Surgical cardiac denervation therapy for treatment of congenital ion channelopathies in pediatric patients: a contemporary, single institutional experience.

BACKGROUND: Congenital ion channel disorders, including congenital long QT syndrome (LQTS), cause significant morbidity in pediatric patients. When medication therapy does not control symptoms or arrhythmias, more invasive treatment strategies may be necessary. This study examines our institution's clinical experience with surgical cardiac denervation therapy for management of these arrhythmogenic disorders in children. METHODS: An institutional review board-approved retrospective review identified ten pediatric patients with congenital ion channelopathies who underwent surgical cardiac denervation therapy at a single institution between May 2011 and April 2014. Eight patients had a diagnosis of congenital LQTS, two patients were diagnosed with catecholaminergic polymorphic ventricular tachycardia (CPVT). All patients underwent sympathectomy and partial stellate ganglionectomy via video-assisted thoracoscopic surgery (VATS). RESULTS: Six of the ten patients had documented ventricular arrhythmias preoperatively, and 70% of the patients had preoperative syncope. The corrected QT interval decreased in 75% of patients with LQTS following sympathectomy. Postoperative arrhythmogenic symptoms were absent in 88% of congenital LQTS patients, but both patients with CPVT continued to have symptoms throughout the duration of follow-up. All patients were alive after a median follow-up period of 10 months. CONCLUSIONS: Surgical cardiac denervation therapy via VATS is a useful treatment strategy for congenital LQTS patients who fail medical management, and its potential benefit in the management of CPVT is unclear. A prospective comparison of the efficacy of surgical cardiac denervation therapy and implantable cardioverter-defibrillator use in congenital ion channelopathies is timely and crucial.

Management of pediatric tachyarrhythmias on mechanical support.

BACKGROUND: Pediatric patients with persistent arrhythmias may require mechanical cardiopulmonary support. We sought to classify the population, spectrum, and success of current treatment strategies. METHODS AND RESULTS: A multicenter retrospective chart review was undertaken at 11 sites. Inclusion criteria were (1) patients <21 years, (2) initiation of mechanical support for a primary diagnosis of arrhythmias, and (3) actively treated on mechanical support. A total of 39 patients were identified with a median age of 5.5 months and median weight of 6 kg. A total of 69% of patients were cannulated for supraventricular tachycardia with a median rate of 230 beats per minute. A total of 90% of patients were supported with extracorporeal membrane oxygenation for an average of 5 days. The remaining 10% were supported with ventricular assist devices for an average of 38 (20-60) days. A total of 95% of patients were treated with antiarrhythmics, with 43% requiring >1 antiarrhythmic. Amiodarone was the most frequently used medication alone or in combination. A total of 33% patients underwent electrophysiology study/transcatheter ablation. Radiofrequency ablation was successful in 9 patients on full flow extracorporeal membrane oxygenation with 3 radiofrequency-failures/conversion to cryoablation. One patient underwent primary cryoablation. A total of 15% of complications were related to electrophysiology study/ablation. At follow-up, 23 patients were alive, 8 expired, and 8 transplanted. CONCLUSIONS: Younger patients were more likely to require support in the presented population. Most patients were treated with antiarrhythmics and one third required electrophysiology study/ablation. Radiofrequency ablation is feasible without altering extracorporeal membrane oxygenation flows. There was a low frequency of acute adverse events in patients undergoing electrophysiology study/ablation, while on extracorporeal membrane oxygenation.

Status of propranolol for treatment of infantile hemangioma and description of a randomized clinical trial.

OBJECTIVES: Our primary objective was to review the current use of propranolol for treatment of infantile hemangioma (IH), specifically regarding 1) the age at initiation of therapy, 2) the method of initiation, 3) the use of other adjuvant therapy, 4) the duration of therapy and relapse rate, 5) the adverse events, and 6) the outcome. Our secondary objective was to describe a randomized, controlled, single-blinded trial comparing propranolol to prednisolone for treatment of IH. METHODS: Ovid Medline and PubMed searches were completed for the MeSH keywords "propranolol" and "hemangioma." Forty-nine English-language articles were published between June 2008 and September 2010, and 28 of these reported data from a total of 213 patients. Only 6 studies treated more than 10 patients, and these were selected for review in detail (154 patients). RESULTS: The treatment was initiated during infancy in 92.9% of patients (mean, 4.5 months). Sixty-five percent of patients were treated with 2 mg/kg per day, and 25.3% with 3 mg/kg per day. Patients were monitored overnight at initiation of treatment in 3 series (59 patients), for 4 to 6 hours as outpatients in 2 series (62 patients), and initially as inpatients but later as outpatients in 1 series (32 patients). Propranolol was used as sole therapy in about two thirds of patients (103 patients). Treatment was ongoing in 46% of patients at the time of publication. The average treatment duration in the remaining patients was 5.1 months. Rebound growth occurred in 21% of patients after a mean of 4.3 months of therapy. Adverse events occurred in 18.1% of patients and included hypotension in 6, somnolence in 6, wheezing in 4, insomnia, agitation, and/or nightmares in 6, cool hands or night sweats in 2, gastroesophageal reflux in 3, and psoriasis-like rash in 1. All authors reported a favorable outcome with propranolol, but the definition of efficacy was not standardized. CONCLUSIONS: Propranolol is an attractive alternative to other treatments for IH. Despite apparent widespread use of this medication, the data are limited, and prospective studies are lacking for this indication. The relatively high rate of adverse effects supports the need for careful monitoring of patients on this therapy. Fastidious reporting of adverse events and objective evaluation of early and late outcomes are necessary to improve our understanding of the use of propranolol for this indication.

Physiological and gene expression analysis of inhibition of Desulfovibrio vulgaris hildenborough by nitrite.

A Desulfovibrio vulgaris Hildenborough mutant lacking the nrfA gene for the catalytic subunit of periplasmic cytochrome c nitrite reductase (NrfHA) was constructed. In mid-log phase, growth of the wild type in medium containing lactate and sulfate was inhibited by 10 mM nitrite, whereas 0.6 mM nitrite inhibited the nrfA mutant. Lower concentrations (0.04 mM) inhibited the growth of both mutant and wild-type cells on plates. Macroarray hybridization indicated that nitrite upregulates the nrfHA genes and downregulates genes for sulfate reduction enzymes catalyzing steps preceding the reduction of sulfite to sulfide by dissimilatory sulfite reductase (DsrAB), for two membrane-bound electron transport complexes (qmoABC and dsrMKJOP) and for ATP synthase (atp). DsrAB is known to bind and slowly reduce nitrite. The data support a model in which nitrite inhibits DsrAB (apparent dissociation constant K(m) for nitrite = 0.03 mM), and in which NrfHA (K(m) for nitrite = 1.4 mM) limits nitrite entry by reducing it to ammonia when nitrite concentrations are at millimolar levels. The gene expression data and consideration of relative gene locations suggest that QmoABC and DsrMKJOP donate electrons to adenosine phosphosulfate reductase and DsrAB, respectively. Downregulation of atp genes, as well as the recorded cell death following addition of inhibitory nitrite concentrations, suggests that the proton gradient collapses when electrons are diverted from cytoplasmic sulfate to periplasmic nitrite reduction.