Type 8 long QT syndrome: pathogenic variants in CACNA1C-encoded Cav1.2 cluster in STAC protein binding site.

AIMS: Pathogenic gain-of-function variants in CACAN1C cause type-8 long QT syndrome (LQT8). We sought to describe the electrocardiographic features in LQT8 and utilize molecular modelling to gain mechanistic insights into its genetic culprits. METHODS AND RESULTS: Rare variants in CACNA1C were identified from genetic testing laboratories. Treating physicians provided clinical information. Variant pathogenicity was independently assessed according to recent guidelines. Pathogenic (P) and likely pathogenic (LP) variants were mapped onto a 3D modelled structure of the Cav1.2 protein. Nine P/LP variants, identified in 23 patients from 19 families with non-syndromic LQTS were identified. Six variants, found in 79% of families, clustered to a 4-residue section in the cytosolic II-III loop region which forms a region capable of binding STAC SH3 domains. Therefore, variants may affect binding of SH3-domain containing proteins. Arrhythmic events occurred in similar proportions of patients with II-III loop variants and with other P/LP variants (53% vs. 48%, P = 0.41) despite shorter QTc intervals (477 ± 31 ms vs. 515 ± 37 ms, P = 0.03). A history of sudden death was reported only in families with II-III loop variants (60% vs. 0%, P = 0.03). The predominant T-wave morphology was a late peaking T wave with a steep descending limb. Exercise testing demonstrated QTc prolongation on standing and at 4 min recovery after exercise. CONCLUSION: The majority of P/LP variants in patients with CACNA1C-mediated LQT8 cluster in an SH3-binding domain of the cytosolic II-III loop. This represents a 'mutation hotspot' in LQT8. A late-peaking T wave with a steep descending limb and QT prolongation on exercise are commonly seen.

Green synthesis of gold nanoparticles reduced and stabilized by sodium glutamate and sodium dodecyl sulfate.

The Turkevich method has been used for many years in the synthesis of gold nanoparticles. Lately, the use of plant extracts and amino acids has been reported, which is valuable in the field of biotechnology and biomedicine. The AuNPs was synthesized from the reduction of HAuCl4 3H2O by sodium glutamate and stabilized with sodium dodecyl sulfate. The optimum concentrations for sodium glutamate and sodium dodecyl sulfate in the synthesis process were determined. The characteristics of the synthesized AuNPs was analysed through UV-Vis Spectroscopy and SEM. The AuNPs have spherical shape with a mean diameter of approximately 21.62 ± 4.39 nm and is well dispersed. FTIR analysis of the AuNPs reflected that the sulfate head group of sodium dodecyl sulfate is adsorbed at the surface of the AuNPs. Thus, we report herein the synthesis of AuNPs using sodium glutamate and sodium dodecyl sulfate.

A transbaffle approach to ablation in a child with an extracardiac fontan.

We present the case of an 11-year-old with D-transposition, double inlet left ventricle, and dextrocardia 8 years following an extracardiac Fontan with supraventricular tachycardia mediated by a concealed accessory pathway. A transbaffle puncture was performed with fluoroscopic and transesophageal echocardiography guidance and the pathway location as well as its proximity to the HIS bundle were identified. The pathway was successfully ablated and the patient is asymptomatic for 12 months postablation.

Frequent Premature Ventricular Contractions: An Electrical Link to Cardiomyopathy.

Heart failure is common and is associated with significant morbidity and mortality. Identifying potentially modifiable risk factors for the development of ventricular dysfunction is important in both the prevention and the treatment of this condition. Arrhythmia disorders are increasingly recognized as contributory to the development of ventricular failure. Poorly controlled supraventricular tachyarrhythmias, altered left ventricular activation due to left bundle branch block or right ventricular pacing, and frequent premature ventricular contractions (PVCs) constitute the main subtypes of arrhythmia disorders that are associated with the development of ventricular dysfunction. PVCs are common and are considered benign in the absence of structural heart disease. Frequent PVCs, defined as greater than 20% of all QRS complexes on standard 24-hour Holter monitoring, are associated with the presence or subsequent development of left ventricular dilatation and dysfunction. Catheter ablation of frequent PVCs has been demonstrated to be effective at PVC suppression and is associated with improvement or normalization of ventricular function; thus defining a specific, reversible form of ventricular dysfunction termed PVC cardiomyopathy. In patients presenting with high burden PVCs, an assessment for symptoms and associated cardiomyopathy is warranted and, in the appropriate clinical setting, PVC catheter ablation may be a reasonable treatment option.

Relation of smoking status to outcomes after cardiopulmonary resuscitation for in-hospital cardiac arrest.

In-hospital cardiac arrest (IHCA) is common and is associated with poor prognosis. Data on the effect of smoking on outcomes after IHCA are limited. We analyzed the Nationwide Inpatient Sample databases from 2003 to 2011 for all patients aged≥18 years who underwent cardiopulmonary resuscitation (CPR) for IHCA to examine the differences in survival to hospital discharge and neurologic status between smokers and nonsmokers. Of the 838,464 patients with CPR for IHCA, 116,569 patients (13.9%) were smokers. Smokers were more likely to be younger, Caucasian, and male. They had a greater prevalence of dyslipidemia, coronary artery disease, hypertension, chronic pulmonary disease, obesity, and peripheral vascular disease. Atrial fibrillation, heart failure, and diabetes mellitus with complications were less prevalent in smokers. Smokers were more likely to have a primary diagnosis of acute myocardial infarction (14.8% vs 9.1%, p<0.001) and ventricular tachycardia or ventricular fibrillation as the initial cardiac arrest rhythm (24.3% vs 20.5%, p<0.001). Smokers had a higher rate of survival to hospital discharge compared with nonsmokers (28.2% vs 24.1%, adjusted odds ratio 1.06, 95% confidence interval 1.05 to 1.08, p<0.001). Smokers were less likely to have a poor neurologic status after IHCA compared with nonsmokers (3.5% vs 3.9%, adjusted odds ratio 0.92, 95% confidence interval 0.89 to 0.95, p<0.001). In conclusion, among patients aged ≥18 years who underwent CPR for IHCA, we observed a higher rate of survival in smokers than nonsmokers-consistent with the "smoker's paradox." Smokers were also less likely to have a poor neurologic status after IHCA.

Catheter ablation of postinfarction ventricular tachycardia: ten-year trends in utilization, in-hospital complications, and in-hospital mortality in the United States.

BACKGROUND: There is a paucity of data regarding the complications and in-hospital mortality after catheter ablation for ventricular tachycardia (VT) in patients with ischemic heart disease. OBJECTIVE: The purpose of this study was to determine the temporal trends in utilization, in-hospital mortality, and complications of catheter ablation of postinfarction VT in the United States. METHODS: We used the 2002-2011 Nationwide Inpatient Sample (NIS) database to identify all patients ≥18 years of age with a primary diagnosis of VT (International Classification of Diseases, Ninth Edition, Clinical Modification [ICD-9-CM] code 427.1) and who also had a secondary diagnosis of prior history of myocardial infarction (ICD-9-CM 412). Patients with supraventricular arrhythmias were excluded. Patients who underwent catheter ablation were identified using ICD-9-CM procedure code 37.34. Temporal trends in catheter ablation, in-hospital complications, and in-hospital mortality were analyzed. RESULTS: Of 81,539 patients with postinfarct VT, 4653 (5.7%) underwent catheter ablation. Utilization of catheter ablation increased significantly from 2.8% in 2002 to 10.8% in 2011 (Ptrend < .001). The overall rate of any in-hospital complication was 11.2% (523/4653), with vascular complications in 6.9%, cardiac in 4.3%, and neurologic in 0.5%. In-hospital mortality was 1.6% (75/4653). From 2002 to 2011, there was no significant change in the overall complication rates (8.4% to 10.2%, Ptrend = .101; adjusted odds ratio [per year] 1.02, 95% confidence interval 0.98-1.06) or in-hospital mortality (1.3% to 1.8%, Ptrend = .266; adjusted odds ratio [per year] 1.03, 95% confidence interval 0.92-1.15). CONCLUSION: The utilization rate of catheter ablation as therapy for postinfarct VT has steadily increased over the past decade. However, procedural complication rates and in-hospital mortality have not changed significantly during this period.

Chiral anthracene and anthrone templates as stereocontrolling elements in Diels-Alder/retro Diels-Alder sequences.

The development of chiral anthracene templates for use in Diels-Alder/retro Diels-Alder sequences is described. A summary of past results and new progress is reported.