Cha, Yong‐Mei

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.

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.

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.

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 Optimal management in patients presenting with persistent atrial fibrillation, cardiomyopathy, and atrial as well as ventricular dyssynchrony with left bundle branch block is unclear. Results and Methods A 67‐year‐old female patient presented with persistent atrial fibrillation, cardiomyopathy with a newly reduced ejection fraction (EF), increased P wave duration on electrocardiogram (ECG) and left bundle branch block. After shared decision making, the patient elected to proceed with Bachman bundle/left bundle branch area pacing plus atrioventricular (AV) node ablation. At 6‐month follow‐up post procedure, a repeat echocardiogram showed normalized atrial size and EF (65%). Device interrogation demonstrated no recurrent atrial fibrillation with the patient off antiarrhythmic and heart failure medical therapy. Conclusions Integrated atrial and ventricular synchronization through Bachmann bundle and left bundle branch area pacing may help break the cycle of dyssynchrony, remodeling, and arrhythmia. In combination with AV node ablation, it may be considered as an alternative treatment option in certain cases after shared decision making.

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: Patients with cardiac implantable electronic devices (CIEDs) undergoing radiation therapy face potential risks of device malfunction. Proton beam therapy (PBT), with its reduced neutron scatter, has emerged as a potentially safer alternative, yet real-world safety data remain scarce. Methods: We conducted a retrospective cohort study of 100 patients with CIEDs (76 pacemakers, 24 ICDs) who underwent PBT from 2016 to 2023 at a quaternary center. Baseline and serial device interrogations were performed before, during, and after treatment to assess lead impedance, capture thresholds, battery function, and arrhythmic events. Patients were stratified by pacemaker dependence and monitored accordingly. Primary outcomes included device malfunction and new-onset arrhythmias during treatment. Secondary outcomes included device parameter changes, one-year arrhythmia incidence, and cardiac-related hospitalizations. Results: No treatment-related deaths or major device failures occurred. Device malfunction was rare (2 pacemaker patients, 2.6%), with no malfunctions in ICD recipients. Transient, non-clinically significant changes in lead impedance and capture thresholds were observed. Arrhythmias during treatment occurred in 26% of pacemaker and 25% of ICD patients, but only 4% developed new arrhythmias. At one year, device-related complications and cardiac outcomes remained comparable across groups. Independent predictors of arrhythmias during treatment included a higher radiation dose per fraction (OR 1.45; p=0.001), a longer treatment duration (OR 1.12; p=0.04), and a higher number of fractions (OR 1.20; p=0.01). Conclusion: Proton beam therapy appears safe in patients with CIEDs, with a low incidence of clinically significant device malfunctions or arrhythmias. These findings support the integration of PBT into routine practice for this population and underscore the importance of structured monitoring protocols and prospective guideline refinement.

Abstract Aims The increasing adoption of transcatheter tricuspid valve replacement (TTVR) offers a promising therapeutic option for patients with severe tricuspid regurgitation. However, many of these patients have pre-existing cardiac implantable electronic devices (CIEDs), raising concerns about potential lead-related complications. Despite these concerns, limited data exist on the impact of TTVR on CIED integrity and function. This study aimed to evaluate the impact of TTVR on CIED lead function, including pacing thresholds, sensing, and impedance, in patients undergoing TTVR with the EVOQUE valve system. Methods and results A retrospective observational study was conducted at Mayo Clinic Rochester, including 32 consecutive patients who underwent TTVR with pre-existing CIEDs. A total of 32 patients were included, with a mean age of 79.2 ± 8.4 years; 59% were female. A total of 62.5% had a permanent pacemaker, 12.5% had an implantable cardioverter-defibrillator, 15.6% had a cardiac resynchronization therapy pacemaker, and 9.4% had a cardiac resynchronization therapy defibrillator. Following TTVR, 10 (31%) of patients developed lead function changes during a median device follow-up of 210 days (IQR: 43–307 days). The right ventricular lead was primarily affected, with only one case involving an atrial lead. Neither the Ottawa score nor the anatomical lead position reliably predicted lead abnormality (P = 0.86 and P = 0.53, respectively). R-wave sensing changes were the most common lead change observed, affecting 55% of cases. In 67% of these cases, R-wave sensing alterations occurred as an isolated finding, with no significant change in impedance or thresholds, and were managed conservatively without any need for device reprogramming. Four patients (13%) had findings concerning for a lead insulation breach, in which one (3%) required a lead revision. Among five patients with follow-up exceeding 600 days, two patients exhibited a statistically significant gradual decline in impedance without other lead dysfunction, suggesting potential subclinical lead degradation. Conclusion Transcatheter tricuspid valve replacement with the EVOQUE system in the setting of cardiac device leads is associated with lead function changes in 31%. The majority of lead-related changes were managed conservatively, but 13% of patients had findings concerning for an insulation breach. Future studies should focus on refining implantation techniques and defining optimal strategies for managing device-lead interactions in this population.

ABSTRACT Background Valve‐in‐valve transcatheter aortic valve replacement (ViV‐TAVR) is increasingly used to treat structural valve degeneration. Permanent pacemaker implantation (PPI) following TAVR is associated with increased morbidity and mortality, yet predictors specific to ViV‐TAVR remain poorly defined. Objective To identify clinical and procedural predictors of PPI in patients undergoing ViV‐TAVR. Methods We conducted a retrospective observational study of consecutive ViV‐TAVR cases at the Mayo Clinic from 2012 to 2022. Clinical, ECG, procedural data and fluoroscopic measurements were analyzed, and propensity score matching was used to adjust for confounding. Predictors of PPI were identified using multivariable logistic regression. Results Among 261 patients, 24 (9.2%) underwent PPI. Balloon‐expandable valves were used in 66.7% and self‐expanding valves in 33.3%. Predictors of PPI included Preprocedural bifascicular block (OR 12.15, 95% CI: 2.52–68.89, p = 0.003), greater septal implantation depth (OR 1.29, 95% CI: 1.04–1.65, p = 0.019), and post‐procedural new left (OR 23.56, 95% CI: 4.91–48.52, p = 0.0004) and right bundle branch blocks (OR 24.4, 95% CI: 3.82–30.51, p = 0.001). Aortic regurgitation as the mechanism of prosthetic valve failure was associated with reduced PPI odds (OR 0.28, 95% CI: 0.10–0.76, p = 0.014). Pacing requirement—defined as > 90% ventricular pacing—increased from 25% at 3 months to 56.25% at 12 months. At a median follow‐up of 962.5 days (IQR 481.5–1555.3), adjusted mortality was significantly higher in the PPI group (aOR 9.4, 95% CI: 1.9–60.4, p = 0.028). Conclusion Bifascicular block, greater septal depth, and new bundle branch blocks predict PPI post‐ViV‐TAVR, while aortic regurgitation appears protective. Risk stratification and procedural planning are critical.