Circulation. Arrhythmia and electrophysiology最新文献

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.

Background: Despite the rise of pulsed-field ablation (PFA), predicting and titrating lesion geometry remains challenging. This study aimed to find modifiable parameters that can accurately and repeatedly predict focal PFA lesions across a range of dimensions and to develop a model to predict lesion geometry.

Methods: An in vivo study was performed in 9 swine using an investigational dual-energy contact-force focal catheter with local impedance. Ablations were performed endocardially in the right and left ventricles using settings specifically selected to provide a wide range of lesion dimensions. Predefined PFA applications (1, 2, or 4) were delivered while maintaining different contact-force values (5-45 g). Four different voltages were used (1.0, 1.4, 2.0, and 2.2 kV). Following a 1-week survival period, the animals were euthanized for histopathologic examination.

Results: In the study characterization data set, a total of 78 PFA lesions were analyzed. Lesion depth ranged from 1.4 mm to 12.3 mm, while lesion width ranged from 3.3 mm to 21.2 mm. All 3 tested parameters-contact force, number of applications, and voltage-demonstrated a positive linear correlation with lesion depth (P<0.01). The proposed formula (Focal FARAPULSE Index Model) showed a strong positive correlation with lesion depth (R=0.83; P<0.0001) and lesion width (R=0.76; P<0.0001). A perpendicular catheter orientation was correlated with deeper lesions than a parallel orientation. No ST-segment elevations or sustained ventricular arrhythmias were observed.

Conclusions: Our findings demonstrate that PFA can be effectively titrated and predicted using the Focal FARAPULSE Index Model to create lesions of varying depths (1-12 mm), with these results being specific to the proprietary waveform and catheter used.