IV Sotalol Use in Pediatric and Congenital Heart Patients: A Multicenter Registry Study.

Background There is limited information regarding the clinical use and effectiveness of IV sotalol in pediatric patients and patients with congenital heart disease, including those with severe myocardial dysfunction. A multicenter registry study was designed to evaluate the safety, efficacy, and dosing of IV sotalol. Methods and Results A total of 85 patients (age 1 day-36 years) received IV sotalol, of whom 45 (53%) had additional congenital cardiac diagnoses and 4 (5%) were greater than 18 years of age. In 79 patients (93%), IV sotalol was used to treat supraventricular tachycardia and 4 (5%) received it to treat ventricular arrhythmias. Severely decreased cardiac function by echocardiography was seen before IV sotalol in 7 (9%). The average dose was 1 mg/kg (range 0.5-1.8 mg/kg/dose) over a median of 60 minutes (range 30-300 minutes). Successful arrhythmia termination occurred in 31 patients (49%, 95% CI [37%-62%]) with improvement in rhythm control defined as rate reduction permitting overdrive pacing in an additional 18 patients (30%, 95% CI [19%-41%]). Eleven patients (16%) had significant QTc prolongation to >465 milliseconds after the infusion, with 3 (4%) to >500 milliseconds. There were 2 patients (2%) for whom the infusion was terminated early. Conclusions IV sotalol was safe and effective for termination or improvement of tachyarrhythmias in 79% of pediatric patients and patients with congenital heart disease, including those with severely depressed cardiac function. The most common dose, for both acute and maintenance dosing, was 1 mg/kg over ~60 minutes with rare serious complications.

Medical Management of Infants With Supraventricular Tachycardia: Results From a Registry and Review of the Literature.

Background: Several medication choices are available for acute and prophylactic treatment of refractory supraventricular tachycardia (SVT) in infants. There are almost no controlled trials, and medication choices are not necessarily evidence based. Our objective was to report the effectiveness of management strategies for infant SVT. Methods: A registry of infants admitted to hospital with re-entrant SVT and no haemodynamically significant heart disease were prospectively followed at 11 international tertiary care centres. In addition, a systematic review of studies on infant re-entrant SVT in MEDLINE and EMBASE was conducted. Data on demographics, symptoms, acute and maintenance treatments, and outcomes were collected. Results: A total of 2534 infants were included: n = 108 from the registry (median age, 9 days [0-324 days], 70.8% male) and n = 2426 from the literature review (median age, 14 days; 62.3% male). Propranolol was the most prevalent acute (61.4%) and maintenance treatment (53.8%) in the Registry, whereas digoxin was used sparingly (4.0% and 3.8%, respectively). Propranolol and digoxin were used frequently in the literature acutely (31% and 33.2%) and for maintenance (17.8% and 10.1%) (P < 0.001). No differences in acute or prophylactic effectiveness between medications were observed. Recurrence was higher in the Registry (25.0%) vs literature (13.4%) (P < 0.001), and 22 (0.9%) deaths were reported in the literature vs none in the Registry. Conclusion: This was the largest cohort of infants with SVT analysed to date. Digoxin monotherapy use was rare amongst contemporary paediatric cardiologists. There was limited evidence to support one medication over another. Overall, recurrence and mortality rates on antiarrhythmic treatment were low.

Contexte: De nombreux choix de médicaments existent pour le traitement aigu et prophylactique de la tachycardie supraventriculaire (TSV) réfractaire chez les nourrissons. Or, il n'y a presque pas d'essais contrôlés à ce sujet, et les choix de médicaments ne sont pas nécessairement fondés sur des données probantes. Notre objectif était de faire état de l'efficacité des stratégies de prise en charge de la TSV chez les nourrissons. Méthodologie: Un registre des nourrissons admis à l'hôpital pour une TSV par réentrée, sans cardiopathie d'importance hémodynamique, a été tenu de façon prospective dans 11 centres de soins tertiaires à l'échelle mondiale. De plus, une revue systématique des études sur la TSV par réentrée chez le nourrisson a été effectuée dans MEDLINE et EMBASE. Des données sur les caractéristiques démographiques, les symptômes, les traitements aigus et d'entretien, et les résultats ont été recueillis. Résultats: Un total de 2 534 nourrissons ont été inclus : n = 108 du registre (âge médian de 9 jours [0-324 jours], 70,8 % de sexe masculin) et n = 2 426 de la revue de la littérature (âge médian de 14 jours; 62,3 % de sexe masculin). Le propranolol était le traitement de soins aigus (61,4 %) et d'entretien (53,8 %) le plus fréquent dans le registre, alors que la digoxine a été utilisée occasionnellement (respectivement dans 4,0 % et 3,8 % des cas). Dans la littérature, le propranolol et la digoxine étaient fréquemment utilisés en soins aigus (31 % et 33,2 %) et en traitement d'entretien (17,8 % et 10,1 %) (p < 0,001). Aucune différence n'a été observée entre les médicaments au chapitre de l'efficacité du traitement de soins aigus ou du traitement prophylactique. Le taux de récurrence était plus élevé dans le registre (25,0 %) que dans la littérature (13,4 %) (p < 0,001), et 22 (0,9 %) décès ont été signalés dans la littérature, mais aucun dans le registre. Conclusion: Il s'agit de la plus grande cohorte de nourrissons atteints de TSV analysée à ce jour. De nos jours, les cardiologues pédiatriques prescrivent rarement la digoxine en monothérapie. Peu de données probantes favorisent l'utilisation d'un médicament par rapport à l'autre. Dans l'ensemble, les taux de récurrence et de mortalité sous traitement antiarythmique étaient faibles.

Cost analysis of combining congenital cardiac catheterization and electrophysiology procedures in an outpatient setting.

BACKGROUND: Patients with congenital heart disease require multiple procedures over their lifetime. These procedures increase cost and time commitment. Previous studies in the field of medicine have shown that combining procedures is an effective method to reduce cost and time. There has been no such study to evaluate the cost and efficiency of combining pediatric cardiac procedures. OBJECTIVE: The objective of this study was to compare the cost and time commitment of combined cardiac catheterization (cath) and electrophysiology (EP) outpatient procedures against separate cath and EP procedure. METHODS: Outpatient combination procedures performed in the pediatric cardiac cath lab from 2013 to 2016 were matched to a control population of two or three similar single outpatient procedures from 2009 to 2016 for patients of similar age and cardiac anatomy. Procedure duration, recovery duration, length of stay, equipment charges, physician charges, all other hospital charges, and total admission charges were analyzed. The two groups were compared using an unpaired t-test. RESULTS: A total of 92 subjects, 32 study subjects and 60 control subjects, were included in this study. Study group procedures had a significantly shorter recovery duration (P = 0.04) and length of stay (P = 0.01). Study group procedure duration trended shorter on average but statistically insignificant (P = 0.20). The total median savings for patients undergoing combined procedures in the study group was $13,181 (interquartile range $423.8-$26710). CONCLUSIONS: Combining cath and EP outpatient procedures reduces the time commitment and provides some economic advantage.

Atrial Antitachycardia Pacing in Complex Congenital Heart Disease: A Case Series.

Among the congenital heart disease (CHD) population, intra-atrial reentrant tachycardia (IART) is a common sequela resulting from anatomical anomalies and surgical scars that significantly increases morbidity and mortality. Atrial antitachycardia pacing (ATP) delivered by atrial antitachycardia devices (ATDs) has been used to treat IART in the CHD population. However, there remains limited data on the safety and efficacy of ATP, as well as on comparisons of its effects amongst different CHD subtypes. The purpose of the current study is to describe the clinical history and ATP efficacy in three patients with unique forms of complex CHD. During this study, a single-center review of three patients with ATDs was performed. One patient with each of the following CHD anomalies was selected for inclusion: systemic left ventricle, systemic right ventricle, and single ventricle. Data collected included ATP success rates, medications in use, direct current (DC) cardioversions, and any complications related to the ATDs. Study findings revealed the patient with a systemic left ventricle had an ATD implanted for approximately 9.5 years, with 695 of 956 (73%) episodes successfully converted. Unsuccessfully treated episodes were generally asymptomatic and self-terminating in this patient. The patient with a systemic right ventricle had an ATD implanted for approximately 16 years, with 333 of 348 (96%) episodes being successfully converted. The patient with a single ventricle had an ATD implanted for approximately 12.5 years, with 404 of 416 (97%) episodes successfully converted. The patients with biventricular physiology were able to forgo DC cardioversion after receiving their ATDs. However, due to medical noncompliance as well as multiple episodes of IART, which presented with 1:1 conduction or low rates, the single-ventricle patient still required DC cardioversions post-ATD implantation. In conclusion, this study's findings demonstrate that, while ATP can be effective in a wide variety of CHDs, experiences can vary based on individual arrhythmia substrates, cardiac anatomy, and medical compliance. Additionally, challenges remain in IART detection in patients with especially complex CHD anatomies.

Safety and efficacy of atrial antitachycardia pacing in congenital heart disease.

BACKGROUND: Intra-atrial reentrant tachycardia (IART) is a common sequela in the congenital heart disease (CHD) population, and it significantly increases morbidity and mortality. Atrial antitachycardia devices (ATDs) capable of atrial antitachycardia pacing (ATP) therapy have been used to manage IART in the CHD population, but there are limited data on their safety and efficacy. OBJECTIVES: To determine whether ATD implantation was associated with reduced direct current (DC) cardioversions and to compare ATP success between different CHD diagnoses and ATP programs. METHODS: A single-center retrospective chart review was performed on CHD patients with ATDs. Demographic data were collected in addition to the number of DC cardioversions required before and after ATD implantation; data on ATP efficacy and the specific ATP program utilized; and adverse events related to ATD implantation or subsequent ATP treatments. RESULTS: ATD implantation in 91 CHD patients was associated with a significant reduction in DC cardioversions (P < .01). Overall, 72% of IART episodes were successfully terminated by ATP. Patients with levo-transposition of the great arteries experienced lower rates of ATP success than the remainder of the cohort (P < .01). There was no evidence of degeneration to ventricular arrhythmia or death directly attributed to ATP. CONCLUSION: ATD implantation was associated with reduced DC cardioversion burden. Patients with levo-transposition of the great arteries may experience lower ATP efficacy than patients with other CHDs; however, a larger patient population is required to better determine subgroup efficacy. These results support the safety and efficacy of ATP in the CHD population.

The Debate in Cuba's Scientific Community on Sudden Cardiac Death.

Sudden cardiac death poses a challenge to modern medicine because of its high incidence, the unexpected and dramatic nature of the event, and years of potential life lost. What's more, despite modest decreases in global mortality attributed to cardiovascular diseases, incidence of sudden cardiac death has not declined. Cuba, like most of the Americas, suffers from knowledge gaps that hamper adequate strategies to address sudden cardiac death as a population health problem. We suggest that a generally accepted operational definition of sudden cardiac death be agreed upon, and a national registry developed that recognizes this cause of death on death certificates. These two actions will enable Cuba's public health authorities to assess the extent of the problem and to design intervention strategies for the population with intermediate and lower cardiovascular risk, the group in which most cases occur. KEYWORDS Sudden cardiac death, cardiovascular disease, sudden death, sudden cardiac arrest, risk reduction, prevention and control, Cuba.

Ubiquitin-specific peptidase 8 (USP8) regulates endosomal trafficking of the epithelial Na+ channel.

Ubiquitination plays a key role in trafficking of the epithelial Na(+) channel (ENaC). Previous work indicated that ubiquitination enhances ENaC endocytosis and sorting to lysosomes for degradation. Moreover, a defect in ubiquitination causes Liddle syndrome, an inherited form of hypertension. In this work, we identified a role for USP8 in the control of ENaC ubiquitination and trafficking. USP8 increased ENaC current in Xenopus oocytes and collecting duct epithelia and enhanced ENaC abundance at the cell surface in HEK 293 cells. This resulted from altered endocytic sorting; USP8 abolished ENaC degradation in the endocytic pathway, but it had no effect on ENaC endocytosis. USP8 interacted with ENaC, as detected by co-immunoprecipitation, and it deubiquitinated ENaC. Consistent with a functional role for deubiquitination, mutation of the cytoplasmic lysines of ENaC reduced the effect of USP8 on ENaC cell surface abundance. In contrast to USP8, USP2-45 increased ENaC surface abundance by reducing endocytosis but not degradation. Thus, USP8 and USP2-45 selectively modulate ENaC trafficking at different steps in the endocytic pathway. Together with previous work, the data indicate that the ubiquitination state of ENaC is critical for the regulation of epithelial Na(+) absorption.

Primed innate immunity leads to autoinflammatory disease in PSTPIP2-deficient cmo mice.

The mouse Lupo (I282N) mutation in proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2) leads to reduced expression of PSTPIP2 that is associated with a macrophage-mediated autoinflammatory disease. Another mutation in PSTPIP2, L98P, termed chronic multifocal osteomyelits (cmo), leads to a disease in mice that resembles chronic recurrent multifocal osteomyelits in humans. The cellular basis of cmo disease was investigated. cmo disease develops independently of lymphocytes and is cured by bone marrow transplantation. Macrophages, mast cells, and osteoclasts from cmo mice fail to express detectable PSTPIP2 protein. Asymptomatic Pstpip2(cmo/cmo) mice have increased circulating levels of macrophage inflammatory protein 1-alpha and interleukin-6, and their macrophages exhibit increased production of these inflammatory mediators, which is normalized by retroviral expression of wild-type PSTPIP2. Spleens of asymptomatic cmo mice contain increased numbers of macrophage precursors, and cmo mice mobilize more macrophage precursors in response to a sterile inflammatory stimulus. Signal transducer and activator of transcription 1 is elevated in cmo splenic macrophages, which also exhibit increased colony-stimulating factor-1-stimulated proliferation and increased extracellular signal-regulated kinase 1/2 phosphorylation. PSTPIP2 overexpression in macrophages leads to the opposite phenotype. Thus, PSTPIP2 deficiency causes both an expansion of macrophage progenitors and increased responsiveness of mature macrophages to activating stimuli, which together prime the organism for exaggerated and sustained responses leading to autoinflammatory disease.

Experiencia y resultado del tratamiento de las fracturas diafisiarias de tibia con el uso del clavo UTN y el dispositivo de bloqueo distal DAD / Experience and results of treatment of diaphyseal tibial fractures with the UTN nail and use the block device distal (DAD)

Se trata de un estudio de tipo retrospectivo, donde se evaluaron a 25 pacientes con diagnóstico de fracturas diafisiarias de tibia cerradas y abiertas, tratadas por el Servicio de Ortopedia y Traumatología del Hospital Sor Juana Inés de la Cruz en la ciudad de Mérida durante el período comprendido entre enero de 1997 a diciembre de 1999. En este estudio el promedio de edad de los pacientes fue de 25 años (con rango de 15 años a 62 años), con predominio del sexo masculino sobre el femenino con un 64%. La etiología más frecuente de esta patología correspondió a los accidentes de transito con 48%. El tratamiento efectuado para todos los casos en este tipo de fracturas diafisiaria de tibia fue la colocación de clavo endomedular macizo no fresado para tibia (UTN), con la utilización del dispositivo de bloqueo distal (DAD) y en su mayoría a se realiazo a cielo cerrado. Se analizaron los resultados obtenidos del enclavamiento endomedular de tibia observándose lo siguiente: satisfactorios 84%, insatisfactorios 16%, complicaciones de tejidos blando 4%, fatiga de material 12% errores técnicos 4%, duración del tiempo quirúrgico en promedio de 25 minutos (con rango de 15 a 40 minutos) y con sangramiento escaso. Los resultados globales son de 84% satisfactorio y un 16% de resultado no satisfactorios.

A missense mutation in pstpip2 is associated with the murine autoinflammatory disorder chronic multifocal osteomyelitis.

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disorder that primarily affects bone but is often accompanied by inflammation of the skin and/or gastrointestinal tract. The etiology is unknown but evidence suggests a genetic component to disease susceptibility. Although most cases of CRMO are sporadic, there is an autosomal recessive syndromic form of the disease, called Majeed syndrome, which is due to homozygous mutations in LPIN2. In addition, there is a phenotypically similar mouse, called cmo (chronic multifocal osteomyelitis) in which the disease is inherited as an autosomal recessive disorder. The cmo locus has been mapped to murine chromosome 18. In this report, we describe phenotypic abnormalities in the cmo mouse that include bone, cartilage and skin inflammation. Utilizing a backcross breeding strategy, we refined the cmo locus to a 1.3 Mb region on murine chromosome 18. Within the refined region was the gene pstpip2, which shares significant sequence homology to the PSTPIP1. Mutations in PSTPIP1 have been shown to cause the autoinflammatory disorder PAPA syndrome (pyogenic arthritis, pyoderma gangrenosum and acne). Mutation analysis, utilizing direct sequencing, revealed a single base pair change c.293T --> C in the pstpip2 gene resulting in a highly conserved leucine at amino acid 98 being replaced by a proline (L98P). No other mutations were found in the coding sequence of the remaining genes in the refined interval, although a 50 kb gap remains unexplored. These data suggest that mutations in pstpip2 may be the genetic explanation for the autoinflammatory phenotype seen in the cmo mouse.