Acute Cardiovascular Manifestations in 286 Children With Multisystem Inflammatory Syndrome Associated With COVID-19 Infection in Europe.

BACKGROUND: The aim of the study was to document cardiovascular clinical findings, cardiac imaging, and laboratory markers in children presenting with the novel multisystem inflammatory syndrome associated with coronavirus disease 2019 (COVID-19) infection. METHODS: This real-time internet-based survey has been endorsed by the Association for European Paediatric and Congenital Cardiologists Working Groups for Cardiac Imaging and Cardiovascular Intensive Care. Children 0 to 18 years of age admitted to a hospital between February 1 and June 6, 2020, with a diagnosis of an inflammatory syndrome and acute cardiovascular complications were included. RESULTS: A total of 286 children from 55 centers in 17 European countries were included. The median age was 8.4 years (interquartile range, 3.8-12.4 years) and 67% were boys. The most common cardiovascular complications were shock, cardiac arrhythmias, pericardial effusion, and coronary artery dilatation. Reduced left ventricular ejection fraction was present in over half of the patients, and a vast majority of children had raised cardiac troponin when checked. The biochemical markers of inflammation were raised in most patients on admission: elevated C-reactive protein, serum ferritin, procalcitonin, N-terminal pro B-type natriuretic peptide, interleukin-6 level, and D-dimers. There was a statistically significant correlation between degree of elevation in cardiac and biochemical parameters and the need for intensive care support (P<0.05). Polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 was positive in 33.6%, whereas immunoglobulin M and immunoglobulin G antibodies were positive in 15.7% cases and immunoglobulin G in 43.6% cases, respectively, when checked. One child in the study cohort died. CONCLUSIONS: Cardiac involvement is common in children with multisystem inflammatory syndrome associated with the Covid-19 pandemic. The majority of children have significantly raised levels of N-terminal pro B-type natriuretic peptide, ferritin, D-dimers, and cardiac troponin in addition to high C-reactive protein and procalcitonin levels. In comparison with adults with COVID-19, mortality in children with multisystem inflammatory syndrome associated with COVID-19 is uncommon despite multisystem involvement, very elevated inflammatory markers, and the need for intensive care support.

Medium-Term Cardiac Outcomes in Young People with Multi-system Inflammatory Syndrome: The Era of COVID-19.

Multi-system inflammatory syndrome in children (MIS-C) causes widespread inflammation including a pancarditis in the weeks following a COVID infection. As we prepare for further coronavirus surges, understanding the medium-term cardiac impacts of this condition is important for allocating healthcare resources. A retrospective single-center study of 67 consecutive patients with MIS-C was performed evaluating echocardiographic and electrocardiographic (ECG) findings to determine the point of worst cardiac dysfunction during the admission, then at intervals of 6-8 weeks and 6-8 months. Worst cardiac function occurred 6.8 ± 2.4 days after the onset of fever with mean 3D left ventricle (LV) ejection fraction (EF) 50.5 ± 9.8%. A pancarditis was typically present: 46.3% had cardiac impairment; 31.3% had pericardial effusion; 26.8% demonstrated moderate (or worse) valvar regurgitation; and 26.8% had coronary dilatation. Cardiac function normalized in all patients by 6-8 weeks (mean 3D LV EF 61.3 ± 4.4%, p < 0.001 compared to presentation). Coronary dilatation resolved in all but one patient who initially developed large aneurysms at presentation, which persisted 6 months later. ECG changes predominantly featured T-wave changes resolving at follow-up. Adverse events included need for ECMO (n = 2), death as an ECMO-related complication (n = 1), LV thrombus formation (n = 1), and subendocardial infarction (n = 1). MIS-C causes a pancarditis. In the majority, discharge from long-term follow-up can be considered as full cardiac recovery is expected by 8 weeks. The exception includes patients with medium sized aneurysms or greater as these may persist and require on-going surveillance.

Electrocardiographic Changes in Children with Multisystem Inflammation Associated with COVID-19: Associated with Coronavirus Disease 2019.

OBJECTIVE: To analyze findings and trends on serial electrocardiograms (ECGs) in multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease taken during the course of illness and at follow-up. STUDY DESIGN: We included all children presenting with MIS-C at a single center with 3 or more ECGs taken during the course of their illness. We measured ECG intervals (PR, QRSd, and QTc) and amplitudes (R-, S-, and T-waves) on each ECG and documented any arrhythmias and ST-segment changes. RESULTS: A majority of children (n = 42, 67%) showed ECG changes. The most common findings were low QRS amplitudes and transient T-wave inversion. ST changes were uncommon and included ST-segment elevation consistent with pericarditis in 1 child and acute coronary ischemia in 1 child. Arrhythmias were seen in 13 children (21%) but were benign with the exception of 1 child who was compromised by an atrial tachycardia requiring support with extracorporeal membrane oxygenation. No children were found to have high-grade atrioventricular block. CONCLUSIONS: MIS-C is associated with electrocardiographic changes over the course of the illness, with low amplitude ECGs on presentation, followed by transient T-wave inversion, particularly in the precordial leads. There was a low prevalence of ST-segment changes and tachyarrhythmias.

How should we diagnose and differentiate hearts with double-outlet right ventricle?

Many, if not most, of the controversies regarding the description of the congenitally malformed heart have been resolved over the turn of the 20th century. A group of lesions that remains contentious is the situation in which both arterial trunks, in their greater part, are supported by the morphologically right ventricle. It was considered, for many years, that presence of bilateral infundibulums, or conuses, was a necessity for such a diagnosis. It has now been appreciated that this suggestion founders on many counts. In the first instance, such bilateral infundibulums are to be found in patients with other ventriculo-arterial connections, including the otherwise normal heart. In the second instance, it is clear that such an approach abrogates the important principle now known as the morphological method. This states that entities should be defined in terms of their intrinsic morphology and not on the basis of other variable features. It is now also clear that, when assessed simply on the basis of the ventricular origin of the arterial trunks, a significant number of patients fulfil the criteria for so-called "200%" origin of the trunks from the right ventricle when there is fibrous continuity between the leaflets of the atrioventricular and arterial valves. In this review, we show how attention to the morphology of the channel between the ventricles now provides the key to accurately diagnose the ventriculo-arterial connection in patients with suspected double-outlet right ventricle. This is because, when both arterial trunks arise exclusively or predominantly from the morphologically right ventricle, the outlet septum, of necessity, is itself a right ventricular structure. The channel between the ventricles, therefore, is roofed by the inner heart curvature, whether that structure is fibrous or muscular. Our observations then confirm that it is the attachment of the outlet septum, which itself can be muscular or fibrous, which determines the commitment of the interventricular communication to the subarterial outlets. The interventricular communication itself, when directly committed to the ventricular outlets, opens between the limbs of the septomarginal trabeculation or septal band. The defect is subaortic when the outlet septum is attached to the cranial limb of the trabeculation, subpulmonary when attached to the caudal limb, and doubly committed when attached to the inner heart curvature in the roof of the defect. Non-committed defects are no longer positioned within the limbs of the septomarginal trabeculation. Although readily demonstrable by a skilled echocardiographer, we show how these anatomical features are more easily demonstrated with added accuracy when using CT data sets.

Multimodality cardiac evaluation in children and young adults with multisystem inflammation associated with COVID-19.

AIMS: Following the peak of the UK COVID-19 epidemic, a new multisystem inflammatory condition with significant cardiovascular effects emerged in young people. We utilized multimodality imaging to provide a detailed sequential description of the cardiac involvement. METHODS AND RESULTS: Twenty consecutive patients (mean age 10.6 ± 3.8 years) presenting to our institution underwent serial echocardiographic evaluation on admission (median day 5 of illness), the day coinciding with worst cardiac function (median day 7), and the day of discharge (median day 15). We performed cardiac computed tomography (CT) to assess coronary anatomy (median day 15) and cardiac magnetic resonance imaging (CMR) to assess dysfunction (median day 20). On admission, almost all patients displayed abnormal strain and tissue Doppler indices. Three-dimensional (3D) echocardiographic ejection fraction (EF) was <55% in half of the patients. Valvular regurgitation (75%) and small pericardial effusions (10%) were detected. Serial echocardiography demonstrated that the mean 3D EF deteriorated (54.7 ± 8.3% vs. 46.4 ± 8.6%, P = 0.017) before improving at discharge (P = 0.008). Left main coronary artery (LMCA) dimensions were significantly larger at discharge than at admission (Z score -0.11 ± 0.87 vs. 0.78 ± 1.23, P = 0.007). CT showed uniform coronary artery dilatation commonly affecting the LMCA (9/12). CMR detected abnormal strain in all patients with global dysfunction (EF <55%) in 35%, myocardial oedema in 50%, and subendocardial infarct in 5% (1/20) patients. CONCLUSIONS: Pancarditis with cardiac dysfunction is common and associated with myocardial oedema. Patients require close monitoring due to coronary artery dilatation and the risk of thrombotic myocardial infarction.

Echocardiographic predictors of reoperation for subaortic stenosis in children and adults.

OBJECTIVES: Subaortic stenosis (SAS) can present as various types of obstruction of the left ventricular outflow tract (LVOT) below the level of the aortic valve. Even though corrective surgery has been identified as the most effective treatment, SAS more frequently reoccurs requiring reoperation in a significant proportion of the patients. Previous studies have focused on predictors of recurrence in various subgroups of patients with SAS, but rarely in the overall population of patients with SAS. The aim of this study was to determine the predictors of recurrence of SAS after initial corrective surgery. METHODS: Patients from the database of the Congenital Cardiology Department of the University Hospital of Southampton with significant SAS requiring corrective surgery were included in the study. Data retrieved were obtained and used to determine the predictors of SAS recurrence after the initial corrective surgery. RESULTS: Eighty-two patients (paediatric, n = 72 and adult, n = 10) who underwent initial successful resection were included in the analysis. Thirty patients required reoperation for recurrent SAS. These were significantly younger (median age 3.0 vs 6.7 years, P = 0.002). The recurrence of SAS was more common in patients with an interrupted aortic arch (23.3% vs 3.8%, P = 0.010) and unfavourable left ventricle geometry (43.3% vs 7.6%, P < 0.001), with steeper aortoseptal angle (131.0° ± 8.7° vs 136.1° ± 8.6°, P = 0.030), shorter distance between the point of obstruction of the LVOT and the aortic valve annulus in systole and diastole (median 4.30 vs 5.90 mm, P = 0.003 and 3.65 vs 4.95 mm, P = 0.006, respectively) and in those who had higher residual peak and mean LVOT gradients postoperatively (29.3 ± 16.0 vs 19.8 ± 10.7 mmHg, P = 0.006 and 15.9 ± 8.3 vs 10.1 ± 5.8 mmHg, P = 0.002, respectively). Overall, the presence of an interrupted aortic arch [odds ratio (OR) 10.34, 95% confidence interval (CI) 1.46-73.25; P < 0.019] and unfavourable left ventricle geometry (OR 10.42, 95% CI 1.86-58.39; P < 0.008) could independently predict reoperation for SAS after initial successful resection. CONCLUSIONS: Patients who have initial corrective surgery for SAS at a younger age, unfavourable left ventricle geometry, an interrupted aortic arch and higher early postoperative LVOT gradients are more likely to have recurrent SAS requiring reoperation.

Morbidity and mortality patterns in small-for-gestational age infants born preterm.

OBJECTIVE: Small-for-gestational age (SGA) neonates born prematurely may be at higher risk for adverse effects during the early postnatal period than premature neonates born appropriate for gestational age (AGA).This study aims to study comparatively morbidity and mortality in SGA and AGA neonates born with low gestational age (GA). METHODS: The study population included all preterm infants born alive with GA 24-31 weeks in Northwestern Greece during a 9-year period and hospitalized in the regional neonatal intensive care unit (NICU). The association of SGA status with neonatal death, and with chronic lung disease (CLD), intraventricular haemorrhage (IVH), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), respiratory distress syndrome (RDS), patent ductus arteriosus (PDA), and sepsis was assessed, using multiple logistic regression analysis. RESULTS: Of 210 infants without congenital anomalies born at GA 24-31 weeks, 51 were SGA and 159 were AGA. CLD was more common in SGA than in AGA neonates (57.1% vs 29.3%, p < 0.05), but no differences were found in the rates of IVH, NEC, ROP, RDS, and sepsis. The mortality rate in the SGA group was 33.3% vs 17% in the AGA group (p < 0.01), and in the subgroups 28-31 weeks 24.1% vs 6.3%, respectively, (p < 0.01). In logistic regression analysis, SGA status was strongly associated with increased mortality and CLD, independent of confounding factors [odd ratios and confidence intervals: 3.4 (CI: 1.8-10.6) p = 0.03 and 3.9 (CI: 1.7-11.5) p < 0.01, respectively. CONCLUSIONS: SGA neonates with GA 24-31 weeks were at increased risk of development of CLD and of neonatal death compared with AGA neonates of the same GA.

Renal glomerular and tubular function in neonates with perinatal problems.

OBJECTIVE: To investigate perinatal risk factors that may be associated with impaired renal function during the first 2 weeks of life. METHODS: The case notes of 150 neonates of gestational age (GA) 34-36 weeks and 494 of GA > 36 weeks were studied. Clinical risk factors were retrieved, along with indices of renal function: serum creatinine (SeCr), fractional excretion (FE) of sodium (FENa) and potassium (FEK), and the urinary calcium to creatinine ratio (UCa/UCr). Associations were identified by multiple and logistic regression analysis. RESULTS: In infants with GA > 36 weeks, raised SeCr was related to perinatal stress, odds ratio (OR): 1.9, confidence interval (CI): 1.2-2.9, p < 0.05, and to duration of treatment with aminoglycosides (AGs) (t = 2.4, p < 0.01); FEK was associated with jaundice (t = -3.1, p < 0.01), and FENa with duration of AGs treatment (t = 2.6, p < 0.01). Full-term neonates with both hypoxic-ischemic encephalopathy (HIE) and AGs administration had an 80% increase in OR for impaired SeCr levels. In infants of GA 34-36 weeks, SeCr was related to perinatal stress (OR: 9, CI: 1.3-38, p < 0.05), FEK to jaundice (t = -2.1, p < 0.05), and FENa to duration of AGs administration (t = 2.2, p < 0.05) and antenatal steroid treatment (OR: 0.8, CI: 0.6-0.95, p < 0.05). CONCLUSION: In neonates, renal impairment, being multifactorial in origin, may be caused by the additive effect of different perinatal factors. The strong negative relationship observed between jaundice and K excretion merits further investigation.

Low gestational age and chronic lung disease are synergistic risk factors for retinopathy of prematurity.

AIMS: This retrospective, population based study was designed to investigate risk factors for development of retinopathy of prematurity (ROP) and their possible interrelationships, in neonates of gestational age (GA) <32 weeks born in a well-defined geographical region. STUDY DESIGN-SUBJECTS: The study population included all preterm infants born alive with GA 24-32 weeks in Northwestern Greece during a 9-year period and hospitalised in the regional neonatal intensive care unit (NICU). OUTCOME MEASUREMENTS: The association was assessed of the presence of ROP with maternal factors: age, pathology of pregnancy, in-vitro fertilisation, multiple gestation, mode of delivery, perinatal factors: gender, antenatal steroids, transportation, resuscitation, GA, birth weight (BW), small for GA status and postnatal morbidity: chronic lung disease (CLD), intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC), respiratory distress syndrome (RDS), maximum O(2) needs, hypoxic/hyperoxic episodes, patent ductus arteriosus (PDA), sepsis, using multiple logistic regression analysis. RESULTS: Of 189 infants without congenital anomalies born at GA 24-32 weeks ROP was diagnosed in 24 (12.7%) (>grade 2: 6). Logistic regression analysis showed ROP to be strongly associated with GA, odds ratio (OR) 2.1, confidence interval (CI) 1.3-3.3, p<0.01 and CLD, OR 10.2, CI 2.3-44, p<0.01, respectively, independent of confounding factors. By estimating interaction on an additive scale it was shown that the combined risk effect of GA and CLD was larger than the sum of the individual risk effects, implying synergistic effect. CONCLUSIONS: ROP was closely and independently related to both low GA and the diagnosis of CLD, which were interrelated in the development of ROP.

Changes in vascular function and structure in juvenile idiopathic arthritis.

OBJECTIVE: Chronic inflammatory diseases in adults have been associated with increased cardiovascular risk and impaired vascular function. We aimed to assess the presence of early vascular dysfunction in patients with juvenile idiopathic arthritis (JIA) and investigate the role of inherent inflammatory process of JIA in vascular health. METHODS: Thirty patients with JIA (age range 7-18 years) were compared to 33 age- and sex-matched controls. Endothelial function (brachial artery flow-mediated dilation [FMD]), carotid intima-media thickness (IMT), and arterial stiffness were examined. Endothelial inflammation was assessed by intercellular adhesion molecule 1 (ICAM-1) and P-selectin measurements. RESULTS: Patients with JIA showed decreased FMD compared to controls (P = 0.001), independent of age (P = 0.9 among age subgroups). Baseline differences in erythrocyte sedimentation rate, ICAM-1, and glucose between the 2 groups accounted for the difference in FMD. The presence of systemic JIA was associated with greater IMT compared to patients with oligoarticular disease, polyarticular disease, or controls (P = 0.014, P = 0.069, and P = 0.046, respectively). The difference in IMT between systemic versus oligoarticular/polyarticular JIA was attributed to the following risk factors: age, body mass index, blood pressure, disease activity, and corticosteroids use. There were no differences in arterial stiffness indices between JIA patients and controls or between patients with systemic versus nonsystemic disease. CONCLUSION: Endothelial function is impaired in patients with JIA at a very young age, while IMT is increased only in the presence of systemic JIA. Vascular dysfunction may be partly attributed to the effects of disease-related characteristics (inflammation, disease activity, and medications).

Serum transferrin receptor, ferritin, and reticulocyte maturity indices during the first year of life in 'large' preterm infants.

BACKGROUND: Preterm infants are at risk of developing iron deficiency; among the iron status and hemopoiesis indices the serum transferrin receptor (sTfr) has been shown to be a useful indicator in assessing iron status, while immature reticulocyte production is regarded as an estimator of erythropoiesis. OBJECTIVE: To investigate age-related changes in iron status infants born 'moderately' preterm, with a gestational age (GA) of 32-36 wk, and identify associations between sTfr and other hematological and biochemical iron indices. DESIGN: Hospital-based prospective, longitudinal study in preterm infants. METHODS: Iron and erythropoiesis parameters were evaluated in 181 formula-fed preterm infants at 2 and 6 wk and 3, 6, 9, and 12 months chronological age. Hemoglobulin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), reticulocytes, serum iron (sFe), serum ferritin (sFer), sTfr, and reticulocyte subpopulations were measured. RESULTS: A total of 756 measurements were performed. After an initial decline, Hb rose from month 3 to 12 of life. SFe and sFer and immature reticulocyte count decreased from the second week to the third month and remained stable thereafter. STfr was lower up to 6 wk and stable from month 3 to 12. Iron deficiency anemia (IDA) was found in 5.5% of infants. In 76 measurements sFer was <12 microg/L, implying storage iron deficiency (SID). A negative correlation was observed between sTfr and other indices of iron status such as Hb, Hct, MCV, sFe, and sFer. Infants with sFer <12 microg/L had lower sTfr than those with sFer >12 microg/L. Reticulocyte production was positively associated with STfr, but this association was dependent on the chronological age of the infant. CONCLUSION: Iron depletion is common in formula-fed preterm (32-36 wk GA) infants between month 3 and 12 of life. STfr appears to be an indicator of iron status in preterm infants during the first year of life.