Circulation. Arrhythmia and electrophysiology最新文献

Background: The LEADR (Lead Evaluation for Defibrillation and Reliability) trial evaluated the small-diameter (4.7F), lumenless, integrated bipolar OmniaSecure defibrillation lead. The trial exceeded primary safety and efficacy objective thresholds, demonstrating favorable efficacy at implant and a low rate of complications. Three-year term outcomes of the LEADR trial assessing the OmniaSecure lead are reported here.

Methods: The LEADR trial is a prospective, multicenter, single-arm clinical trial. Patients with an indication for de novo implantable cardioverter defibrillator/cardiac resynchronization therapy defibrillator were implanted with the OmniaSecure lead in standard right ventricle locations and followed at prespecified intervals. The lead was evaluated for safety, efficacy, and reliability through final follow-up.

Results: There were 643/657 patients (97.9%) successfully implanted with the OmniaSecure lead with a mean follow-up of 32.4±9.1 months (26% female, 61.9±12.9 years). Pacing capture threshold, pacing impedance, and R-wave amplitudes remained stable throughout. There was a 96.5% freedom from major study lead-related complications at 3 years. At 3 years, 22.3% of patients received appropriate therapies, that is, shock and antitachycardia pacing, with a 75.4% antitachycardia pacing efficacy. Inappropriate shock rate was 2.7% and 5.9% at 1 and 3 years, respectively.

Conclusions: The final results of the LEADR trial demonstrated 3-year term safety, efficacy, and reliability of the OmniaSecure lead, emphasizing the potential utility of this lead in a wide variety of patients.

Background: Cardiac radioablation is emerging as a treatment modality for refractory ventricular tachycardia. This study aimed to evaluate the effects of radiation on the coronary arteries in a swine model of proton beam cardiac radioablation.

Methods: Eighteen swine underwent single-fraction 30 to 40 Gy pencil-beam scanning proton therapy targeting the left ventricle and were euthanized 12 to 40 weeks later. Treatment planning was performed without restricting the dose to the coronary arteries. The maximum point dose (D_max) to the epicardial coronary arteries was calculated. In secondary analyses, the mean (D_mean) and minimum dose received by the highest irradiated 0.01 cm³ (D_0.01) of each coronary artery were also calculated. Coronary artery segments were harvested from the D_max sites for histological analysis, and the D_max was correlated with stenosis severity.

Results: Ninety-six coronary arteries were analyzed. No stenoses were observed by computed tomography imaging preirradiation. By histological analysis posteuthanasia, 25/96 (26%) coronaries sampled at their D_max sites had ≥75% stenosis. The median D_max was 4.7 Gy for the <75% stenosis group and 29.7 Gy for the ≥75% stenosis group (P<0.001). The AUC-ROC for the association between D_max and stenosis ≥75% was 92.2%. A D_max value of 20.1 Gy best predicted stenosis ≥75%, with sensitivity 92.3% and specificity 87.1%. The AUC-ROCs for the associations of D_mean and D_0.01 with stenosis ≥75% were 84.8% and 91.6%, respectively. In histopathologic analysis, intimal hyperplasia was the most common coronary artery abnormality at the D_max sites, and it was present in 61.5% of all arteries and in 93.9% of arteries with D_max ≥20 Gy.

Conclusions: In this preclinical model of proton beam cardiac radioablation, coronary stenoses occurred in a dose-dependent manner, with D_max showing the closest correlation with stenosis ≥75%. These data provide for the first time a framework for dose constraint considerations for the coronary arteries during treatment planning for cardiac radioablation and thoracic malignancy radiation.

Background: Premature ventricular contractions (PVCs) are the most prevalent ventricular arrhythmia in adults. High PVC burden can lead to left ventricular systolic dysfunction, eccentric hypertrophy, and an increased risk of heart failure and sudden cardiac death. Inadequate angiogenesis is a key determinant in the transition from adaptive to maladaptive cardiac hypertrophy, and fibrosis is a risk factor for arrhythmia and sudden cardiac death. We quantitatively assessed structural remodeling and transcriptional alterations in PVC-induced cardiomyopathy (PVC-CM).

Methods: Animals were implanted with modified pacemakers to deliver bigeminal PVCs (200-220 ms coupling interval) for 12 weeks. Collagen deposition and interstitial ultrastructure of left ventricular samples were analyzed using light and transmission electron microscopy, respectively. Pericytes, fibroblasts, myocytes, smooth muscle, and endothelial cells were imaged using confocal microscopy, quantified with an artificial intelligence-based segmentation analysis, and compared using hierarchical statistics. Transcriptional changes were assessed via RNAseq, and protein expression was assessed using western blot.

Results: Although cardiomyocytes hypertrophied in PVC-CM, capillary rarefaction was overcome by an increase in the capillary-to-myocyte ratio. Additionally, thicker blood vessels were more abundant in PVC-CM. Fibroblast-to-myocyte ratio more than doubled, interstitial collagen fibers increased, and interstitial space thickened in PVC-CM. Transcripts involved in interstitial remodeling, inflammatory response, and alarmins were strongly elevated in PVC-CM, showing enrichment of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) transcriptional signature. These results coincide with elevated levels of the proinflammatory cytokine IL (interleukin)‑1β, the inflammasome component NLRP3 (nucleotide-binding domain, leucine-rich repeat family, pyrin domain containing 3), and increased expression of NF‑κB p65 (RelA).

Conclusions: Although the angiogenic response meets the metabolic demands of cardiac hypertrophy, upregulated markers of inflammation and cardiomyopathy linked to reactive fibrosis collectively represent an adverse left ventricular remodeling in PVC-CM that could provide the substrate for heart failure, arrhythmias, and sudden cardiac death in PVC-CM.

Background: Ventricular ectopic beats (VEBs) are frequently observed in athletes, but their clinical significance remains debated. We aimed to assess the prevalence, pattern of exercise-induced VEBs, and their association with exercise-induced cardiac remodeling (EICR) in elite athletes.

Methods: We analyzed a large cohort of Olympic athletes who underwent comprehensive preparticipation screening, including exercise-electrocardiography test and echocardiography. VEB morphology was classified as common (left bundle branch block, with inferior axis, and fascicular) or uncommon, including polymorphic.

Results: We enrolled 2525 athletes (mean age, 25.7±5.2 years; 45.1% women); 14.8% of athletes had exercise-induced VEBs, more frequently men (16.7% versus 12.4%; P=0.002), with no differences between sport disciplines (P=0.295). The VEB pattern was defined in 283 (ie, 76%), including 135 (48%) common and 148 (52%) uncommon, including polymorphic. Prevalence of common VEBs increased proportionally with the functional capacity (as W/kg), ranging from 16.3.% in I quartile to 40% in IV quartile (P<0.0001), while no differences existed in those with uncommon VEBs (P=0.140). Moreover, athletes with common VEBs showed a greater EICR, including a larger right ventricle (with wider right ventricular outflow tract; P=0.014; right ventricular end-diastolic area; P=0.016) and left ventricle (greater left ventricular mass indexed; P=0.037; a higher prevalence of eccentric remodeling; P=0.019). On the contrary, no relationship with cardiac remodeling or exercise capacity was seen in athletes with uncommon VEBs and in those without VEBs.

Conclusions: Exercise-induced common VEBs in athletes seem to be associated with EICR and superior exercise performance and may represent a benign phenomenon, expression of the pathophysiologic consequences of EICR. Instead, uncommon VEBs were not related to the extent of EICR or the level of exercise performance, suggesting a nonphysiological nature.

Background: GLP-1 (glucagon-like peptide-1) receptor agonists (GLP-1RAs), initially developed for glycemic control in type 2 diabetes, have shown cardiometabolic benefits including weight loss, improved endothelial function, and reduced inflammation. Recent data suggest potential anti-arrhythmic effects via modulation of atrial substrate and autonomic tone. Their impact on obese, nondiabetic patients remains underexplored. This study examines whether GLP-1RA use is associated with reduced atrial fibrillation recurrence after catheter ablation in obese patients, using real-world data from a large multicenter database.

Methods: We conducted a retrospective cohort study using the TriNetX research network, which contains de-identified electronic health records from >100 million patients. Adult patients (age ≥18 years) with obesity (body mass index >30 kg/m²) who underwent atrial fibrillation (AF) ablation between January 2015 and January 2025 were eligible. The cohort was divided into GLP-1RA users (n=3350) and nonusers (n=3350), with 1:1 propensity score matching performed across 82 clinical and demographic variables, including age, sex, race, AF subtype, cardiovascular comorbidities, and baseline medications.

Results: During a median follow-up of 2 years (interquartile range, 0.8-3.2) AF recurrence was significantly lower in GLP-1RA users versus non users (6.66% versus 7.72%; hazard ratio [HR], 0.82 [95% CI, 0.76-0.88]; P<0.0001) Progression to permanent AF occurred less frequently in GLP-1RA users (3.16% versus 3.38%; HR, 0.77 [95% CI, 0.63-0.93]; P=0.01). Risk of all-cause mortality was lower in the GLP-1RA group (HR, 0.73 [95% CI, 0.59-0.91]; P=0.01) HF hospitalization (HR, 0.80 [95% CI, 0.71-0.90]; P<0.0001) and cardiovascular hospitalizations (HR, 0.85 [95% CI, 0.77-0.93]; P=0.001) were also significantly lower with GLP-1RA use. No significant difference was found for redo ablation.

Conclusions: In a large real-world cohort of obese patients undergoing catheter ablation for AF, GLP-1RA therapy was associated with lower risks of AF recurrence, progression to permanent AF, cardiovascular hospitalizations, and mortality.

Background: MODULAR antitachycardia pacing (ATP), a multicenter, international trial, assesses a modular cardiac rhythm management system: a subcutaneous implantable cardioverter defibrillator in wireless communication with a leadless pacemaker (LP) capable of pace-terminating ventricular tachycardia.

Methods: Enrolees had one or more clinical risk factors for ventricular tachycardia and did not require chronic pacing. Complications included prespecified major LP system- and procedure-related complications, and any complication related to the LP, subcutaneous implantable cardioverter defibrillator, implantation, or study protocol. Survival analysis was performed to identify complication-free rates, therapy delivery, and all-cause mortality.

Results: The 297 patients enrolled had an ejection fraction of 35±13%, 43% secondary prevention indications, and 59% with prior ventricular arrhythmias. Of 286 patients undergoing LP implantation (100% success), 251 patients completed 12-month follow-up. Mortality rate was 6%, with none related to the implant procedure. Median follow-up duration was 23.4 months (interquartile range, 17.9-28.1). The LP major complication-free rate was 97.2%, exceeding the performance goal. The overall LP+ subcutaneous implantable cardioverter defibrillator system-related complication-free rate was 88.5%. Appropriate tachyarrhythmia-therapy (ATP+shock) rates were 14.4%, and appropriate shock rates were 8.5%. Inappropriate total tachyarrhythmia therapy was 9.5% of which 8.5% were shocks. ATP was 67.3% successful in terminating ventricular arrhythmia episodes and accelerated ventricular arrhythmias in 10.1% of episodes. Overall therapy burden (ATP+shock) was 96/100 patient-years, of which 44/100 patient-years was for shock delivery.

Conclusions: One-year outcomes of the first modular pacing-defibrillator system reveal low system and LP complication rates and good ATP efficacy rates, suggesting that the modular cardiac rhythm management is a viable alternative to single-chamber implantable cardioverter defibrillators using low-energy pacing capability without the need for transvenous leads.

Clinical trial registration: URL: https://clinicaltrials.gov/; Unique identifier: NCT04798768.

Background: Suboptimal left ventricular (LV) and right ventricular lead positioning has been associated with a lesser response to cardiac resynchronization therapy. The MAPIT-CRT (MRI Allocation of Pacing Targets in Cardiac Resynchronization Therapy) randomized controlled trial evaluated a novel, cardiac magnetic resonance-generated 4-dimensional phenomics cardiac magnetic resonance imaging (4DPcmr) lead placement strategy.

Methods: A total of 202 participants with New York Heart Association class II to IV heart failure on optimal medical therapy, LV ejection fraction ≤35%, and QRS duration ≥120 ms were analyzed from 7 Canadian sites. Participants were randomized to 4DPcmr-guided lead placement using a web-based application or standard lead placement. 4DPcmr-recommended LV and right ventricular (RV) lead locations were generated using the combined consideration of (1) regional scar distribution and burden, (2) maximal regional delay in LV peak systolic strain, and (3) maximal interlead distance.

Results: The primary end point, an increase in LV ejection fraction ≥5% at 6 months, was reached in 69 of 105 4DPcmr-guided participants (65.7%) versus 50 of 96 control participants (52.1%; risk ratio, 1.80 [95% CI, 1.02-3.17]; P=0.04). The absolute increases in LV ejection fraction observed for the respective study arms were 10.8% versus 5.8% (P=0.01). No differences were identified in the secondary end points of all-cause mortality or heart failure hospitalization at 12 months, rate of adverse outcomes, or procedural times between the 2 study arms.

Conclusions: 4DPcmr-guided LV/RV cardiac resynchronization therapy lead implantation using a practical web application was clinically feasible, safe, and was associated with greater LV ejection fraction improvement at 6 months versus standard of care with no increase in procedural times or complications.

Registration: URL: https://clinicaltrials.gov/study/NCT01640769; Unique identifier: NCT01640769.

Background: Conventional atrial pacing at the right atrial appendage may impair interatrial synchrony. Posterosuperior bundle (PSB) pacing has been observed to offer anatomic accessibility by targeting the interatrial muscular connection within the superior vena cava. The study aimed to further validate the feasibility of PSB pacing and to observe mid-term outcomes through a retrospective cohort analysis.

Methods: This cohort enrolled 33 consecutive patients with pacing indications. PSB pacing was performed using a pacing lead delivered via a catheter to the medial wall of the superior vena cava, ≈1.5 cm superior to the junction of superior vena cava and right atrium. Electrophysiological and echocardiographic parameters were assessed before the procedure (baseline), acute phase, and at least 3 months after implantation.

Results: The mean follow-up period was 7.6±3.6 months, and PSB pacing was successful in all patients (100%), with stable lead fixation and no procedural complications, such as increased atrial capture threshold, atrial lead perforation, or atrial lead dislodgement. P-wave duration significantly shortened from baseline (120±15 ms) to follow-up (104±18 ms; P<0.05), particularly in patients with interatrial conduction delay (indicated by intrinsic P-wave duration ≥120 ms; baseline: 130±10 ms, follow-up: 111±17 ms; P<0.05). Atrial capture threshold (1.0±0.4 V) and sensing amplitudes (2.0±1.4 mV) remained stable. Structural and functional echocardiography showed maintained parameters in this study. Clinical events were minimal (1 heart failure hospitalization, 1 atrial fibrillation recurrence hospitalization, 1 syncope unrelated to pacing).

Conclusions: PSB pacing is a feasible, safe, and effective strategy for atrial pacing. It maintains interatrial electrical synchrony, offers stable pacing parameters, and may provide potential functional benefits, especially in interatrial conduction delay, offering a new option for atrial physiological pacing. Further research is necessary to validate long-term outcomes.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT06995027.