Circulation. Arrhythmia and electrophysiology最新文献

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.

Background: Horses are one of the few animals that spontaneously develop atrial fibrillation (AF), making them a powerful model for studying AF mechanisms and treatment effects. Despite the initial effectiveness of treatment in horses and humans, AF-induced atrial remodeling compromises its long-term success. Observational studies have suggested that metformin may reduce the risk of AF, but its effects on progressive AF-induced atrial remodeling have yet to be evaluated in a high-fidelity large animal model.

Methods: Here, we used a longitudinal horse model of tachypacing-induced self-sustained AF to characterize the electrical, molecular, and metabolic atrial changes over 4 months of disease, with and without metformin treatment (30 mg/kg orally, twice daily; initiated before AF induction, N=24 horses). Electrophysiological and multiomic approaches were combined with histology, echocardiography, biochemical, and mitochondrial analyses to evaluate disease progression and treatment response.

Results: The horse model replicated critical aspects of AF-induced atrial remodeling observed in Humans, including electrical and structural changes. Despite upregulation of metabolic genes and proteins in AF, no significant ultrastructural mitochondrial changes were detected. Metformin plasma trough levels confirmed stable therapeutic exposure. Metformin-treated horses were protected against early AF stabilization and sustained a less complex AF substrate in the right atrium after 4 months of disease. These protective effects were associated with increased right atrial activity of the metabolic regulator, AMPK (AMP-activated protein kinase), changes in metabolic pathways, and modulation of ion-channel gene expression.

Conclusions: Metformin treatment conferred protection against early AF stabilization and selectively attenuated right atrial substrate complexity in a translationally relevant preclinical model. These findings support metformin as a lead molecule for AF prevention, warranting further mechanistic and clinical studies.

Background: In a previous study, on pulsed-field ablation (PFA) in the swine ventricle, we found that lesion depth was described (±1 mm accuracy) by a logarithmic function of contact force (CF) and the number of PFA pulses (PF-ablation index). This study was designed to validate prospectively whether the novel PF-ablation index would allow PFA lesions to be created at depths of 3.5, 4.5, 5.5, and 6.5 mm with high prediction accuracy in a swine-beating heart model.

Methods: A 7.5F catheter with a 3.5 mm ablation electrode and CF sensor (ThermoCool SmartTouch SF-Dual Energy) was connected to a PFA system (TRUPULSE 2). In 6 closed-chest swine, a biphasic PFA pulse was delivered between the ablation electrode and a skin patch at 123 separate ventricular sites at 5 different levels of CF (1) low (average CF: 4-15 g; median, 12 g; n=25), (2) moderate (16-30 g; median, 23 g; n=41); 3) high (31-45 g; median, 36 g; n=27), (4) very high (46-68 g; median, 52 g; n=18); or (5) no electrode contact, 1 to 2 mm from the endocardium (n=12). PFA application was terminated when the PF-ablation index reached a predicted lesion depth of 3.5 mm (27 sites), 4.5 mm (25 sites), 5.5 mm (29 sites), and 6.5 mm (30 sites). Swine were euthanized 2 hours after ablation. Lesion size was measured using triphenyl tetrazolium chloride staining.

Results: Predicted lesion depth by the PF-ablation index correlated well with actual lesion depthwith ±1.0 mm accuracy in 97/106 (92%) lesions and ±1.5 mm accuracy in all 106 lesions. There were no or poor relationships between intracardiac electrogram attenuation, impedance decrease, electrode temperature, and lesion size. No detectable lesions were created without electrode contact.

Conclusions: A novel PF-ablation index incorporating CF and the number of PFA pulses provides high accuracy in predicting lesion depth in real-time. Intracardiac electrogram attenuation, impedance decrease, and electrode temperature are poor predictors of PFA lesion size.

Background: Activation recovery interval (ARI), extracted from unipolar electrograms, serves as a practical surrogate for repolarization during experimental studies in vivo. Far-field signal contamination and low spatial resolution obscure regional repolarization gradients and duration alternans detection using unipolar ARI. We hypothesized that the attenuation of far-field contamination with the principal component-referenced unipole will allow for a more accurate assessment of true local repolarization gradients and spatially assess action potential duration alternans.

Methods: Unipolar ARI and the novel method, Repol^Loc, were validated for the detection of spatial and temporal repolarization changes using simultaneous optical and electrical mapping in a rabbit Langendorff model. Repolarization changes were created using global infusion of ibutilide or pinacidil, or topical application of lidocaine. Epicardial mapping was conducted in a porcine Langendorff model following the topical application of lidocaine to investigate the spatial resolution of each method. Generalized linear models of the two methods were used to compare with optical action potential duration (APD80).

Results: Following the infusion of antiarrhythmic drugs, the Repol^Loc method (slope=0.90) had a slightly higher correlation to optical APD80 than the ARI method (slope=0.79). Following regional application of lidocaine, Repol^Loc was better able to localize the site of drug administration with an average 26.12% reduction as compared with 18.66% reduction in unipolar ARI (P=0.0046). Additionally, temporal repolarization alternans and restitution changes assessed by Repol^Loc method tracked optical APD80 quantified time domain changes.

Conclusions: Repol^Loc has higher sensitivity to local spatiotemporal repolarization heterogeneities and alternans than traditional ARI. Although ARI only correlates with uniformly distributed changes in repolarization in the entire myocardium, Repol^Loc also provided accurate regional gradient assessment and duration alternans of repolarization. These findings suggest ARI has significant far-field contamination and Repol^Loc may provide a better clinical mapping tool for spatiotemporal repolarization gradient mapping.