Atrioventricular Block in Children with Multisystem Inflammatory Syndrome Audrey Dionne, Douglas Y
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Atrioventricular Block in Children With Multisystem Inflammatory Syndrome Audrey Dionne, MD,a,b Douglas Y. Mah, MD,a,b Mary Beth F. Son, MD,b,c Pui Y. Lee, MD, PhD,b,c Lauren Henderson, MD, MMSc,b,c Annette L. Baker, MSC, PNP,a,b Sarah D. de Ferranti, MD,a,b David R. Fulton, MD,a,b Jane W. Newburger, MD, MPH,a,b Kevin G. Friedman, MDa,b BACKGROUND: Children are at risk for multisystem inflammatory syndrome in children (MIS-C) abstract after infection with severe acute respiratory syndrome coronavirus 2. Cardiovascular complications, including ventricular dysfunction and coronary dilation, are frequent, but there are limited data on arrhythmic complications. METHODS: Retrospective cohort study of children and young adults aged #21 years admitted with MIS-C. Demographic characteristics, electrocardiogram (ECG) and echocardiogram findings, and hospital course were described. RESULTS: Among 25 patients admitted with MIS-C (60% male; median age 9.7 [interquartile range 2.7–15.0] years), ECG anomalies were found in 14 (56%). First-degree atrioventricular block (AVB) was seen in 5 (20%) patients a median of 6 (interquartile range 5–8) days after onset of fever and progressed to second- or third-degree AVB in 4 patients. No patient required intervention for AVB. All patients with AVB were admitted to the ICU (before onset of AVB) and had ventricular dysfunction on echocardiograms. All patients with second- or third- degree AVB had elevated brain natriuretic peptide levels, whereas the patient with first- degree AVB had a normal brain natriuretic peptide level. No patient with AVB had an elevated troponin level. QTc prolongation was seen in 7 patients (28%), and nonspecific ST segment changes were seen in 14 patients (56%). Ectopic atrial tachycardia was observed in 1 patient, and none developed ventricular arrhythmias. CONCLUSIONS: Children with MIS-C are at risk for atrioventricular conduction disease, especially those who require ICU admission and have ventricular dysfunction. ECGs should be monitored for evidence of PR prolongation. Continuous telemetry may be required in patients with evidence of first-degree AVB because of risk of progression to high-grade AVB. ’ cDivision of Immunology and aDepartment of Cardiology, Boston Children’s Hospital, Boston, Massachusetts; and WHAT S KNOWN ON THIS SUBJECT: Children with bDepartment of Pediatrics, Harvard Medical School, Harvard University, Boston, Massachusetts multisystem inflammatory syndrome are at risk for cardiovascular complication, including ventricular Dr Dionne conceptualized and designed the study, collected the data, interpreted the data, drafted dysfunction and coronary artery dilation. the initial manuscript, and reviewed and revised the manuscript; Drs Mah, Son, Lee, and Henderson, Ms Baker, and Drs de Ferranti, Fulton, and Newburger were responsible for acquisition and WHAT THIS STUDY ADDS: Patients with multisystem interpretation of the data and critically reviewed the manuscript for important intellectual content; inflammatory syndrome are also at risk for Dr Friedman conceptualized and designed the study, interpreted the data, and critically reviewed atrioventricular conduction disease, especially those who the manuscript for important intellectual content; and all authors approved the final manuscript as present with hypotension or shock and ventricular submitted. dysfunction. PR prolongation on the electrocardiogram DOI: https://doi.org/10.1542/peds.2020-009704 may be used to identify patients at risk for progression to high-grade atrioventricular block. Accepted for publication Aug 21, 2020 ’ Address correspondence to Audrey Dionne, MD, Department of Cardiology, Boston Childrens To cite: Dionne A, Mah DY, Son MBF, et al. Atrioventricular Hospital, 300 Longwood Ave, Boston, MA 02115. E-mail: [email protected] Block in Children With Multisystem Inflammatory Syndrome. Pediatrics. 2020;146(5):e2020009704 Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 146, number 5, November 2020:e2020009704 ARTICLE The severe acute respiratory 2020. Patients with previously chain reaction (RT-PCR), serology syndrome coronavirus 2 (SARS-CoV- diagnosed atrioventricular test, or antigen test; or exposed to 2) is the cause of the current conduction disease were excluded COVID-19 within the 4 weeks worldwide coronavirus disease 2019 from analysis. This included 1 patient before the onset of symptoms.5 (COVID-19) pandemic, with .5 with cardiac surgery complicated by million confirmed cases in the United complete heart block the week before Hypotension or shock was defined as States. Children were initially thought MIS-C diagnosis. Because most of the requirement for fluid resuscitation to be largely spared from severe cardiac and ECG findings described in (.20 mL/kg) or inotropic support. disease.1,2 In April 2020, initial this series were not applicable to this An elevated troponin T level was reports emerged from the United patient in the immediate defined as a troponin value Kingdom of patients presenting with postoperative period, he was .0.09 ng/mL. An elevated brain Kawasaki disease–like features and excluded from analysis. This study natriuretic peptide (BNP) level was a severe inflammatory syndrome. was approved under exemption from defined as a value .100 pg/mL. Most cases occurred in children informed consent by the Institutional Echocardiograms were reviewed testing positive for current or recent Review Board at Boston Children’s during hospital admission and follow- infection with SARS-CoV-2. Children Hospital. up after discharge for ventricular presented with fever, hypotension, function, valvar function, pericardial effusion, and coronary artery multiorgan involvement, and Data Collection and Definitions markedly elevated inflammatory dimensions. Ventricular dysfunction markers. Gastrointestinal and Data elements, including was defined as a left ventricular myocardial involvement was demographic characteristics, ECG and ejection fraction ,55%. Coronary fi frequently observed, whereas echocardiogram ndings, and artery z scores were calculated for respiratory symptoms were rarely hospital course, were collected from the left main coronary artery, seen.3 Additional cases were reported the electronic medical record. The proximal right coronary artery, and fi throughout Europe4 and America, following criteria were used to de ne proximal left anterior descending 7 leading to a health advisory from the individuals with MIS-C on the basis of artery by using the Boston formula. US Centers for Disease Control and the Centers for Disease Control and Coronary artery dilation was defined fi Prevention in May 2020 for Prevention case de nition: as a coronary artery z score $2 but multisystem inflammatory syndrome • aged ,21 years; ,2.5. On the basis of the American Heart Association guidelines, in children (MIS-C) associated with • presenting with fever ($38.0°C for 5 coronary artery aneurysm was COVID-19. $24 hours); defined as a coronary artery z score • Cardiovascular complications, presenting with laboratory $2.5 and classified as small if the z fl including shock, decreased left evidence of in ammation score was $2.5 to ,5, medium if the $ ventricular systolic function, coronary (including, but not limited to, 1of z score was $5to,10, and large or artery dilation, and aneurysms, were the following: elevated values for giant if the z score was $10 or reported in a high proportion of C-reactive protein, the erythrocyte $8 mm absolute measurement in patients in the initial European sedimentation rate, fibrinogen, 8 3,6 diameter. On the basis of normal reports. In our institutional procalcitonin, d-dimer, ferritin, values for age, first-degree experience, we also observed lactic acid dehydrogenase, or atrioventricular block (AVB) was arrhythmias and electrocardiogram interleukin 6; an elevated defined as delayed conduction (ECG) changes in children with MIS-C. neutrophil count; a reduced (prolonged PR interval) from the In this single-center series, we lymphocyte count; and a low atrium to the ventricle without characterize the incidence of albumin level); interruption in atrial to ventricular arrhythmias and ECG changes in • presenting with evidence of conduction.9 Second-degree AVB was patients with MIS-C. clinically severe illness requiring defined as intermittent atrial hospitalization, with multisystem conduction to the ventricle and METHODS ($2) organ involvement (cardiac, further classified as Mobitz type I renal, respiratory, hematologic, (with progressive PR prolongation Population gastrointestinal, dermatologic, or before the dropped beat) or Mobitz II We completed a retrospective cohort neurologic), and no alternative (without progressive PR prolongation study of children and young adults plausible diagnosis; before the dropped beat). Third- aged 0 to 21 years who were • testing positive for current or degree AVB was defined as no atrial admitted with a diagnosis of MIS-C recent SARS-CoV-2 infection by conduction to the ventricle. between March 1, 2020, and May 30, reverse transcription polymerase Prolonged QTc interval was defined Downloaded from www.aappublications.org/news by guest on September 27, 2021 2 DIONNE et al as a QTc interval in the .98th TABLE 1 Baseline Characteristics of Patients With MIS-C Based on Presence or Absence of Second- or percentile for age and sex.9 All ECGs Third-Degree AVB were reviewed by the investigator All Patients AVB (n = 5) No AVB (n = 20) (A.D.) blinded to patients’ clinical (N = 25) course. Age, y, median