JACC. Clinical electrophysiology最新文献

Background: Stereotactic arrhythmia radioablation (STAR) was introduced to treat ventricular tachycardia (VT) refractory to catheter ablation. No data are now available in the septal VT substrate setting, representing a challenge when using conventional techniques.

Objectives: This study sought to evaluate the arrhythmic burden in patients with septal VT treated with magnetic resonance-guided STAR (MRgSTAR).

Methods: We enrolled consecutive patients with septal VT substrate. The therapy target was achieved by combining anatomic/functional and electrophysiologic information. Patients were treated with a single fraction of 25 Gy adopting MRgSTAR. All patients were clinically followed up, and all implantable cardiac devices were remotely monitored. The efficacy outcome included recurrences of any sustained VT beyond the 6-week blanking period after MRgSTAR. The safety outcome was the incidence of adverse events and atrioventricular block.

Results: We included 11 patients with septal substrate VT (median age: 68 years; Q1-Q3: 64.5-78 years; 100% male). Clinical presentation was an electrical storm in 81.8% of patients. No complications occurred after MRgSTAR, and 6 (54.5%) patients were discharged on the same day of treatment. During a mean follow-up of 12 ± 6 months, the efficacy outcome occurred in 3 (27.3%) cases. A significative reduction of implantable cardioverter-defibrillator (ICD) therapy (23.6 before MRgSTAR vs 1.7 after MRgSTAR; P < 0.001) was observed. Left ventricular ejection fraction increased significantly after treatment (38% [Q1-Q3: 33.5%-42.0%] before MRgSTAR vs 43.8% [Q1-Q3: 35%-47%] after MRgSTAR; P = 0.04). No adverse effects were observed in the implantable cardioverter-defibrillator and lead system; in the 7 patients with preserved atrioventricular conduction, no atrioventricular block was reported.

Conclusions: MRgSTAR represents a safe and effective strategy for treating septal VT.

Background: Effective and safe pharmacological approaches for atrial defibrillation offer several potential advantages over techniques like ablation. Pharmacological therapy is noninvasive, involving no risk associated with the procedure or resulting complications. Moreover, acute drug intervention with existing drugs is likely to be low cost and broadly accessible, thereby addressing a central tenet of health equity.

Objectives: This study aims to investigate ibutilide-mediated action potential prolongation to promote use-dependent effects of flecainide on Na⁺ channels by reducing the diastolic interval and, consequently, drug unbinding to reduce action potential excitability in atrial tissue and terminate re-entrant arrhythmia.

Methods: Here we utilize a modeling and simulation approach to predict the specific combinations of sodium- and potassium-channel blocking drugs to chemically terminate atrial re-entry.

Results: Computational modeling and simulation show that acute application of flecainide and ibutilide is a promising example of drug repurposing that may constitute a promising combination for chemical atrial defibrillation.

Conclusions: We predict the drug concentrations that promote efficacy of flecainide and ibutilide used in combination for atrial chemical defibrillation. We also predict the potential safety pharmacology impact of this drug combination on ventricular electrophysiology.

Left bundle branch area pacing is an innovative technique employed to maintain left ventricular synchrony. However, the operator can face challenges in penetrating the lead into the septum during screwing. Two pitfalls-helix-only penetration and shallow penetration-hinder lead penetration. The research, conducted in 2 phases on patients and swine hearts, tested 2 techniques to overcome these issues. The results highlight the impact of endocardial involvement and suggest that the optimal technique involves intentionally creating an endocardial breach rather than simply unscrewing and rescrewing. This solution could facilitate the procedure by minimizing the number of attempts to reach the pacing site and thus reducing the risk of complications.

Background: Substantial sex-based differences have been reported in atrial fibrillation (AF), but the underlying mechanisms are poorly understood.

Objectives: This study sought to gain a mechanistic understanding of Ca²⁺-handling disturbances and Ca²⁺-driven arrhythmogenic events in male vs female atrial cardiomyocytes and establish their responses to Ca²⁺-targeted interventions.

Methods: We integrated reported sex differences and AF-associated changes (ie, expression and phosphorylation of Ca²⁺-handling proteins, cardiomyocyte ultrastructural characteristics, and dimensions) into our human atrial cardiomyocyte model that couples electrophysiology with spatially detailed Ca²⁺-handling processes. Sex-specific responses of atrial cardiomyocytes to arrhythmia-provoking protocols and Ca²⁺-targeted interventions were evaluated.

Results: Simulated quiescent cardiomyocytes showed increased incidence of Ca²⁺ sparks in female vs male myocytes in AF, in agreement with previous experimental reports. Additionally, our female model exhibited elevated propensity to develop pacing-induced spontaneous Ca²⁺ releases (SCRs) and augmented beat-to-beat variability in action potential (AP)-elicited Ca²⁺ transients compared with the male model. Sensitivity analysis uncovered distinct arrhythmogenic contributions of each component involved in sex and/or AF alterations. Specifically, increased ryanodine receptor phosphorylation emerged as the major SCR contributor in female AF cardiomyocytes, whereas reduced L-type Ca²⁺ current was protective against SCRs for male AF cardiomyocytes. Furthermore, simulated Ca²⁺-targeted interventions identified potential strategies (eg, t-tubule restoration, and inhibition of ryanodine receptor and sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase) to attenuate Ca²⁺-driven arrhythmogenic events in women, and revealed enhanced efficacy when applied in combination.

Conclusions: Sex-specific modeling uncovers increased Ca²⁺-driven arrhythmogenic events in female vs male atria in AF, and suggests combined Ca²⁺-targeted interventions are promising therapeutic approaches in women.

Background: Atrial conduction velocity (CV) is influenced by autonomic tone and contributes to the pathophysiology of re-entrant arrhythmias and atrial fibrillation. Cardiac sympathetic nerve activation has been reported via electrical stimulation within the vertebral vein (VV).

Objectives: This study sought to characterize changes in right atrial (RA) CV associated with sympathetic stimulation from pharmacologic (isoproterenol) or direct electrical (VV stimulation) approaches.

Methods: Subjects undergoing catheter ablation for atrial fibrillation had baseline RA electroanatomic maps performed in sinus rhythm (SR). RA mapping was repeated during right VV stimulation (20 Hz; up to 20 mA) and again with both RA pacing and during isoproterenol infusion, each titrated to the heart rate achieved with VV stimulation.

Results: A total of 100 RA maps were analyzed from 25 subjects (mean age: 58 ± 14 years; 56% male), and CV was calculated from 51,534 electroanatomic map points. VV stimulation increased heart rate from baseline in all subjects (22.5 ± 5.5 beats/min). The average CV increased with VV stimulation (82.0 ± 34.5 cm/s) or isoproterenol (83.7 ± 35.0 cm/s) when compared to SR (70.8 ± 32.5 cm/s; P < 0.001). Heterogeneity of CV decreased with VV stimulation or isoproterenol when compared to SR (coefficient of variation: 0.33 ± 0.21 vs 0.35 ± 0.23 vs 0.57 ± 0.29; P < 0.001). There was no difference in CV or CV heterogeneity between SR and RA pacing, suggesting that these changes were independent of heart rate.

Conclusions: Global RA CV is enhanced, and heterogeneity of CV is reduced, with either pharmacologic or direct electrical sympathetic stimulation via the right VV.