Children and CHD ICD recipients have significant appropriate and inappropriate shock frequencies. Optimizing programming, medical management, and compliance may diminish inappropriate shocks. Despite concerns regarding generator recalls, lead failure remains the major cause of inappropriate shocks, complications, and system malfunction in children. Prospective assessment of ICD usage in this population may identify additional important factors in pediatric and CHD patients.

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder mainly affecting females and is associated with mutations in MECP2, the gene encoding methyl CpG-binding protein 2. Mouse models suggest that recombinant human insulinlike growth factor 1 (IGF-1) (rhIGF1) (mecasermin) may improve many clinical features. We evaluated the safety, tolerability, and pharmacokinetic profiles of IGF-1 in 12 girls with MECP2 mutations (9 with RTT). In addition, we performed a preliminary assessment of efficacy using automated cardiorespiratory measures, EEG, a set of RTT-oriented clinical assessments, and two standardized behavioral questionnaires. This phase 1 trial included a 4-wk multiple ascending dose (MAD) (40-120 μg/kg twice daily) period and a 20-wk open-label extension (OLE) at the maximum dose. Twelve subjects completed the MAD and 10 the entire study, without evidence of hypoglycemia or serious adverse events. Mecasermin reached the CNS compartment as evidenced by the increase in cerebrospinal fluid IGF-1 levels at the end of the MAD. The drug followed nonlinear kinetics, with greater distribution in the peripheral compartment. Cardiorespiratory measures showed that apnea improved during the OLE. Some neurobehavioral parameters, specifically measures of anxiety and mood also improved during the OLE. These improvements in mood and anxiety scores were supported by reversal of right frontal alpha band asymmetry on EEG, an index of anxiety and depression. Our data indicate that IGF-1 is safe and well tolerated in girls with RTT and, as demonstrated in preclinical studies, ameliorates certain breathing and behavioral abnormalities.

ICD therapy can effectively manage malignant arrhythmias in selected pediatric and congenital heart patients. Spurious shocks or ICD storm may increase morbidity and emphasize the need for concomitant medical and ablative therapy. ICD lead failure was relatively frequent in this population.

Background-Studies

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Children and CHD patients treated with CRT have acute improvement in ventricular function, but implantation may require individualized planning and unconventional approaches. Future important goals include preimplant determination of CRT responders in pediatric and CHD patients, optimizing lead placement and programing, as well as long-term CRT device management issues.

Clinically significant arrhythmias occurred in 24% of pediatric patients with cardiac tumors, VT being the most common type. Surgical excision for VT associated with rhabdomyomas and fibromas in selected patients is an important and effective management strategy in these patients.

Improvement of acute RFCA outcomes was contemporaneous with introduction of novel technologies. Intra-atrial re-entrant tachycardia recurrence was common, and no effect on mortality was discerned, but most patients had effective palliation of symptoms. Chronic outcome predictors included the underlying disease severity, application of novel technologies and successful ablation of all targeted arrhythmia circuits.