Clinical presentation and early predictors for poor outcomes in pediatric myocarditis:A retrospective study

BACKGROUND Myocarditis is an important cause of morbidity and mortality in children, leading to long-term sequelae including chronic congestive heart failure, dilated cardiomyopathy, heart transplantation, and death. The initial diagnosis of myocarditis is usually based on clinical presentation, but this widely ranges from the severe sudden onset of a cardiogenic shock to asymptomatic patients. Early recognition is essential in order to monitor and start supportive treatment prior to the development of severe adverse events. Of note, many cases of fulminant myocarditis are usually misdiagnosed as otherwise minor conditions during the weeks before the unexpected deterioration.AIM To provide diagnostic clues to make an early recognition of pediatric myocarditis.To investigate early predictors for poor outcomes.METHODS We conducted a retrospective cross-sectional single-center study from January 2008 to November 2017 at the Pediatric Department of our institution, including children < 18-years-old diagnosed with myocarditis. Poor outcome was defined as the occurrence of any of the following facts: death, heart transplant, persistent left ventricular systolic dysfunction or dilation at hospital discharge(early poor outcome), or after 1 year of follow-up(late poor outcome). We analyzed different clinical features and diagnostic test findings in order to provide diagnostic clues for myocarditis in children. Multivariable stepwise logistic regression analysis was performed using all variables that had been selected by univariate analysis to determine independent factors that predicted a poor early or late outcome in our study population.RESULTS A total of 42 patients [69% male; median age of 8(1.5-12) years] met study inclusion criteria. Chest pain(40%) was the most common specific cardiac symptom. Respiratory tract symptoms(cough, apnea, rhinorrhea)(38%),shortness of breath(35%), gastrointestinal tract symptoms(vomiting, abdominal pain, diarrhea)(33%), and fever(31%) were the most common non-cardiac initial complaints. Tachycardia(57%) and tachypnea(52%) were the most common signs on the initial physical exam followed by nonspecific signs of respiratory tract infection(44%) and respiratory distress(35%). Specific abnormal signs of heart failure such as heart murmur(26%), systolic hypotension(24%), gallop rhythm(20%), or hepatomegaly(20%) were less prevalent. Up to 43% of patients presented an early poor outcome, and 16% presented a late poor outcome. In multivariate analysis, an initial left ventricular ejection fraction(LVEF) < 30%remained the only significant predictor for early [odds ratio(OR)(95%CI) = 21(2-456), P = 0.027) and late [OR(95%CI) = 8(0.56-135), P = 0.047) poor outcome in children with myocarditis. LVEF correlated well with age(r = 0.51, P = 0.005),days from the initiation of symptoms(r =-0.31, P = 0.045), and N-terminal probrain natriuretic peptide levels(r = 0.66, P < 0.001), but not with troponin T(r =-0.05, P = 0.730) or C-reactive protein levels(r =-0.13, P = 0.391). N-terminal probrain natriuretic peptide presented a high diagnostic accuracy for LVEF < 30% on echocardiography with an area under curve of 0.931(95%CI: 0.858-0.995, P <0.001). The best cut-off point was 2000 pg/mL with a sensitivity of 90%,specificity of 81%, positive predictive value of 60%, and negative predictive value of 96%.CONCLUSION The diagnosis of myocarditis in children is challenging due to the heterogeneous and unspecific clinical presentation. The presence of LVEF < 30% on echocardiography on admission was the major predictor for poor outcomes.Younger ages, a prolonged course of the disease, and N-terminal pro-brain natriuretic peptide levels could help to identify these high-risk patients.

Cardiovascular impact of COVID-19 with a focus on children: A systematic review

BACKGROUND Since the beginning of the pandemic,coronavirus disease-2019(COVID-19)in children has shown milder cases and a better prognosis than adults.Although the respiratory tract is the primary target for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),cardiovascular involvement is emerging as one of the most significant and life-threatening complications of SARS-CoV-2 infection in adults.AIM To summarize the current knowledge about the potential cardiovascular involvement in pediatric COVID-19 in order to give a perspective on how to take care of them during the current pandemic emergency.METHODS Multiple searches in MEDLINE,PubMed were performed using the search terms“COVID-19”or“SARS-CoV-2"were used in combination with“myocardial injury”or"arrhythmia"or“cardiovascular involvement”or"heart disease"or"congenital heart disease"or“pulmonary hypertension”or"long QT"or“cardiomyopathies”or“channelopathies”or"Multisystem inflammatory system"or"PMIS"or“MIS-C”or”Pediatric multisystem inflammatory syndrome"or"myocarditis"or"thromboembolism to identify articles published in English language from January 1st,2020 until July 31st,2020.The websites of World Health Organization,Centers for Disease control and Prevention,and the Johns Hopkins Coronavirus Resource Center were reviewed to provide up to date numbers and infection control recommendations.Reference lists from the articles were reviewed to identify additional pertinent articles.Retrieved manuscripts concerning the subject were reviewed by the authors,and the data were extracted using a standardized collection tool.Data were subsequently analyzed with descriptive statistics.For Pediatric multisystemic inflammatory syndrome temporally associated with COVID-19(PMIS),multiple meta-analyses were conducted to summarize the pooled mean proportion of different cardiovascular variables in this population in pseudo-cohorts of observed patients.RESULTS A total of 193 articles were included.Most publications used in this review were single case reports,small case series,and observational small-sized studies or literature reviews.The meta-analysis of 16 studies with size>10 patients and with complete data about cardiovascular involvement in children with PMIS showed that PMIS affects mostly previously healthy school-aged children and adolescents presenting with Kawasaki disease-like features and multiple organ failure with a focus on the heart,accounting for most cases of pediatric COVID-19 mortality.They frequently presented cardiogenic shock(53%),ECG alterations(27%),myocardial dysfunction(52%),and coronary artery dilation(15%).Most cases required PICU admission(75%)and inotropic support(57%),with the rare need for extracorporeal membrane oxygenation(4%).Almost all of these children wholly recovered in a few days,although rare deaths have been reported(2%).Out of PMIS cases we identified 10 articles reporting sporadic cases of myocarditis,pulmonary hypertension and cardiac arrythmias in previously healthy children.We also found another 10 studies reporting patients with preexisting heart diseases.Most cases consisted in children with severe COVID-19 infection with full recovery after intensive care support,but cases of death were also identified.The management of different cardiac conditions are provided based on current guidelines and expert panel recommendations.CONCLUSION There is still scarce data about the role of cardiovascular involvement in COVID-19 in children.Based on our review,children(previously healthy or with preexisting heart disease)with acute COVID-19 requiring hospital admission should undergo a cardiac workup and close cardiovascular monitoring to identify and treat timely life-threatening cardiac complications.

Age-adjusted NT-proBNP could help in the early identification and follow-up of children at risk for severe multisystem inflammatory syndrome associated with COVID-19(MIS-C)

BACKGROUND Multisystem inflammatory syndrome in children(MIS-C) has emerged as a new disease associated with COVID-19 that presents in acute critically ill children with acute cardiovascular dysfunction.AIM To determine whether the age-adjusted N-terminal pro-brain natriuretic peptide(NT-proBNP) value(Z-log-NT-proBNP) is associated with severe MIS-C and myocardial dysfunction.METHODS A retrospective study was conducted which included children with MIS-C managed at our institution between April 1,2020,and February 28,2022.We divided the population into groups depending on severity based on pediatric intensive care unit(PICU) admission.We compared Z-log-NT-proBNP values across these groups and analyzed Z-log-NT-proBNP dynamics during the onemonth follow-up.RESULTS We included 17 participants [median age 3(2-9) years] and seven(41%) required PICU admission.All(100%) of these cases presented very high(Z-log > 4) levels of NT-proBNP at the time of admission compared to only 5(50%) patients with non-severe MIS-C(P = 0.025).NT-proBNP was significantly correlated with highsensitive Troponin I levels(P = 0.045),Ross modified score(P = 0.003) and left ventricle ejection fraction(P = 0.021).CONCLUSION Raised NT-proBNP,specifically very high values(Z-log-NT-proBNP > 4) could help in the early identification of MIS-C patients with myocardial dysfunction requiring inotropic support and PICU admission.