Citations

Background— Ventricular tachycardia and premature ventricular complexes (PVCs) most frequently occur in the context of structural heart disease. However, the burden of idiopathic ventricular arrhythmias (IVA) in the general population is unknown. Methods and Results— We identified incident cases of IVA between 2005 and 2013 from Olmsted County, Minnesota, using the Rochester Epidemiology Project database. For PVC cohorts, we included those with frequent (defined as ≥100 PVC/24 hours) symptomatic PVCs. We defined IVA-associated cardiomyopathy as a drop in ejection fraction of ≥10% from baseline. Between 2005 and 2013, we identified 614 individuals with incident IVA (229 [37.3%] were male; average age was 52.1±17.2 years). Of these, 177 (28.8%) had idiopathic ventricular tachycardia, 408 (66.5%) had symptomatic PVCs, and 29 (4.7%) had IVA-associated cardiomyopathy. The age- and sex-adjusted incidence rates in 2005 to 2007, 2008 to 2010, and 2011 to 2013 were 44.9 per 100 000 (95% confidence interval [CI], 38.0–51.8), 47.6 per 100 000 (95% CI, 40.8–54.5), and 62.0 per 100 000 (95% CI, 54.4–69.6), respectively. In idiopathic ventricular tachycardia, there was an increase in incidence rate with ages ( P <0.001) but not between sexes ( P =0.12). The age-adjusted incidence of symptomatic PVC was higher in females than in males (46.2 per 100 000 [95% CI, 40.9–51.6] versus 20.5 per 100 000 [95% CI, 16.8–24.3]; P <0.001). The small number of individuals with IVA-associated cardiomyopathy precluded any formal testing. Conclusions— The incidence of IVA is increasing. Furthermore, overall incidence increases with age. Although the rate of idiopathic ventricular tachycardia is similar across sexes, women have a higher incidence of symptomatic PVC.

AbstractObjectiveTo identify the molecular basis and elucidate the pathogenesis of a fatal congenital myasthenic syndrome.MethodsWe performed clinical electrophysiology studies, exome and Sanger sequencing, and analyzed functional consequences of the identified mutation.ResultsClinical electrophysiology studies of the patient revealed several‐fold potentiation of the evoked muscle action potential by high frequency nerve stimulation pointing to a presynaptic defect. Exome sequencing identified a homozygous c.340delA frameshift mutation in synaptobrevin 1 (SYB1), one of the three SNARE proteins essential for synaptic vesicle exocytosis. Analysis of both human spinal cord gray matter and normal human muscle revealed expression of the SYB1A and SYB1D isoforms, predicting expression of one or both isoforms in the motor nerve terminal. The identified mutation elongates the intravesicular C‐terminus of the A isoform from 5 to 71, and of the D isoform from 4 to 31 residues. Transfection of either mutant isoform into bovine chromaffin cells markedly reduces depolarization‐evoked exocytosis, and transfection of either mutant isoform into HEK cells significantly decreases expression of either mutant compared to wild type.InterpretationThe mutation is pathogenic because elongation of the intravesicular C‐terminus of the A and D isoforms increases the energy required to move their C‐terminus into the synaptic vesicle membrane, a key step for fusion of the synaptic vesicle with the presynaptic membrane, and because it is predicted to reduce expression of either isoform in the nerve terminal.

BackgroundAlthough sudden death (SD) is a rare complication after atrioventricular junction (AVJ) ablation and permanent pacemaker implantation, the risk factors leading to this SD remain unknown. The purpose of this study was to investigate SD and its risk factors after ablate‐and‐pace strategy for rate control in atrial fibrillation (AF) patients during long‐term follow‐up.HypothesisMethodsFrom January 2005 to December 2009, we enrolled into this study 517 AF patients with AVJ ablation and right ventricular pacemaker implantation. Patients were divided into 2 groups, SD and non‐SD. Cox proportional hazards models were used to assess potential risk factors for overall mortality and SD.ResultsDuring a mean follow‐up of 25.8 ± 18.6 months (range, 3 days to 63.8 months), 53 patients died (15 with SD). Cox proportional hazards models showed that the presence of congestive heart failure, New York Heart Association functional class, chronic renal failure, and nonsustained ventricular tachycardia were risk factors that predicted overall mortality. For SD, the presence of dilated cardiomyopathy and mitral stenosis were associated risk factors. SD was exclusively seen in patients who had narrow QRS complex or right bundle branch block prior to AVJ ablation and pacemaker implantation; SD was not seen in any patient with preexisting complete left bundle branch block.ConclusionsDilated cardiomyopathy, mitral stenosis, and baseline QRS morphology should be examined as potential risk factors for SD after AVJ ablation and pacemaker implantation.

Abstract Background: Common cancers develop through a multistep process often including inherited susceptibility. Collaboration among multiple institutions, and funding from multiple sources, has allowed the development of an inexpensive genotyping microarray, the OncoArray. The array includes a genome-wide backbone, comprising 230,000 SNPs tagging most common genetic variants, together with dense mapping of known susceptibility regions, rare variants from sequencing experiments, pharmacogenetic markers, and cancer-related traits. Methods: The OncoArray can be genotyped using a novel technology developed by Illumina to facilitate efficient genotyping. The consortium developed standard approaches for selecting SNPs for study, for quality control of markers, and for ancestry analysis. The array was genotyped at selected sites and with prespecified replicate samples to permit evaluation of genotyping accuracy among centers and by ethnic background. Results: The OncoArray consortium genotyped 447,705 samples. A total of 494,763 SNPs passed quality control steps with a sample success rate of 97% of the samples. Participating sites performed ancestry analysis using a common set of markers and a scoring algorithm based on principal components analysis. Conclusions: Results from these analyses will enable researchers to identify new susceptibility loci, perform fine-mapping of new or known loci associated with either single or multiple cancers, assess the degree of overlap in cancer causation and pleiotropic effects of loci that have been identified for disease-specific risk, and jointly model genetic, environmental, and lifestyle-related exposures. Impact: Ongoing analyses will shed light on etiology and risk assessment for many types of cancer. Cancer Epidemiol Biomarkers Prev; 26(1); 126–35. ©2016 AACR.

The incidence and prevalence of most cardiovascular disorders increase with age, and cardiovascular disease ( CVD ) is the leading cause of death and major disability in adults aged 75 and older. Despite the effect of CVD on quality of life, morbidity, and mortality in older adults, individuals aged 75 and older have been markedly underrepresented in most major cardiovascular trials, and virtually all trials have excluded older adults with complex comorbidities, significant physical or cognitive disabilities, frailty, or residence in nursing homes and assisted living facilities. As a result, current guidelines are unable to provide evidence‐based recommendations for diagnosis and treatment of older adults typical of those encountered in routine clinical practice. The objectives of this scientific statement are to summarize current guideline recommendations as they apply to older adults, identify critical gaps in knowledge that preclude informed evidence‐based decision‐making, and recommend future research to close existing knowledge gaps. To achieve these objectives, a detailed review was conducted of current American College of Cardiology/American Heart Association ( ACC / AHA ) and American Stroke Association ( ASA ) guidelines to identify content and recommendations that explicitly targeted older adults. A pervasive lack of evidence to guide clinical decision‐making in older adults with CVD was found, as well as a paucity of data on the effect of diagnostic and therapeutic interventions on outcomes that are particularly important to older adults, such as quality of life, physical function, and maintenance of independence. Accordingly, there is a critical need for a multitude of large population‐based studies and clinical trials that include a broad spectrum of older adults representative of those seen in clinical practice and that incorporate relevant outcomes important to older adults in the study design. The results of these studies will provide the foundation for future evidence‐based guidelines applicable to older adults and enhance person‐centered care of older individuals with CVD in the United States and around the world.

The Pipeline Embolization Device (PED) was approved for the treatment of intracranial aneurysms from the petrous to the superior hypophyseal segment of the internal carotid artery. However, since its approval, its use for treatment of intracranial aneurysms in other locations and non-sidewall aneurysms has grown tremendously. The authors report on a cohort of 15 patients with 16 cerebral aneurysms that incorporated an end vessel with no significant distal collaterals, which were treated with the PED. The cohort includes 7 posterior communicating artery aneurysms, 5 ophthalmic artery aneurysms, 1 superior cerebellar artery aneurysm, 1 anterior inferior cerebellar artery aneurysm, and 2 middle cerebral artery aneurysms. None of the aneurysms achieved significant occlusion at the last follow-up evaluation (mean 24 months). Based on these observations, the authors do not recommend the use of flow diverters for the treatment of this subset of cerebral aneurysms.