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.
Pulmonary hypertension (PH) is diagnosed using cardiac catheterization and is defined as an elevation of mean pulmonary artery pressure (PAP) greater than 25 mmHg. Although invasive hemodynamics ...remains the gold standard and is mandatory for disease confirmation, transthoracic echocardiography (TTE) is an extremely useful non-invasive and widely available tool that allows for screening and follow-up, in particular, in the acute setting. TTE may be a valuable alternative, allowing for direct measurement and/or indirect assessment of PAP. Because of the complex geometric shape and pattern of contraction of the right ventricle (RV), as well as the inherent complexity of cardiac repair, no single view or measurement can provide definite information on RV function and PAP and/or pulmonary vascular resistance. In addition, specific training and expertise may be necessary to obtain the views and measurements required. Some simple measurements may be of help when rapid evaluation is mandatory and potentially life saving: the assessment of tricuspid and/or pulmonary valve regurgitant jet and the use of the Bernoulli equation allow for measurement of PAP. Measurements such as the analysis of the pulmonary Doppler wave flow, the septal curvature, or the eccentricity index, assessing ventricular interdependence, are useful for indirect assessment. A four-chamber view of the RV gives information on its size, hypertrophy, function (fractional area change), and tricuspid annular plane systolic excursion as an evaluation of the longitudinal function. Based on these simple measurements, TTE can provide detection of PH, measurement or estimation of PAP, and assessment of cardiac function. TTE is also of importance in follow up of PH as well as providing an assessment of therapeutic strategies in the postoperative setting of cardiac surgery. However, PAP may be misleading as it is dependent on cardiac output and requires accurate measurements. In the presence of residual lesions, analyses of some Doppler measurements may be misleading and not reflect real PAP. Should the TTE evaluation reveal non-conclusive, invasive hemodynamics remains the gold standard.
Objectives The aim of this study was to determine the effects of physical activity on systemic blood pressure (BP) and early markers of atherosclerosis in pre-pubertal obese children. Background ...Hypertension and endothelial dysfunction are premature complications of obesity. Methods We performed a 3-month randomized controlled trial with a modified crossover design: 44 pre-pubertal obese children (age 8.9 ± 1.5 years) were randomly assigned (1:1) to an exercise (n = 22) or a control group (n = 22). We recruited 22 lean children (age 8.5 ± 1.5 years) for baseline comparison. The exercise group trained 60 min 3 times/week during 3 months, whereas control subjects remained relatively inactive. Then, both groups trained twice/week during 3 months. We assessed changes at 3 and 6 months in office and 24-h BP, arterial intima-media thickness (IMT) and stiffness, endothelial function (flow-mediated dilation), body mass index (BMI), body fat, cardiorespiratory fitness (maximal oxygen consumption VO2 max), physical activity, and biological markers. Results Obese children had higher BP, arterial stiffness, body weight, BMI, abdominal fat, insulin resistance indexes, and C-reactive protein levels, and lower flow-mediated dilation, VO2 max, physical activity, and high-density lipoprotein cholesterol levels than lean subjects. At 3 months, we observed significant changes in 24-h systolic BP (exercise −6.9 ± 13.5 mm Hg vs. control 3.8 ± 7.9 mm Hg, −0.8 ± 1.5 standard deviation score SDS vs. 0.4 ± 0.8 SDS), diastolic BP (−0.5 ± 1.0 SDS vs. 0 ± 1.4 SDS), hypertension rate (−12% vs. −1%), office BP, BMI z -score, abdominal fat, and VO2 max. At 6 months, change differences in arterial stiffness and IMT were significant. Conclusions A regular physical activity program reduces BP, arterial stiffness, and abdominal fat; increases cardiorespiratory fitness; and delays arterial wall remodeling in pre-pubertal obese children. (Effects of Aerobic Exercise Training on Arterial Function and Insulin Resistance Syndrome in Obese Children: A Randomized Controlled Trial; NCT00801645 )
In order to provide an overview of current knowledge, the literature was systematically examined for clinical studies, which evaluate the safety and effectiveness of bosentan in pediatric pulmonary ...arterial hypertension (PAH).
3 databases (MEDLINE, EMBASE and BIOSIS) were searched for the period January 2000 - October 2007 using the key words 'pulmonary arterial hypertension', 'bosentan', and 'pediatric patients/children'.
Of 165 identified publications, 21 clinical studies were selected: 1 interventional prospective, 6 observational prospective, 5 observational retrospective, and 9 case reports/case series. In the absence of controlled trials, these 21 studies represent the current evidence on the effectiveness and safety of bosentan in the treatment of pediatric PAH. Bosentan appears to improve long-term functional status and hemodynamics in children with PAH but improvement in exercise capacity is not consistently demonstrated. Promising results are reported for the combination of bosentan with other PAH-specific treatments although guidelines for instituting combination therapy have not been defined. Overall, no safety concern is raised by these studies; adverse events, including liver enzyme elevations, appear to be less frequent than reported in the adult PAH clinical trials.
Recent experience, although uncontrolled, suggests that bosentan is a well-tolerated and effective therapy for pediatric PAH.
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.
Summary Background Paediatric pulmonary hypertension, is an important cause of morbidity and mortality, and is insufficiently characterised in children. The Tracking Outcomes and Practice in ...Pediatric Pulmonary Hypertension (TOPP) registry is a global, prospective study designed to provide information about demographics, treatment, and outcomes in paediatric pulmonary hypertension. Methods Consecutive patients aged 18 years or younger at diagnosis with pulmonary hypertension and increased pulmonary vascular resistance were enrolled in TOPP at 31 centres in 19 countries from Jan 31, 2008, to Feb 15, 2010. Patient and disease characteristics, including age at diagnosis and at enrolment, sex, ethnicity, presenting symptoms, pulmonary hypertension classification, comorbid disorders, medical and family history, haemodynamic indices, and functional class were recorded. Follow-up was decided by the patients' physicians according to the individual's health-care needs. Findings 362 of 456 consecutive patients had confirmed pulmonary hypertension (defined as mean pulmonary artery pressure ≥25 mm Hg, pulmonary capillary wedge pressure ≤12 mm Hg, and pulmonary vascular resistance index ≥3 WU/m−2 ). 317 (88%) patients had pulmonary arterial hypertension (PAH), which was idiopathic IPAH or familial FPAH in 182 (57%), and associated with other disorders in 135 (43%), of which 115 (85%) cases were associated with congenital heart disease. 42 patients (12%) had pulmonary hypertension associated with respiratory disease or hypoxaemia, with bronchopulmonary dysplasia most frequent. Finally, only three patients had either chronic thromboembolic pulmonary hypertension or miscellaneous causes of pulmonary hypertension. Chromosomal anomalies, mainly trisomy 21, were reported in 47 (13%) of patients with confirmed disease. Median age at diagnosis was 7 years (IQR 3–12); 59% (268 of 456) were female. Although dyspnoea and fatigue were the most frequent symptoms, syncope occurred in 31% (57 of 182) of patients with IPAH or FPAH and in 18% (eight of 45) of those with repaired congenital heart disease; no children with unrepaired congenital systemic-to-pulmonary shunts had syncope. Despite severe pulmonary hypertension, functional class was I or II in 230 of 362 (64%) patients, which is consistent with preserved right-heart function. Interpretation TOPP identifies important clinical features specific to the care of paediatric pulmonary hypertension, which draw attention to the need for paediatric data rather than extrapolation from adult studies. Funding Actelion Pharmaceuticals.
The aim of a clinical classification of pulmonary hypertension (PH) is to group together different manifestations of disease sharing similarities in pathophysiologic mechanisms, clinical ...presentation, and therapeutic approaches. In 2003, during the 3rd World Symposium on Pulmonary Hypertension, the clinical classification of PH initially adopted in 1998 during the 2nd World Symposium was slightly modified. During the 4th World Symposium held in 2008, it was decided to maintain the general architecture and philosophy of the previous clinical classifications. The modifications adopted during this meeting principally concern Group 1, pulmonary arterial hypertension (PAH). This subgroup includes patients with PAH with a family history or patients with idiopathic PAH with germline mutations (e.g., bone morphogenetic protein receptor-2, activin receptor-like kinase type 1, and endoglin). In the new classification, schistosomiasis and chronic hemolytic anemia appear as separate entities in the subgroup of PAH associated with identified diseases. Finally, it was decided to place pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis in a separate group, distinct from but very close to Group 1 (now called Group 1′). Thus, Group 1 of PAH is now more homogeneous.
Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease, and is now predominantly among patients with uncorrected left-to-right shunts. A growing population is ...characterized by persistent or recurrent PAH after surgical or interventional correction of left-to-right shunts; the latter having a worse prognosis than other forms of PAH associated with congenital heart disease. New treatments for PAH have been shown to be effective in improving PAH exercise capacity and hemodynamics, raising the hope for making previously inoperable congenital heart defects operable and shifting the framework for the assessment of operability. This review focuses on current methods for assessing operability in PAH associated with congenital heart disease, and the possibility of “treat-and-repair” vs. “repair-and-treat” strategies for patients with inoperable or borderline PAH. (Circ J 2014; 78: 4–11)
Objective To evaluate the efficacy, safety, and pharmacokinetics of the endothelin receptor antagonist bosentan as adjunctive therapy for neonates with persistent pulmonary hypertension of the ...newborn (PPHN). Study design This was a phase 3, multicenter, randomized, placebo-controlled exploratory trial (FUTURE-4). Eligible patients were >34 weeks gestation, <7 days old, receiving inhaled nitric oxide (iNO) treatment (≥4 hours), and had persistent respiratory failure (oxygenation index OI ≥12). After 2:1 randomization, bosentan 2 mg/kg or placebo was given by nasogastric tube twice daily for ≥48 hours and up to 1 day after iNO weaning. Results Twenty-one neonates received a study drug (13 bosentan, 8 placebo). Compared with the placebo group, the group treated with bosentan had a higher median baseline OI and greater need for vasoactive agents. One treatment failure (need for extracorporeal membrane oxygenation) occurred in the group treated with bosentan. The time to weaning from iNO or mechanical ventilation was not different between the groups. Bosentan was well tolerated and did not adversely affect systemic blood pressure or hepatic transaminase levels. Anemia and edema were more frequent in patients receiving bosentan. Blood concentrations of bosentan were low and variable on day 1, and achieved steady state on day 5. Conclusion Adjunctive bosentan was well tolerated, but did not improve oxygenation or other outcomes in our patients with PPHN. This effect may be related to delayed absorption of bosentan on treatment initiation in critically ill neonates or to more severe illness of the neonates who received bosentan. Trial registration ClinicalTrials.gov: NCT01389856
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