To define the frequency and characteristics of acute neurologic complications in children hospitalised with infective endocarditis and to identify risk factors for neurologic complications.
...Retrospective cohort study of children aged 0-18 years hospitalised at a tertiary children's hospital from 1 January, 2008 to 31 December, 2017 with infective endocarditis.
Sixty-eight children met Duke criteria for infective endocarditis (43 definite and 25 possible). Twenty-three (34%) had identified neurologic complications, including intracranial haemorrhage (25%, 17/68) and ischaemic stroke (25%, 17/68). Neurologic symptoms began a median of 4.5 days after infective endocarditis symptom onset (interquartile range 1, 25 days), though five children were asymptomatic and diagnosed on screening neuroimaging only. Overall, only 56% (38/68) underwent neuroimaging during acute hospitalisation, so additional asymptomatic neurologic complications may have been missed. Children with identified neurologic complications compared to those without were older (48 versus 22% ≥ 13 years old, p = 0.031), more often had definite rather than possible infective endocarditis (96 versus 47%, p < 0.001), mobile vegetations >10mm (30 versus 11%, p = 0.048), and vegetations with the potential for systemic embolisation (65 versus 29%, p = 0.004). Six children died (9%), all of whom had neurologic complications.
Neurologic complications of infective endocarditis were common (34%) and associated with mortality. The true frequency of neurologic complications was likely higher because asymptomatic cases may have been missed without screening neuroimaging. Moving forward, we advocate that all children with infective endocarditis have neurologic consultation, examination, and screening neuroimaging. Additional prospective studies are needed to determine whether early identification of neurologic abnormalities may direct management and ultimately reduce neurologic morbidity and overall mortality.
Thrombotic complications are increasingly being recognized as a significant cause of morbidity and mortality in pediatric and congenital heart disease. The objective of this article is to review the ...medications currently available to prevent and treat such complications.
Online searches were conducted using PubMed.
Studies were selected for inclusion based on their scientific merit and applicability to the pediatric cardiac population.
Pertinent information from each selected study or scientific review was extracted for inclusion.
Four classes of medications were identified as potentially beneficial in this patient group: anticoagulants, antiplatelet agents, thrombolytic agents, and novel oral anticoagulants. Data on each class of medication were synthesized into the follow sections: mechanism of action, pharmacokinetics, dosing, monitoring, reversal, considerations for use, and evidence to support.
Anticoagulants, antiplatelet agents, and thrombolytic agents are routinely used successfully in the pediatric patient with heart disease for the prevention and treatment of a wide range of thrombotic complications. Although the novel oral anticoagulants have been approved for a limited number of indications in adults, studies on the safety and efficacy of these agents in children are pending.
Patients with multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) have overlapping clinical features. We compared demographics, clinical presentation, management, and ...outcomes of patients according to evidence of previous SARS-CoV-2 infection.
The International Kawasaki Disease Registry (IKDR) enrolled KD and MIS-C patients from sites in North, Central, and South America, Europe, Asia, and the Middle East. Evidence of previous infection was defined as: Positive (household contact or positive polymerase chain reaction PCR/serology), Possible (suggestive clinical features of MIS-C and/or KD with negative PCR or serology but not both), Negative (negative PCR and serology and no known exposure), and Unknown (incomplete testing and no known exposure).
Of 2345 enrolled patients SARS-CoV-2 status was Positive for 1541 (66%) patients, Possible for 89 (4%), Negative for 404 (17%) and Unknown for 311 (13%). Clinical outcomes varied significantly among the groups, with more patients in the Positive/Possible groups presenting with shock, having admission to intensive care, receiving inotropic support, and having longer hospital stays. Regarding cardiac abnormalities, patients in the Positive/Possible groups had a higher prevalence of left ventricular dysfunction, and patients in the Negative and Unknown groups had more severe coronary artery abnormalities.
There appears to be a spectrum of clinical features from MIS-C to KD with a great deal of heterogeneity, and one primary differentiating factor is evidence for previous acute SARS-CoV-2 infection/exposure. SARS-CoV-2 Positive/Possible patients had more severe presentations and required more intensive management, with a greater likelihood of ventricular dysfunction but less severe coronary artery adverse outcomes, in keeping with MIS-C.
Le syndrome inflammatoire multisystémique de l’enfant (SIME) et la maladie de Kawasaki (MK) ont des caractéristiques cliniques qui se chevauchent. Nous avons comparé les données démographiques, le tableau clinique, la prise en charge et les résultats cliniques des patients en fonction des preuves d’une infection antérieure au SRAS-CoV-2.
Des patients atteints de la MK et du SIME d’établissements de l’Amérique du Nord, de l’Amérique centrale, de l’Amérique du Sud, de l’Europe, de l’Asie et du Moyen-Orient étaient inscrits au registre international de la maladie de Kawasaki (IKDR, de l’anglais International Kawasaki Disease Registry). Les preuves d’une infection antérieure étaient définies comme suit : positives (contacts familiaux ou réaction en chaîne par polymérase PCR, de l’anglais polymerase chain reaction)/sérologie positives), possibles (caractéristiques cliniques suggestives de SIME et/ou de la MK, une PCR ou une sérologie négative, mais non les 2), négatives (PCR et sérologie négatives, et aucune exposition connue) et inconnues (tests incomplets et aucune exposition connue).
Au sein des 2 345 patients inscrits, 1 541 (66 %) patients étaient positifs au SRAS-CoV-2 (groupe positif), 89 (4 %) étaient possiblement positifs ou non (groupe possible), 404 (17 %) étaient négatifs (groupe négatif), et 311 (13 %) l’ignoraient (groupe inconnu). Les résultats cliniques variaient de façon significative entre les groupes : les patients des groupes positif et possible avaient plus souvent un choc, étaient plus souvent admis aux soins intensifs, recevaient plus souvent un traitement inotrope et avaient plus souvent des séjours à l’hôpital plus longs. En ce qui concerne les anomalies cardiaques, la prévalence de dysfonction ventriculaire gauche chez les patients des groupes positif et possible était plus élevée, et les patients des groupes négatif et inconnu avaient plus souvent des anomalies plus graves des artères coronaires.
Il semble y avoir un spectre de caractéristiques cliniques d’une grande hétérogénéité entre le SIME et la MK, et l’un des principaux facteurs de différenciation est la preuve d’une infection/exposition aiguë précédente au SRAS-CoV-2. Les patients qui étaient positifs/possiblement positifs ou non au SRAS-CoV-2 avaient des symptômes plus graves et avaient plus souvent besoin d’une prise en charge aux soins intensifs, et une plus forte probabilité de dysfonction ventriculaire, mais moins d’anomalies défavorables aux artères coronaires en relation avec le SIME.
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Pediatric pulmonary embolism (PE) is rare and potentially life-threatening. Though thrombolysis and thrombectomy are increasingly used in adult PE, trends in pediatric treatment and outcomes remain ...incompletely described.
The purpose of this study was to describe the incidence of PE, proportion of cases treated with anticoagulation alone, systemic thrombolysis, and directed therapy (local thrombolysis and thrombectomy), clinical outcomes, and total costs.
A multicenter observational study was performed using administrative data from the Pediatric Health Information System database to study PE treated at U.S. pediatric hospitals from 2015 to 2021. Outcomes by treatment were evaluated using multivariable generalized linear mixed effects models.
Of 3,136 subjects, 70% were at least 12 years of age, and 46% were male. Sixty-two percent had at least 1 comorbidity, and congenital heart disease of any kind was the most prevalent (20%). Eighty-eight percent of subjects received anticoagulation alone, 7% received systemic thrombolysis, and 5% received directed therapy. Overall in-hospital mortality was 7.5%. Treatment approach did not change over time (P = 0.98). After adjusting for patient characteristics, directed therapy was associated with a lower risk of mortality (adjusted percentage −3%, 95% CI: −5% to 0%) than anticoagulation alone. Systemic thrombolysis was associated with a greater total cost of hospitalization ($113,043 greater 95% CI: $62,866, $163,219). Length of hospital stay did not differ by treatment.
Pediatric patients with PE have a high incidence of underlying chronic disease. Anticoagulation alone remains the mainstay of treatment, with thrombolysis and thrombectomy rarely being used. Given the relative rarity of pediatric PE, additional research requiring innovative study designs is paramount.
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The substantial risk of thrombosis in large coronary artery aneurysms (CAAs) (maximum z-score ≥ 10) after Kawasaki disease (KD) mandates effective thromboprophylaxis. We sought to determine the ...effectiveness of anticoagulation (low-molecular-weight heparin LMWH or warfarin) for thromboprophylaxis in large CAAs.
Data from 383 patients enrolled in the International KD Registry (IKDR) were used. Time-to-event analysis was used to account for differences in treatment duration and follow-up.
From diagnosis onward (96% received acetylsalicylic acid concomitantly), 114 patients received LMWH (median duration 6.2 months, interquartile range IQR 2.5-12.7), 80 warfarin (median duration 2.2 years, IQR 0.9-7.1), and 189 no anticoagulation. Cumulative incidence of coronary artery thrombosis with LMWH was 5.7 ± 3.0%, with warfarin 6.7 ± 3.7%, and with no anticoagulation 20.6 ± 3.0% (P < 0.001) at 2.5 years after the start of thromboprophylaxis (LMWH vs warfarin HR 1.5, 95% confidence interval CI 0.4-5.1; P = 0.56). A total of 51/63 patients with coronary artery thrombosis received secondary thromboprophylaxis (ie, thromboprophylaxis after a previous thrombus): 27 LMWH, 24 warfarin. There were no differences in incidence of further coronary artery thrombosis between strategies (HR 2.9, 95% CI 0.6-13.5; P = 0.19). Severe bleeding complications were generally rare (1.6 events per 100 patient-years) and were noted equally for patients on LMWH and warfarin (HR 2.3, 95% CI 0.6-8.9; P = 0.25).
LMWH and warfarin appear to have equivalent effectiveness for preventing thrombosis in large CAAs after KD, although event rates for secondary thromboprophylaxis and safety outcomes were low. Based on our findings, all patients with CAA z-score ≥ 10 should receive anticoagulation, but the choice of agent might be informed by secondary risk factors and patient preferences.
Le risque considérable de thrombose dans les cas de gros anévrismes coronariens (score Z maximal ≥ 10) après une maladie de Kawasaki commande une thromboprophylaxie efficace. Cette étude tentait de déterminer l’efficacité réelle de l’anticoagulothérapie (héparine de bas poids moléculaire HBPM ou warfarine) en guise de thromboprophylaxie chez les patients présentant de gros anévrismes coronariens.
L’étude reposait sur les données recueillies auprès de 383 patients inscrits au registre international de la maladie de Kawasaki. Une analyse du temps écoulé avant la survenue de l’événement d’intérêt a été utilisée pour tenir compte des différences quant aux périodes de traitement et de suivi.
À partir du moment où ils ont reçu un diagnostic, 114 patients ont reçu une HBPM (durée médiane du traitement : 6,2 mois; intervalle interquartile IIQ : 2,5-12,7), 80 patients ont reçu de la warfarine (durée médiane du traitement : 2,2 ans; IIQ : 0,9-7,1), et 189 patients n’ont reçu aucune anticoagulothérapie (96 % des patients ont reçu de l’acide acétylsalicylique en concomitance). Deux ans et demi après l’instauration de la thromboprophylaxie, l’incidence cumulative des cas de thrombose coronarienne était de 5,7 ± 3,0 % dans le groupe HBPM, de 6,7 ± 3,7 % dans le groupe warfarine et de 20,6 ± 3,0 % dans le groupe ne recevant aucune anticoagulothérapie (p < 0,001) (rapport des risques instantanés RRI, HBPM vs warfarine : 1,5; intervalle de confiance IC à 95 % : 0,4-5,1; p = 0,56). Sur les 63 patients qui ont subi une thrombose coronarienne, 51 ont reçu une thromboprophylaxie secondaire (c.-à-d. une thromboprophylaxie subséquente à une thrombose) : 27 de ces patients ont reçu une HBPM et 24, de la warfarine. Aucune différence n’a été observée entre les stratégies quant à la survenue d’une nouvelle thrombose coronarienne (RRI : 2,9; IC à 95 % : 0,6-13,5; p = 0,19). Les complications hémorragiques graves étaient généralement rares (1,6 événement par 100 années-patients) et sont survenues aussi bien dans le groupe HBPM que dans le groupe warfarine (RRI : 2,3; IC à 95 % : 0,6-8,9; p = 0,25).
L’HBPM et la warfarine semblent aussi efficaces l’une que l’autre pour ce qui est de prévenir la thrombose dans les cas de gros anévrismes coronariens après une maladie de Kawasaki, bien que les événements associés à la thromboprophylaxie secondaire et les problèmes liés à l’innocuité aient été peu nombreux. Les résultats semblent indiquer que tous les patients présentant de gros anévrismes coronariens de score Z ≥ 10 devraient recevoir une anticoagulothérapie, mais le choix de l’agent thérapeutique devrait aussi tenir compte des facteurs de risque secondaires et des préférences du patient.
Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 show clinical overlap and both lack definitive diagnostic testing, making differentiation ...challenging. We sought to determine how cardiac biomarkers might differentiate KD from MIS-C. The International Kawasaki Disease Registry enrolled contemporaneous KD and MIS-C pediatric patients from 42 sites from January 2020 through June 2022. The study population included 118 KD patients who met American Heart Association KD criteria and compared them to 946 MIS-C patients who met 2020 Centers for Disease Control and Prevention case definition. All included patients had at least one measurement of amino-terminal prohormone brain natriuretic peptide (NTproBNP) or cardiac troponin I (TnI), and echocardiography. Regression analyses were used to determine associations between cardiac biomarker levels, diagnosis, and cardiac involvement. Higher NTproBNP (≥ 1500 ng/L) and TnI (≥ 20 ng/L) at presentation were associated with MIS-C versus KD with specificity of 77 and 89%, respectively. Higher biomarker levels were associated with shock and intensive care unit admission; higher NTproBNP was associated with longer hospital length of stay. Lower left ventricular ejection fraction, more pronounced for MIS-C, was also associated with higher biomarker levels. Coronary artery involvement was not associated with either biomarker. Higher NTproBNP and TnI levels are suggestive of MIS-C versus KD and may be clinically useful in their differentiation. Consideration might be given to their inclusion in the routine evaluation of both conditions.
Despite progress in pharmacotherapy in pediatric pulmonary hypertension, real-world patterns of directed pulmonary hypertension therapy have not been studied in the current era. A retrospective ...observational study of children (≤18 years) with pulmonary hypertension was performed using data from the MarketScan® Commercial and Medicaid claims databases. Associations between etiology of pulmonary hypertension and pharmaceutical regimen were evaluated, as were the associations between subject social and geographic characteristics (insurance-type, race, and/or census region) and regimen. Annualized costs of single- and multi-class regimens were calculated. In total, 873 subjects were studied, of which 94% received phosphodiesterase-5 inhibitors, 31% endothelin receptor antagonist, 9% prostacyclin analogs, and 7% calcium channel blockers. Monotherapy was used in 72% of subjects. Phosphodiesterase-5 inhibitors monotherapy was the most common regimen (93%). Subjects with idiopathic pulmonary hypertension, congenital heart disease, and unclassified pulmonary hypertension receive more than one agent and were more likely to receive both endothelin receptor antagonist and prostacyclin analogs than other forms of pulmonary hypertension. Compared to recipients of public insurance, subjects with commercial insurance were more likely to receive more intense therapy (p = 0.003), which was confirmed in multivariable analysis (OR: 1.4, p = 0.03). Receipt of commercial insurance was also associated with increased annual costs across all subjects (p < 0.001) and for the most common specific regimens. The majority of children with pulmonary hypertension receive phosphodiesterase monotherapy, followed by phosphodiesterase–endothelin receptor antagonist two drug regimens, and finally the addition of prostacyclin analogs for three-drug therapy. However, even after adjustment for measurable confounders, commercial insurance was associated with higher intensity care and higher costs (even within specific classes of pulmonary vasodilators). The effect of these associations on clinical outcome cannot be discerned from the current data set, but patterns of treatment deserve further attention.
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