Augmentation of Atrial Conduction Velocity With Pharmacological and Direct Electrical Sympathetic Stimulation.

BACKGROUND: Atrial conduction velocity (CV) is influenced by autonomic tone and contributes to the pathophysiology of re-entrant arrhythmias and atrial fibrillation. Cardiac sympathetic nerve activation has been reported via electrical stimulation within the vertebral vein (VV). OBJECTIVES: This study sought to characterize changes in right atrial (RA) CV associated with sympathetic stimulation from pharmacologic (isoproterenol) or direct electrical (VV stimulation) approaches. METHODS: Subjects undergoing catheter ablation for atrial fibrillation had baseline RA electroanatomic maps performed in sinus rhythm (SR). RA mapping was repeated during right VV stimulation (20 Hz; up to 20 mA) and again with both RA pacing and during isoproterenol infusion, each titrated to the heart rate achieved with VV stimulation. RESULTS: A total of 100 RA maps were analyzed from 25 subjects (mean age: 58 ± 14 years; 56% male), and CV was calculated from 51,534 electroanatomic map points. VV stimulation increased heart rate from baseline in all subjects (22.5 ± 5.5 beats/min). The average CV increased with VV stimulation (82.0 ± 34.5 cm/s) or isoproterenol (83.7 ± 35.0 cm/s) when compared to SR (70.8 ± 32.5 cm/s; P < 0.001). Heterogeneity of CV decreased with VV stimulation or isoproterenol when compared to SR (coefficient of variation: 0.33 ± 0.21 vs 0.35 ± 0.23 vs 0.57 ± 0.29; P < 0.001). There was no difference in CV or CV heterogeneity between SR and RA pacing, suggesting that these changes were independent of heart rate. CONCLUSIONS: Global RA CV is enhanced, and heterogeneity of CV is reduced, with either pharmacologic or direct electrical sympathetic stimulation via the right VV.

Long-term Risk of Right Coronary Artery Injury Following Catheter Ablation of Cavotricuspid Isthmus-dependent Flutter.

BACKGROUND: Radiofrequency ablation (RFA) of cavotricuspid isthmus (CTI)-dependent atrial flutter requires ablation of the tricuspid annulus overlying the right coronary artery (RCA). While considered safe, reports of acute and subacute RCA injury in human and animal studies raise the possibility of late RCA stenosis. OBJECTIVE: To compare the incidence and severity of angiographic RCA stenoses in patients who have undergone CTI RFA to a control group to assess the long-term risk of RCA damage. METHODS: A two-center retrospective case-cohort study was performed including all patients from 2002-2018 undergoing atrial fibrillation (AF) with CTI ablation (CTI+AF) or AF ablation alone with subsequent coronary angiography (CAG). The AF alone group served as controls due to anticipated similarity of baseline characteristics. Coronary arteries that are anatomically remote to the CTI were examined as prespecified falsification endpoints. CAG was scored by a blinded observer. RESULTS: 156 patients who underwent PVI with subsequent CAG (CTI+AF, n=81; AF alone, n=75) had no difference in baseline characteristics including age, sex, comorbidities, and medications. Mean time from ablation to CAG was similar (CTI+AF 5.0±3.7 years vs AF alone 5.4 ±3.9 years, p=0.5). The mid and distal RCA showed no difference in the average number of angiographic stenoses or lesion severity. In regression analysis, CTI ablation was not a predictor of RCA stenosis severity (p=0.6). There was no difference in coronary disease at sites remote to the CTI ablation (p=NS for all). CONCLUSION: There was no observed relationship between CTI RFA and the number or severity of angiographically apparent RCA stenoses in long-term follow up.

Integrative multi-omics characterization of hepatocellular carcinoma in hispanic patients.

BACKGROUND: The incidence and mortality rates of hepatocellular carcinoma (HCC) among Hispanic individuals in the United States are much higher than in non-Hispanic white people. We conducted multi-omics analyses to elucidate molecular alterations in HCC among Hispanic patients. METHODS: Paired tumor and adjacent non-tumor samples were collected from 31 Hispanic HCCs in South Texas (STX-Hispanic) for genomic, transcriptomic, proteomic, and metabolomic profiling. Serum lipids were profiled in 40 Hispanic and non-Hispanic patients with or without clinically diagnosed HCC. RESULTS: Exome sequencing revealed high mutation frequencies of AXIN2 and CTNNB1 in STX Hispanic HCCs, suggesting a predominant activation of the Wnt/ß-catenin pathway. TERT promoter mutations were also significantly more frequent in the Hispanic cohort (Fisher's exact test, p < .05). Cell cycles and liver function were positively and negatively enriched, respectively, with gene set enrichment analysis. Gene sets representing specific liver metabolic pathways were associated with dysregulation of corresponding metabolites. Negative enrichment of liver adipogenesis and lipid metabolism corroborated with a significant reduction in most lipids in serum samples of HCC patients (paired t-test, p < .0001). Two HCC subtypes from our Hispanic cohort were identified and validated with the TCGA liver cancer cohort. Patients with better overall survival showed higher activity of immune and angiogenesis signatures, and lower activity of liver function-related gene signatures. They also had higher levels of immune checkpoint and immune exhaustion markers. CONCLUSIONS: Our study revealed specific molecular features of Hispanic HCC and potential biomarkers for therapeutic management. It provides a unique resource for studying Hispanic HCC.

Intraoperative pectoral nerve blocks during cardiac implantable electronic device procedures.

BACKGROUND: Cardiac implantable electronic device (CIED) procedures can cause significant postoperative pain. Opioid use for postoperative pain is associated with risk of persistent use. The benefits of pectoral nerve (PECs) blocks have been established for other chest wall surgeries, but adoption in electrophysiology has been limited. OBJECTIVES: The purpose of this study was to evaluate the efficacy of intraoperative ultrasound-guided PECs blocks performed at the time of CIED procedures by the implanting physician from within the device pocket. METHODS: Patients undergoing a pectoral CIED procedure at 7 centers from 2022-2023 were included. Patients underwent intraoperative PECs blocks and subcutaneous local anesthetic vs subcutaneous local anesthetic only at the discretion of the operator. Patients were prospectively evaluated for postoperative pain. RESULTS: Six hundred ten patients (age 67 ± 15 years old; 63% male) were enrolled. and half (n = 305) underwent PECs block. Patients who underwent PECs block were more likely to have a history of chronic pain (32% vs 11%, P <.001). PECs block was associated with lower pain scores in the 4 hours after the procedure (1.5 ± 2.1 vs 4.5 ± 2.5, P <.001). Pain scores were not different after 24 hours (2.8 ± 1.7 vs 3.1 ± 2.2) and 2 weeks (0.9 ± 1.4 vs 0.9 ± 1.2). PECs block patients were less likely to receive inpatient opioids (10% vs 48%, P <.001) and to be discharged with an opioid prescription (15% vs 59%, P <.001). In multivariable linear regression, PECs block (P <.001), age (P = .002), and absence of chronic pain (P = .009) were associated with lower acute postoperative pain. CONCLUSION: Intraoperative PECs block can reduce postoperative pain and opioid use. This procedure can be readily performed by the implanting physician from within the device pocket.

Network-based integrative multi-omics approach reveals biosignatures specific to COVID-19 disease phases.

Background: COVID-19 disease is characterized by a spectrum of disease phases (mild, moderate, and severe). Each disease phase is marked by changes in omics profiles with corresponding changes in the expression of features (biosignatures). However, integrative analysis of multiple omics data from different experiments across studies to investigate biosignatures at various disease phases is limited. Exploring an integrative multi-omics profile analysis through a network approach could be used to determine biosignatures associated with specific disease phases and enable the examination of the relationships between the biosignatures. Aim: To identify and characterize biosignatures underlying various COVID-19 disease phases in an integrative multi-omics data analysis. Method: We leveraged a multi-omics network-based approach to integrate transcriptomics, metabolomics, proteomics, and lipidomics data. The World Health Organization Ordinal Scale WHO Ordinal Scale was used as a disease severity reference to harmonize COVID-19 patient metadata across two studies with independent data. A unified COVID-19 knowledge graph was constructed by assembling a disease-specific interactome from the literature and databases. Disease-state specific omics-graphs were constructed by integrating multi-omics data with the unified COVID-19 knowledge graph. We expanded on the network layers of multiXrank, a random walk with restart on multilayer network algorithm, to explore disease state omics-specific graphs and perform enrichment analysis. Results: Network analysis revealed the biosignatures involved in inducing chemokines and inflammatory responses as hubs in the severe and moderate disease phases. We observed distinct biosignatures between severe and moderate disease phases as compared to mild-moderate and mild-severe disease phases. Mild COVID-19 cases were characterized by a unique biosignature comprising C-C Motif Chemokine Ligand 4 (CCL4), and Interferon Regulatory Factor 1 (IRF1). Hepatocyte Growth Factor (HGF), Matrix Metallopeptidase 12 (MMP12), Interleukin 10 (IL10), Nuclear Factor Kappa B Subunit 1 (NFKB1), and suberoylcarnitine form hubs in the omics network that characterizes the moderate disease state. The severe cases were marked by biosignatures such as Signal Transducer and Activator of Transcription 1 (STAT1), Superoxide Dismutase 2 (SOD2), HGF, taurine, lysophosphatidylcholine, diacylglycerol, triglycerides, and sphingomyelin that characterize the disease state. Conclusion: This study identified both biosignatures of different omics types enriched in disease-related pathways and their associated interactions (such as protein-protein, protein-transcript, protein-metabolite, transcript-metabolite, and lipid-lipid interactions) that are unique to mild, moderate, and severe COVID-19 disease states. These biosignatures include molecular features that underlie the observed clinical heterogeneity of COVID-19 and emphasize the need for disease-phase-specific treatment strategies. The approach implemented here can be used to find associations between transcripts, proteins, lipids, and metabolites in other diseases.

Kinanthropometry and dietary habits of non-professional rugby players.

Introduction: Evaluating the body composition and dietary habits of non-professional athletes can help identify areas for improvement to enhance sports performance. The present study aimed to describe the anthropometric and body composition features, as well as the dietary habits, of non-professional rugby players in Argentina. Methods: Fifty-seven rugby players from a Group III Club of the Unión de Rugby de Buenos Aires (URBA) were assessed using extensive anthropometric measurements according to the International Society for the Advancement of Kinanthropometry (ISAK) protocol. Reference data from professional rugby players in Group I clubs were used as a control for body composition comparisons. Dietary intake was evaluated using the 24-h recall method, and nutrient analysis was performed with SARA software. Results: Non-professional rugby players were shorter (Forwards: 175.9 vs. 181.5 cm; Backs: 172.5 vs. 175.7 cm), had higher body fat percentages (Forwards: 16.4 vs. 12.3%; Backs: 11.0 vs. 9.3%), and were less muscular (Forwards: 46.0 vs. 48.8%; Backs: 48.4 vs. 50.2%) compared to professional rugby players. The average dietary intake was 3,363 Kcal, with protein and carbohydrate intakes of 1.4 g kg-1 day-1 and 4.1 g kg-1 day-1, respectively, and 35% of energy intake from fat. Backs reported a higher caloric intake than forwards (3,682 vs. 2,827 Kcal). There was a high prevalence of insufficient intake of calcium (58%), vitamin A (49%), and vitamin C (65%), the latter two corresponding with a low intake of fruits and vegetables (6% of total energy intake). Meal pattern analysis showed that 46% of total energy was ingested at dinner. Conclusions: The body composition of non-professional rugby players from low-income clubs could be improved to enhance rugby performance, as compared to players in more competitive tiers. Economic constraints might contribute to a sub-optimal nutritional profile, potentially affecting body composition and on-field performance negatively. Recommendations to improve dietary intake should be made considering the budget constraints of these players.

Incidental ablation of ganglionated plexus during atrial fibrillation ablation.

BACKGROUND: Cardioneuroablation targeting the autonomic nerves within ganglionated plexus (GP) has been used to treat atrial fibrillation (AF). Incidental cardioneuroablation may be an important mechanism by which pulmonary vein isolation (PVI) is effective. Automated fractionation mapping software can identify regions of fractionation correlating with GP locations. OBJECTIVE: To examine the overlap between standard PVI ablation lesions and fractionated electrograms suggestive of GP. METHODS: We retrospectively examined AF ablations performed from 2021 to 2023 that included only PVI performed using wide antral circumferential isolation without prospective evaluation of fractionation. Retrospectively, a fractionation map was created (width 10 ms, refractory time 30 ms, roving sensitivity 0.1 mv, and threshold of 2). We evaluated the anatomic overlap between PVI lesions and fractionation in regions associated with GP. RESULTS: Among 52 patients (mean 65 (IQR 46-74) years, 82% male, and 69% paroxysmal AF), sites of fractionation corresponding to GP locations were seen in all cases. PVI ablation incidentally overlapped with fractionation in 50 (96%) patients. On average, 26% of the fractionation corresponding with GP locations were incidentally ablated. The highest proportion of fractionated areas were ablated in the left superior (36%) and right superior (31%) GP regions. More complete incidental ablation of these regions was associated with a greater intraprocedural increase in heart rate (ρ = 0.46, p < 0.001), which was subsequently associated with freedom from AF during 15.9 ± 5.2 months of follow-up. CONCLUSION: Patients undergoing AF ablation universally have fractionated electrograms corresponding to anticipated sites of GP. Partial ablation of these regions frequently occurs incidentally during PVI.