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.

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.

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.

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.

Value of high-output pace-mapping of the right phrenic nerve for enabling safe radiofrequency ablation of atrial fibrillation: insights from three-dimensional computed tomography segmentation.

AIMS: Right phrenic nerve (RPN) injury is a disabling but uncommon complication of atrial fibrillation (AF) radiofrequency ablation. Pace-mapping is widely used to infer RPN's course, for limiting the risk of palsy by avoiding ablation at capture sites. However, information is lacking regarding the distance between the endocardial sites of capture and the actual anatomic RPN location. We aimed at determining the distance between endocardial sites of capture and anatomic CT location of the RPN, depending on the capture threshold. METHODS AND RESULTS: In consecutive patients undergoing AF radiofrequency ablation, we defined the course of the RPN on the electroanatomical map with high-output pacing at up to 50 mA/2 ms, and assessed RPN capture threshold (RPN-t). The true anatomic course of the RPN was delineated and segmented using CT scan, then merged with the electroanatomical map. The distance between pacing sites and the RPN was assessed. In 45 patients, 1033 pacing sites were analysed. Distances from pacing sites to RPN ranged from 7.5 ± 3.0 mm (min 1) when RPN-t was ≤10 mA to 19.2 ± 6.5 mm (min 9.4) in cases of non-capture at 50 mA. A distance to the phrenic nerve > 10 mm was predicted by RPN-t with a ROC curve area of 0.846 [0.821-0.870] (P < 0.001), with Se = 80.8% and Sp = 77.5% if RPN-t > 20 mA, Se = 68.0% and Sp = 91.6% if RPN-t > 30 mA, and Se = 42.4% and Sp = 97.6% if non-capture at 50 mA. CONCLUSION: These data emphasize the utility of high-output pace-mapping of the RPN. Non-capture at 50 mA/2 ms demonstrated very high specificity for predicting a distance to the RPN > 10 mm, ensuring safe radiofrequency delivery.

Incremental Benefit of Stepwise Nonpulmonary Vein Trigger Provocation During Catheter Ablation of Atrial Fibrillation.

BACKGROUND: The importance of nonpulmonary vein (PV) triggers for the initiation/recurrence of atrial fibrillation (AF) is well established. OBJECTIVES: This study sought to assess the incremental benefit of provocative maneuvers for identifying non-PV triggers. METHODS: We included consecutive patients undergoing first-time AF ablation between 2020 and 2022. The provocation protocol included step 1, identification of spontaneous non-PV triggers after cardioversion of AF and/or during sinus rhythm; step 2, isoproterenol infusion (3, 6, 12, and 20-30 µg/min); and step 3, atrial burst pacing to induce AF followed by cardioversion during residual or low-dose isoproterenol infusion or induce focal atrial tachycardia. Non-PV triggers were defined as non-PV ectopic beats triggering AF or sustained focal atrial tachycardia. RESULTS: Of 1,372 patients included, 883 (64.4%) underwent the complete stepwise provocation protocol with isoproterenol infusion and burst pacing, 334 (24.3%) isoproterenol infusion only, 77 (5.6%) burst pacing only, and 78 (5.7%) no provocative maneuvers (only step 1). Overall, 161 non-PV triggers were found in 135 (9.8%) patients. Of these, 51 (31.7%) non-PV triggers occurred spontaneously, and the remaining 110 (68.3%) required provocative maneuvers for induction. Among those receiving the complete stepwise provocation protocol, there was a 2.2-fold increase in the number of patients with non-PV triggers after isoproterenol infusion, and the addition of burst pacing after isoproterenol infusion led to a total increase of 3.6-fold with the complete stepwise provocation protocol. CONCLUSIONS: The majority of non-PV triggers require provocative maneuvers for induction. A stepwise provocation protocol consisting of isoproterenol infusion followed by burst pacing identifies a 3.6-fold higher number of patients with non-PV triggers.

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.

Prognostic value of noninvasive programmed stimulation in primary prevention implantable cardioverter-defibrillator recipients.

Background: Implantable cardioverter-defibrillator (ICD) offers an opportunity to study inducibility of ventricular tachycardia (VT) or ventricular fibrillation (VF) by performing noninvasive programmed ventricular stimulation (NIPS). Whether NIPS can predict future arrhythmic events or mortality in patients with primary prevention ICD, has not yet been examined. Methods: From the NIPS-ICD study (ClinicalTrials ID: NCT02373306) 41 consecutive patients (34 males, age 64 ± 11 years, 76% ischemic cardiomyopathy [ICM]) had ICD for primary prevention indication. Patients underwent NIPS using a standardized protocol of up to three premature extrastimuli at 600, 500 and 400 ms drive cycle lengths. NIPS was classified as positive if sustained VT or VF was induced. The study endpoint was occurrence of sustained VT/VF during the follow-up. Results: At baseline NIPS, VT/VF was induced in 8 (20%) ICM patients. During the 5-year follow-up, the VT/VF occurred in 7 (17%) patients, all with ICM. The difference between NIPS-inducible versus NIPS-noninducible patients regarding VT/VF occurrence did not meet statistical significance (38% vs. 12%, log rank test p = .11). After a 5-year follow-up, the mortality rate was significantly higher in patients who had VT/VF induced at NIPS versus no VT/VF at NIPS (38% vs. 12%, p = .043). The occurrence of a composite endpoint consisting of VT/VF recurrence or death in patients with ICM was also most frequent in the NIPS-inducible group (75% vs. 35%, p = .037). Conclusions: Inducibility of VT/VF during NIPS in ICM patients with primary prevention ICD is associated with higher mortality and higher incidence of composite endpoint consisting of death or VT/VF during a long-term observation.

The Safety and Efficacy of Epicardial Carbon Dioxide Insufflation Compared With Conventional Epicardial Access.

BACKGROUND: Epicardial (Epi) access is commonly required during ventricular tachycardia ablation. Conventional Epi (ConvEpi) access targets a "dry" pericardial space presenting technical challenges and risk of complications. Recently, intentional puncture of coronary venous branches with Epi carbon dioxide insufflation (EpiCO2) has been described as a technique to improve Epi access. The safety of this technique relative to conventional methods remains unproven. OBJECTIVES: The authors sought to compare the feasibility and safety of EpiCO2 to ConvEpi access. METHODS: All patients at a high-volume center undergoing Epi access between January 2021 and December 2023 were included and grouped according to ConvEpi or EpiCO2 approach. Access technique was according to the discretion of the operator. RESULTS: Epi access was attempted in 153 cases by 17 different operators (80 ConvEpi vs 73 EpiCO2). There was no difference in success rate whether the ConvEpi or EpiCO2 approach was used (76 [95%] cases vs 67 [91.8%] cases; P = 0.4). Total Epi access time was shorter in the ConvEpi group compared with the EpiCO2 group (16.3 ± 11.6 minutes vs 26.9 ± 12.7 minutes; P < 0.001), though the total procedure duration was similar. Major Epi access-related complications occurred in only the ConvEpi group (6 [7.5%] ConvEpi vs 0 [0%] EpiCo2; P = 0.02). Bleeding ≥80 mL was more frequently observed following ConvEpi access (14 [17.5%] cases vs 4 [5.5%] cases; P = 0.02). After adjusting for age, repeat Epi access, and antithrombotic therapy, EpiCO2 was associated with a reduction in bleeding ≥80 mL (OR: 0.27; 95% CI: 0.08-0.89; P = 0.03). CONCLUSIONS: EpiCO2 access is associated with lower rates of major complication and bleeding when compared with ConvEpi access.

Long-Term Freedom From Ventricular Arrhythmias in ARVC With Endocardial Only Ablation: Predictors of Success.

BACKGROUND: Although the epicardial predominance of substrate abnormalities has been well demonstrated in early stages of arrhythmogenic right ventricular cardiomyopathy (ARVC), endocardial (ENDO) ablation may suffice to eliminate ventricular tachycardia (VT) in some patients. OBJECTIVES: This study aimed to report the long-term outcomes of ENDO-only ablation in ARVC patients and factors that predict VT-free survival. METHODS: We included consecutive patients with Task Force Criteria diagnosis of ARVC undergoing a first ENDO-only VT ablation between 1998 and 2020. Ablation was predominantly guided by activation/entrainment mapping for mappable VTs and pace mapping/targeting abnormal electrograms for unmappable VTs. The primary endpoint was freedom from any recurrent sustained VT after the last ENDO-only ablation. RESULTS: Seventy-four ARVC patients underwent ENDO-only VT ablation. VT noninducibility was achieved in 49 (66%) patients. During median follow-up of 6.6 years (Q1-Q3: 3.4-11.2 years), 40 (54.1%) patients remained free from any VT recurrence with rare VT ≤2 episodes in additional 12.2%. Among patients with noninducibility, VT-free survival was 75.5% during long-term follow-up. In multivariable analysis, >45 y of age at diagnosis (HR: 0.41; 95% CI: 0.17-0.98) and VT noninducibility (HR: 0.36; 95% CI: 0.16-0.80) were predictors of VT-free survival. CONCLUSIONS: Long-term VT-free survival can be achieved in over half of ARVC patients following ENDO-only VT ablation, increasing to over 75% if VT noninducibility is achieved. Our results support consideration of a stepwise ENDO-only approach before proceeding to epicardial ablation if VT noninducibility can be achieved particularly in older patients.

Utility of noninvasive electrocardiographic imaging in the localization of nonpulmonary vein triggers of atrial fibrillation determined by pacing common trigger sites.

INTRODUCTION: Identifying the origin of nonpulmonary vein atrial fibrillation (AF) triggers (NPVTs) after pulmonary vein isolation (PVI) can be challenging. We aimed to determine if noninvasive electrocardiographic imaging (ECGi) could localize pacing from common NPVT sites. ECGi combines measured body surface potentials with heart-torso geometry acquired from computed tomography (CT) to generate an activation map. METHODS: In 12 patients with AF undergoing first time ablation, the ECGi vest was fitted for preprocedural CT scan and worn during the procedure. After PVI, we performed steady-state pacing from 15 typical anatomic NPVT sites at a cycle length of 700-800 ms. We co-registered the invasive anatomic map with the CT-based ECGi epicardial activation map to compare ECGi predicted to true pacing origin. RESULTS: In the study cohort (67% male, 58% persistent AF, and 67% with left atrial dilation), 148 (82%) pacing sites had both capture and adequate anatomy acquired from the three-dimensional mapping system to co-register with ECGi activation map. Median distance between true pacing sites and point of earliest epicardial activation derived from the ECGi maps for all sites was 17 mm (interquartile range, 10-22 mm). Assuming paced sites treated as regions with a radius of 2.5 cm, the earliest activation site on ECGi map falls within the region with 94% accuracy. CONCLUSION: ECGi can approximate the origin of paced beats from common NPVT sites to within a median distance of 17 mm. A rapidly identified region may then be the focus of more detailed catheter-based mapping techniques to facilitate successful localization and ablation of NPVTs.

Temperature-dependent iron motion in extremophile rubredoxins - no need for 'corresponding states'.

Extremophile organisms are known that can metabolize at temperatures down to - 25 °C (psychrophiles) and up to 122 °C (hyperthermophiles). Understanding viability under extreme conditions is relevant for human health, biotechnological applications, and our search for life elsewhere in the universe. Information about the stability and dynamics of proteins under environmental extremes is an important factor in this regard. Here we compare the dynamics of small Fe-S proteins - rubredoxins - from psychrophilic and hyperthermophilic microorganisms, using three different nuclear techniques as well as molecular dynamics calculations to quantify motion at the Fe site. The theory of 'corresponding states' posits that homologous proteins from different extremophiles have comparable flexibilities at the optimum growth temperatures of their respective organisms. Although 'corresponding states' would predict greater flexibility for rubredoxins that operate at low temperatures, we find that from 4 to 300 K, the dynamics of the Fe sites in these homologous proteins are essentially equivalent.

Lipomatous Metaplasia Is Associated With Ventricular Tachycardia Recurrence Following Ablation in Patients With Nonischemic Cardiomyopathy.

BACKGROUND: Ventricular tachycardia (VT) recurrence rates remain high following ablation among patients with nonischemic cardiomyopathy (NICM). OBJECTIVES: This study sought to define the prevalence of lipomatous metaplasia (LM) in patients with NICM and VT and its association with postablation VT recurrence. METHODS: From patients who had ablation of left ventricular VT, we retrospectively identified 113 consecutive NICM patients with preprocedural contrast-enhanced cardiac computed tomography (CECT), from which LM was segmented. Nested within this cohort were 62 patients that prospectively underwent CECT and cardiac magnetic resonance from which myocardial border zone and dense late gadolinium enhancement (LGE) were segmented. A control arm of 30 NICM patients without VT with CECT was identified. RESULTS: LM was identified among 57% of control patients without VT vs 83% of patients without VT recurrence and 100% of patients with VT recurrence following ablation. In multivariable analyses, LM extent was the only independent predictor of VT recurrence, with an adjusted HR per 1-g LM increase of 1.1 (P < 0.001). Patients with LM extent ≥2.5 g had 4.9-fold higher hazard of VT recurrence than those with LM <2.5 g (P < 0.001). In the nested cohort with 32 VT recurrences, LM extent was independently associated with VT recurrence after adjustment for border zone and LGE extent (HR per 1 g increase: 1.1; P = 0.036). CONCLUSIONS: Myocardial LM is prevalent in patients with NICM of a variety of etiologies, and its extent is associated with postablation VT recurrence independent of the degree of fibrosis.

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

Background: The incidence and mortality rates of hepatocellular carcinoma (HCC) among Hispanics in the United States are much higher than those of non-Hispanic whites. We conducted comprehensive multi-omics analyses to understand molecular alterations in HCC among Hispanic patients. Methods: Paired tumor and adjacent non-tumor samples were collected from 31 Hispanic HCC in South Texas (STX-Hispanic) for genomic, transcriptomic, proteomic, and metabolomic profiling. Additionally, 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. The TERT promoter mutation frequency was also remarkably high in the Hispanic cohort. Cell cycles and liver functions were identified as 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 the serum samples of HCC patients. Two HCC subtypes from our Hispanic cohort were identified and validated with the TCGA liver cancer cohort. The subtype with better overall survival showed higher activity of immune and angiogenesis signatures, and lower activity of liver function-related gene signatures. It also had higher levels of immune checkpoint and immune exhaustion markers. Conclusions: Our study revealed some specific molecular features of Hispanic HCC and potential biomarkers for therapeutic management of HCC and provides a unique resource for studying Hispanic HCC.