Citations

ABSTRACT Background Patients with end‐stage renal disease (ESRD) undergoing dialysis have an increased risk of pacemaker‐related complications due to limited vascular access and increased susceptibility to infection. Leadless pacemakers (LPMs) may mitigate these risks compared with conventional transvenous pacemakers (TPMs), but long‐term comparative data in this population remain limited. Methods We conducted a retrospective cohort study using the TriNetX Research Network, including adults (≥ 18 years) with ESRD on dialysis who underwent LPM or TPM implantation between May 2016 and December 2020. Propensity score matching (1:1) was performed using demographics and comorbidities. Outcomes assessed over up to 5 years included all‐cause hospitalization, heart failure hospitalization, device re‐intervention, device‐related complications, infection‐related hospitalization, pacemaker‐induced cardiomyopathy, and all‐cause mortality. Results After matching, 901 patients were included in each group with well‐balanced baseline characteristics. LPM implantation was associated with a significantly lower risk of device re‐intervention compared with TPM (4.1% vs. 9.3%; hazard ratio [HR] 0.44; 95% confidence interval [CI] 0.28–0.69; p < 0.01). There were no significant differences between groups in all‐cause hospitalization (65.5% vs. 68.3%; p = 0.22), heart failure hospitalization (26.9% vs. 30.2%; p = 0.13), all‐cause mortality (37.5% vs. 35.3%; p = 0.34), device‐related complications (14.5% vs. 14.3%; p = 0.94), infection‐related hospitalization (1.6% vs. 2.1%; p = 0.35), or pacemaker‐induced cardiomyopathy (9.0% vs. 8.6%; p = 0.66). Conclusion In a large, propensity‐matched cohort of patients with ESRD on dialysis, LPMs were associated with fewer device re‐interventions and comparable long‐term clinical outcomes compared with TPMs.

ABSTRACT Background Atrial fibrillation (AF) is common in patients with hypertrophic cardiomyopathy (HCM) and is associated with increased morbidity, heart failure (HF) exacerbations, and adverse long‐term outcomes. Although catheter ablation is an established rhythm‐control strategy, data comparing its long‐term clinical outcomes with anti‐arrhythmic drug (AAD) therapy in patients with HCM remain limited. Objective To compare long‐term clinical outcomes of catheter ablation versus medical therapy with AADs in patients with HCM and AF. Methods We conducted a retrospective cohort study using the TriNetX Research Network, a global federated database of electronic health records. Adult patients with HCM and AF between January 2010 and December 2020 were identified and stratified according to treatment with catheter ablation or AAD therapy. Outcomes included all‐cause mortality, HF exacerbations, AAD‐related adverse events, all‐cause hospitalization, ischemic stroke, repeat ablation, need for cardioversion, need for long‐term AAD use, and atrioventricular nodal ablation. A 1:1 propensity score matching (PSM) analysis was performed to balance baseline characteristics. Kaplan–Meier survival analysis and Cox proportional hazards models were used to estimate hazard ratios (HRs). Results After PSM, 3144 patients were included (1572 in each cohort) with a mean follow‐up of approximately 3.4 years. Catheter ablation was associated with lower all‐cause mortality compared with AAD therapy (9.5% vs. 14.8%; HR: 0.60; 95% CI: 0.49–0.74; p < 0.001). Ablation was also associated with reduced risk of HF exacerbations (38.4% vs. 43.3%; HR: 0.79; 95% CI: 0.71–0.88; p < 0.001) and fewer AAD‐related adverse events (8.4% vs. 11.2%; HR: 0.71; 95% CI: 0.55–0.93; p = 0.011). Rates of all‐cause hospitalization (HR: 0.93; p = 0.11) and ischemic stroke (HR: 0.78; p = 0.10) were similar between groups. Conclusion In this large real‐world cohort of patients with HCM and AF, catheter ablation was associated with lower mortality, reduced HF hospitalizations, and decreased AAD therapy‐related adverse events, as compared with medical therapy. These findings suggest that catheter ablation may provide meaningful clinical benefits in selected patients with HCM and AF, although prospective studies are needed to confirm these observations.

Abstract Chromosome 5p15.33 harbors several independent association signals which demonstrate antagonistic pleiotropy across cancer types, with causal mechanisms largely unresolved. To identify functional variants and enhancer elements at this locus, we performed statistical fine-mapping followed by massively parallel reporter assays (MPRA) and proliferation based CRISPRi screens. This approach identified eight multi-cancer functional variants (MCFVs) across three GWAS signals. Targeting rs421629 (part of the CLPTM1L signal marked by rs465498) with CRISPRi revealed opposing effects on TERT expression in pancreatic versus lung cancer cells, consistent with the antagonistic pleiotropy observed for this signal. Furthermore, CRISPRi nominated an intronic CLPTM1L variable number tandem repeat (VNTR) as a potent enhancer. Long-read sequencing established VNTR polymorphisms as potential causal variants for the rs465498 signal. We showed that Hippo-pathway transcription factors mediate VNTR enhancer activity in lung and pancreatic cancer cells. Together, these findings indicate that cancer susceptibility at 5p15.33 may be mediated by both SNPs and VNTRs and provide an integrated framework for resolving complex pleiotropic loci.

ABSTRACT Background Transvenous lead removal (TLR) in patients with a history of mediastinal radiation poses unique challenges due to potential radiation‐induced fibrosis, vascular changes, and anatomical distortion, which may increase procedural complexity and complication risk. However, contemporary data on clinical outcomes in this population remain limited. Methods We analyzed the National Readmissions Database (2016–2021) to identify adults (≥ 18 years) undergoing TLR. Patients were stratified by prior mediastinal radiation. Baseline characteristics were compared using standard statistical tests. Multivariable logistic regression was used to evaluate the association between prior mediastinal radiation and in‐hospital outcomes, 30‐day mortality, and 30‐day readmissions after adjustment for demographics and comorbidities. Results A total of 48,985 patients underwent TLR, of whom 735 (1.5%) had a history of mediastinal radiation. Compared with patients without radiation, those with prior radiation were older (70.1 vs. 66.2 years, p < 0.01), were more frequently females (38.2% vs. 31.6%, p < 0.01), and had higher rates of valvular heart disease, atrial fibrillation, and peripheral vascular disease. Adjusted analyses demonstrated no increased risk of in‐hospital mortality (2.3% vs. 3.4%; adjusted odds ratio [aOR] 0.65, 95% confidence interval [CI] 0.41–1.18, p = 0.29) or major complications, including cardiac arrest, pericardial complications, vascular injury, pulmonary complications, or embolic events. Similarly, (3.6% vs. 5.3%; aOR 0.76, 95% CI 0.48–1.43, p = 0.35) and 30‐day all‐cause readmissions (8.7% vs. 9.1%; aOR 0.81, 95% CI 0.64–1.28, p = 0.70) were not significantly different between groups. Subgroup analyses by indication for TLR (infection vs. mechanical complication) revealed no differences in outcomes. Conclusion Despite theoretical concerns, prior mediastinal radiation was not associated with excess procedural risk or worse short‐term outcomes after TLR. These findings may inform procedural planning and risk counseling in clinical practice.

Background: Outcomes after arthroscopic rotator cuff repair (RCR) are frequently measured through clinically significant outcomes (CSOs) such as the minimal clinically important difference, the substantial clinical benefit, and the Patient Acceptable Symptom State. Global achievement of CSOs is challenging to predict. Purpose: To determine if unsupervised machine learning can identify distinct patient subgroups based on CSO achievement after elective arthroscopic RCR. Study Design: Case-control study; Level of evidence, 3. Methods: A prospectively collected database was analyzed to identify patients who underwent elective arthroscopic RCR from 2015 to 2017. Tear dimensions were measured on magnetic resonance imaging utilizing a validated technique. CSO achievements on the American Shoulder and Elbow Surgeons, the Single Assessment Numeric Evaluation, and the Constant-Murley subjective score at 2-year follow-up were calculated. An unsupervised random forest algorithm was utilized to develop and internally validate patient subgroups with significantly different rates of CSO achievement. Patient subgroup membership, along with a total of 30 demographic and clinical variables, as well as preoperative patient-reported outcomes, were incorporated into a stepwise multivariable logistic regression to identify factors predictive of optimal CSO achievement. Results: A total of 346 patients (192 male; mean ± SD age, 57.2 ± 9.1 years; body mass index, 30.1 ± 5.4 kg/m 2 ) were eligible for inclusion and followed for a mean of 3.8 years (range, 2.0-6.2 years) Of these, a total of 333 patients were partitioned by the random forest algorithm into 2 subgroups (stability, 0.16; connectivity: 180.8; Dunn: 0.16; silhouette: 0.05), with 176 patients in the optimal achievement subgroup and 157 patients in the suboptimal achievement subgroup. The 2 subgroups differed significantly (all P ≤ .004) in the likelihood of achievement of all CSOs. Stepwise multivariable logistic regression identified an increase of 1 mm in tear size in the sagittal dimension beyond 1.9 cm to predict a 10% increase in the probability of suboptimal achievement. Additional risk factors for suboptimal CSO achievement included increasing number of tendons involved (odds ratio [OR], 14.07; 95% CI, 4.50-44.02; P < .001), subscapularis involvement (OR, 8.67; 95% CI, 2.45-30.71; P = .01), and increased preoperative CMS score (OR, 1.11; 95% CI, 1.04-1.18; P = .001). Protective factors included performance of a subpectoral biceps tenodesis compared with biceps tenotomy (OR, 0.22; 95% CI, 0.05-0.92; P = .03). Conclusion: Clinically meaningful subgroups were uncovered using an unsupervised machine learning algorithm in patients undergoing arthroscopic RCR. Tear size, number of tendons involved, and subscapularis involvement were significant and additive predictors of suboptimal CSO achievement at 2-year minimum follow-up. Treatment of concurrent biceps pathology with tenodesis conferred 78% increased likelihood of CSO achievement compared with tenotomy.

ABSTRACT Background Transvenous lead removal (TLR) is a Class I indication for patients with cardiac implantable electronic device (CIED) infections. However, disparities in the utilization of TLR have not been fully explored, particularly concerning demographic and socioeconomic factors. Objectives This study aims to examine whether disparities exist among patients hospitalized for CIED infections with respect to the utilization of TLR, focusing on sex, race, and income characteristics. Methods We utilized the 2019 National Inpatient Sample (NIS) to assess patients hospitalized with CIED infections and identify those who underwent TLR. Multiple logistic regression was used to examine risk factors for TLR utilization, including age, sex, race/ethnicity, and socioeconomic characteristics. Results A total of 56 709 patients were hospitalized for CIED infection in the United States in 2019, of which 9867 (17.4%) underwent TLR. On an adjusted analysis, females and Black patients were found to have lower odds of undergoing TLR compared to males and White patients (OR: 0.62; 95% CI: 0.59–0.78; p < 0.01; and OR: 0.47; 95% CI: 0.39–0.57; p < 0.01, respectively). Hispanic patients also had reduced odds of TLR (OR: 0.73; 95% CI: 0.58–0.93; p = 0.01). No significant associations were observed between income or insurance status and the likelihood of receiving TLR after adjustment. Conclusions This study identified significant disparities in the utilization of TLR among patients hospitalized for CIED infections. Female, Black, and Hispanic patients were significantly less likely to receive TLR.

ABSTRACT Background Obesity is an important risk factor associated with atrial fibrillation (AF). The impact of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) on recurrent AF among patients undergoing catheter ablation is not well described. Objective This study aimed to evaluate the effect of GLP‐1 RA on the recurrence of AF among obese patients after catheter ablation. Methods Utilizing the TriNetX research network, we identified patients aged over 18 with obesity (BMI ≥ 30) who underwent AF ablation from January 1, 2015, to December 1, 2022, using Current Procedural Terminology codes. Patients were categorized based on their baseline GLP‐1 RA use. Through propensity‐score matching, each cohort comprised 1558 patients. The primary outcome encompassed a composite of cardioversion, initiation of new antiarrhythmic drug (AAD) therapy, or redo AF ablation. Additional outcomes during the 12‐month follow‐up included AF readmission, heart failure readmissions, readmissions due to ischemic stroke, and mortality, with a separate analysis done for patients with BMI > 40. Results GLP‐1 RA use in patients with obesity undergoing AF ablation was linked to a significantly reduced risk of cardioversion, new AAD therapy, and the need for redo AF ablation (hazard ratio [HR] 0.72 [0.65–0.80]; p < 0.001). At 12 months, individuals on GLP‐1 agonists exhibited a lower likelihood of mortality (HR 0.61 [0.40–0.93]; p < 0.001). Although all other secondary outcomes were lower in the GLP‐1 RA group, there was no significant difference in ischemic stroke between the groups. These results were consistent among patients with BMI > 40, although apart from ischemic stroke, there was no difference in mortality between the two groups. Conclusion The utilization of GLP‐1 RA in individuals with obesity is linked to a decreased likelihood of arrhythmia recurrence following AF ablation, leading to a reduced requirement for cardioversion, AAD therapy, or redo AF ablation.

Introduction: Advances in cardiac implanted electronic devices (CIED) have significantly improved outcomes for patients with heart failure. However, there is a bereft of recent real- world data on the relative effectiveness of cardiac resynchronization therapy with pacing and defibrillator (CRT-D) and continuous resynchronization therapy with pacing (CRT-P) in patients with nonischemic cardiomyopathy (NICM). We hypothesized that the addition of defibrillation therapy in patients with NICM would offer no significant benefit. Methods: We searched the National Readmissions Database (NRD) from 2016-2020 to identify hospitalizations with NICM using appropriate ICD-10 diagnosis and procedure codes. The cohort was further divided into groups with NICM and CRT-D implantation and NICM with CRTP implantation. Results and Discussion: Our final cohort included 8,801 hospitalizations with NICM and CRT-D implantation and 3,399 hospitalizations with NICM and CRT-P implantation. Propensity matching was performed using comorbidities through multivariate logistic regression. Two thousand nine hundred seventeen hospitalizations were included in each of the two groups, CRT-D and CRT-P. Analysis of the propensity-matched cohorts at 180 days revealed a trend toward lower heart failure readmission, all-cause readmission, and all-cause mortality rates in the group with CRTP implantation. However, there was no difference noted in the 180-day hazard ratios of HF readmission [1.08 (0.98-1.19); p = 0.1], all-cause readmission [1.04 (0.87-1.12); p = 0.23], and all-cause mortality [0.83 (0.58-1.19); p = 0.32]. Conclusion: It was found that NICM patients with CRT-D have a trend towards higher HF readmissions, all-cause readmission, and all-cause mortality compared to those with CRT-P, but no significant difference was noted in hazard ratios. The findings of our study raise further questions about the need for defibrillator therapy in patients with NICM and merit further studies to better select candidates for each of these therapies.

Purpose To assess the relation between tendon migration, as measured by radiostereometric analysis, and patient‐reported outcome measures (PROMs) after biceps tenodesis (BT); to determine the likelihood of achieving clinically significant outcomes (CSOs) after BT; and to identify factors that impact CSO achievement. Methods Patients undergoing arthroscopic suprapectoral or open subpectoral BT at a single, high‐volume academic medical center were prospectively enrolled. A tantalum bead sutured to the tenodesis construct was used as a radiopaque marker. Biceps tendon migration was measured on calibrated radiographs at 12 weeks postoperatively. PROMs (Constant‐Murley, Single Assessment Numeric Evaluation [SANE], and Patient‐Reported Outcomes Measurement Information System–Upper Extremity [PROMIS‐UE] scores) were collected preoperatively and at minimum 2‐year follow‐up. Results Of 115 patients enrolled, 94 (82%) were included (median age, 52 years; median body mass index, 31.4). At a mean follow‐up of 2.9 years, the median Constant‐Murley, SANE, and PROMIS‐UE scores were 33 (interquartile range [IQR], 26‐35), 90 (IQR, 80‐99), and 47 (IQR, 42‐58), respectively. Median tantalum bead migration was 6.5 mm (IQR, 1.8‐13.8 mm). There were significant correlations between migration and Constant‐Murley score ( r 2 = 0.222; β = –0.554 [95% confidence interval (CI), –1.027 to –0.081]; P = .022), SANE score ( r 2 = 0.238; β = –0.198 [95% CI, –0.337 to –0.058]; P = .006), and PROMIS‐UE score ( r 2 = 0.233; β = –0.406 [95% CI, –0.707 to –0.104]; P = .009). On univariable analysis, higher body mass index was associated with achievement of substantial clinical benefit (unadjusted odds ratio [OR], 1.078 [95% CI, 1.007 to 1.161]; P = .038). Greater bead migration was negatively associated with achievement of the minimal clinically important difference (unadjusted OR, 0.969 [95% CI, 0.943 to 0.993]; P = .014) and patient acceptable symptomatic state (unadjusted OR, 0.965 [95% CI, 0.937 to 0.989]; P = .008) on all 3 instruments. Conclusions A 1‐cm increase in post‐tenodesis biceps tendon migration was associated with a decrease in the Constant‐Murley, SANE, and PROMIS‐UE scores of 6, 2, and 4 points, respectively, at a mean of 2.9 years after surgery. Most patients achieved CSOs for these PROMs by latest follow‐up, and greater biceps tendon construct migration was negatively associated with the likelihood of CSO achievement. Level of Evidence Level IV, retrospective case series.

Summary Background Glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) show anti‐inflammatory properties. Aim To evaluate their clinical impact on inflammatory bowel disease (IBD) outcomes. Methods Retrospective cohort study utilising the TriNetX database comparing IBD‐specific outcomes in patients with ulcerative colitis (UC) or Crohn's disease (CD) and type 2 diabetes mellitus (T2DM) on GLP‐1RA compared to oral hypoglycaemic agents. The primary outcome was hospitalisation requiring intravenous steroids and IBD‐related surgery within 3 years. We performed 1:1 propensity score matching (PSM) for demographics, co‐morbid conditions, BMI, laboratory values, HbA1c, and IBD medications including steroids. Results We identified 1130 patients in the UC GLP‐1RA cohort (mean age: 58.9 ± 11.6 years, 56.3% female, 70.2% White, 57.2% with obesity) and 1140 patients in the CD GLP‐1RA cohort (mean age: 56.7 ± 11.5, 61.9% female, 73.6% White, 56.2% with obesity). After PSM, there was no difference in the risk of intravenous steroid use (aHR: 1.21, 95% CI: 0.92–1.59) but a lower risk of colectomy (aHR: 0.37, 95% CI: 0.14–0.97) between the UC GLP‐1RA and control cohort. There was no difference in the risk of intravenous steroid use (aHR: 1.04, 95% CI: 0.80–1.34) but a lower risk of surgery (aHR: 0.55, 95% CI: 0.36–0.84) between the CD GLP‐1RA and CD control cohort. There was no difference in the risk of oral steroid use or advanced therapy initiation in the UC and CD GLP‐1RA than control cohorts. Conclusions We found an association between lower risk of IBD‐related surgery and GLP‐1RA use for T2DM in patients with UC or CD.