RESUMEN
BACKGROUND: Primary cytomegalovirus (CMV) infection during pregnancy carries a risk of congenital infection and possible severe sequelae. There is no established intervention for preventing congenital CMV infection. METHODS: In this multicenter, double-blind trial, pregnant women with primary CMV infection diagnosed before 24 weeks' gestation were randomly assigned to receive a monthly infusion of CMV hyperimmune globulin (at a dose of 100 mg per kilogram of body weight) or matching placebo until delivery. The primary outcome was a composite of congenital CMV infection or fetal or neonatal death if CMV testing of the fetus or neonate was not performed. RESULTS: From 2012 to 2018, a total of 206,082 pregnant women were screened for primary CMV infection before 23 weeks of gestation; of the 712 participants (0.35%) who tested positive, 399 (56%) underwent randomization. The trial was stopped early for futility. Data on the primary outcome were available for 394 participants; a primary outcome event occurred in the fetus or neonate of 46 of 203 women (22.7%) in the group that received hyperimmune globulin and of 37 of 191 women (19.4%) in the placebo group (relative risk, 1.17; 95% confidence interval [CI] 0.80 to 1.72; P = 0.42). Death occurred in 4.9% of fetuses or neonates in the hyperimmune globulin group and in 2.6% in the placebo group (relative risk, 1.88; 95% CI, 0.66 to 5.41), preterm birth occurred in 12.2% and 8.3%, respectively (relative risk, 1.47; 95% CI, 0.81 to 2.67), and birth weight below the 5th percentile occurred in 10.3% and 5.4% (relative risk, 1.92; 95% CI, 0.92 to 3.99). One participant in the hyperimmune globulin group had a severe allergic reaction to the first infusion. Participants who received hyperimmune globulin had a higher incidence of headaches and shaking chills while receiving infusions than participants who received placebo. CONCLUSIONS: Among pregnant women, administration of CMV hyperimmune globulin starting before 24 weeks' gestation did not result in a lower incidence of a composite of congenital CMV infection or perinatal death than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences; ClinicalTrials.gov number, NCT01376778.).
Asunto(s)
Infecciones por Citomegalovirus/congénito , Inmunoglobulinas Intravenosas/uso terapéutico , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Adulto , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/mortalidad , Infecciones por Citomegalovirus/prevención & control , Método Doble Ciego , Femenino , Muerte Fetal/etiología , Muerte Fetal/prevención & control , Enfermedades Fetales/prevención & control , Humanos , Incidencia , Lactante , Mortalidad Infantil , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Infusiones Intravenosas , Embarazo , Insuficiencia del TratamientoAsunto(s)
Infecciones por Citomegalovirus , Complicaciones Infecciosas del Embarazo , Femenino , Humanos , Embarazo , Infecciones por Citomegalovirus/congénito , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/terapia , Inmunoglobulinas/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéutico , Complicaciones Infecciosas del Embarazo/etiología , Complicaciones Infecciosas del Embarazo/inmunología , Complicaciones Infecciosas del Embarazo/terapia , Resultado del TratamientoRESUMEN
Human cytomegalovirus (HCMV) is the most common congenital infection worldwide, frequently causing hearing loss and brain damage in afflicted infants. A vaccine to prevent maternal acquisition of HCMV during pregnancy is necessary to reduce the incidence of infant disease. The glycoprotein B (gB) + MF59 adjuvant subunit vaccine platform is the most successful HCMV vaccine tested to date, demonstrating â¼50% efficacy in preventing HCMV acquisition in multiple phase 2 trials. However, the mechanism of vaccine protection remains unknown. Plasma from 33 postpartum women gB/MF59 vaccinees at peak immunogenicity was tested for gB epitope specificity as well as neutralizing and nonneutralizing anti-HCMV effector functions and compared with an HCMV-seropositive cohort. gB/MF59 vaccination elicited IgG responses with gB-binding magnitude and avidity comparable to natural infection. Additionally, IgG subclass distribution was similar with predominant IgG1 and IgG3 responses induced by gB vaccination and HCMV infection. However, vaccine-elicited antibodies exhibited limited neutralization of the autologous virus, negligible neutralization of multiple heterologous strains, and limited binding responses against gB structural motifs targeted by neutralizing antibodies including AD-1, AD-2, and domain I. Vaccinees had high-magnitude IgG responses against AD-3 linear epitopes, demonstrating immunodominance against this nonneutralizing, cytosolic region. Finally, vaccine-elicited IgG robustly bound membrane-associated gB on the surface of transfected or HCMV-infected cells and mediated virion phagocytosis, although were poor mediators of NK cell activation. Altogether, these data suggest that nonneutralizing antibody functions, including virion phagocytosis, likely played a role in the observed 50% vaccine-mediated protection against HCMV acquisition.
Asunto(s)
Anticuerpos Neutralizantes/inmunología , Infecciones por Citomegalovirus/inmunología , Vacunas contra Citomegalovirus/inmunología , Citomegalovirus/inmunología , Vacunas de Subunidad/inmunología , Proteínas del Envoltorio Viral/inmunología , Adulto , Anticuerpos Antivirales/inmunología , Células Cultivadas , Epítopos/inmunología , Femenino , Humanos , Inmunoglobulina G/inmunología , Polisorbatos , Escualeno/inmunología , Adulto JovenRESUMEN
Human cytomegalovirus (HCMV) is the most common congenital infection worldwide and a frequent cause of hearing loss and debilitating neurologic disease in newborn infants. Thus, a vaccine to prevent HCMV-associated congenital disease is a public health priority. One potential strategy is vaccination of women of child bearing age to prevent maternal HCMV acquisition during pregnancy. The glycoprotein B (gB) plus MF59 adjuvant subunit vaccine is the most efficacious tested clinically to date, demonstrating 50% protection against primary HCMV infection in a phase 2 clinical trial. Yet, the impact of gB/MF59-elicited immune responses on the population of viruses acquired by trial participants has not been assessed. In this analysis, we employed quantitative PCR as well as multiple sequencing methodologies to interrogate the magnitude and genetic composition of HCMV populations infecting gB/MF59 vaccinees and placebo recipients. We identified several differences between the viral dynamics in acutely infected vaccinees and placebo recipients. First, viral load was reduced in the saliva of gB vaccinees, though not in whole blood, vaginal fluid, or urine. Additionally, we observed possible anatomic compartmentalization of gB variants in the majority of vaccinees compared to only a single placebo recipient. Finally, we observed reduced acquisition of genetically related gB1, gB2, and gB4 genotype "supergroup" HCMV variants among vaccine recipients, suggesting that the gB1 genotype vaccine construct may have elicited partial protection against HCMV viruses with antigenically similar gB sequences. These findings suggest that gB immunization had a measurable impact on viral intrahost population dynamics and support future analysis of a larger cohort.IMPORTANCE Though not a household name like Zika virus, human cytomegalovirus (HCMV) causes permanent neurologic disability in one newborn child every hour in the United States, which is more than that for Down syndrome, fetal alcohol syndrome, and neural tube defects combined. There are currently no established effective measures to prevent viral transmission to the infant following HCMV infection of a pregnant mother. However, the glycoprotein B (gB)/MF59 vaccine, which aims to prevent pregnant women from acquiring HCMV, is the most successful HCMV vaccine tested clinically to date. Here, we used viral DNA isolated from patients enrolled in a gB vaccine trial who acquired HCMV and identified several impacts that this vaccine had on the size, distribution, and composition of the in vivo viral population. These results have increased our understanding of why the gB/MF59 vaccine was partially efficacious, and such investigations will inform future rational design of a vaccine to prevent congenital HCMV.
Asunto(s)
Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Vacunas contra Citomegalovirus/inmunología , Citomegalovirus/inmunología , Proteínas del Envoltorio Viral/inmunología , Adyuvantes Inmunológicos , Sangre/virología , Células Cultivadas , Citomegalovirus/clasificación , Citomegalovirus/genética , Femenino , Humanos , Embarazo , Epitelio Pigmentado de la Retina/citología , Saliva/virología , Seroconversión , Orina/virología , Vacunación , Vacunas de Subunidad/inmunología , Carga Viral/inmunologíaRESUMEN
OBJECTIVE: To assess clinical characteristics and outcomes of severe acute respiratory syndrome coronavirus 2-associated multisystem inflammatory syndrome in children (MIS-C). STUDY DESIGN: Children with MIS-C admitted to pediatric intensive care units in New York City between April 23 and May 23, 2020, were included. Demographic and clinical data were collected. RESULTS: Of 33 children with MIS-C, the median age was 10 years; 61% were male; 45% were Hispanic/Latino; and 39% were black. Comorbidities were present in 45%. Fever (93%) and vomiting (69%) were the most common presenting symptoms. Depressed left ventricular ejection fraction was found in 63% of patients with median ejection fraction of 46.6% (IQR, 39.5-52.8). C-reactive protein, procalcitonin, d-dimer, and pro-B-type natriuretic peptide levels were elevated in all patients. For treatment, intravenous immunoglobulin was used in 18 (54%), corticosteroids in 17 (51%), tocilizumab in 12 (36%), remdesivir in 7 (21%), vasopressors in 17 (51%), mechanical ventilation in 5 (15%), extracorporeal membrane oxygenation in 1 (3%), and intra-aortic balloon pump in 1 (3%). The left ventricular ejection fraction normalized in 95% of those with a depressed ejection fraction. All patients were discharged home with median duration of pediatric intensive care unit stay of 4.7 days (IQR, 4-8 days) and a hospital stay of 7.8 days (IQR, 6.0-10.1 days). One patient (3%) died after withdrawal of care secondary to stroke while on extracorporeal membrane oxygenation. CONCLUSIONS: Critically ill children with coronavirus disease-2019-associated MIS-C have a spectrum of severity broader than described previously but still require careful supportive intensive care. Rapid, complete clinical and myocardial recovery was almost universal.
Asunto(s)
Infecciones por Coronavirus/complicaciones , Neumonía Viral/complicaciones , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Adolescente , Betacoronavirus , Proteína C-Reactiva/análisis , COVID-19 , Niño , Preescolar , Infecciones por Coronavirus/tratamiento farmacológico , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Lactante , Unidades de Cuidado Intensivo Pediátrico , Masculino , Péptido Natriurético Encefálico/sangre , Ciudad de Nueva York , Pandemias , Polipéptido alfa Relacionado con Calcitonina/análisis , Estudios Retrospectivos , SARS-CoV-2 , Síndrome de Respuesta Inflamatoria Sistémica/terapia , Resultado del Tratamiento , Función Ventricular Izquierda , Adulto Joven , Tratamiento Farmacológico de COVID-19RESUMEN
Cytomegalovirus is the most common congenital infection, affecting 0.5-2% of all live births and the main nongenetic cause of congenital sensorineural hearing loss and neurological damage. Congenital cytomegalovirus can follow maternal primary infection or nonprimary infection. Sensorineurological morbidity is confined to the first trimester with up to 40-50% of infected neonates developing sequelae after first-trimester primary infection. Serological testing before 14 weeks is critical to identify primary infection within 3 months around conception but is not informative in women already immune before pregnancy. In Europe and the United States, primary infection in the first trimester are mainly seen in young parous women with a previous child younger than 3 years. Congenital cytomegalovirus should be evoked on prenatal ultrasound when the fetus is small for gestation and shows echogenic bowel, effusions, or any cerebral anomaly. Although the sensitivity of routine ultrasound in predicting neonatal symptoms is around 25%, serial targeted ultrasound and magnetic resonance imaging of known infected fetuses show greater than 95% sensitivity for brain anomalies. Fetal diagnosis is done by amniocentesis from 17 weeks. Prevention consists of both parents avoiding contact with body fluids from infected individuals, especially toddlers, from before conception until 14 weeks. Candidate vaccines failed to provide more than 75% protection for >2 years in preventing cytomegalovirus infection. Medical therapies such as cytomegalovirus hyperimmune globulins aim to reduce the risk of vertical transmission but 2 randomized controlled trials have not found any benefit. Valaciclovir given from the diagnosis of primary infection up to amniocentesis decreased vertical transmission rates from 29.8% to 11.1% in the treatment group in a randomized controlled trial of 90 pregnant women. In a phase II open-label trial, oral valaciclovir (8 g/d) given to pregnant women with a mildly symptomatic fetus was associated with a higher chance of delivering an asymptomatic neonate (82%), compared with an untreated historical cohort (43%). Valganciclovir given to symptomatic neonates is likely to improve hearing and neurological symptoms, the extent of which and the duration of treatment are still debated. In conclusion, congenital cytomegalovirus infection is a public health challenge. In view of recent knowledge on diagnosis and pre- and postnatal management, health care providers should reevaluate screening programs in early pregnancy and at birth.
Asunto(s)
Infecciones por Citomegalovirus/congénito , Infecciones por Citomegalovirus/transmisión , Complicaciones Infecciosas del Embarazo/virología , Infecciones por Citomegalovirus/complicaciones , Femenino , Enfermedades Fetales/diagnóstico , Enfermedades Fetales/epidemiología , Enfermedades Fetales/virología , Pérdida Auditiva Sensorineural/virología , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Imagen por Resonancia Magnética , Enfermedades del Sistema Nervioso/virología , Atención Preconceptiva , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/epidemiología , Primer Trimestre del Embarazo , Diagnóstico Prenatal , Pruebas Serológicas , Ultrasonografía Prenatal , Valaciclovir/administración & dosificaciónRESUMEN
BACKGROUND: The ability to differentiate right ventricular outflow tract (RVOT) from coronary cusp (CC) site of origin (SOO) by 12-lead ECG in pediatric patients may impact efficacy and procedural time. The objective of this study was to predict RVOT versus CC SOO by ECG in pediatric patients. METHODS: Pediatric patients (<21 years) without structural heart disease with RVOT or CC premature ventricular contraction (PVC) ablations performed (2014-2018) were evaluated through multi-institution retrospective review. Demographics, ECG PVC parameters, ablation site, recurrence, and repeat procedures were collected. RESULTS: Thirty-seven patients were evaluated (mean age 14.6 years, weight 60.6 kg): 11 CC and 26 RVOT PVC SOO. CC PVCs were less likely to exhibit left bundle branch block (64% vs 100%, P = .005), had larger R-wave amplitude in V1 (0.27 vs 0.11 mV, P = .03), larger R/S ratio in V1 (0.37 vs 0.09, P = .003), and had precordial transition in V3 or earlier (73% vs 15%, P = .002). A composite score was created with the following variables: isodiphasic or positive QRS in V1, R/S ratio in V1 > 0.05, S wave in V1 < 0.9 mV, and precordial transition at or before V3. Composite score ≥ 2 was associated with a CC SOO (OR 42.0, P = .001, and AUC 0.86). CONCLUSIONS: 12-lead ECG of PVCs from the CC was associated with larger V1 R-wave amplitude, larger R/S ratio in V1, and precordial transition at or before V3. A composite score may help predict PVC/VT arising from the CC.
Asunto(s)
Electrocardiografía , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatología , Complejos Prematuros Ventriculares/diagnóstico , Complejos Prematuros Ventriculares/fisiopatología , Adolescente , Algoritmos , Ablación por Catéter , Niño , Preescolar , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Taquicardia Ventricular/cirugía , Complejos Prematuros Ventriculares/cirugía , Adulto JovenRESUMEN
OBJECTIVES: Assigning patients to a call team every fourth day (bolus system) caused the maldistribution of patients among resident teams and required additional faculty effort for overflow patient care. We changed to a continuous daily rotation (drip system) and examined the effect on clinical workload among resident teams, resident education, and faculty utilization. METHODS: This is a retrospective study based on the daily records of 7 am team census, the attending physician schedules for a pediatric hospital medicine service with 5 teams, and the measures of resident education, including noon conference attendance, scores on in-service examinations, and duty hour violations. Data from the bolus system (May 2014-June 2015) were compared with the drip system (May 2016-June 2017). RESULTS: Data from 348 bolus days and 338 drip days were analyzed. There was a decrease in interteam variation from 6.2 to 3.9 patients (P < 0.001). There were fewer days with the following: large interteam variation (143 to 25, P < 0.001), days with resident teams at or above capacity (26 to 11, P = 0.01), resident teams below a minimum 7 am census (133 to 18, P < 0.001), and days when additional faculty were pulled for clinical care (61 to 9, P < 0.001). Resident noon conference attendance was unchanged and there was no adverse effect on examination scores or duty hour violations. CONCLUSIONS: Changing from a bolus to a drip model for admissions to inpatient teams resulted in a more even distribution of the workload and a more efficient use of physician resources without negatively affecting resident education.
Asunto(s)
Internado y Residencia/organización & administración , Carga de Trabajo , Centros Médicos Académicos/organización & administración , Centros Médicos Académicos/estadística & datos numéricos , Humanos , Internado y Residencia/estadística & datos numéricos , Admisión del Paciente , Grupo de Atención al Paciente/organización & administración , Grupo de Atención al Paciente/estadística & datos numéricos , Estudios Retrospectivos , Carga de Trabajo/estadística & datos numéricosRESUMEN
BACKGROUND: Axillary venous access with ultrasound guidance for pediatric transvenous lead implantation may reduce risks for pneumothorax and hemothorax. The objective was to retrospectively evaluate ultrasound-guided axillary vein access as an alternative to the subclavian approach. METHODS: The technique consists of ultrasonographic identification of the axillary vein at the deltopectoral groove after initial contrast venography. A micropuncture kit is used for initial ultrasound-guided percutaneous access with fluoroscopic confirmation of wire position. Pocket creation is performed, and sheath insertion and lead implantation proceed as usual. Demographic, procedural, and radiation exposure data were collected and analyzed. RESULTS: Sixteen patients (median age = 13 years, 8-50 years; median weight = 56 kg, 29-77 kg) underwent lead implantation; two additional patients required fluoroscopy due to poor acoustic windows (89% success). Fifteen of 21 leads (71%) were ventricular; 50% of implants were pacemakers, and 31% were dual chamber. Median time to venous access was 13 min (interquartile range (IQR) = 9.25-20.25) and median implant procedure time was 156 min (IQR = 112-172). Median fluoroscopy time was 18.0 min (IQR = 11.9-29.6), median air kerma was 9.0 mGy (IQR = 3.0-28.5), and median dose-area product was 30.2 Gy-cm2 (IQR = 16.1-234.5). One patient required generator pocket revision 2 days postprocedure without lead dislodgement. There were no other complications encountered. CONCLUSIONS: Transvenous pacemaker and implantable cardioverter-defibrillator lead implantation in the pediatric and adult congenital population through ultrasound-guided axillary venous access is safe and efficacious. This technique may provide a low-risk alternative for vascular access for pediatric implantation procedures.
Asunto(s)
Desfibriladores Implantables , Marcapaso Artificial , Implantación de Prótesis/métodos , Cirugía Asistida por Computador , Ultrasonografía Intervencional , Adolescente , Adulto , Vena Axilar , Niño , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
Induction of nucleotide-binding oligomerization domain 2 (NOD2) and downstream receptor-interacting serine/threonine-protein kinase 2 (RIPK2) by human cytomegalovirus (HCMV) is known to up-regulate antiviral responses and suppress virus replication. We investigated the role of nucleotide-binding oligomerization domain 1 (NOD1), which also signals through RIPK2, in HCMV control. NOD1 activation by Tri-DAP (NOD1 agonist) suppressed HCMV and induced IFN-ß. Mouse CMV was also inhibited through NOD1 activation. NOD1 knockdown (KD) or inhibition of its activity with small molecule ML130 enhanced HCMV replication in vitro. NOD1 mutations displayed differential effects on HCMV replication and antiviral responses. In cells overexpressing the E56K mutation in the caspase activation and recruitment domain, virus replication was enhanced, but in cells overexpressing the E266K mutation in the nucleotide-binding domain or the wild-type NOD1, HCMV was inhibited, changes that correlated with IFN-ß expression. The interaction of NOD1 and RIPK2 determined the outcome of virus replication, as evidenced by enhanced virus growth in NOD1 E56K mutant cells (which failed to interact with RIPK2). NOD1 activities were executed through IFN-ß, given that IFN-ß KD reduced the inhibitory effect of Tri-DAP on HCMV. Signaling through NOD1 resulting in HCMV suppression was IKKα-dependent and correlated with nuclear translocation and phosphorylation of IRF3. Finally, NOD1 polymorphisms were significantly associated with the risk of HCMV infection in women who were infected with HCMV during participation in a glycoprotein B vaccine trial. Collectively, our data indicate a role for NOD1 in HCMV control via RIPK2- IKKα-IRF3 and suggest that its polymorphisms predict the risk of infection.
Asunto(s)
Infecciones por Citomegalovirus/metabolismo , Citomegalovirus/fisiología , Proteína Adaptadora de Señalización NOD1/fisiología , Animales , Células Cultivadas , Infecciones por Citomegalovirus/genética , Infecciones por Citomegalovirus/virología , Femenino , Expresión Génica , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Quinasa I-kappa B/metabolismo , Factor 3 Regulador del Interferón/metabolismo , Interferón beta/metabolismo , Ratones Endogámicos BALB C , Proteína Adaptadora de Señalización NOD2/fisiología , Polimorfismo de Nucleótido Simple , Proteína Serina-Treonina Quinasa 2 de Interacción con Receptor/metabolismo , Transducción de Señal , Replicación ViralRESUMEN
There are few data on the incidence of echocardiographic (echo) abnormalities following catheter ablation in children in the era of 3D mapping. Wide practice variation exists regarding routine post-ablation echo. We hypothesized a low incidence of clinically significant echo abnormalities following SVT ablation in otherwise healthy children. Single center data from 2009 to 2015 were reviewed; routine post-ablation echo was standard practice. Cases were categorized as utilizing fluoroscopy alone (FLUORO) or 3D mapping with a low fluoroscopic protocol (CARTO3). Congenital heart disease was excluded. Outcomes of interest included new valvular abnormalities, pericardial effusions, and wall motion abnormalities. Findings were compared to baseline studies when available and classified as normal/unchanged, clinically insignificant, or clinically significant. Outcomes were compared between FLUORO and CARTO3 groups. Of 347 ablations, 319 (92%) underwent post-procedural echo: 57% male; 55% FLUORO; mean age 13.4 ± 3.6 years. The most common ablation target was an accessory pathway (AP) in 66% (n = 144 WPW, 66 concealed), followed by AVNRT in 32% (n = 102). Radiofrequency (RF) energy was utilized in 82% (n = 262). Post-ablation echos were normal in 81% (n = 259). Clinically insignificant findings were seen in 18% (n = 58), most commonly trivial-small pericardial effusions in 11% (n = 34). Two significant findings required additional follow-up or treatment. There were no cases of wall motion abnormalities or clinically significant effusions. There were no differences in frequency of echo abnormalities between the FLUORO and CARTO3 groups. Clinically significant echocardiographic abnormalities are rare following SVT ablation in children with structurally normal hearts, independent of the use of 3D mapping.
Asunto(s)
Mapeo del Potencial de Superficie Corporal/efectos adversos , Ablación por Catéter/efectos adversos , Ecocardiografía/estadística & datos numéricos , Fluoroscopía/efectos adversos , Taquicardia Supraventricular/cirugía , Adolescente , Mapeo del Potencial de Superficie Corporal/métodos , Niño , Femenino , Fluoroscopía/métodos , Humanos , Incidencia , Masculino , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Catheter stability, an important factor in ablation success, is affected by ventilation. Optimal ventilation strategies for pediatric catheter ablation are not known. We hypothesized that small tidal volume and positive end-expiratory pressure are associated with reduced ablation catheter movement at annular positions. Subjects aged 5-25 years undergoing ablation for supraventricular tachycardia (SVT) or WPW at two centers from March 2015 to September 2016 were prospectively enrolled and randomized to receive mechanical ventilation with either positive end-expiratory pressure of 5 cm H2O (PEEP) or 0 cm H2O (ZEEP). Movement of the ablation catheter tip at standard annular positions was measured using 3D electroanatomic mapping systems under two conditions: small tidal volume (STV) (3-5 mL/kg) or large TV (LTV) (6-8 mL/kg). 58 subjects (mean age 13.8 years) were enrolled for a total of 266 separate observations of catheter movement. STV ventilation was associated with significantly reduced catheter movement, compared to LTV at all positions (right posteroseptal: 2.5 ± 1.4 vs. 5.2 ± 3.1 mm, p < 0.0001; right lateral: 2.7 ± 1.6 vs. 6.3 ± 3.5 mm, p < 0.0001; left lateral: 1.8 ± 1.0 vs. 4.3 ± 1.9 mm, p < 0.0001). The presence or absence of PEEP had no effect on catheter movement. In multivariable analysis, STV was associated with a 3.1-mm reduction in movement (95% CI 2.6-3.5, p < 0.0001), adjusting for end-expiratory pressure, annular location, and patient size. We conclude that STV ventilation is associated with reduced ablation catheter movement compared to a LTV strategy, independent of PEEP and annular position.
Asunto(s)
Ablación por Catéter/métodos , Respiración con Presión Positiva/métodos , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Respiración con Presión Positiva/efectos adversos , Estudios Prospectivos , Taquicardia Supraventricular/cirugía , Volumen de Ventilación Pulmonar , Adulto JovenRESUMEN
BACKGROUND: Concealed left-sided accessory pathways (CLAP) are a cause of supraventricular tachycardia (SVT) in the young. Most are mapped with right ventricular (RV) apical/outflow pacing. Rarely, alternative means of mapping are required. We review our experience from three pediatric electrophysiology (EP) centers with a rare form of "hidden" CLAP. METHODS: All patients <21 years undergoing EP study from 2008 to 2014 with a "hidden" CLAP (defined as an accessory pathway [AP] for which RV pacing at cycle lengths [CL] stable for mapping did not demonstrate eccentric retrograde conduction) were included. EXCLUSION CRITERIA: preexcitation. Demographic, procedural, and follow-up data were collected. RESULTS: A total of 23 patients met the criteria (median age, 14.3 years [range 7-21], weight, 51 kg [31-99]). 21 (96%) had SVT and one AFIB (4%). APs were adenosine sensitive in 7/20 patients (35%) and VA conduction was decremental in six (26%). CLAP conduction was demonstrable with orthodromic reentrant tachycardia in all patients, with RV extrastimulus testing in seven (30%) and with rapid RV pacing (Asunto(s)
Fascículo Atrioventricular Accesorio/fisiopatología
, Mapeo Epicárdico/métodos
, Taquicardia Supraventricular/fisiopatología
, Fascículo Atrioventricular Accesorio/cirugía
, Adolescente
, Estimulación Cardíaca Artificial
, Niño
, Femenino
, Humanos
, Masculino
, Ablación por Radiofrecuencia
, Estudios Retrospectivos
, Taquicardia Supraventricular/cirugía
, Resultado del Tratamiento
, Adulto Joven
RESUMEN
The kinetics of cytomegalovirus (CMV) DNA in infected asymptomatic hosts are largely unknown. We measured viral load (VL) in 124 fluid samples (oral, urine, vaginal, blood) collected from 21 women who acquired CMV. A quantitative real-time polymerase chain reaction assay of US17, which correlated with clinical assays, was used. VL decreased following primary infection in all fluids. The geometric mean VL of vaginal fluid was significantly higher than that of other sources: oral (3.89; 95% confidence interval [CI], 1.43-10.57), urine (6.36; 95% CI, 2.48-16.32), and whole blood (11.88; 95% CI, 4.12-34.20). Vaginal CMV shedding may provide a route for sexual and possibly perinatal transmission.
Asunto(s)
Infecciones por Citomegalovirus/transmisión , Infecciones por Citomegalovirus/virología , Citomegalovirus , Carga Viral/fisiología , Adolescente , Adulto , Líquidos Corporales/virología , Citomegalovirus/genética , Citomegalovirus/aislamiento & purificación , Citomegalovirus/patogenicidad , ADN Viral/análisis , ADN Viral/genética , ADN Viral/aislamiento & purificación , Femenino , Humanos , Reacción en Cadena de la Polimerasa , Vagina/virología , Adulto JovenRESUMEN
BACKGROUND: Ablation within the aortic cusp is safe and effective in adults. There are little data on aortic cusp ablation in the pediatric literature. We investigated the safety and efficacy of aortic cusp ablation in young patients. METHODS: A retrospective, descriptive study of aortic cusp ablation in five pediatric electrophysiology centers from 2008 to 2014 was performed. All patients <21 years of age who underwent ablation in the aortic cusps were included. Factors analyzed included patient demographics, procedural details, outcomes, and complications. RESULTS: Thirteen patients met inclusion criteria (median age 16 years [range 10-20.5] and median body surface area 1.58 m2 [range 1.12-2.33]). Substrates for ablation included: nine premature ventricular contractions or sustained ventricular tachycardia (69%), two concealed anteroseptal accessory pathways (APs) (15%), one Wolff-Parkinson-White with an anteroseptal AP (8%), and one ectopic atrial tachycardia (8%). Three-dimensional electroanatomic mapping in combination with fluoroscopy was used in 12/13 (92%) patients. Standard 4-mm-tip radiofrequency (RF) current was used in 11/13 (85%) and low-power irrigated-tip RF in 2/13 (15%). Angiography was used in 13/13 and intracardiac echocardiography was additionally utilized in 3/13 (23%). Ablation locations included: eight noncoronary (62%), three left (23%), and two right (15%) cusps. Ablation was acutely successful in all patients. At median follow-up of 20 months, there was one recurrence of PVCs (8%). There were no ablation-related complications and no valvular injuries observed. CONCLUSION: Arrhythmias originating from the coronary cusps in this series were successfully and safely ablated in young people without injury to the coronary arteries or the aortic valve.
Asunto(s)
Válvula Aórtica/cirugía , Arritmias Cardíacas/cirugía , Ablación por Catéter/métodos , Adolescente , Arritmias Cardíacas/fisiopatología , Mapeo del Potencial de Superficie Corporal , Niño , Técnicas Electrofisiológicas Cardíacas , Femenino , Fluoroscopía , Humanos , Masculino , Ondas de Radio , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: CARTO3 is frequently used during ablation but is not designed to allow visualization of non-CARTO3 ablation catheters. We describe how cryoablation catheters can be visualized and recorded using CARTO3 with minimal fluoroscopy (FLUORO) usage. METHODS: Retrospective review of patients ≤21 years undergoing cryoablation with CARTO3 from 2010 to 2013 for ablation of supraventricular tachycardia. After mapping with a Navistar catheter, the Navistar was removed and a cryocatheter was utilized. The cryocatheter was connected to the pin box via a jumper cable and the pin box was connected to the CARTO3 patient interface unit. Locations of ablation attempts with the cryocatheter were recorded with the "Create Snapshot" tool. Clinical characteristics and radiation doses were compared between patients undergoing cryoablation (cryoenergy [CRYO]) to an age- and diagnosis-matched control group (CONTROL) undergoing RF ablation. RESULTS: A total of 174 ablations were performed and 14 patients underwent cryoablation (CRYO, 13.3 ± 4.7 years, weight 42 ± 14 kg). Indications for cryoablation were: five atrioventricular nodal reentry tachycardia (36%), four ectopic atrial tachycardia (29%), three concealed accessory pathways (21%), and two Wolff-Parkinson-White syndromes (14%). Acute success was achieved in all patients (100%) with no complications and one recurrence (7%). The site of successful cryoablation was successfully recorded on the CARTO3 system in all cases. Radiation doses were low and not different from an age-, era-, and diagnosis-matched control group undergoing RF ablation (CRYO 3.2 ± 0.8 mGy vs CONTROL 1.6 ± 0.4 mGy, P = 0.07). CONCLUSIONS: Though a "closed" system, CARTO3 can be "tricked" to allow for the use of cryoablation, allowing clear catheter visualization, mapping, and recording of ablation lesions with minimal FLUORO usage.
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Criocirugía/instrumentación , Imagenología Tridimensional/instrumentación , Exposición a la Radiación/análisis , Exposición a la Radiación/prevención & control , Cirugía Asistida por Computador/instrumentación , Taquicardia Supraventricular/cirugía , Adolescente , Niño , Criocirugía/métodos , Diseño de Equipo , Análisis de Falla de Equipo , Femenino , Fluoroscopía/instrumentación , Fluoroscopía/métodos , Humanos , Imagenología Tridimensional/métodos , Masculino , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Cirugía Asistida por Computador/métodos , Resultado del Tratamiento , Rayos XRESUMEN
UNLABELLED: Atrioventricular block is classified as congenital if diagnosed in utero, at birth, or within the first month of life. The pathophysiological process is believed to be due to immune-mediated injury of the conduction system, which occurs as a result of transplacental passage of maternal anti-SSA/Ro-SSB/La antibodies. Childhood atrioventricular block is therefore diagnosed between the first month and the 18th year of life. Genetic variants in multiple genes have been described to date in the pathogenesis of inherited progressive cardiac conduction disorders. Indications and techniques of cardiac pacing have also evolved to allow safe permanent cardiac pacing in almost all patients, including those with structural heart abnormalities. CONCLUSION: Early diagnosis and appropriate management are critical in many cases in order to prevent sudden death, and this review critically assesses our current understanding of the pathogenetic mechanisms, clinical course, and optimal management of congenital and childhood AV block. WHAT IS KNOWN: ⢠Prevalence of congenital heart block of 1 per 15,000 to 20,000 live births. AV block is defined as congenital if diagnosed in utero, at birth, or within the first month of life, whereas childhood AV block is diagnosed between the first month and the 18th year of life. As a result of several different etiologies, congenital and childhood atrioventricular block may occur in an entirely structurally normal heart or in association with concomitant congenital heart disease. Cardiac pacing is indicated in symptomatic patients and has several prophylactic indications in asymptomatic patients to prevent sudden death. ⢠Autoimmune, congenital AV block is associated with a high neonatal mortality rate and development of dilated cardiomyopathy in 5 to 30 % cases. What is New: ⢠Several genes including SCN5A have been implicated in autosomal dominant forms of familial progressive cardiac conduction disorders. ⢠Leadless pacemaker technology and gene therapy for biological pacing are promising research fields. In utero percutaneous pacing appears to be at high risk and needs further development before it can be adopted into routine clinical practice. Cardiac resynchronization therapy is of proven value in case of pacing-induced cardiomyopathy.
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Bloqueo Atrioventricular/congénito , Bloqueo Atrioventricular/terapia , Estimulación Cardíaca Artificial/métodos , Factores de Edad , Bloqueo Atrioventricular/diagnóstico , Bloqueo Atrioventricular/genética , Electrocardiografía , Cardiopatías/complicaciones , Humanos , Recién Nacido , Diagnóstico PrenatalRESUMEN
INTRODUCTION: Three-dimensional mapping (3-D) systems are frequently used for ablation of supraventricular tachycardia. Prior studies have demonstrated radiation dosage reduction with 3-D, but there are no data on whether 3-D improves the efficacy of ablation of Wolff-Parkinson-White syndrome (WPW). We sought to determine if 3-D improves the success rate for ablation of WPW in children. METHODS: Multicenter retrospective study including patients ≤21 years of age with WPW undergoing ablation from 2008 to 2012. Success rates using the 2 techniques (3-D vs. fluoroscopy alone [FLUORO]) were compared. RESULTS: Six hundred and fifty-one cases were included (58% male, mean age 13 ± 4 years, 366 [56%] 3-D). Baseline characteristics including gender, weight, accessory pathway (AP) location, number of APs, and repeat ablation attempts were similar between the 2 groups (3-D and FLUORO) The 3-D group was slightly younger (12.7 ± 4.0 vs. 13.3 ± 4.0 years; P = 0.04) and less likely to undergo ablation utilizing cryoenergy (38 [10%] vs. 56 [20%]; P < 0.01). The 3-D group had a higher acute success rate of ablation (355 [97%] vs. 260 [91%]; P < 0.01). No differences were seen in recurrence (16 [5%] vs. 26 [9%]; P = 0.09) or complication rates (1 [0.3%] vs. 1 [0.4%]; P = 0.86) between the groups. On multivariable analysis, 3-D was shown to significantly improve success at ablation with an odds ratio of 3.1 (95% CI 1.44-6.72; P < 0.01). CONCLUSIONS: Use of 3-D significantly improved success rates for ablation of WPW in children. The increase in acute success associated with 3-D suggests it is an important adjunct for catheter ablation of WPW in children.
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Ablación por Catéter/métodos , Técnicas Electrofisiológicas Cardíacas , Sistema de Conducción Cardíaco/cirugía , Radiografía Intervencional/métodos , Síndrome de Wolff-Parkinson-White/cirugía , Potenciales de Acción , Adolescente , Factores de Edad , Ablación por Catéter/efectos adversos , Distribución de Chi-Cuadrado , Niño , Electrocardiografía , Femenino , Fluoroscopía , Sistema de Conducción Cardíaco/fisiopatología , Humanos , Modelos Logísticos , Masculino , Análisis Multivariante , Oportunidad Relativa , Valor Predictivo de las Pruebas , Dosis de Radiación , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Estados Unidos , Síndrome de Wolff-Parkinson-White/diagnóstico , Síndrome de Wolff-Parkinson-White/fisiopatología , Adulto JovenRESUMEN
PURPOSE: To compare the efficacy, safety, and cost-effectiveness of a three-catheter approach with a conventional five-catheter approach for the mapping and ablation of supraventricular tachycardia in pediatric patients with Wolff-Parkinson-White Syndrome (WPW) and concealed accessory pathways (APs). METHODS: A retrospective review from 2008 to 2012 of patients less than 21 years with WPW who underwent a three-catheter radiofrequency (RF) ablation of a left-sided AP (ablation, right ventricular [RV] apical, and coronary sinus [CS] decapolar catheters) was performed. The three-catheter group was compared to a control group who underwent a standard five-catheter (ablation, RV apical, CS decapolar, His catheter, and right atrial catheter) ablation for the treatment of left-sided WPW or concealed AP. Demographics, ablation outcomes, and costs were compared between groups. RESULTS: Twenty-eight patients met inclusion criteria with 28 control patients. The groups did not differ in gender, age, weight, or body surface area. Locations of the AP on the mitral annulus were similar between the groups. All patients were ablated via transseptal approach. Note that 28 of 28 in the three-catheter group (100%) and 27 of 28 (96%) controls were acutely successfully ablated (P = 0.31). No complications were encountered. There was no difference in procedural time, time to loss of AP conduction, or number of RF applications. Use of the three-catheter technique resulted in a total savings of $2,465/case, which includes the $680 savings from using fewer catheters as well as the savings from a shortened procedure time. CONCLUSIONS: Ablation in patients with WPW and a left-sided AP can be performed using three catheters with similar efficacy and safety while offering significant cost savings compared to a conventional five-catheter approach.
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Ablación por Catéter/economía , Ablación por Catéter/instrumentación , Análisis Costo-Beneficio/economía , Costos de la Atención en Salud/estadística & datos numéricos , Síndrome de Wolff-Parkinson-White/economía , Síndrome de Wolff-Parkinson-White/cirugía , Fascículo Atrioventricular Accesorio/cirugía , Adolescente , Análisis Costo-Beneficio/métodos , Femenino , Humanos , Masculino , Modelos Económicos , Estudios Retrospectivos , Resultado del Tratamiento , Estados UnidosRESUMEN
Exercise testing is commonly performed in children for evaluation of cardiac disease. Few data exist, however, on the prevalence, types of arrhythmias, predictors for arrhythmias, and safety of exercise testing in children. A retrospective review of all patients ≤21 years undergoing exercise testing at our center from 2008 to 2012 was performed. Patients with clinically relevant arrhythmias were compared to those not experiencing a significant arrhythmia. 1,037 tests were performed in 916 patients. The mean age was 14 ± 4 years, 537 (55 %) were male, 281 (27 %) had congenital heart disease, 178 (17 %) had a history of a prior arrhythmia, and 17 (2 %) had a pacemaker or ICD. 291 (28 %) patients had a rhythm disturbance during the procedure. Clinically important arrhythmias were noted in 34 (3 %) patients and included: 19 (1.8 %) increasing ectopy with exercise, 5 (0.5 %) VT, 5 (0.5 %) second degree AV block, 3 (0.3 %) SVT, and 2 (0.2 %) AFIB. On multivariate logistic regression, variables associated with the development of clinically relevant arrhythmias included severe left ventricular (LV) dysfunction on echo (OR 1.99, CI 1.20-3.30) and prior history of a documented arrhythmia (OR 2.94, CI 1.25-6.88). There were no adverse events related to testing with no patient requiring cardioversion, defibrillation, or acute anti-arrhythmic therapy. A total of 28 % of children developed a rhythm disturbance during exercise testing and 3 % were clinically important. Severe LV dysfunction and a history of documented arrhythmia were associated with the development of a clinically important arrhythmia.