DeSimone, Christopher V.

BACKGROUND: Ventricular fibrillation (VF) remains a leading cause of sudden cardiac death with an incompletely characterized electrophysiological substrate. Traditional large-animal VF models are limited by hemodynamic collapse and myocardial ischemia. This study establishes a reproducible swine model using dual mechanical circulatory devices to enable high-density electroanatomic mapping under nonischemic conditions. METHODS: Five Yorkshire swine (55–65 kg) underwent sustained VF supported by venoarterial extracorporeal membrane oxygenation (2.5–3.0 L/min) and percutaneous left ventricular unloading (Impella CP, P-2–P-4). High-density electroanatomic mapping using CARTO 7 was performed at baseline and after defibrillation. Bipolar voltage was acquired from 7 predefined ventricular regions (21 measurements per animal per time point; n=210 paired observations). Unipolar voltage mapping and continuous surface ECG monitoring were used to assess acute ischemic injury. Systemic perfusion was maintained at systolic arterial pressure ≥80 mm Hg. Linear mixed-effects modeling was used to analyze voltage changes from pre-VF to post-VF. RESULTS: Sustained VF (10±1 minutes) was reproducibly induced and maintained with consistent hemodynamics (systolic arterial pressure, 90±5 mm Hg; extracorporeal membrane oxygenation flow, 2.5±0.5 L/min). All animals were successfully defibrillated. High-density mapping was feasible in all experiments (1000±300 points per chamber). Bipolar voltage showed no change from pre-VF (5.86±2.56 mV) to post-VF (6.53±2.22 mV; mean difference, 0.67 mV [95% CI, –0.31 to 1.65]; P =0.15). Both left ( P =0.17) and right ventricles ( P =0.08) demonstrated voltage preservation. Regional analysis showed no significant changes (all P >0.05); post-VF voltages remained above viability thresholds (>1.5 mV). Unipolar voltage maps recovered toward baseline, with no ECG injury pattern identified after defibrillation. CONCLUSIONS: Dual mechanical circulatory support with venoarterial extracorporeal membrane oxygenation and Impella CP enables reproducible, high-fidelity electroanatomic mapping and preserves myocardial substrate after sustained VF in a large-animal model. This platform overcomes key technical barriers in VF research, providing a nonischemic foundation for future mechanistic and translational studies.

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 Recurrence of symptomatic atrial fibrillation (AF) after catheter ablation (CA) is not uncommon. However, real-world long-term data on clinical outcomes of rhythm control strategies in patients with recurrent AF after CA remain limited. Methods Using the TriNetX database, we identified adult patients (≥18 years) with recurrent AF after index CA. A 3-month blanking period was applied, during which no rhythm-control therapy was received. Patients were classified into two groups: repeat CA or initiation of antiarrhythmic drug (AAD) therapy. Propensity score matching (PSM) was performed to balance baseline characteristics. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Outcomes included all-cause mortality, all-cause hospitalization, heart failure (HF) exacerbation, ischemic stroke, and major bleeding over 5 years. Results Among 4,056 patients with recurrent AF post-CA, 17.2% underwent repeat CA. After PSM, 697 patients in the repeat CA group (mean age 68.9 ± 9.6 years; 35.7% female) and 697 in the AAD group (mean age 68.4 ± 10.0 years; 37.6% female) were analyzed. Repeat CA was associated with lower all-cause mortality (3.3% vs 8.2%; HR 0.44; 95% CI, 0.27–0.72; P &lt; 0.01), all-cause hospitalization (42.8% vs 56.4%; HR 0.71; 95% CI, 0.61–0.82; P &lt; 0.01) and HF exacerbation (12.5% vs 24.8%; HR 0.50; 95% CI, 0.39–0.64; P &lt; 0.01). No differences were observed in ischemic stroke (5.3% vs 4.7%; HR 1.22; 95% CI, 0.77–1.96; P = 0.40) or major bleeding (4.6% vs 6.2%; HR 0.82; 95% CI, 0.52–1.29; P = 0.39). Conclusions Repeat CA was associated with lower mortality, hospitalization, and HF exacerbation over 5 years.

Abstract Background Vagally mediated syncope and functional bradyarrhythmias can cause recurrent symptoms, injury and a need for permanent pacing, yet standard therapies do not address the underlying autonomic reflex. Cardioneuroablation (CNA) targets this mechanism, but adoption has been limited by uncertainty about patient selection, procedural endpoints and durable outcomes. Methods We studied 95 consecutive patients with vagally mediated syncope (n=78) or functional bradyarrhythmia (n=17) who underwent CNA at a single center by a single lead operator under a uniform, prospectively maintained protocol. Extracardiac vagal stimulation (ECVS) was performed before and after ablation to confirm vagally mediated sinus or atrioventricular (AV) nodal responses and to verify their attenuation. Outcomes through 1 year included clinical recurrence, quality of life, pacing burden and pacemaker extraction. Results Before ablation, ECVS provoked sinus pauses in 95.8% of patients and AV block in 91.6%; after ablation, sinus pauses were abolished in every patient and residual AV block was present in 4.2%. One-year freedom from recurrent syncope and from bradyarrhythmia-related events was 93.8% and 94.1%. Syncope burden fell from a median of 2.7 episodes per year to none, and disease-specific quality of life improved substantially (P<0.001). Among patients with pre-existing devices, atrial pacing burden fell from a median of 22% to 0%. There were no strokes, deaths or myocardial infarctions. Conclusions In this single-center cohort, physiology-guided CNA was associated with durable symptom control, improved quality of life and reduced pacing across vagally mediated bradyarrhythmia syndromes. Multicenter controlled studies are needed to confirm these findings.

Isolated pulmonary valve endocarditis (PV-IE) is a rare condition. Its epidemiology, clinical profile, and management remain poorly characterized. A systematic review was conducted to provide a contemporary characterization (2020–2025) of adult cases with isolated PV-IE. Individuals with previous cardiac surgeries, cardiac implantable electronic devices (CIEDs), or long-term venous catheters were excluded. Of 1902 citations identified, 72 studies were selected with 79 eligible cases, mostly case reports. Patients were predominantly male (78.5%) with a median age of 43 years. Congenital heart disease (CHD) and injection drug use (IDU) were risk factors in 30.4% and 27.8% of cases, respectively, while 41.8% had neither (No-CHD/IDU group). Staphylococcus aureus was the leading pathogen (39%), followed by streptococci (16.5%) and Enterococcus faecalis (8.9%). Vegetations were large (median, 19.5 mm), and pulmonary septic emboli highly prevalent (~93% of cases). More than half (54.4%) of patients underwent surgery. Hospital mortality was low (7.6%). Differences across risk factor subgroups were observed, with higher median age in No-CHD/IDU patients and more staphylococcal etiology in patients with IDU, although treatment approaches and mortality did not differ. This review highlights distinct characteristics and the overall favorable short-term prognosis of isolated PV-IE, underscoring the need for larger, systematically collected datasets.

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 Aims Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist, and both increase the risk of thromboembolism and bleeding. We aim to investigate the impact of CKD in patients with AF undergoing left atrial appendage occlusion (LAAO). Methods and results We conducted a retrospective analysis using the TriNetX database, from April 2015 to February 2023. Patients aged ≥ 18 years with AF undergoing their first LAAO were included. We performed a comparative analysis of patients with CKD/end-stage renal disease (ESRD) vs. those without. Propensity Score Matching (PSM) (1:1) was employed based on baseline characteristics. The primary outcomes were ischaemic stroke/transient ischaemic attack (TIA)/systemic embolism (SE) and major bleeding over a three-year follow-up. We included 10 689 patients, of whom 4140 had CKD/ESRD, and 6549 had no CKD. PSM resulted in 3085 patients in each cohort. CKD/ESRD was significantly associated with a higher risk of major bleeding [HR: 1.179, 95% CI (1.080, 1.288), P &lt; 0.001], acute myocardial infarction, acute heart failure, acute kidney injury, cardiac-related haemodynamic instability (CRHI), hospitalizations, and all-cause mortality (P &lt; 0.001), with no significant difference in ischaemic stroke/TIA/SE [HR: 1.019, 95% CI (0.909, 1.141), P = 0.750]. Conclusion Our study suggests that CKD/ESRD was significantly associated with a higher risk of major bleeding, acute myocardial infarction, acute heart failure, acute kidney injury, CRHI, hospitalizations, and all-cause mortality, with no significant difference in ischaemic stroke/TIA/SE among patients with AF undergoing LAAO.

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.