JACC. Clinical electrophysiology最新文献

Background: Pathogenic/likely pathogenic variants in the KCNH2-encoded Kv11.1 potassium channel cause type 2 long QT syndrome (LQT2). Despite the updated 2015 American College of Medical Genetics (ACMG) variant interpretation guidelines, the burden of KCNH2 variants of uncertain significance (VUS) in patients evaluated for long QT syndrome (LQTS) remains ∼30%. Previously, we developed and validated phenotype-enhanced (PE) ACMG variant adjudication for type 1 long QT syndrome.

Objectives: The purpose of this study was to determine whether a PE-ACMG variant classification approach can reduce the VUS burden in patients with clinically suspected LQT2.

Methods: Retrospective analysis was performed on 209 unique missense variants within KCNH2 from 2 LQTS specialty centers. Each variant was categorized based on the classification on the initial genetic test reports. Subsequently, all VUS were re-adjudicated with the use of a PE-ACMG framework that incorporates the patient's phenotype using the LQTS clinical diagnostic Schwartz score plus 2 LQT2-defining features: 1) biphasic/notches T waves, and 2) LQTS-triggered events during emotional stress or auditory stimuli.

Results: In total, 69/209 (33%) unique KCNH2 variants were classified as VUS based on their initial genetic test report. Mean Schwartz score for patients with a VUS was 3.6, and 41 patients (29%) had a score over 3.5. After PE-ACMG adjudication, 31/69 variants (45%) were upgraded to pathogenic, 18 (26%) to likely pathogenic, and 11 (16%) were downgraded to benign variants. Only 9 of 69 variants (13%) remained VUS. Overall, the VUS burden decreased from 69 of 209 (33%) to 9/209 (4%; P < 0.0001).

Conclusions: Phenotype-guided variant adjudication significantly decreased the VUS burden of LQT2 case-derived KCNH2 missense variants from 2 LQTS specialty centers. There is clear value in incorporating LQT2-specific phenotype/clinical data to aid in the interpretation of KCNH2 missense variants identified during LQTS genetic testing, thereby facilitating prompt initiation of LQT2-guided therapy and cascade testing of appropriate relatives.

Background: Atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) are both associated with increased morbidity and mortality. Ablation-based rhythm control, particularly using radiofrequency ablation with disparate strategies, has demonstrated clinical benefit. However, prospective data evaluating a pulmonary vein isolation (PVI)-only strategy in HFrEF are lacking, and no studies have directly compared ablation efficacy between patients with and without HFrEF.

Objectives: This study sought to assess whether a PVI-only approach using cryoballoon ablation in patients with HFrEF (LVEF ≤40%) is noninferior to PVI-only in patients without HFrEF regarding rhythm control efficacy, and to describe safety outcomes.

Methods: We conducted a prospective, investigator-initiated, single-center, noninferiority, observational study with propensity score matching. The primary efficacy endpoint was the first documented recurrence of any atrial arrhythmia after a 90-day blanking period. Safety endpoints included death, cerebrovascular events, and procedure-related adverse events.

Results: A total of 1,420 patients (paroxysmal and persistent AF) underwent PVI. With propensity score matching, 1,044 patients were analyzed in a 1:5 ratio. Over a mean follow-up of 2 years, the primary efficacy endpoint occurred in 76 (43.7%) of 174 patients with HFrEF and in 379 (43.6%) of 870 without HFrEF (HR: 1.01; 95% CI: -∞ to 1.24; P < 0.001 for noninferiority). The incidence of all-cause mortality was numerically higher in patients with HFrEF (6.3% vs 3.4%; P = 0.07), while rates of procedure-related safety events were similar between groups (2.9% vs 4.1%; P = 0.53).

Conclusions: In patients with AF undergoing ablation, a PVI-only approach shows noninferior rhythm control efficacy and comparable procedural safety in patients with HFrEF compared with those without HFrEF. (Cryoballoon Pulmonary Isolation for Atrial Fibrillation With Heart Failure [POLAR-HF]; NCT04461691).

Background: Titin truncating variants (TTNtvs) are the leading genetic cause of dilated cardiomyopathy (DCM). Although recommended, routine genetic testing is frequently not performed owing to resource constraints.

Objectives: This study sought to identify electrocardiography (ECG) parameters predictive of an underlying TTNtv in DCM patients, comparing conventional ECG analysis with an ECG-based deep neural network (DNN) to identify patients that would benefit most from targeted genetic testing.

Methods: This retrospective multinational study compared baseline ECGs from 99 DCM patients with (likely) pathogenic TTNtv with 318 gene-elusive DCM patients. Conventional ECG parameters (eg, QRS duration) were extracted. The DNN was trained to compress ECGs into 21 explainable factors, summarizing relevant ECG features. Discriminative performances of both created models, built using LASSO regularization for variable selection to fit logistic regression model, were compared (eg, C-statistics).

Results: TTNtv patients were younger (50.5 vs 56.9 years; P < 0.001), predominantly male (69.7 vs 54.7%; P = 0.008), and had lower left ventricular ejection fraction (28.0% vs 35.0%; P < 0.001) compared with gene-elusive patients. Conventional ECG analysis identified shorter QRS duration (P < 0.001), prolonged PR interval (P < 0.001), and a trend toward reduced QRS voltage (P = 0.098) as TTNtv characteristics. In the DNN model, factors F1 (inferolateral T wave inversion) and F9 (anterior T-wave inversion), among others, were associated with TTNtv. The conventional and DNN models showed good predictive performance for TTNtv (C-statistics: conventional 0.83, DNN 0.86; P = 0.197).

Conclusions: Conventional ECG and DNN analyses demonstrated similar good predictive performance in distinguishing TTNtv from gene-elusive DCM patients, emphasizing their potential as clinical tools to guide targeted genetic testing.

Background: Evidence regarding the benefits of catheter ablation in patients aged ≥80 years with nonvalvular atrial fibrillation (AF) remains limited.

Objectives: This study sought to evaluate the clinical effectiveness of catheter ablation compared with conservative management in elderly patients (age ≥80 years) with nonvalvular AF.

Methods: This prospective, registry-based, multicenter observational study involved 703 patients aged ≥80 years with nonvalvular AF enrolled from 47 hospitals in Japan (June 2022-December 2023). Among them, 249 underwent catheter ablation and 454 received nonablation management.

Results: The nonablation group was slightly older, with more comorbidities and modestly worse baseline characteristics; however, most were potential ablation candidates, and the differences were small. During a median follow-up of 504 days (Q1-Q3: 375-667 days), the primary outcome (a composite of stroke, transient ischemic attack, systemic embolism, cardiovascular events, bleeding, or all-cause death) did not differ between groups in the unmatched (HR: 0.78; P = 0.30) or matched (HR: 0.65; P = 0.21) cohorts. However, in the matched cohort, multivariable adjustment for log-N-terminal pro-B-type natriuretic peptide and albumin levels showed a significant benefit of ablation (adjusted HR: 0.44; P = 0.029). At 1 year, ablation improved symptoms, quality of life, N-terminal pro-B-type natriuretic peptide levels, and left atrial diameter, as well as better preservation of Mini-Mental State Examination and frailty scores. These benefits remained significant after adjustment.

Conclusions: The REHEALTH AF Study (Registry for Evaluating Healthy Life Expectancy and Long-Term Outcomes After Catheter Ablation of Atrial Fibrillation in the Very Elderly) study is the first prospective comparison of ablation vs nonablation in patients aged ≥80 years with AF. Although ablation improved functional and structural outcomes, its prognostic benefit was limited without adjustment but emerged after multivariable correction. Ablation may offer meaningful advantages in well-selected elderly patients, supporting individualized treatment strategies. (Registry for Evaluating Healthy Life Expectancy and Long-Term Outcomes After Catheter Ablation of Atrial Fibrillation in the Very Elderly [REHEALTH AF]; UMIN000047023).