Heart rhythm最新文献

Much of our understanding of the atrioventricular conduction axis has been derived from early 20th-century histologic investigations. These studies, although foundational, are constrained by their 2-dimensional representation of complex 3-dimensional anatomy. The variability in the course of the atrioventricular conduction axis, and its relationship to surrounding cardiac structures, necessitates a more advanced imaging approach. Using hierarchical phase-contrast tomography of an autopsied heart specimen with cellular resolution, this review provides a contemporary understanding of the atrioventricular conduction axis. By correlating these findings with 3-dimensional computed tomographic reconstructions in living patients, we offer clinicians the insights needed accurately to predict the location of the atrioventricular conduction axis. This novel approach overcomes the inherent limitations of 2-dimensional histology, enhancing our ability to understand and visualize the intricate relationships of the conduction axis within the heart.

Background: Guideline-directed device therapy for long QT syndrome (LQTS) has evolved during the years, and indications for an implantable cardioverter-defibrillator (ICD) vary between professional cardiac societies.

Objective: We aimed to identify the subset of patients with LQTS who satisfied a class I or class II 2022 European Society of Cardiology guideline-based recommendation for an ICD and to determine the outcomes of those patients who received an ICD compared with those treated without an ICD.

Methods: Retrospective analysis was conducted of 2861 patients with LQT1, LQT2, or LQT3 to identify patients meeting contemporary recommendations for guideline-directed device therapy. Basic demographics, clinical characteristics, and frequency/type of breakthrough cardiac events (BCEs) were extracted, and outcomes/complications were compared between patients treated with an ICD and those treated without one.

Results: Of the 290 patients (approximately 10%) who met a guideline-based recommendation, 53 (18%) satisfied a class I/level B indication for an ICD; 56 (19%), a class I/level C indication; 19 (7%), a class IIa/level C indication; and 162 (56%), a class IIb/level B indication. However, most patients (156/290 [54%]) did not receive an ICD. Of those who received an ICD, 55 of 134 (41%) experienced ≥1 appropriate ventricular fibrillation-terminating ICD therapy, whereas ICD-related complications occurred in 13 patients (10%). Of those who were treated without an ICD, only 6 of 156 patients (4%) had nonlethal BCEs, which was significantly lower compared with the ICD group (P < .001).

Conclusion: With >1200 years of combined follow-up, the experience and evidence from our 2 LQTS specialty centers suggest that many patients who satisfy a recommendation for an ICD based on the latest 2022 European Society of Cardiology guidelines may not need one. This is particularly true when the indication stemmed from a BCE while receiving beta blocker therapy or in asymptomatic patients with an increased 1-2-3-LQTS-Risk score.

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia disorder associated with lethal arrhythmias. Most CPVT cases are caused by inherited variants in the gene encoding ryanodine receptor type 2 (RYR2).

Objective: The goal of this study was to investigate the structure-activity relationship of tetracaine derivatives and to test a lead compound in a mouse model of CPVT.

Methods: We synthesized >200 tetracaine derivatives and characterized 11 of those. The effects of these compounds on Ca²⁺ handling in cardiomyocytes from R176Q/+ mice was tested with confocal microscopy. The effects of lead compound MSV1302 on arrhythmia inducibility and cardiac contractility were tested by programmed electrical stimulation and echocardiography, respectively. Plasma and microsomal stability and cytotoxicity assays were also performed.

Results: Ca²⁺ imaging revealed that 3 of 11 compounds suppressed sarcoplasmic reticulum Ca²⁺ leak through mutant RyR2. Two compounds selected for further testing exhibited a half-maximal effective concentration of 146 nM (MSV1302) and 49 nM (MSV1406). Whereas neither compound altered baseline electrocardiogram intervals, only MSV1302 suppressed stress- and pacing-induced ventricular tachycardia in vivo in R176Q/+ mice. Echocardiography revealed that the lead compound MSV1302 did not negatively affect cardiac inotropy and chronotropy. Finally, compound MSV1302 did not block I_Na, I_Ca,L, or I_Kr; it exhibited excellent stability in plasma and microsomes, and it was not cytotoxic.

Conclusion: Structure-activity relationship studies of second-generation tetracaine derivatives identified lead compound MSV1302 with a favorable pharmacokinetic profile. MSV1302 normalized aberrant RyR2 activity in vitro and in vivo, without altering cardiac inotropy, chronotropy, or off-target effects on other ion channels. This compound may be a strong candidate for future clinical studies to determine its efficacy in CPVT patients.

Background: No evidence exists regarding whether tissue proximity indication (TPI), an impedance-based contact indicator, can improve in vivo lesion formation and durability during pulsed field ablation (PFA).

Objective: This in vivo study investigated the relationship between catheter-tissue contact and lesion formation.

Methods: In 5 porcine subjects, PFA applications were delivered at 35 atrial target sites using the VARIPULSE variable-loop circular catheter with the CARTO 3 mapping system. We compared acute ablative low-voltage zones (LVZs; <0.5 mV), chronic LVZs, and pathologic lesions between no/minimum contact (TPI-negative/flickering TPI-positive status) and consistent tissue contact (consistent TPI-positive status) for typical clinical scenarios and tissue tenting (TPI-positive status with electrodes extensively away from the 3-dimensional mapping surface) for safety margin. Ultrasound imaging also confirmed contact category assessments.

Results: Acute and chronic LVZs were significantly larger with consistent contact compared with no/minimum contact, including pathologic lesion length (36.0 ± 12.5 mm vs 17.4 ± 15.2 mm; P = .002) and maximum width (10.3 ± 2.7 mm vs 5.7 ± 5.1 mm; P = .035); results with tenting (length: 34.6 ± 11.7 mm; width: 11.3 ± 1.9 mm) were comparable to consistent contact. Lesion transmurality was achieved in all lesions with consistent contact or tissue tenting but only in 54.5% with no/minimum contact (P = .001 for each). The TPI-based electrode contact distance, measured as the cumulative length of the multielectrode catheter tip positive for TPI, significantly correlated with lesion length, maximum width, and transmurality.

Conclusion: Consistent TPI-based contact during PFA was strongly associated with distinct chronic transmural lesions, emphasizing the importance of tissue contact in optimizing circumferential lesion formation with circular PFA catheters.