The rationale and design of the Shockless IMPLant Evaluation (SIMPLE) trial: A randomized, controlled trial of defibrillation testing at the time of defibrillator implantation

Defibrillation testing (DT) has been an integral part of defibrillator (implantable cardioverter defibrillator [ICD]) implantation; however, there is little evidence that it improves outcomes. Surveys show a trend toward ICD implantation without DT, which now exceeds 30% to 60% in some regions. Because there is no evidence to support dramatic shift in practice, a randomized trial is urgently needed. The SIMPLE trial will determine if ICD implantation without any DT is noninferior to implantation with DT. Patients will be eligible if they are receiving their first ICD using a Boston Scientific device (Boston Scientific, Natick, MA). Patients will be randomized to DT or no DT at the time of ICD implantation. In the DT arm, physicians will make all reasonable efforts to ensure 1 successful intraoperative defibrillation at 17 J or 2 at 21 J. The first clinical shock in all tachycardia zones will be set to 31 J for all patients. The primary outcome of SIMPLE will be the composite of ineffective appropriate shock or arrhythmic death. The safety outcome of SIMPLE will include a composite of potentially DT-related procedural complications within 30 days of ICD implantation. Several secondary outcomes will be evaluated, including all-cause mortality and heart failure hospitalization. Enrollment of 2,500 patients with 3.5-year mean follow-up will provide sufficient statistical power to demonstrate noninferiority. The study is being performed at approximately 90 centers in Canada, Europe, Israel, and Asia Pacific with final results expected in 2013.     

The Moya-Moya syndrome: a report of two children

Two patients with Moya-Moya syndrome are reported. The first patient has a trisomy 21 and is to our knowledge the third patient reported with the association of Down's syndrome and Moya-Moya. The second patient also demonstrates the typical Moya-Moya picture in angiography. Angiographic follow-up is demonstrated. The presenting age and symptoms, the symptoms in the course of the disease and the prognosis of 120 non-mongoloid cases of Moya-Moya are reviewed.     

Cardiac sarcoidosis: improved prognosis through new diagnostic tests and treatment

Cardiac sarcoidosis was diagnosed in 3 patients: 2 men aged 52 and 51 years, respectively, and a woman aged 55 years. Both men had ventricular tachycardia. In the first man, a right-ventricle biopsy revealed a non-caseating granuloma. The second man had active granulomatous cardiac infiltration, according to a gallium scintigram. The first man recovered after receiving immunosuppression, heart-failure medication, and an implantable defibrillator; the second received the same plus radio-frequency catheter ablation, but experienced serious heart failure. The woman was being treated for pulmonary sarcoidosis but complained of progressive cardiac symptoms. She recovered after receiving heart-failure medication, immunosuppression, and a biventricular pacemaker. Sarcoidosis is a multi-system granulomatous disorder of unknown aetiology with cardiac involvement in 20 to 30% of patients, resulting in severe morbidity and mortality. With the help ofgadolinium MRI and positron emission tomography (PET), these conditions can be detected at an earlier stage, which allows for improved evaluation of the efficacy of available therapies. The use of resynchronisation therapy and implantable defibrillators has improved the prognosis of patients with cardiac sarcoidosis.     

Unrecognized failure of a narrow caliber defibrillation lead: the role of defibrillation threshold testing in identifying an unprotected individual

In this case report we describe a short circuit in the Riata 1570 defibrillator lead (Riata 1570, St. Jude Medical, St. Paul, MN, USA) that was unsuspected owing to normal lead parameters until defibrillator threshold testing at the time of elective generator change. On this occasion, the short circuit manifested as unsuccessful defibrillation of ventricular fibrillation with immediate battery depletion. This report adds weight to existing concerns over narrow caliber leads, it draws attention to the possibility of lead malfunction despite unremarkable interrogation, and lastly it highlights the potential role of routine defibrillator threshold testing, particularly at elective generator change (an issue that remains sparingly addressed in the existing literature).     

Neurophysiological studies in the Leigh syndrome

We performed neurophysiological studies in 12 patients with the Leigh syndrome (6 pathologically confirmed and 6 clinically diagnosed). The results are compared with data derived from a literature survey of 173 Leigh syndrome patients. We found no positive contribution of neurophysiological studies towards the diagnosis of the Leigh syndrome.     

Impaired fertility and motor function in a zebrafish model for classic galactosemia

Classic galactosemia is a genetic disorder of galactose metabolism, caused by severe deficiency of galactose-1-phosphate uridylyltransferase (GALT) enzyme activity due to mutations of the GALT gene. Its pathogenesis is still not fully elucidated, and a therapy that prevents chronic impairments is lacking. In order to move research forward, there is a high need for a novel animal model, which allows organ studies throughout development and high-throughput screening of pharmacologic compounds. Here, we describe the generation of a galt knockout zebrafish model and present its phenotypical characterization. Using a TALEN approach, a galt knockout line was successfully created. Accordingly, biochemical assays confirm essentially undetectable galt enzyme activity in homozygotes. Analogous to humans, galt knockout fish accumulate galactose-1-phosphate upon exposure to exogenous galactose. Furthermore, without prior exposure to exogenous galactose, they exhibit reduced motor activity and impaired fertility (lower egg quantity per mating, higher number of unsuccessful crossings), resembling the human phenotype(s) of neurological sequelae and subfertility. In conclusion, our galt knockout zebrafish model for classic galactosemia mimics the human phenotype(s) at biochemical and clinical levels. Future studies in our model will contribute to improved understanding and management of this disorder.