Outcomes of Catheter Ablation of Ventricular Tachycardia in the Setting of Structural Heart Disease.

Sustained ventricular tachycardias are common in the setting of structural heart disease, either due to prior myocardial infarction or a variety of non-ischemic etiologies, including idiopathic dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy. Over the past two decades, percutaneous catheter ablation has evolved dramatically and has become an effective tool for the control of ventricular arrhythmias. Single and multicenter observational studies as well as several prospective randomized trials have begun to investigate long-term outcomes after catheter ablation procedures. These studies encompass a wide range of mapping and ablation techniques, including conventional activation mapping/entrainment criteria, substrate modification guided by pacemapping, late potential and abnormal electrogram ablation, scar de-channeling, and core isolation. While large-scale, multicenter prospective randomized clinical trials are somewhat limited, the published data demonstrate favorable outcomes with respect to a reduction in overall ventricular tachycardia (VT) burden, reduction of implantable cardioverter defibrillator (ICD) shocks, and discontinuation of anti-arrhythmic medications across varying disease subtypes and convincingly support the use of catheter ablation as the standard of care for many patients with VT in the setting of structural heart disease.

Update on the prenatal diagnosis and treatment of congenital adrenal hyperplasia due to 11beta-hydroxylase deficiency.

11beta-Hydroxylase deficiency is a common form of congenital adrenal hyperplasia causing virilization of the female fetus and hypertension. DNA analysis of the gene (CYP11B1) encoding 11beta-hydroxylase has been reported previously to be effective in the prenatal diagnosis of one affected female fetus. In that case, prenatal treatment with dexamethasone resulted in normal female genitalia. We now report five new pregnancies that underwent prenatal diagnosis for 11beta-hydroxylase deficiency. In the first family, the proband is homozygous for a T318M mutation and all fetuses from four subsequent pregnancies are carriers. In a second family, the mother is homozygous for a A331V mutation and was started on dexamethasone, but identification of a homozygous normal fetus led to the discontinuation of treatment. In another family, the fetus was a male homozygous for R384Q and treatment was discontinued. Lastly, a novel G444D mutation in exon 8 was identified and proven to reduce 11beta-hydroxylase activity.

The natural history and genotype-phenotype nonconcordance of HLA identical siblings with the same mutations of the 21-hydroxylase gene.

The correlation of genotype to phenotype in congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency has been investigated thoroughly since the mapping of the CYP21 gene to the short arm of chromosome 6. In most instances, it is possible to accurately predict the phenotype based on genoytpe; however, in a small number of patients, individuals with identical mutations demonstrate variable phenotypes. We report two HLA-identical brothers who represent a striking case of genotype-phenotype nonconcordance in CAH. Molecular genetic analysis showed both patients had mutations in intron 2 and exon 10 of CYP21. Both brothers underwent salt-deprivation tests at similar ages over three separate hospital admissions. Patient 1 was diagnosed with simple virilizing CAH and was able to maintain sodium balance during salt deprivation tests. Patient 2, 3 years younger, was diagnosed with salt-wasting CAH and was unable to maintain sodium balance but progressively increased his aldosterone secretion with age.