortography and subclavian arteriography during first-time coronary angiography. 1

Myocardial Effects

Acute Myocarditis with Long-Term Implications

Myocarditis occurs in 50-70% of patients during acute disease, and myocardial biopsy studies reveal persistent abnormalities including fibrosis, cellular disarrangement, myocyte hypertrophy, and abnormal branching detected 2 months to 11 years after disease onset. 1

• These histopathologic abnormalities occur independent of coronary artery involvement. 1
• Despite concerning biopsy findings, long-term myocardial contractility measured by echocardiography appears normal except in patients with ischemic heart disease. 1
• The full impact on adult heart function remains unknown and requires ongoing surveillance. 1

Valvular Complications

Mitral Regurgitation

Mitral regurgitation occurs in approximately 1% of patients and may result from papillary muscle dysfunction, myocardial infarction, or valvulitis. 1

• Resolution occurs in about 50% of cases, while others experience persistent dysfunction or death from MI. 1
• Late-onset mitral regurgitation after the acute stage is usually secondary to myocardial ischemia. 1

Aortic Regurgitation

Aortic regurgitation occurs in approximately 4-5% of patients, attributed to valvulitis, and late-onset aortic regurgitation may rarely require valve replacement. 1

Systemic Vascular Changes

Patients with coronary artery lesions demonstrate reduced carotid artery distensibility and increased wall thickness 6-20 years after disease onset, independent of lipid profile alterations. 1

• These arterial wall changes suggest potential predisposition to accelerated atherosclerosis, though this remains controversial. 1
• Whether patients without coronary abnormalities face similar risks requires further study. 1

Risk Stratification for Long-Term Management

The American Heart Association stratifies patients into five risk levels based on coronary involvement: 1

Risk Level I (No coronary changes)

• No pharmacological therapy beyond 6-8 weeks
• No activity restrictions beyond 6-8 weeks
• Cardiovascular risk assessment every 5 years
• However, research suggests possible subclinical endothelial dysfunction and altered myocardial flow reserve even in this group. 1

Risk Level III-V (Aneurysms present)

• Long-term antiplatelet therapy with aspirin 3-5 mg/kg/day minimum 1
• β-blockers should be considered to reduce myocardial oxygen consumption, particularly for large or giant aneurysms 1
• Serial stress testing and myocardial imaging are mandatory 1
• Risk level may change over time as coronary morphology evolves 1

Critical Management Pitfalls

The most dangerous misconception is assuming that angiographic regression of aneurysms indicates complete resolution—these vessels remain pathologically abnormal with persistent thrombotic and ischemic risk. 1

• Patients with "regressed" aneurysms require ongoing surveillance, though optimal management remains controversial. 1
• Children without apparent cardiac sequelae in the first month appear clinically well but may harbor subclinical abnormalities requiring decades of follow-up to fully characterize. 1
• Adult cardiologists increasingly encounter these patients but often lack awareness of the condition and its unique management requirements compared to atherosclerotic disease. 2, 3