Cardiac injury and myocarditis have been described in adults with coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is typically ...minimally symptomatic. We report a series of febrile pediatric patients with acute heart failure potentially associated with SARS-CoV-2 infection and the multisystem inflammatory syndrome in children as defined by the US Centers for Disease Control and Prevention.
Over a 2-month period, contemporary with the SARS-CoV-2 pandemic in France and Switzerland, we retrospectively collected clinical, biological, therapeutic, and early outcomes data in children who were admitted to pediatric intensive care units in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state.
Thirty-five children were identified and included in the study. Median age at admission was 10 years (range, 2-16 years). Comorbidities were present in 28%, including asthma and overweight. Gastrointestinal symptoms were prominent. Left ventricular ejection fraction was <30% in one-third; 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation. Inflammation markers were suggestive of cytokine storm (interleukin-6 median, 135 pg/mL) and macrophage activation (D-dimer median, 5284 ng/mL). Mean BNP (B-type natriuretic peptide) was elevated (5743 pg/mL). Thirty-one of 35 patients (88%) tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. All patients received intravenous immunoglobulin, with adjunctive steroid therapy used in one-third. Left ventricular function was restored in the 25 of 35 of those discharged from the intensive care unit. No patient died, and all patients treated with extracorporeal membrane oxygenation were successfully weaned.
Children may experience an acute cardiac decompensation caused by severe inflammatory state after SARS-CoV-2 infection (multisystem inflammatory syndrome in children). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.
To describe presentation, hospital course, and predictors of bad outcome in multisystem inflammatory syndrome in children (MIS-C).
Retrospective data review of a case series of children meeting the ...published definition for MIS-C who were discharged or died between March 1, 2020, and June 15, 2020, from 33 participating European, Asian, and American hospitals. Data were collected through a Web-based survey and included clinical, laboratory, electrocardiographic, and echocardiographic findings and treatment management.
We included 183 patients with MIS-C: male sex, 109 (59.6%); mean age 7.0 ± 4.7 years; Black race, 56 (30.6%); obesity, 48 (26.2%). Overall, 114 of 183 (62.3%) had evidence of severe acute respiratory syndrome coronavirus 2 infection. All presented with fever, 117 of 183 (63.9%) with gastrointestinal symptoms, and 79 of 183 (43.2%) with shock, which was associated with Black race, higher inflammation, and imaging abnormalities. Twenty-seven patients (14.7%) fulfilled criteria for Kawasaki disease. These patients were younger and had no shock and fewer gastrointestinal, cardiorespiratory, and neurologic symptoms. The remaining 77 patients (49.3%) had mainly fever and inflammation. Inotropic support, mechanical ventilation, and extracorporeal membrane oxygenation were indicated in 72 (39.3%), 43 (23.5%), and 4 (2.2%) patients, respectively. A shorter duration of symptoms before admission was found to be associated with poor patient outcome and for extracorporeal membrane oxygenation and/or death, with 72.3% (95% confidence interval: 0.56-0.90;
= .006) increased risk per day reduction and 63.3% (95% confidence interval: 0.47-0.82;
< .0001) increased risk per day reduction respectively.
In this case series, children with MIS-C presented with a wide clinical spectrum, including Kawasaki disease-like, life-threatening shock and milder forms with mainly fever and inflammation. A shorter duration of symptoms before admission was associated with a worse outcome.
The European Pediatric Pulmonary Vascular Disease Network is a registered, non-profit organization that strives to define and develop effective, innovative diagnostic methods and treatment options in ...all forms of pediatric pulmonary hypertensive vascular disease, including pulmonary hypertension (PH) associated with bronchopulmonary dysplasia, PH associated with congenital heart disease (CHD), persistent PH of the newborn, and related cardiac dysfunction. The executive writing group members conducted searches of the PubMed/MEDLINE bibliographic database (1990-2018) and held face-to-face and web-based meetings. Ten section task forces voted on the updated recommendations, based on the 2016 executive summary. Clinical trials, meta-analyses, guidelines, and other articles that include pediatric data were searched using the term "pulmonary hypertension" and other keywords. Class of recommendation (COR) and level of evidence (LOE) were assigned based on European Society of Cardiology/American Heart Association definitions and on pediatric data only, or on adult studies that included >10% children or studies that enrolled adults with CHD. New definitions by the World Symposium on Pulmonary Hypertension 2018 were included. We generated 10 tables with graded recommendations (COR/LOE). The topics include diagnosis/monitoring, genetics/biomarkers, cardiac catheterization, echocardiography, cardiac magnetic resonance/chest computed tomography, associated forms of PH, intensive care unit/lung transplantation, and treatment of pediatric PH. For the first time, a set of specific recommendations on the management of PH in middle- and low-income regions was developed. Taken together, these executive, up-to-date guidelines provide a specific, comprehensive, detailed but practical framework for the optimal clinical care of children and young adults with PH.
Abstract Hypertension continues to be a common and potentially serious problem in patients who have undergone anatomically successful repair of aortic coarctation. Objective To assess the prevalence ...of hypertension after aortic coarctation repair, the factors that affect the prevalence and the hypotheses behind hypertension in this cohort of patients. Design A systematic review of all articles reporting on systolic blood pressure (SBP) in patients who have undergone aortic coarctation repair. Data sources An electronic search of all English articles using PUBMED and The Cochrane Controlled Trials Register was performed. A manual search of references lists of relevant studies and a search of conference abstracts were also conducted. Inclusion criteria We restricted inclusion to articles published between 1987 and 2012 that reported on SBP in patients who have undergone aortic coarctation repair. Data extraction Independent extraction of articles was performed by two authors using predefined data fields. One author then proceeded to extract information of interest from these articles. Results The first search yielded 12,914 articles. After screening titles, abstracts and full text articles 26 articles were included in this review article. In papers reporting the prevalence of hypertension late after anatomically satisfactory coarctation repair, the median prevalence was 32.5% (range 25–68%). Conclusion Hypertension remains a common complication following aortic coarctation repair. Factors that influence the reported prevalence of hypertension include the age at the time of surgery, age at follow up, the method used to measure blood pressure and the type of intervention performed.
Abstract Background Myocarditis is inflammation of the heart muscle that can follow various viral infections. Why children only rarely develop life-threatening acute viral myocarditis (AVM), given ...that the causal viral infections are common, is unknown. Genetic lesions might underlie such susceptibilities. Mouse genetic studies demonstrated that interferon (IFN)-α/β immunity defects increased susceptibility to virus-induced myocarditis. Moreover, variations in human TLR3 , a potent inducer of IFNs, were proposed to underlie AVM. Objectives This study sought to evaluate the hypothesis that human genetic factors may underlie AVM in previously healthy children. Methods We tested the role of TLR3-IFN immunity using human induced pluripotent stem cell-derived cardiomyocytes. We then performed whole-exome sequencing of 42 unrelated children with acute myocarditis (AM), some with proven viral causes. Results We found that TLR3- and STAT1 -deficient cardiomyocytes were not more susceptible to Coxsackie virus B3 (CVB3) infection than control cells. Moreover, CVB3 did not induce IFN-α/β and IFN-α/β-stimulated genes in control cardiomyocytes. Finally, exogenous IFN-α did not substantially protect cardiomyocytes against CVB3. We did not observe a significant enrichment of rare variations in TLR3- or IFN-α/β-related genes. Surprisingly, we found that homozygous but not heterozygous rare variants in genes associated with inherited cardiomyopathies were significantly enriched in AM-AVM patients compared with healthy individuals (p = 2.22E-03) or patients with other diseases (p = 1.08E-04). Seven of 42 patients (16.7%) carried rare biallelic (homozygous or compound heterozygous) nonsynonymous or splice-site variations in 6 cardiomyopathy-associated genes ( BAG3 , DSP , PKP2 , RYR2 , SCN5A , or TNNI3 ). Conclusions Previously silent recessive defects of the myocardium may predispose to acute heart failure presenting as AM, notably after common viral infections in children.
Pulmonary veno-occlusive disease (PVOD) is a rare and devastating cause of pulmonary hypertension that is characterized histologically by widespread fibrous intimal proliferation of septal veins and ...preseptal venules and is frequently associated with pulmonary capillary dilatation and proliferation. PVOD is categorized into a separate pulmonary arterial hypertension-related group in the current classification of pulmonary hypertension. PVOD presents either sporadically or as familial cases with a seemingly recessive mode of transmission. Using whole-exome sequencing, we detected recessive mutations in EIF2AK4 (also called GCN2) that cosegregated with PVOD in all 13 families studied. We also found biallelic EIF2AK4 mutations in 5 of 20 histologically confirmed sporadic cases of PVOD. All mutations, either in a homozygous or compound-heterozygous state, disrupted the function of the gene. These findings point to EIF2AK4 as the major gene that is linked to PVOD development and contribute toward an understanding of the complex genetic architecture of pulmonary hypertension.
Diastolic dysfunction refers to a structural or functional abnormality of the left ventricle, resulting in impaired filling of the heart. Severe diastolic dysfunction can lead to congestive heart ...failure even when the left ventricle systolic function is normal. Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of the hospitalizations for acute heart failure in the adult population but the clinical recognition and understanding of HFpEF in children is poor. The condition is certainly much less frequent than in the adult population but the confirmatory diagnosis of diastolic dysfunction in children is also challenging. The underlying causes of HFpEF in children are diverse and differ from the main cause in adults. This review addresses the underlying causes and prognostic factors of HFpEF in children. We describe the pulmonary hypertension profiles associated with this cardiac condition. We discuss diagnosis difficulties in clinical practice, and we provide a simplified diagnostic algorithm for HFpEF in children.
Pediatric Pulmonary Hypertension Ivy, D. Dunbar, MD; Abman, Steven H., MD; Barst, Robyn J., MD ...
Journal of the American College of Cardiology,
12/2013, Letnik:
62, Številka:
25
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
Pulmonary hypertension (PH) is a rare disease in newborns, infants, and children that is associated with significant morbidity and mortality. In the majority of pediatric patients, PH is idiopathic ...or associated with congenital heart disease and rarely is associated with other conditions such as connective tissue or thromboembolic disease. Incidence data from the Netherlands has revealed an annual incidence and point prevalence of 0.7 and 4.4 for idiopathic pulmonary arterial hypertension and 2.2 and 15.6 for pulmonary arterial hypertension, respectively, associated with congenital heart disease (CHD) cases per million children. The updated Nice classification for PH has been enhanced to include a greater depth of CHD and emphasizes persistent PH of the newborn and developmental lung diseases, such as bronchopulmonary dysplasia and congenital diaphragmatic hernia. The management of pediatric PH remains challenging because treatment decisions continue to depend largely on results from evidence-based adult studies and the clinical experience of pediatric experts.
A ventricular septal defect (VSD) is an integral part of most congenital heart defects (CHD). To determine the prevalence of VSD in various types of CHD and the distribution of their anatomic types.
...We reviewed 1178 heart specimens with CHD from the anatomic collection of the French Reference Centre for Complex Congenital Heart Defects. During the morphologic study a special attention was paid to the localisation of the VSD viewed from the right ventricular side. The VSDs were classified as muscular, central perimembranous, outlet located between the two limbs of the septal band, and inlet. The specimens were classified according to the 9 categories and 23 subcategories of the anatomic and clinical classification of CHD1 (ACC-CHD).
Ventricular septum was almost always intact in anomalies of pulmonary veins (4/73, 5%), Ebstein anomaly (3/21, 14%), and double-inlet right ventricle (DIRV, 1/10, 10%). There was always a VSD in tetralogy of Fallot and variants (TOF, 123 cases) and common arterial trunk (CAT, 55 cases), always of the outlet type. There was almost always a VSD in double inlet left ventricle (33/34, 97%, always muscular), congenitally corrected transposition of great arteries (ccTGA, 23/24, 96%), interrupted aortic arch (IAA, 25/27, 93%), and double outlet right ventricle (DORV, 92/106, 87%). A VSD was found in 68% of aortic coarctation (CoA, 43/63), 62% of heterotaxy syndromes (21/34), 54% of transposition of the great arteries (TGA, 104/194). The VSD was located between the two limbs of the septal band in 100% of TOF and CAT, 80% of IAA, 77% of DORV, 82% of DD. The VSD was of the inlet type in 17% of cc TGA and in 71% of heterotaxy syndromes. In TGA, the VSD was outlet in 40%, central perimembranous in 25%, muscular in 25%, inlet in 10%. In CoA, the VSD was outlet in 44%, central perimembranous in 35%, muscular in 21%. In the 10% hearts with isolated VSD, the distribution was outlet in 44%, central perimembranous in 36%, muscular in 18%, and inlet in 2%.
The anatomic distribution of VSD is similar in isolated VSD, CoA and TGA, while the VSD is predominantly outlet in outflow tract defects except TGA. This reinforces the allegedly different mechanisms in TGA and cardiac neural crest defects. This anatomic approach could provide new insights in the grouping and aetiology of CHD.
Abstract Background Pre-natal diagnosis of congenital heart disease (CHD) allows anticipation of urgent neonatal treatment and provides adequate information to the parents on cardiac outcomes. ...Objectives This study sought to analyze the discordances between expert fetal cardiac diagnosis and final diagnosis of CHD and their impact on neonatal and long-term care strategies. Methods We included 1,258 neonates with a pre-natally diagnosed CHD and 189 fetopsies following termination of pregnancy at our tertiary center over a 10-year period. Pre-natal echocardiographic and final diagnoses were compared. Results For live births, we identified 368 (29.3%) discordances between pre- and post-natal diagnoses. The pre-natal diagnosis was different from the post-natal diagnosis in 36 cases (2.9%) and partially different with a major impact on neonatal treatment of the CHD in 97 cases (7.7%). In 235 cases (18.7%), the diagnosis was partially different with no impact on neonatal planned treatment. The discordances had a negative impact on late care strategy in 62 cases (4.9%): more complex CHD that was unsuitable for biventricular repair, leading to unplanned compassionate care, additional surgery or increase of the complexity level of the Aristotle score. A positive impact was found in 31 cases (2.5%): less complex CHD that allowed biventricular repair, fewer surgical procedures, or decrease of the complexity of the Aristotle score. For 275 patients (21.9%), there was no impact on late care strategy. Of the 872 terminations of pregnancy and intrauterine fetal deaths, 189 fetopsies were available: 16 (8.5%) different diagnoses, 27 (14.3%) major differences, and 60 (31.7%) minor differences. Conclusions Correcting fetal cardiac diagnosis after birth can lead to significant changes in neonatal (10.6%) and late (7.4%) care strategies. Tools should be developed to try to improve the accuracy of pre-natal diagnosis of CHD. Clinicians should be cautious when predicting required treatment and outcomes during pre-natal counseling.
PDF
