JACC. Clinical electrophysiology最新文献

Background: A catheter platform allowing power- and temperature-controlled ablation (temperature-guided ablation) has recently been introduced. Clinical outcomes after ventricular tachycardia (VT) ablation using this technology remain uncertain.

Objectives: The goal of this study was to evaluate the safety and efficacy of temperature-guided VT ablation and compare the findings vs those from standard power-controlled ablation.

Methods: This multicenter cohort study enrolled consecutive patients undergoing temperature-guided VT ablation using the QDOT MICRO catheter (Biosense Webster) at 8 referral centers in Europe and the United States (2021-2024). For comparison, a multicenter cohort of patients receiving power-controlled ablation with the THERMOCOOL SMARTTOUCH or SMARTTOUCH SurroundFlow (Biosense Webster) catheters was also included. The primary safety endpoint was procedure-related complications. The primary efficacy endpoint was sustained VT/ventricular fibrillation recurrence during long-term follow-up, assessed in the overall cohort and in propensity score-matched patients.

Results: The study included 286 patients: 109 treated with temperature-guided ablation and 177 with power-controlled ablation. Ischemic cardiomyopathy was the predominant VT substrate (n = 125 [44%]); approximately one-half presented with electrical storm. Propensity score matching based on baseline clinical data yielded 101 pairs. Procedure-related complications were significantly lower with temperature-guided ablation (temperature-guided: n = 3 [3%]; power-controlled: n = 23 [13%]; P = 0.003), a result that remained significant after matching (temperature-guided: n = 3 [3%]; power-controlled: n = 12 [12%]; P = 0.028) and excluding vascular complications (temperature-guided: n = 1 [1%]; power-controlled: n = 14 [8%]; P = 0.012). Use of temperature-guided ablation was associated with lower odds of nonvascular complications in multivariable analysis (adjusted OR: 0.095; P = 0.028). Over a median follow-up of 24 months, VT/ventricular fibrillation recurrence rates were similar between groups in both overall (log-rank test, P = 0.570) and matched (log-rank test, P = 0.850) cohorts. Subgroup analyses showed no signal of heterogeneity.

Conclusions: In this multicenter VT ablation registry, a novel temperature-guided ablation modality showed favorable safety and efficacy relative to power-controlled ablation.

Background: Pulmonary veins (PVs) are major sources of atrial fibrillation (AF) triggers, but patients may also have non-PV (NPV) triggers. Data on the impact of targeting NPV triggers on AF ablation outcomes are limited.

Objectives: This study aimed to assess the outcome of patients undergoing AF ablation based on their NPV trigger status.

Methods: Patients undergoing first-time AF ablation using radiofrequency energy between 2018 and 2023 who received trigger provocative maneuvers were included. The provocative maneuvers consisted of cardioversion of AF, incremental isoproterenol infusion (3, 6, 12, and 20-30 μg/min) and/or an atrial burst pacing protocol. NPV triggers were defined as ectopic foci initiating AF, sustained focal atrial tachycardia (AT), or atrioventricular nodal reentrant tachycardia. Recurrence was defined as AF/AT >30 seconds after a 90-day blanking period.

Results: Of 2,315 patients included, 2,046 (88.4%) did not have NPV triggers, 233 (10.1%) had NPV triggers that were ablated, and 36 (1.6%) had NPV triggers that were not targeted or failed localization/ablation attempts. One-year recurrence rate was 29.5% in patients without NPV triggers, 38.2% in those with ablated NPV triggers (adjusted HR: 1.35; 95% CI: 1.08-1.69), and 72.2% in those with untreated NPV triggers (adjusted HR: 3.71; 95% CI: 2.48-5.54). This response pattern remained consistent regardless of NPV trigger subtype (AF vs focal AT) or provocation method (spontaneous vs induced triggers).

Conclusions: Failure to ablate induced NPV triggers is associated with a high risk of recurrence. Although the ablation of NPV triggers reduces recurrence rates to levels approaching those without such triggers, their presence indicates a modestly worse prognosis.

Background: Caveolae are nanoscale, plasma membrane invaginations that compartmentalize ion channels and transporters, including those involved in sinoatrial node (SAN) activity. However, role of caveolae in cardiac pacemaking remains unknown.

Objectives: This study sought to determine the role of caveolae in SAN pacemaking and sinus node dysfunction (SND).

Methods: In vivo electrocardiography, ex vivo optical mapping, in vitro Ca²⁺ imaging, immunofluorescent and electron microscopy were performed in wild-type, cardiac-specific Cav3 knockout and 8-week post-myocardial infarction heart failure mice. Mouse and human donor SAN tissues were used for biochemical protein copurification studies. A novel 3-dimensional single SAN cell mathematical model was used to determine the impact of protein localization on SAN pacemaking.

Results: In both mouse and human SANs, caveolae compartmentalized HCN4, Ca_v1.2, Ca_v1.3, Ca_v3.1, and Na⁺-Ca²⁺ exchanger (NCX1) proteins within discrete pacemaker signalosomes via direct association with Cav3. This compartmentalization positioned electrogenic sarcolemmal proteins near the subsarcolemmal sarcoplasmic reticulum membrane and ensured fast and robust activation of NCX1 by subsarcolemmal local sarcoplasmic reticulum Ca²⁺ release events, which diffuse across ∼15-nm subsarcolemmal cleft. Disruption of caveolae led to the development of SND via suppression of pacemaker automaticity through a 50% decrease of the L-type Ca²⁺ current, a negative shift of the HCN current (I_f) activation curve, and a 40% reduction of NCX1 function, along with ∼2.3-times widening of the sarcolemma-sarcoplasmic reticulum distance. These changes significantly decreased the SAN depolarizing force, both during diastolic depolarization and upstroke phase, leading to bradycardia, sinus pauses, recurrent development of SAN quiescence, and significant increase in heart rate lability. Computational modeling, supported by biochemical studies, identified NCX1 redistribution to extracaveolar membrane as the primary mechanism of SAN pauses and quiescence due to the impaired ability of NCX1 to be effectively activated by local sarcoplasmic reticulum Ca²⁺ release events and trigger action potentials. Heart failure remodeling mirrored caveolae disruption leading to NCX1-local sarcoplasmic reticulum Ca²⁺ release event uncoupling and SND.

Conclusions: SAN pacemaking is driven by complex protein interactions within a nanoscale caveolar pacemaker signalosome. Disruption of caveolae leads to SND, demonstrating a new dimension of SAN remodeling and revealing a novel therapeutic target.