The Long-term Cardiac and Noncardiac Prognosis of Kawasaki Disease: A Systematic Review


The Long-term Cardiac and Noncardiac Prognosis of Kawasaki Disease: A Systematic Review.

Lee JJY, Lin E, Widdifield J, Mahood Q, McCrindle BW, Yeung RSM, Feldman BM.

Pediatrics. 2022 Mar 1;149(3):e2021052567. doi: 10.1542/peds.2021-052567. PMID: 35118494


Take Home Message

  1. A systematic review of all studies reporting on long term outcome of Kawasaki disease (KD) was performed.
  2. Overall long term is favorable, with over 90% survival 30 years after KD

  3. Patients with KD and coronary involvement are at increased risk for Major Adverse Cardiovascular Events (MACE) over a follow up of 30 years. It is still unclear if children with KD without coronary involvement are at increased risk for development of MACE with up to 30 years of follow up
  4. Patients with KD may be at higher risk than the general population for atherosclerosis, and allergic diseases.

Commentary from Dr. Anna Tsirka (Hartford, CT, USA), section editor of Pediatric and Fetal Cardiology Journal Watch


KD is the leading cause of childhood acquired heart disease in developed countries.

The objective of this systematic review of the literature was to determine the long-term prognosis of individuals with KD. Specifically, if previous KD exposure resulted in an increased risk in the following outcomes:

  1. all-cause mortality;
  2. major adverse cardiac events (MACE), including MI, cerebrovascular disease, heart failure, and cardiac interventions (catheterizations, coronary artery bypass graft [CABG] surgeries);
  3. chronic cardiac conditions or related comorbidities (hypertension, dyslipidemia, early atherosclerosis); and
  4. noncardiac diseases.


A search of databases that included Ovid Medline, Embase, and Cochrane Central Register of Controlled Trials from inception to June 2020 was performed.

A total of 77 studies were included in the review process. All studies were observational and were published between 1982 to 2020. The studies included a total of 72 487 patients from 13 countries. Fifty-five (74%) studies originated from East Asian countries. 



10 studies reported on mortality outcomes in all patients with KD, with or without coronary involvement during the acute phase and found all cause mortality of 0-6% at 4-24 years of follow up. After the acute phase, patients with KD without aneurysms did not appear to be at increased risk for all-cause mortality compared with the general population

19 studies evaluated mortality in patients with coronary artery aneurysms. None of these studies had non KD comparators. The findings are shown in figure 2 below:


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MACE were evaluate in 14 studies of KD patients regardless of the presence of aneurysms aneurysms and MI prevalence ranged from 0-7%.

Among the 24 studies that evaluated MACE in patients with coronary artery aneurysms, MACE-free survival estimates ranged from 72% to 100% at 5 years, 66% to 91% at 10 years, 57% to 84% at 15 years, 29% to 74% at 20 years, 25% to 68.5% at 25 years, and 36% to 96% at 30 years as seen in figure 3


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The development of chronic cardiovascular conditions was reported in several studies as shown in figure 4

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Of 10 studies that evaluated the long term development of hypertension (HTN), 1 found increased risk of HTN, while 8 studies did not.

Studies on hyperlipidemia showed mixed results. Two studies concluded an increased risk compared with healthy comparators, 5 reported no difference, and 4 were inconclusive.

Atherosclerosis was evaluated via markers of endothelial dysfunction and arterial wall thickness or stiffness such as flow- mediated dilatation, pulse wave velocity and intima-media thickness (thickness of the carotid artery).  Of 10 studies, 7 studies concluded an increased risk, 2 reported no difference, and 1 was inconclusive.

Twelve studies evaluated non cardiovascular outcomes; 6 focused on allergic diseases (asthma, atopic dermatitis, allergic rhinitis, urticaria, allergic conjunctivitis), 2 on cognition and behavior, 1 on malignancy, 1 on health-related quality of life, 1 on exercise performance, 1 on obstetrical outcomes, and 1 on respiratory infections (figure 4).

The one study that evaluated the incidence of cancer, found a standardized incidence rate of 2.9 (95% CI, 1.6–5.2) with onset at least 6 years post KD.


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As treatment has resulted in a significant decrease in the development of coronary artery aneurysms in the KD population, further studies are needed to evaluate the long term outcome of those without coronary artery involvement in the acute phase. Risk factors for MACE such as treatment resistance, time from onset of symptoms to treatment and age will need to be evaluated.

This review did not include studies evaluating outcomes of KD like illness during the COVID 19 pandemic.