Disparities in the implantation of secondary prevention implantable cardioverter defibrillator in the United States.

BACKGROUND: The annual incidence of sudden cardiac death is over 300,000 in the United States (US). Historically, inpatient implantation of secondary prevention implantable cardioverter defibrillator (ICD) has been variable and subject to healthcare disparities. OBJECTIVE: To evaluate contemporary practice trends of inpatient secondary prevention ICD implants within the US on the basis of race, sex, and socioeconomic status (SES). METHODS: The study is a retrospective analysis of the National Inpatient Sample from 2016 to 2020 of adult discharges with a primary diagnosis of ventricular tachycardia (VT), ventricular flutter, and fibrillation (VF). Adjusted ICD implantation rates based on race, sex, and SES and associated temporal trends were calculated using multivariate regression. RESULTS: A total of 193,600 primary VT/VF discharges in the NIS were included in the cohort, of which 57,895 (29.9%) had ICD placement. There was a significant racial and ethnic disparity in ICD placement for Black, Hispanic, Asian, and Native American patients as compared to White patients; adjusted odds ratio (aOR): 0.86 [p < .01], 0.90 [p  =  .03], 0.81[p < .01], 0.45 [p < .01], respectively. Female patients were also less likely to receive an ICD compared to male patients (aOR: 0.75, p < .01). Disparities in ICD placement remained stable over the study period (ptrend ≥ .05 in all races, both sexes and income categories). CONCLUSION: Racial, sex, and SES disparities persisted for secondary prevention ICD implants in the US. An investigation into contributing factors and subsequent approaches are needed to address the modifiable causes of disparities in ICD implantation as these trends have not improved compared to historic data.

Ventricular arrhythmias involving the His-Purkinje system in the structurally abnormal heart.

His-Purkinje-related ventricular arrhythmias are a subset of ventricular tachycardias that use the specialized cardiac conduction system. These arrhythmias can occur in various different forms of structural heart disease. Here, we review the basic science discoveries and their analogous clinical observations that implicate the His-Purkinje system as a crucial component of the arrhythmia circuit. While mutations serve the molecular basis for arrhythmias in the heritable cardiomyopathies, transcriptional and posttranslational changes constitute the adverse remodeling leading to arrhythmias in acquired structural heart disease. Additional studies on the electrical properties of the His-Purkinje network and its interactions with the surrounding myocardium will improve the clinical diagnosis and treatment of these arrhythmias.

Integrative Tissue-Specific Functional Annotations in the Human Genome Provide Novel Insights on Many Complex Traits and Improve Signal Prioritization in Genome Wide Association Studies.

Extensive efforts have been made to understand genomic function through both experimental and computational approaches, yet proper annotation still remains challenging, especially in non-coding regions. In this manuscript, we introduce GenoSkyline, an unsupervised learning framework to predict tissue-specific functional regions through integrating high-throughput epigenetic annotations. GenoSkyline successfully identified a variety of non-coding regulatory machinery including enhancers, regulatory miRNA, and hypomethylated transposable elements in extensive case studies. Integrative analysis of GenoSkyline annotations and results from genome-wide association studies (GWAS) led to novel biological insights on the etiologies of a number of human complex traits. We also explored using tissue-specific functional annotations to prioritize GWAS signals and predict relevant tissue types for each risk locus. Brain and blood-specific annotations led to better prioritization performance for schizophrenia than standard GWAS p-values and non-tissue-specific annotations. As for coronary artery disease, heart-specific functional regions was highly enriched of GWAS signals, but previously identified risk loci were found to be most functional in other tissues, suggesting a substantial proportion of still undetected heart-related loci. In summary, GenoSkyline annotations can guide genetic studies at multiple resolutions and provide valuable insights in understanding complex diseases. GenoSkyline is available at http://genocanyon.med.yale.edu/GenoSkyline.