Kawasaki Disease

McCrindle, Brian W.

doi:10.1161/circulationaha.109.874800

Cited by 49 publications

(10 citation statements)

References 27 publications

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“…Although systematic long-term data are not available, evidence suggests that these patients are not at increased risk of late mortality attributable to CVD compared with the general population. [309][310][311][312][313] The association with late events is limited to rare case reports. 314,315 For patients defined as having an aneurysm of any size noted at any assessment, ongoing cardiology follow-up is recommended.…”

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confidence: 99%

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association

McCrindle¹,

Rowley²,

Newburger³

et al. 2017

Circulation

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BACKGROUND:Kawasaki disease is an acute vasculitis of childhood that leads to coronary artery aneurysms in ≈25% of untreated cases. It has been reported worldwide and is the leading cause of acquired heart disease in children in developed countries. METHODS AND RESULTS:To revise the previous American Heart Association guidelines, a multidisciplinary writing group of experts was convened to review and appraise available evidence and practice-based opinion, as well as to provide updated recommendations for diagnosis, treatment of the acute illness, and long-term management. Although the cause remains unknown, discussion sections highlight new insights into the epidemiology, genetics, pathogenesis, pathology, natural history, and longterm outcomes. Prompt diagnosis is essential, and an updated algorithm defines supplemental information to be used to assist the diagnosis when classic clinical criteria are incomplete. Although intravenous immune globulin is the mainstay of initial treatment, the role for additional primary therapy in selected patients is discussed. Approximately 10% to 20% of patients do not respond to initial intravenous immune globulin, and recommendations for additional therapies are provided. Careful initial management of evolving coronary artery abnormalities is essential, necessitating an increased frequency of assessments and escalation of thromboprophylaxis. Risk stratification for long-term management is based primarily on maximal coronary artery luminal dimensions, normalized as Z scores, and is calibrated to both past and current involvement. Patients with aneurysms require life-long and uninterrupted cardiology follow-up. CONCLUSIONS:These recommendations provide updated and best evidence-based guidance to healthcare providers who diagnose and manage Kawasaki disease, but clinical decision making should be individualized to specific patient circumstances. K awasaki disease (KD) is an acute, self-limited febrile illness of unknown cause that predominantly affects children <5 years of age. When initially described, the potential for coronary artery complications was not appreciated. KD is now the most common cause of acquired heart disease in children in developed countries. In the absence of pathognomonic tests, the diagnosis continues to rest on the identification of principal clinical findings and the exclusion of other clinically similar entities with known causes. Timely initiation of treatment with intravenous immunoglobulin (IVIG) has reduced the incidence of coronary artery aneurysms defined from absolute luminal dimensions from 25% to ≈4%. Ongoing studies with additional therapies have not substantially reduced this residual risk. The long-term prognosis is determined by the initial and current level of coronary artery involvement. Certain subsets of patients are at risk for myocardial ischemia from coronary artery thrombosis and stenoses. Medical management of such patients hinges on judicious use of thromboprophylaxis and vigilance to identify evolving stenoses. Invasive revascul...

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confidence: 99%

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association

McCrindle¹,

Rowley²,

Newburger³

et al. 2017

Circulation

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2,863

4,124

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“…While only half the patients who qualify receive statin treatment, in those who do, the cross-sectional Lipid Treatment Assessment Project 2 study reported that about 70% now reach their goals in the US, which is chiefly attributed to greater use of high-potency statins 429. However, only about 29% of those at high risk reach the current goal of LDL cholesterol ≤1.81 mmol/L (70 mg/dL).…”

Section: Adherence and Performance In Risk Reductionmentioning

confidence: 99%

Molecular sources of residual cardiovascular risk, clinical signals, and innovative solutions: relationship with subclinical disease, undertreatment, and poor adherence: implications of new evidence upon optimizing cardiovascular patient outcomes

Kones¹

2013

VHRM

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Residual risk, the ongoing appreciable risk of major cardiovascular events (MCVE) in statin-treated patients who have achieved evidence-based lipid goals, remains a concern among cardiologists. Factors that contribute to this continuing risk are atherogenic non-low-density lipoprotein (LDL) particles and atherogenic processes unrelated to LDL cholesterol, including other risk factors, the inherent properties of statin drugs, and patient characteristics, ie, genetics and behaviors. In addition, providers, health care systems, the community, public policies, and the environment play a role. Major statin studies suggest an average 28% reduction in LDL cholesterol and a 31% reduction in relative risk, leaving a residual risk of about 69%. Incomplete reductions in risk, and failure to improve conditions that create risk, may result in ongoing progression of atherosclerosis, with new and recurring lesions in original and distant culprit sites, remodeling, arrhythmias, rehospitalizations, invasive procedures, and terminal disability. As a result, identification of additional agents to reduce residual risk, particularly administered together with statin drugs, has been an ongoing quest. The current model of atherosclerosis involves many steps during which disease may progress independently of guideline-defined elevations in LDL cholesterol. Differences in genetic responsiveness to statin therapy, differences in ability of the endothelium to regenerate and repair, and differences in susceptibility to nonlipid risk factors, such as tobacco smoking, hypertension, and molecular changes associated with obesity and diabetes, may all create residual risk. A large number of inflammatory and metabolic processes may also provide eventual therapeutic targets to lower residual risk. Classically, epidemiologic and other evidence suggested that raising high-density lipoprotein (HDL) cholesterol would be cardioprotective. When LDL cholesterol is aggressively lowered to targets, low HDL cholesterol levels are still inversely related to MCVE. The efflux capacity, or ability to relocate cholesterol out of macrophages, is believed to be a major antiatherogenic mechanism responsible for reduction in MCVE mediated in part by healthy HDL. HDL cholesterol is a complex molecule with antioxidative, anti-inflammatory, anti-thrombotic, antiplatelet, and vasodilatory properties, among which is protection of LDL from oxidation. HDL-associated paraoxonase-1 has a major effect on endothelial function. Further, HDL promotes endothelial repair and progenitor cell health, and supports production of nitric oxide. HDL from patients with cardiovascular disease, diabetes, and autoimmune disease may fail to protect or even become proinflammatory or pro-oxidant. Mendelian randomization and other clinical studies in which raising HDL cholesterol has not been beneficial suggest that high plasma levels do not necessarily reduce cardiovascular risk. These data, coupled with extensive preclinical information about the functional heterogeneity of HDL, challenge the ...

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“…KD causes both a myocarditis and a vasculitis that damages the coronary arteries and other medium-sized muscular arteries leading to the formation of aneurysms (Tanaka 1979, Yonesaka, Nakada et al 1989). The major sequelae of aneurysms include thrombosis, late coronary artery stenosis, myocardial ischemia, myocardial infarction, and death (Kato, Sugimura et al 1996, Gordon, Kahn et al 2009, McCrindle 2009). Treatment with intravenous immunoglobulin (IVIG) reduces the risk of aneurysm formation from 25% to 5% (Newburger, Takahashi et al 1986).…”

Section: Introduction and Rationalementioning

confidence: 99%

Rationale and study design for a phase I/IIa trial of anakinra in children with Kawasaki disease and early coronary artery abnormalities (the ANAKID trial)

Tremoulet

Jain

Kim

et al. 2016

Contemporary Clinical Trials

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Background Although Kawasaki disease (KD) is the most common cause of acquired heart disease in children and may result in coronary artery aneurysms (CAA) with an attendant risk of myocardial infarction, there is no recommended therapy to halt progression of arterial wall damage and prevent aneurysm formation in the acute phase of the vasculitis. While intravenous immunoglobulin (IVIG) reduces the risk of CAA, up to 20% of KD patients are IVIG resistant and have a higher risk for developing CAA. The IL-1 pro-inflammatory pathway is upregulated in children with acute KD and plays a critical role in the experimental animal model of KD. Thus, IL-1 is a logical therapeutic target. Objectives The goal of this study is to determine the safety, tolerability, pharmacokinetics, and immunomodulatory effects of anakinra, a recombinant human IL-1 receptor antagonist, in acute KD patients with coronary artery abnormalities on the baseline echocardiogram. Design This is a two-center dose-escalation Phase I/IIa trial in 30 acute KD patients ≥8 months old with a coronary artery Z score ≥3.0 in the right coronary artery and/or left anterior descending artery or an aneurysm. Subjects will receive a 2- to 6-week course of anakinra by daily subcutaneous injection and will be assessed for resolution of inflammation and dose limiting toxicities (leukopenia, anaphylactoid reaction, or severe infection). Conclusion The safety and tolerability of blocking both IL-1α and Il-1β by anakinra will be evaluated as a strategy to prevent or attenuate coronary artery damage in infants and children with acute KD.

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Kawasaki Disease

Cited by 49 publications

References 27 publications

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association

Molecular sources of residual cardiovascular risk, clinical signals, and innovative solutions: relationship with subclinical disease, undertreatment, and poor adherence: implications of new evidence upon optimizing cardiovascular patient outcomes

Rationale and study design for a phase I/IIa trial of anakinra in children with Kawasaki disease and early coronary artery abnormalities (the ANAKID trial)

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