DeSimone, Christopher V

BACKGROUND: It is unknown whether cardiac resynchronization therapy (CRT) improves systemic metabolomic profile by enhancing left ventricular function. The observational cohort study aimed to investigate the effect of CRT on left ventricular ejection fraction (LVEF) and circulating plasma metabolites in patients who had heart failure with reduced LVEF. METHODS: We prospectively screened patients with ischemic cardiomyopathy and nonischemic cardiomyopathy who received CRT with a defibrillator for LVEF ≤35% according to current guidelines. Clinical assessment included echocardiography and device interrogation. Blood samples for metabolomic analysis were collected before CRT and at 6-month follow-up. Plasma was subjected to gas chromatography-mass spectrometry and 1 H nuclear magnetic resonance-based metabolomic analysis. RESULTS: Totally 92 patients were enrolled, with a mean age of 67.3±11.3 years (37.0% female). LVEF was significantly improved from 28.9±7.6% at baseline to 36.0±11.3% at 6 months ( P <0.001) and to 40.1±12.6% at 12 months ( P <0.001). After CRT, 42 metabolite features were significantly decreased compared with the baseline. The ketone bodies, including 3-hydroxybutyrate ( P <0.001) and acetone ( P =0.01), were reduced. A branched-chain amino acid, isoleucine, was also decreased after CRT ( P =0.01). These metabolomic changes were mainly observed in the nonischemic cardiomyopathy group, while the metabolomic profile in the ischemic cardiomyopathy group was characterized by enhanced amino acid oxidation and elevated levels of lactate and pyruvate. The improvement in LVEF positively correlated with the ratio of changes in ketone bodies and isoleucine. CONCLUSIONS: CRT may modulate the systemic plasma metabolomic profile, which correlated with improvement in left ventricular function in patients with severe heart failure with reduced ejection fraction.

Background Tirzepatide is a dual agonist for glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1 receptors, with proven efficacy in weight loss and improvement in cardiovascular outcomes. However, the effects of tirzepatide on the incidence of atrial fibrillation in patients with overweight or obesity remain unclear. Methods PubMed, Embase, and Cochrane Library were searched for randomized controlled trials comparing tirzepatide versus placebo for individuals with overweight or obesity. Odds ratios (ORs) with 95% credible intervals (CrIs) were pooled using a Bayesian binomial‐normal hierarchical model, appropriate for rare‐event outcomes. Results Our meta‐analysis included 10 randomized controlled trials, including 6515 individuals, of whom 4491 (68.9%) were randomized to tirzepatide. The pooled OR was 2.20 (95% CrI, 0.81–6.75) for atrial fibrillation, 2.16 (95% CrI, 0.90–5.87) for atrial arrhythmia, and 1.84 (95% CrI, 1.04–3.90) for any arrhythmia. Conclusions Tirzepatide was not associated with atrial fibrillation or atrial arrhythmia. Although higher odds of overall arrhythmias were observed, event rates were low and the findings should be interpreted cautiously.

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 Introduction Frailty is increasingly recognized as an important determinant of outcomes in cardiovascular disease, yet its population‐level impact among patients hospitalized with cardiac implantable electronic device (CIED) infections remains incompletely defined. We examined the prevalence of frailty and its association with clinical outcomes and utilization of transvenous lead removal (TLR) in a contemporary national cohort. Methods and Results We analyzed the National Readmissions Database from 2016–2021 to identify adults hospitalized for CIED infections. Frailty was defined using the Johns Hopkins adjusted clinical groups frailty‐defining diagnoses. Of 288,402 patients hospitalized with CIED infections, 25.1% were classified as frail. Frail patients experienced significantly higher in‐hospital mortality (10.8% vs. 4.6%), 30‐day mortality (9.2% vs. 5.5%), complications, longer length of stay, lower rates of discharge home, and higher 30‐day readmissions compared with non‐frail patients (all p < 0.01). TLR was performed less frequently in frail patients (10.8% vs. 13.4%; adjusted odds ratio [aOR] 0.80, 95% CI 0.76–0.83). On adjusted analyses, TLR was independently associated with lower in‐hospital mortality, 30‐day mortality, and 30‐day readmissions in both frail and non‐frail patients. Conclusion Among patients hospitalized with CIED infections, TLR was independently associated with lower mortality and readmissions in both frail and non‐frail patients, despite lower utilization in frail individuals. Frailty was common (25.1%) and independently associated with significantly worse outcomes. These findings highlight important associations between frailty, treatment patterns, and outcomes that warrant prospective evaluation.

BACKGROUND: Radiofrequency (RF) ablation of premature ventricular complexes (PVCs) originating from the left ventricular summit may be unsuccessful, highlighting the need for alternative approaches. We aimed to assess the efficacy and safety of a novel dual-modality focal catheter in treating left ventricular summit PVCs in patients who had failed previous RF ablation. METHODS: Patients were prospectively enrolled and underwent a redo ablation procedure using an irrigated, contact-force sensing, dual-modality focal catheter (TactiFlex Duo, Abbott) under compassionate use indication. The ablation strategy, including the choice of energy modality (monopolar pulsed field [PF], RF, or both), was left to the operator’s discretion. Safety assessments included serial biomarkers, renal function, and CMR within 36 hours. Efficacy was defined as ≥80% reduction in PVC burden with symptom resolution at 3-month follow-up. RESULTS: Six consecutive patients (4 men; mean age, 53.8±15 years) with symptomatic left ventricular summit PVCs and a prior failed RF ablation (range, 1–2) were prospectively enrolled. All PVCs had an inferior axis, with a left bundle V1 morphology observed in 4 of 6 cases (mean burden, 30.1±5.3%). Acute suppression of PVCs was achieved in all cases. Acute suppression with a single PF application in the great cardiac vein-anterior interventricular vein occurred in 2 patients, while 3 patients required additional RF, PF, or combined RF+PF applications at adjacent sites. One patient with an inaccessible great cardiac vein-anterior interventricular vein was successfully treated in the left ventricular outflow tract with RF+PF application. Transient, reversible left anterior descending vasospasm was observed during PF delivery in 2 of 5 cases that underwent PF application adjacent to a coronary artery, despite pretreatment with intracoronary nitroglycerin without ECG or hemodynamic sequelae. All patients had durable suppression of PVCs at follow-up. CONCLUSIONS: In its first human application, dual-modality ablation was feasible and effective for refractory left ventricular summit PVCs. Transient coronary vasospasm occurred, though it was reversible and without acute clinical consequences.

ABSTRACT Background Concomitant atrial fibrillation (AF) and gastrointestinal (GI) bleeding present a clinical challenge due to recurrent bleeding risk associated with anticoagulation for AF‐associated stroke prevention. Left atrial appendage occlusion (LAAO) offers an alternative stroke prevention strategy, but its impact on recurrent GI bleeding remains unknown. Methods This retrospective, multicenter cohort study used the TriNetX database to identify adults with AF on oral anticoagulation and a history of GI bleeding. Patients were stratified by treatment with or without LAAO. 1:1 propensity score matching (PSM) was employed. The primary outcome was recurrent GI bleeding. Cox regression analysis was used to generate hazard ratios (HRs) with 95% confidence intervals (CIs). Odds ratios (ORs) were used to evaluate effect sizes between groups. Kaplan–Meier curves were used for time‐to‐event analyses. Results After PSM, 9259 patients were compared in each group. Odds of recurrent GI bleeding were consistently lower in patients undergoing LAAO than without LAAO across all follow‐up intervals: at 3 months (OR 0.84; 95% CI 0.78–0.91), 6 months, 1 year, 3 years, and 5 years (OR 0.87; 95% CI 0.82–0.92). Kaplan–Meier analysis demonstrated significantly lower risk of recurrent GI bleeding with LAAO (HR 0.80; 95% CI 0.76–0.84; p < 0.01). Conclusion In patients with AF and prior GI bleeding, LAAO was associated with a significantly lower risk of recurrent GI bleeding at short‐term and long‐term time intervals.

Abstract Background Ventricular arrhythmias (VAs) are a proximate mechanism of sudden cardiac death, yet national patterns in place of death (POD) and their determinants remain sparsely described. We quantified 25-year trends and factors associated with POD among UAs decedents in the United States. Methods We analyzed CDC WONDER Multiple Cause of Death data (1999–2024) for adults ≥25 years with ventricular arrhythmias (ICD-10 I47.2, I49.0) as underlying cause. POD was categorized as inpatient, outpatient/emergency department (ED), home, hospice/nursing, or other/unknown. Covariates included age, sex, race, Hispanic origin, and urbanization. We calculated Annual and Average Annual Percent Changes (AAPCs and APC) using Age-Adjusted Mortality Rates (AAMRs), and fit multinomial logistic regression (reference = inpatient) to obtain adjusted odds ratios (ORs, 95% CIs). Results Among 433,988 ventricular arrhythmia (VA) deaths, POD was inpatient 62.0%, outpatient/ED 18.1%, home 11.1%, hospice/nursing 5.8%, other 3.1%. Inpatient deaths increased from 57.8% (1999) to 66.1% (2024). AAMRs declined sharply from 13.3 per 100,000 in 1999 to 6.3–6.5 during 2010–2019, then rose to 7.4 in 2021 and fell to 6.8 in 2024. In home vs inpatient: ≥85 years, medium/small metropolitan counties and rural counties had higher odds of VA deaths, whereas younger age groups, females, Black, American Indian, Asian/Pacific Islander individuals and Hispanic individuals had lower odds. In outpatient/ED vs inpatient: 25–44 years, 45–64 years, males, Black, American Indian and Asian/Pacific Islander individuals had higher odds, whereas ≥85 years and females had lower odds. In hospice/nursing facilities: ≥85 years, females, Whites, non-Hispanic individuals, medium/small metropolitan counties and rural counties had higher odds of VA deaths, whereas younger age groups, Black, American Indian, Asian/Pacific Islander individuals and Hispanic individuals had markedly lower odds. Conclusion From 1999–2024, VA deaths shifted toward hospitals. Persistent disparities by age, sex, race/ethnicity, and rurality highlight the need to expand equitable advance care planning and device deactivation discussions.