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.

Esophageal luminal temperature monitoring using a multi-sensor probe lowers the risk of esophageal injury in cryo and radiofrequency catheter ablation for atrial fibrillation.

BACKGROUND: Esophageal luminal temperature monitoring is a commonly used strategy to reduce esophageal thermal injury in catheter ablation for atrial fibrillation (AFib). OBJECTIVES: We sought to compare the incidence of endoscopically detected esophageal lesions (EDEL) between two commonly used esophageal luminal temperature probes. METHODS: Consecutive patients undergoing ablation with esophageal luminal temperature monitoring and upper endoscopy within 24 h after ablation were included. RESULTS: Four hundred forty-five patients (64 ± 10 years, 44% female) were included. Esophageal temperature monitoring was done with a single-sensor probe in 213 (48%) and multi-sensor probe in 232 (52%). Cryoballoon (CB) ablation was performed in 118 (27%) and radiofrequency (RF) ablation in 327 (73%) of patients. EDEL was present in 94 (22.9%) of which 85 were mild, 8 were moderate, and 1 was severe, and none progressed to atrial-esophageal fistula. The use of the multi-sensor probe during CB ablation was associated with a reduction in EDEL compared to single sensor (6.8% vs 24.3%; P = 0.016). Similarly, in the RF ablation group, EDEL was present in 19.5% of the multi-sensor group vs 32.8% in the single-sensor group (P = 0.001). Logistic regression showed that multi-sensor probe use was associated with reduction in EDEL with an odds ratio of 0.23 in CB ablation (P = 0.024) and 0.44 for RF ablation (P = 0.001). CONCLUSIONS: Esophageal luminal temperature monitoring during AFib ablation using a multi-sensor probe was associated with a significant reduction in EDEL compared to a single-sensor probe.

Importance of the Activation Sequence of the His or Right Bundle for Diagnosis of Complex Tachycardia Circuits.

In this review, we emphasize the unique value of recording the activation sequence of the His bundle or right bundle branch (RB) for diagnoses of various supraventricular and fascicular tachycardias. A close analysis of the His to RB (H-RB) activation sequence can help differentiate various forms of supraventricular tachycardias, namely atrioventricular nodal reentry tachycardia from concealed nodofascicular tachycardia, a common clinical dilemma. Furthermore, bundle branch reentry tachycardia and fascicular tachycardias often are included in the differential diagnosis of supraventricular tachycardia with aberrancy, and the use of this technique can help the operator make the distinction between supraventricular tachycardias and these other forms of ventricular tachycardias using the His-Purkinje system. We show that this technique is enhanced by the use of multipolar catheters placed to span the proximal His to RB position to record the activation sequence between proximal His potential to the distal RB potential. This allows the operator to fully analyze the activation sequence in sinus rhythm as compared to that during tachycardia and may help target ablation of these arrhythmias. We argue that 3 patterns of H-RB activation are commonly identified-the anterograde H-RB pattern, the retrograde H-RB (right bundle to His bundle) pattern, and the chevron H-RB pattern (simultaneous proximal His and proximal RB activation)-and specific arrhythmias tend to be associated with specific H-RB activation sequences. We show that being able to record and categorize this H-RB relationship can be instrumental to the operator, along with standard pacing maneuvers, to make an arrhythmia diagnosis in complex tachycardia circuits. We highlight the importance of H-RB activation patterns in these complex tachycardias by means of case illustrations from our groups as well as from prior reports.

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.

Rosiglitazone antagonizes vascular endothelial growth factor signaling and nuclear factor of activated T cells activation in cardiac valve endothelium.

Nuclear factor of activated T cells, Cytoplasmic 1 (NFATc1) is required for heart valve formation. Vascular endothelial growth factor (VEGF) signaling, mediated by NFATc1 activation, positively regulates growth of valvular endothelial cells. However, regulators of VEGF/NFATc1 signaling in valve endothelium are poorly understood. Peroxisome proliferator-activated receptor gamma (PPARgamma) inhibits NFATc1 activity in T cells and cardiomyocytes, but it is not known if PPARgamma controls NFATc1 function in endothelial cells. The authors hypothesize PPARgamma antagonizes VEGF signaling in valve endothelium by inhibiting NFATc1. Endothelial cells isolated from human valve leaflet tissue were shown by immunocytochemistry to express the endothelial-specific markers von Willebrand factor (vWF) and platelet endothelial cell adhesion molecule (PECAM)-1. VEGF-induced proliferation and migration of human pulmonary valve endothelial cells (HPVECs) were inhibited by rosiglitazone (ROSI), a specific ligand of PPARgamma activation, suggesting that PPARgamma disrupts VEGF signaling in the valve endothelium. ROSI also antagonized VEGF-mediated NFATc1 nuclear translocation in HPVECs, suggesting that PPARgamma inhibits VEGF signaling of NFATc1 activation in the valve. The effect of ROSI on nonvalve human umbilical vein endothelial cells (HUVECs) was tested in parallel and a similar inhibition of NFATc1 activation was observed. These data provide the first demonstration that ROSI negatively regulates VEGF signaling in the valve endothelium by a mechanism involving NFATc1 activation and nuclear translocation.