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.
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 long-term 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
scores, and is calibrated to both past and current involvement. Patients with aneurysms require life-long and uninterrupted cardiology follow-up.
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.
BACKGROUNDPediatric SARS-CoV-2 infection can be complicated by a dangerous hyperinflammatory condition termed multisystem inflammatory syndrome in children (MIS-C). The clinical and immunologic ...spectrum of MIS-C and its relationship to other inflammatory conditions of childhood have not been studied in detail.METHODSWe retrospectively studied confirmed cases of MIS-C at our institution from March to June 2020. The clinical characteristics, laboratory studies, and treatment response were collected. Data were compared with historic cohorts of Kawasaki disease (KD) and macrophage activation syndrome (MAS).RESULTSTwenty-eight patients fulfilled the case definition of MIS-C. Median age at presentation was 9 years (range: 1 month to 17 years); 50% of patients had preexisting conditions. All patients had laboratory confirmation of SARS-CoV-2 infection. Seventeen patients (61%) required intensive care, including 7 patients (25%) who required inotrope support. Seven patients (25%) met criteria for complete or incomplete KD, and coronary abnormalities were found in 6 cases. Lymphopenia, thrombocytopenia, and elevation in inflammatory markers, D-dimer, B-type natriuretic peptide, IL-6, and IL-10 levels were common but not ubiquitous. Cytopenias distinguished MIS-C from KD and the degree of hyperferritinemia and pattern of cytokine production differed between MIS-C and MAS. Immunomodulatory therapy given to patients with MIS-C included intravenous immune globulin (IVIG) (71%), corticosteroids (61%), and anakinra (18%). Clinical and laboratory improvement were observed in all cases, including 6 cases that did not require immunomodulatory therapy. No mortality was recorded in this cohort.CONCLUSIONMIS-C encompasses a broad phenotypic spectrum with clinical and laboratory features distinct from KD and MAS.FUNDINGThis work was supported by the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Institute of Allergy and Infectious Diseases; Rheumatology Research Foundation Investigator Awards and Medical Education Award; Boston Children's Hospital Faculty Career Development Awards; the McCance Family Foundation; and the Samara Jan Turkel Center.
Acute kidney injury (AKI) after cardiopulmonary bypass (CPB) is associated with a requirement for dialysis, a longer stay in the intensive care unit, a longer hospital length of stay, and mortality. ...An oxygenator arterial outlet temperature greater than 37°C has been reported to be associated with AKI; however, the influence of other rewarming temperatures is unclear. Using multicenter registry data, this study aimed to evaluate the role of CPB rewarming temperatures on AKI.
Data from 8,407 adult patients undergoing coronary artery bypass grafting (CABG) or valve repair or replacement, or a combination, were collected using the Perfusion Downunder Collaborative Database. Primary variables of interest were rewarming temperatures, defined as cumulative time the oxygenator arterial outlet temperature was greater than 36°C, greater than 36.5°C, or greater than 37°C. Propensity scores were calculated to determine the predicted probability of hyperthermic perfusion (rewarming temperature >37°C). The influence of temperature on AKI was determined using separate multivariate models adjusting for propensity score in the entire cohort (n = 6,904) and in propensity-matched patients (n = 2,044).
Overall, 11.8% of patients acquired AKI. The duration of rewarming temperature greater than 36°C or 36.5°C was not associated with AKI. The duration of rewarming temperature greater than 37°C (hyperthermic perfusion) was independently associated with RIFLE (Risk, Injury, Failure, Loss, End-stage renal disease) risk classification or greater (odds ratio OR, 1.42; 95% confidence interval CI, 1.09-1.77; p = 0.012) and injury classification or greater AKI (OR, 1.52; 95% CI, 1.09-1.97; p = 0.016) in the entire cohort, and injury classification or greater AKI (OR, 1.51; 95% CI, 1.15-1.90; p = 0.006) in propensity-matched patients.
The duration of hyperthermic perfusion-rewarming temperature greater than 37°C-was an independent predictor of AKI. Avoidance of hyperthermic perfusion may be more beneficial in reducing AKI than avoidance of rewarming.
Background Accurate prediction of coronary artery aneurysms ( CAAs ) in patients with Kawasaki disease remains challenging in North American cohorts. We sought to develop and validate a risk model ...for CAA prediction. Methods and Results A binary outcome of CAA was defined as left anterior descending or right coronary artery Z score ≥2.5 at 2 to 8 weeks after fever onset in a development cohort (n=903) and a validation cohort (n=185) of patients with Kawasaki disease. Associations of baseline clinical, laboratory, and echocardiographic variables with later CAA were assessed in the development cohort using logistic regression. Discrimination (c statistic) and calibration (Hosmer-Lemeshow) of the final model were evaluated. A practical risk score assigning points to each variable in the final model was created based on model coefficients from the development cohort. Predictors of CAAs at 2 to 8 weeks were baseline Z score of left anterior descending or right coronary artery ≥2.0, age <6 months, Asian race, and C-reactive protein ≥13 mg/ dL (c=0.82 in the development cohort, c=0.93 in the validation cohort). The CAA risk score assigned 2 points for baseline Z score of left anterior descending or right coronary artery ≥2.0 and 1 point for each of the other variables, with creation of low- (0-1), moderate- (2), and high- (3-5) risk groups. The odds of CAA s were 16-fold greater in the high- versus the low-risk groups in the development cohort (odds ratio, 16.4; 95% CI , 9.71-27.7 P<0.001), and >40-fold greater in the validation cohort (odds ratio, 44.0; 95% CI, 10.8-180 P<0.001). Conclusions Our risk model for CAA in Kawasaki disease consisting of baseline demographic, laboratory, and echocardiographic variables had excellent predictive utility and should undergo prospective testing.
The BNT162b2 (Pfizer-BioNTech) messenger RNA COVID-19 vaccine was authorized on May 10, 2021, for emergency use in children aged 12 years and older. Initial reports showed that the vaccine was well ...tolerated without serious adverse events; however, cases of myocarditis have been reported since approval.
To review results of comprehensive cardiac imaging in children with myocarditis after COVID-19 vaccine.
This study was a case series of children younger than 19 years hospitalized with myocarditis within 30 days of BNT162b2 messenger RNA COVID-19 vaccine. The setting was a single-center pediatric referral facility, and admissions occurred between May 1 and July 15, 2021.
All patients underwent cardiac evaluation including an electrocardiogram, echocardiogram, and cardiac magnetic resonance imaging.
Fifteen patients (14 male patients 93%; median age, 15 years range, 12-18 years) were hospitalized for management of myocarditis after receiving the BNT162b2 (Pfizer) vaccine. Symptoms started 1 to 6 days after receipt of the vaccine and included chest pain in 15 patients (100%), fever in 10 patients (67%), myalgia in 8 patients (53%), and headache in 6 patients (40%). Troponin levels were elevated in all patients at admission (median, 0.25 ng/mL range, 0.08-3.15 ng/mL) and peaked 0.1 to 2.3 days after admission. By echocardiographic examination, decreased left ventricular (LV) ejection fraction (EF) was present in 3 patients (20%), and abnormal global longitudinal or circumferential strain was present in 5 patients (33%). No patient had a pericardial effusion. Cardiac magnetic resonance imaging findings were consistent with myocarditis in 13 patients (87%) including late gadolinium enhancement in 12 patients (80%), regional hyperintensity on T2-weighted imaging in 2 patients (13%), elevated extracellular volume fraction in 3 patients (20%), and elevated LV global native T1 in 2 patients (20%). No patient required intensive care unit admission, and median hospital length of stay was 2 days (range 1-5). At follow-up 1 to 13 days after hospital discharge, 11 patients (73%) had resolution of symptoms. One patient (7%) had persistent borderline low LV systolic function on echocardiogram (EF 54%). Troponin levels remained mildly elevated in 3 patients (20%). One patient (7%) had nonsustained ventricular tachycardia on ambulatory monitor.
In this small case series study, myocarditis was diagnosed in children after COVID-19 vaccination, most commonly in boys after the second dose. In this case series, in short-term follow-up, patients were mildly affected. The long-term risks associated with postvaccination myocarditis remain unknown. Larger studies with longer follow-up are needed to inform recommendations for COVID-19 vaccination in this population.
Treatment of acute Kawasaki disease with intravenous immune globulin and aspirin reduces the risk of coronary-artery abnormalities and systemic inflammation, but despite intravenous immune globulin ...therapy, coronary-artery abnormalities develop in some children. Studies have suggested that primary corticosteroid therapy might be beneficial and that adverse events are infrequent with short-term use.
We conducted a multicenter, randomized, double-blind, placebo-controlled trial to determine whether the addition of intravenous methylprednisolone to conventional primary therapy for Kawasaki disease reduces the risk of coronary-artery abnormalities. Patients with 10 or fewer days of fever were randomly assigned to receive intravenous methylprednisolone, 30 mg per kilogram of body weight (101 patients), or placebo (98 patients). All patients then received conventional therapy with intravenous immune globulin, 2 g per kilogram, as well as aspirin, 80 to 100 mg per kilogram per day until they were afebrile for 48 hours and 3 to 5 mg per kilogram per day thereafter.
At week 1 and week 5 after randomization, patients in the two study groups had similar coronary dimensions, expressed as z scores adjusted for body-surface area, absolute dimensions, and changes in dimensions. As compared with patients receiving placebo, patients receiving intravenous methylprednisolone had a somewhat shorter initial period of hospitalization (P=0.05) and, at week 1, a lower erythrocyte sedimentation rate (P=0.02) and a tendency toward a lower C-reactive protein level (P=0.07). However, the two groups had similar numbers of days spent in the hospital, numbers of days of fever, rates of retreatment with intravenous immune globulin, and numbers of adverse events.
Our data do not provide support for the addition of a single pulsed dose of intravenous methylprednisolone to conventional intravenous immune globulin therapy for the routine primary treatment of children with Kawasaki disease. (ClinicalTrials.gov number, NCT00132080 ClinicalTrials.gov.)
To characterize the socioeconomic and racial and/or ethnic disparities impacting the diagnosis and outcomes of multisystem inflammatory syndrome in children (MIS-C).
This multicenter retrospective ...case-control study was conducted at 3 academic centers from January 1 to September 1, 2020. Children with MIS-C were compared with 5 control groups: children with coronavirus disease 2019, children evaluated for MIS-C who did not meet case patient criteria, children hospitalized with febrile illness, children with Kawasaki disease, and children in Massachusetts based on US census data. Neighborhood socioeconomic status (SES) and social vulnerability index (SVI) were measured via a census-based scoring system. Multivariable logistic regression was used to examine associations between SES, SVI, race and ethnicity, and MIS-C diagnosis and clinical severity as outcomes.
Among 43 patients with MIS-C, 19 (44%) were Hispanic, 11 (26%) were Black, and 12 (28%) were white; 22 (51%) were in the lowest quartile SES, and 23 (53%) were in the highest quartile SVI. SES and SVI were similar between patients with MIS-C and coronavirus disease 2019. In multivariable analysis, lowest SES quartile (odds ratio 2.2 95% confidence interval 1.1-4.4), highest SVI quartile (odds ratio 2.8 95% confidence interval 1.5-5.1), and racial and/or ethnic minority background were associated with MIS-C diagnosis. Neither SES, SVI, race, nor ethnicity were associated with disease severity.
Lower SES or higher SVI, Hispanic ethnicity, and Black race independently increased risk for MIS-C. Additional studies are required to target interventions to improve health equity for children.
Objective To describe common associated symptoms within the 10 days before diagnosis in subjects enrolled in the Pediatric Heart Network's trial of steroid therapy in Kawasaki disease (KD). Study ...design Patients with acute KD were enrolled between days 4 and 10 of illness at 8 centers between 2002 and 2004. We defined common associated symptoms as those occurring in ≥10% of patients. Principal clinical criteria for KD were not included in this analysis. Results Among 198 patients, irritability was reported in 98 (50%), vomiting in 88 (44%), decreased food/fluid intake in 73 (37%), cough in 55 (28%), diarrhea in 52 (26%), rhinorrhea in 37 (19%), weakness in 37 (19%), abdominal pain in 35 (18%), and joint pain (arthralgia or arthritis) in 29 (15%). One or more gastrointestinal symptom (vomiting, diarrhea, or abdominal pain) was present in 120 patients (61%) and 69 patients (35%) had ≥ 1 respiratory symptom (rhinorrhea or cough). Conclusions Nonspecific symptoms occur commonly in children with KD. To reduce delays in diagnosis, clinicians should be educated that such symptoms may comprise a significant component in the chief complaint.
Myocarditis is a rare complication of the COVID-19 mRNA vaccine. We previously reported a case series of 15 adolescents with vaccine-associated myocarditis, 87% of whom had abnormalities on initial ...cardiac magnetic resonance (CMR), including late gadolinium enhancement (LGE) in 80%. We performed follow-up CMRs to determine the trajectory of myocardial recovery and better understand the natural history of vaccine-associated myocarditis. Case series of patients age < 19 years admitted to Boston Children’s Hospital with acute vaccine-associated myocarditis following the BNT162b2 vaccine who had abnormal CMR at the time of initial presentation, and underwent follow-up testing. CMR assessment included left ventricular (LV) ejection fraction, T2-weighted myocardial imaging, LV global native T1, LV global T2, extracellular volume (ECV), and late gadolinium enhancement (LGE). Ten patients (9 male, median age 15 years) with vaccine-associated myocarditis underwent follow-up CMR at a median of 92 days (range 76–119) after hospital discharge. LGE was persistent in 80% of patients, though improved from prior in all cases. Two patients (20%) had abnormal LV global T1 at presentation, which normalized on follow-up. ECV decreased between acute presentation and follow-up in 6/10 patients; it remained elevated at follow-up in 1 patient and borderline in 3 patients.
Conclusion
: CMR performed ~3 months after admission for COVID-19 vaccine-associated myocarditis showed improvement of LGE in all patients, but persistent in the majority. Follow-up CMR 6–12 months after acute episode should be considered to better understand the long-term cardiac risks.
What is Known:
• Myocarditis is a rare side effect of COVID-19 mRNA vaccine
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•Late gadolinium enhancement is present on most cardiac magnetic resonance at the time of acute presentation
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What is New:
•Late gadolinium enhancement improved on all repeat cardiac magnetic resonance at 3-month follow-up
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•Most patients still had a small amount of late gadolinium enhancement, the clinical significance of which is yet to be determined
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