Citations

Abstract Background Marfan syndrome (MFS) predisposes individuals to aortic dissections. Recent data suggest that atrial fibrillation and atrial flutter (AF/AFL) may increase complications and mortality in MFS patients; however, their independent role in aortic dissection remains unclear. Purpose This study aims to assess the risk of aortic dissection in MFS patients with and without AF/AFL. Methods Using the TriNetX database and ICD-10 codes, 2,447 MFS patients with AF/AFL and 20,520 without were identified. Demographics (age, sex, race, ethnicity) were evaluated, and aortic dissection outcomes were compared using risk ratios and Kaplan-Meier survival analysis. Results Patients in the AF/AFL cohort were older (mean age 60.9 ± 16.7 years vs. 38 ± 16.6 years) and had higher proportions of males (62.51% vs. 56.76%) and white patients (74.67% vs. 66.3%). Aortic dissections occurred in 13.9% of MFS patients with AF/AFL compared to 3.4% of those without, resulting in a risk difference of 10.5% (95% CI: 9.0%–11.9%) and a risk ratio of 4.04 (95% CI: 3.547–4.603). Kaplan-Meier analysis revealed significantly lower survival rates in the AF/AFL cohort (74.07% vs. 90.63%; log-rank test, p < 0.0001), with a hazard ratio of 4.232 (95% CI: 3.686–4.858). Conclusion In MFS patients, those with AF/AFL were over four times more likely to experience aortic dissection and had over four times the hazard of mortality. Screening and managing AF/AFL may be essential to preventing aortic dissections and improving outcomes in this population.Figure 1

Abstract Introduction High-power short-duration (HPSD) ablation has emerged as a promising alternative to conventional power delivery (CPD) for pulmonary vein isolation (PVI) among patients with atrial fibrillation (AF). However, its efficacy, procedural efficiency, and safety profile remain uncertain. Methods PubMed, Embase, Cochrane Library and ClinicalTrials.Gov databases were systematically searched for randomized controlled trials (RCTs) comparing HPSD with CPD ablation for PVI in patients with AF. Random-effects models were used to pool hazard ratios (HR) and risk ratios (RR) with 95% confidence intervals (CI). Results Seven RCTs with 1,006 patients (514 HPSD, 489 CPD) were included. No significant differences were found in freedom from arrhythmia during the follow-up period (HR 0.77; 95% CI 0.41–1.45; p=0.424). AF recurrence did not differ (RR 0.94; 95% CI 0.65–1.36; p=0.733) between groups. HPSD had a significantly shorter procedural (MD -22.61 min; 95% CI -33.18, -12.04; p<0.001) and RF ablation (MD -15.70 min; 95% CI -20.86, -10.55; p<0.001) times, with comparable fluoroscopy time (MD 0 min; 95% CI -0.44, 0.45; p=0.99) between groups. Conclusion In patients with AF undergoing PVI, HPSD did not increase freedom from arrhythmia as compared with CPD ablation, however it was associated with shorter procedure and RF ablation times. These findings suggest that HPSD may be a more efficient approach without compromising clinical outcomes.

Abstract Background Vascular Ehlers-Danlos syndrome (VEDS) and Marfan’s syndrome are associated with cardiovascular complications, including arrhythmias. However, ventricular tachycardia (VT) risk in these populations has not been frequently reported. Purpose This study aims to assess the VT risk in VEDS and Marfan's syndrome patients through an international database. Methods The TriNetX database was used to pull patients with a diagnosis of VEDS and Marfan's Syndrome. Baseline characteristics (e.g., demographics, cardiovascular comorbidities, etc.) were collected, and propensity score matching was performed to balance the cohorts. Risk analysis and Kaplan-Meier survival were used to assess outcomes. Results A total of 1,114 and 23,172 patients had VEDS and Marfan’s syndrome, respectively. After propensity score matching, each cohort included 1,091 balanced patients regarding demographics and clinical characteristics. The cohorts were balanced with a mean age of 37.7 ± 16.0 years in both groups. 68.7% and 68.8% were females in the VEDS and Marfan cohorts, the majority being White (82.2% in VEDS, 82.9% in Marfan’s). VT Incidence was lower in VEDS (0.9%) compared to Marfan’s syndrome (2.6%), with a risk difference of -0.016 (p = 0.003). Kaplan-Meier survival showed higher survival in VEDS (99.44%) vs. Marfan’s (94.04%, log-rank p = 0.002). The risk ratio for VT in VEDS was 0.357 (95% CI: 0.174, 0.732). Conclusion VEDS patients have a significantly lower VT risk compared to those with Marfan’s syndrome. These findings suggest significant differences in the arrhythmic burden between these connective tissue disorders, which can direct future risk stratification and management strategies.

Abstract Background Many patients with atrial fibrillation (AF) suffer life-limiting symptoms and heart failure. Although enormous advances in rhythm control have been made, device-based therapies for treating recurrent episodes are limited. Using pulsed electric fields (PEF) to induce reversible electroporation of cardiac tissue may effectively terminate AF. Purpose To assess the feasibility of PEF delivery for converting atrial arrhythmias via reversible electroporation. Methods Four swine models were used in this acute study. Custom-made decapolar catheters for PEF delivery were deployed with the following configurations: 1. Endocardial right atrium (RA) and coronary sinus (CS), n=2; 2. Endocardial RA and epicardial left atrium (epiLA), n=2. AF and atrial flutter (AFL) were induced with programmed stimulation. PEF delivery was performed using the BTX 830 generator. For each attempt, a single monophasic pulse at 10 or 20µs pulse width was administered, with voltage varied across attempts (range 750-3000V). Successful (type 1 and 2 breaks) and unsuccessful conversion attempts were recorded. Post-PEF signal changes and arrhythmias were identified. Results A total of 58 AF/AFL (28 and 30 respectively) episodes were induced. Of the 37 successful conversion attempts, 33 (89.1%) were type 1 breaks. Conversion success probabilities generally increased with higher voltages for both configurations. >70% conversion success was seen with ≥1500V for the RA/CS configuration and ≥2000V for the RA/epiLA configuration. Arrhythmias including intra-atrial delay and high-grade atrioventricular block were seen, usually following successive PEF deliveries. Significant muscle stimulation was provoked with the current experimental setup. Conclusion Termination of atrial arrhythmias with PEF delivery is feasible, although further work is required to optimize its efficacy and safety.

Abstract Background Ventricular fibrillation (VF) is a leading cause of sudden cardiac death worldwide. Defibrillation via direct current shocks is effective but associated with significant pain and morbidity, prompting the need for alternative approaches. Reversible electroporation of cardiac tissue with pulsed electric fields (PEF) may be an effective means of terminating VF. Purpose To assess the feasibility of PEF delivery for terminating VF. Methods 5 acute swine models were used. Mechanical circulatory support with peripheral veno-arterial extracorporeal membrane oxygenation +/- percutaneous left ventricular assist device (Impella 5.5 L) was implemented and titrated to a mean arterial pressure ≥65 mmHg. Decapolar catheters were introduced into the endocardial right and/or left ventricle as well as epicardium. VF was induced with R on T shocks or rapid ventricular pacing. PEF was delivered with the endocardial catheter as the cathode and epicardial catheter as the anode; monophasic pulses (5-10) at 3000V, 100µs, and 200ms inter-pulse intervals were used. If VF persisted post-PEF, catheters were repositioned into regions of intact voltages for repeat delivery. Results 10 VF episodes were induced, 7 of which were successfully terminated with PEF delivery (70.0%). The median number of attempts to achieve VF termination was 2 (range 1-5). The post-VF rhythm was complete heart block with ventricular asystole in all successful defibrillation attempts, with no recovery after 30 minutes of observation. Significant muscle stimulation was seen with the utilized PEF parameters and catheter configurations. Conclusion Termination of VF using PEF – pulsed field defibrillation – is possible. However, further study is required to optimize delivery parameters/configurations to improve effectiveness and avoid muscle stimulation as well as conduction abnormalities.

Abstract Background Implantable cardioverter-defibrillator (ICD) is a well-established therapeutic option associated with decreased mortality in patients with ischemic and non-ischemic cardiomyopathies. However, the indications for patients with chronic Chagas cardiomyopathy (CCC) are not well established since these patients were underrepresented in the trials validating ICD use. Purpose This systematic review and single-arm meta-analysis aims to synthetize the available evidence in the literature on the role and outcomes of ICD in CCC. Methods A systematic search of PubMed, Web of Science, Cochrane, and LILACS registries was performed following PRISMA guidelines. Studies evaluating the response to ICD in CCC were included. There were no language restrictions. Data were collected and synthesized using a meta-analysis of proportions with Freeman-Tukey double-arcsine transformation as needed. Results We included 14 observational studies and 1 randomized clinical trial (RCT), comprising 1315 patients with CCC. Mean age at ICD implantation was 58.2 ± 11.8, 65% were male, and 77% received an ICD for secondary prevention. During a mean follow up of 37.3 ± 37.0 months, the all-cause death rate was 22% (95% CI 15 to 29%; Figure 1A), the cardiovascular death rate was 16% (95% CI 11 to 22%; Figure 1B), the sudden cardiac death rate was 3% (95% CI 2 to 5%), and the non-cardiovascular death rate was 7% (95% CI 2 to 5%). In addition, 55% (95% CI 43 to 67%; Figure 1C) of patients received ≥1 appropriate ICD therapy (shocks or antitachycardia pacing), 8% (95% CI 5 to 12%) received inappropriate ICD shocks, and 23% (95% CI 11 to 37%) experienced electrical storms. Conclusion Despite ICD, the mortality rate in patients with CCC remains unacceptably high, primarily driven by cardiovascular causes, with frequent appropriate ICD therapies and electrical storms. Further studies are needed to better delineate the benefits and risks of ICD therapy in patients with CCC.Figure 1

Background: Plasma cell dyscrasia (PCD) is a rare but important cause of end stage kidney disease (ESKD). Kidney transplant is the treatment of choice in patients with ESKD. However, the complexity of PCD care and risk of disease recurrence poses challenges to kidney transplant candidacy and outcomes. We examined the current clinical practice patterns of clinicians who care for patients with PCD and identified barriers to kidney transplantation for patients with PCD. Methods: A web-based survey was developed and distributed from January to July 2024 to kidney transplant clinicians (American Society of Transplant (AST) members), hematologists (PCD experts), and onco-nephrologists. Results: Seventy clinicians (50 transplant nephrologists, 18 hematologists, and two surgeons) from 42 transplant centers in the US participated in the survey. Clinical practice patterns pre and post kidney transplant for patients with PCD are highly variable among institutions, and only 36% reported having a protocol for pre- and post-transplant management for patients with PCD. Particularly, the requirement for pre-transplant hematologic remission criteria, induction and maintenance immunosuppression regimens and protocols for prophylaxis and screening for opportunistic infection are areas of future study. Clinicians listed lack of data and practice guidance as well as communication challenges among multiple specialties especially hematology and kidney transplant clinicians as notable barriers. Conclusions: Our study identified the highly variable current practice patterns when evaluating and managing patients with PCD for kidney transplant. Our findings emphasize the need for collecting and sharing clinical data to support standardized practices and serve as a basis for the upcoming multi-societal management recommendation for kidney transplant for patients with PCD.

ABSTRACT Delayed onset muscle soreness (DOMS) is a musculoskeletal condition that typically follows unaccustomed exercise or muscle overload, most common after loaded eccentric contractions. This soreness manifests within 24–48 hours postexercise and can last several days, impacting muscle performance and recovery. Increased levels of anxiety may prolong the perception of soreness and discomfort. Evidence suggests that recovery times for DOMS vary because of multiple factors, which include psychological influences such as anxiety. This manuscript highlights the interplay between psychological states and the DOMS recovery sequelae. Although further studies are needed to fully understand the mechanisms by which anxiety influences DOMS and to confirm the efficacy of anxiety-reducing treatments, a deeper understanding of this relationship could offer strength and conditioning professionals new pathways for optimizing recovery strategies in individuals experiencing DOMS.

Background and Aims: Cholangiocarcinoma (CCA) is a rare but aggressive malignancy with poorly understood genetic susceptibility. To date, genome-wide association studies (GWAS) investigating germline variants associated with CCA risk remain limited. We aimed to identify genetic risk loci for CCA and its clinical subtypes through comprehensive GWAS and post-GWAS analyses. Approach and Results: We conducted a GWAS of 2366 CCA cases and 11,750 controls of European ancestry. Genome-wide significant loci ( p <5×10 −8 ) were identified and further examined through fine-mapping, functional annotation, and HLA imputation. Subgroup analyses were conducted by CCA subtypes and primary sclerosing cholangitis (PSC) status. Cross-trait linkage disequilibrium score regression and Mendelian randomization were employed to investigate the shared genetic architecture and potential causal relationships with a diverse range of traits. We identified 1 new genome-wide significant variant, rs535777 (OR=1.44), near HLA-DRB1/DQA1 associated with CCA, and 2 variants associated with extrahepatic CCA: rs116224263 (OR=0.17) in LINC02506 at 4p15.1 and rs6914950 (OR=1.63) near HLA-DRB1/DQB1 . Stratified analyses revealed rs2395184 (OR=3.51) near HLA-DRA/DRB5 associated with PSC-related CCA, and rs142674434 (OR=2.98) in THSD7A at 7p21.3 associated with non-PSC-related CCA. HLA imputation uncovered new amino acid residues associated with disease risk. Cross-trait analyses identified shared genetic signals between CCA and anthropometric, lipidemic, lifestyle, and medical traits. Mendelian randomization supported putative causal associations for 12 traits with CCA or its subtypes. Conclusions: Our large-scale GWAS highlights new genetic variants and HLA-linked mechanisms underlying CCA susceptibility. Integrating multi-step post-GWAS approaches enhances understanding of CCA pathogenesis and may facilitate the development of risk biomarkers for early detection and precision prevention strategies.