Cardiac conduction is a central determinant of normal rhythm and arrhythmia susceptibility. Although arrhythmias have traditionally been attributed to abnormal automaticity, triggered activity, and re-entry, emerging evidence indicates that conduction abnormalities integrate structural, electrical, and immune-derived signals into a common arrhythmogenic substrate. This review summarizes multiscale mechanisms of impulse propagation, with an emphasis on gap junction-mediated coupling. Connexin 43 (Cx43), the principal ventricular connexin, maintains intercellular current flow through phosphorylation-dependent localization at intercalated discs; its remodeling leads to conduction slowing, heterogeneous propagation, and reentrant vulnerability. Recent studies have revealed that cardiac resident macrophages preserve ventricular conduction by promoting Cx43 phosphorylation via amphiregulin–epidermal growth factor receptor signaling. Loss of this macrophage-derived pathway causes Cx43 disorganization, atrioventricular block, ventricular fibrillation, and sudden death during cardiac stress, establishing an immune–electrical interface essential for conduction stability. This review further highlights conduction abnormalities in human disease, differences between mice and humans, and insights derived from electrocardiography and advanced computational modeling. Simulations linking molecular alterations to organ-level activation patterns provide a mechanistic bridge between cellular coupling, Purkinje network integrity, fibrosis distribution, and clinical electrophysiology. Together, these findings position conduction as a dynamic, regulated property of the ventricular myocardium and suggest that targeting gap junction and immune pathways may enable future conduction-based precision cardiology.

Short QT syndrome (SQTS) is a very rare inherited arrhythmia characterized by extremely short QT intervals on electrocardiograms and sudden cardiac death in young patients. Among the genotypes of SQTS, gain-of-function variants in the potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene are accountable for SQTS type 2 (SQT2). Pathogenic variants for SQT2 are rare and, among them, the p.Val141Met is relatively prevalent. This review summarizes findings for 5 SQTS patients harboring p.Val141Met we recently encountered and compares them to another 14 patients reported in the literature.

Background: Predicting the origin of premature ventricular contractions (PVCs) is challenging when a transition zone (TZ) appears in leads V3 and V4. The aim of this study was to develop a deep-learning model to predict PVC origins and identify electrocardiographic (ECG) features that contribute to the model’s decisions.

Methods and Results: ECG data from 314 patients with PVCs showing an inferior axis and TZ in leads V3 or V4 who underwent catheter ablation were analyzed. A convolutional neural network (CNN) was trained to predict an origin in the right or left ventricular outflow tract. Patients were divided into 3 cohorts for training, validation, and holdout (3 : 1 : 1 ratio). The CNN model was trained using paired data consisting of PVC and intrinsic QRS (iQRS). Five datasets per patient were used for training and validation; performance was evaluated using a single holdout dataset per patient. The CNN model achieved 92.1% accuracy, an F1 score of 0.91, and an area under the receiver operating characteristic curve of 0.96 on the holdout. Our model demonstrated superior diagnostic performance compared with conventional ECG indices. Gradient-weighted class activation mapping revealed that model attention was primarily focused on leads V3–V4 in iQRS, but was more diffusely distributed in PVC, notably the inferior limb leads and leads V2–V3.

Conclusions: The CNN-based prediction of PVC origin demonstrated clinical utility.

Background: Artificial intelligence-enhanced electrocardiography (AI-ECG) for detecting atrial fibrillation (AF) using sinus rhythm ECGs has shown promise. However, even when AI-ECG results are positive, ECG confirmation of AF may not always be obtained immediately. Repeat testing may be required, particularly in patients with a dilated left atrium, who may warrant more intensive monitoring. We aimed to investigate whether newly detected AF was frequent in patients with both high risk on AI-ECG evaluation and dilated left atrium.

Methods and Results: We used a convolutional neural network-based ECG algorithm to predict AF using data (2010–2022) from the Shinken database (n=12,595 patients without a prior AF event). The 3-year incidence of newly detected AF was compared across 3 left atrial diameter (LAD) categories: <35, 35–39, and ≥40 mm (small, middle, and large, respectively). Patients were stratified by the AI-ECG-generated diagnostic probability of AF (AIECG-AF-DP). The incidence of newly detected AF increased according to LAD category among patients with high (≥0.8) vs. low (<0.8) AIECG-AF-DP: 3.2 vs. 0.5%/year for small; 6.1 vs. 0.6%/year for middle, and 11.6 vs. 1.5%/year for large, respectively (all P<0.001). Although the area under the receiver operating characteristic curve was similar across LAD categories of <35, 35–39, and ≥40 mm (0.770, 0.753, and 0.784, respectively), the area under the precision-recall curve differed markedly (0.083, 0.114, and 0.236, respectively).

Conclusions: Newly detected AF was particularly frequent in patients with both high AIECG-AF-DP and large LAD, suggesting repeated AF screening may be warranted in this population.

Background: The prognostic significance of non-sustained ventricular tachycardia (NSVT) in Japanese patients receiving implantable cardioverter defibrillators (ICDs) for primary prevention remains unclear. This study aimed to verify the prognostic value of NSVT as recommended in the 2018 Japanese Circulation Society guideline.

Methods and Results: We analyzed 638 patients with structural heart disease who received an ICD or cardiac resynchronization therapy with defibrillator for primary prevention in the Nippon Storm Study. Analysis 1 (n=429) evaluated the association between NSVT history and predefined endpoints in patients with ischemic heart disease (IHD) or non-ischemic heart disease (non-IHD) and reduced left ventricular ejection fraction. Analysis 2 (n=357) assessed the prognostic impact of NSVT documented by Holter electrocardiography across 2 subgroups: Subgroup 1, IHD and non-IHD; and Subgroup 2, other cardiac diagnoses. Endpoints included appropriate ICD therapy, electrical storm, ventricular fibrillation (VF), shock therapy, and mortality. In Analysis 1, a history of NSVT was not significantly associated with appropriate ICD therapy or other major adverse outcomes. In Analysis 2, Holter-documented NSVT was independently associated only with appropriate ICD therapy (hazard ratio [HR] 1.82; 95% confidence interval 1.04–3.18; P=0.035). This association was significant in Subgroup 2, but not in Subgroup 1.

Conclusions: NSVT was modestly associated (HR 1.82) with appropriate ICD therapy but not with VF or mortality, suggesting reconsideration of its clinical role.

Background: The EARNEST-PVI trial showed that left atrial ablation in addition to pulmonary vein isolation (PVI) reduced atrial fibrillation (AF) recurrence after catheter ablation for persistent AF; however, the efficacy of left atrial additional ablation in patients with diabetes mellitus (DM) is not well known. The aim of this study was to evaluate the efficacy of left atrial additional ablation after PVI in patients with and without DM.

Methods and Results: This study, a subanalysis of the EARNEST-PVI trial, a multicenter, prospective, randomized, controlled trial, analyzed 493 consecutive patients undergoing initial radiofrequency catheter ablation for persistent AF. Patients were randomized to PVI alone (PVI-alone group) or PVI plus linear and/or complex fractionated atrial electrogram ablation (PVI-plus group). The primary outcome was defined as AF recurrence during the 12-month follow-up period after ablation. A total of 84 (17%) patients had DM. The primary outcome occurred in 120 (24%) patients. In patients without DM, freedom from AF recurrence was significantly higher in the PVI-plus group than in the PVI-alone group (80.0% vs. 71.1%, P=0.034). In contrast, in patients with DM, freedom from AF recurrence was similar between the PVI-plus and PVI-alone groups (75.4% vs. 72.9%, P=0.696).

Conclusions: The efficacy of left atrial additional ablation after PVI in reducing AF recurrence following catheter ablation for persistent AF was diminished in patients with DM.

Background: Incomplete low-voltage area (LVA) ablation may confound evaluation of its true efficacy in persistent atrial fibrillation (AF). This post hoc subanalysis of the multicenter randomized SUPPRESS-AF trial assessed the impact of complete LVA ablation.

Methods and Results: Patients with persistent AF and a left atrial (LA) LVA ≥5 cm²after pulmonary vein isolation were randomized to LVA ablation or no additional ablation. The primary endpoint was freedom from AF or atrial tachycardia recurrence, assessed by 24-h Holter and twice-daily electrocardiogram recordings. Outcomes were compared among 3 groups: no LVA ablation; complete LVA ablation; and incomplete LVA ablation. Among 341 patients, 170 underwent LVA ablation, including 37 with incomplete. LVA size was significantly larger in the incomplete than complete ablation group (22.0 vs. 12.2 cm²; P<0.001). Incomplete LVA ablation was not associated with increased arrhythmia recurrence. Arrhythmia-free survival did not differ significantly between the complete and no LVA ablation groups (hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.56–1.13), including after propensity score matching (HR 0.76; 95% CI 0.51–1.15). However, a trend towards greater benefit of complete LVA ablation was observed with increasing LA diameter (P_interaction=0.099).

Conclusions: Leaving LVA ablation incomplete to avoid complications appears reasonable. Although complete LVA ablation showed no overall superiority, LA enlargement may represent a clinically relevant factor for patient stratification.

Background: Atrial fibrillation (AF) is associated with disrupted right ventricular–pulmonary artery (RV–PA) coupling. Pulsed-field ablation (PFA) is less likely to induce an increase in pulmonary arterial pressure; however, changes in RV–PA coupling following AF ablation using PFA remain unclear.

Methods and Results: We retrospectively analyzed consecutive patients who underwent AF ablation using PFA. RV–PA coupling was assessed using the echocardiographic tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) ratio before and 3 months after ablation. In all, 103 patients were included in this study: 46 with paroxysmal AF (PAF) and 57 with persistent AF (PeAF), with 41 PeAF patients maintaining sinus rhythm (SR) at 3 months. The TAPSE/PASP ratio improved significantly after AF ablation using PFA in the overall cohort (mean [±SD] 0.794±0.313 vs. 0.906±0.294; P=0.009) and in PeAF patients (0.740±0.343 vs. 0.887±0.282, P=0.01); however, no significant change was observed in PAF patients (P=0.26). PASP did not increase after ablation in any group. Among PeAF patients maintaining SR at 3 months, baseline mean heart rate during AF showed a weak association with changes in the TAPSE/PASP ratio.

Conclusions: AF ablation using PFA was associated with an improvement in RV–PA coupling without an increase in pulmonary arterial pressure, particularly in patients with PeAF in whom SR was maintained at 3 months.

Background: The efficacy and safety of early direct oral anticoagulant (DOAC) (re)initiation in patients with non-valvular atrial fibrillation (NVAF) after acute onset of intracranial hemorrhage (ICH) are unknown. This study evaluated ischemic and hemorrhagic risks following early DOAC (re)initiation after ICH in patients with NVAF.

Methods and Results: SAFE-ICH is a multicenter prospective observational single-arm registry study at 32 Japanese hospitals. Eligible patients had NVAF, were aged ≥20 years, and (re)initiated DOAC ≤14 days following symptomatic ICH. Among 240 patients who (re)initiated DOAC (61.3% male; mean [±SD] age 79.4±9.3 years), intraparenchymal hemorrhage predominated (84.6%), followed by subdural (12.9%), intraventricular (1.7%), and epidural (0.8%) hemorrhage. The median (interquartile range) baseline National Institutes of Health Stroke Scale score was 10 (3–16) and time to DOAC (re)initiation was 7 days (5–10 days). Edoxaban, apixaban, and rivaroxaban were used in 55.0%, 35.8%, and 9.2% of patients, respectively. The primary endpoint (composite of symptomatic ICH, any stroke, or death ≤30 days following DOAC [re]initiation) occurred in 12 (5.0%) patients. There were 4 recurrent ICH events (1.7%; all recurrent subdural hemorrhages). Five (2.1%) patients died of non-vascular causes.

Conclusions: In Japanese patients with NVAF, early DOAC (re)initiation ≤14 days after ICH appears to have an acceptable risk for ischemic and hemorrhagic events, particularly in patients with intraparenchymal hemorrhage. In patients with subdural hematoma, early DOAC (re)initiation requires vigilant monitoring.

Background: The Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire is endorsed for symptom and quality-of-life assessment in atrial fibrillation (AF) but is typically measured once. Because patient-reported health status changes with treatment, serial AFEQT assessments may better reflect disease burden over time. We evaluated whether repeated AFEQT measurements are associated with subsequent outcomes and whether the most recent score is informative.

Methods and Results: We analyzed a multicenter, prospective registry of stable outpatients with AF referred to 11 hospitals in Japan (2012–2018). Associations of baseline (“prior”), 12-month (“current”), and change in AFEQT overall summary (os) scores with all-cause death and heart failure (HF) hospitalization were examined using multivariable Cox models. Among 2,743 patients (mean [±SD] age 67.8±11.1 years; 31.9% women), 146 (5.3%) experienced HF hospitalization and 134 (4.9%) died over a median follow-up of 4.0 years. Higher current AFEQT-os and change scores, but not prior AFEQT-os, were associated with a lower risk of death/HF hospitalization, with adjusted hazard ratios (95% confidence intervals) per 5-point increase of 0.94 (0.91–0.97) and 0.96 (0.92–0.99), respectively. When modeled together, only current AFEQT-os remained independently associated with outcomes. In time-varying analyses, time-updated AFEQT-os predicted both death/HF hospitalization and all-cause death.

Conclusions: The most recent AFEQT-os is associated with mortality and HF hospitalization, whereas baseline scores provide limited prognostic value. Updating patient-reported health status may help with risk assessment in AF.

Background: Patients with bradyarrhythmia requiring pacemaker implantation often report disrupted sleep, which could be related to bradyarrhythmia, apprehension of having heart disease and undiagnosed sleep disorders, resulting in impaired quality of life (QOL). We aimed to assess the prevalence of poor subjective sleep quality in patients with bradyarrhythmia requiring pacemaker implantation and its effect on sleep quality.

Methods and Results: Patients undergoing permanent pacemaker implantation for bradyarrhythmia were evaluated for subjective sleep quality and health-related QOL using the Pittsburgh Sleep Quality Index (PSQI) and Short Form-8 (SF-8) before and after pacemaker implantation. Poor subjective sleep quality was defined as PSQI score ≥6. Of 89 enrolled patients, 54 (60.7%) reported poor subjective sleep quality. A greater PSQI score indicative of poor sleep quality was likely to be observed in patients who had greater left ventricular ejection fraction and were treated with calcium-channel blockers, as well as in patients with more frequent sleep disturbance-related complaints/symptoms. After pacemaker implantation, the PSQI score improved significantly (from a median score of 6.0 to 5.0; P=0.015) proportional to an improvement in the mental component summary score.

Conclusions: Poor subjective sleep quality is common among patients with bradyarrhythmia, contributing to impaired QOL. Pacemaker implantation may have a favorable effect on subjective sleep quality, and QOL for such patients.

Background: Chest symptoms, such as angina and palpitation, are common complaints in patients with cardiovascular diseases, but few studies have addressed how cardiac afferent information is processed through the brain.

Methods and Results: We recruited 10 patients (mean age 74.7±1.9 years; 9 men) with cardiac pacemaker implantation. The patients underwent brain H₂¹⁵O positron emission tomography (PET) followed by blood sampling during right ventricular pacing of sham (1.5 V) and stimulation (7.5–8 V) conditions with a 10min interval. A voxel-wise analysis of the brain PET images identified the anterior cingulate cortex (ACC), posterior cingulate cortex, prefrontal cortex, thalamus, amygdala and midbrain as regions of increased regional cerebral blood flow (rCBF) under stimulation compared to sham conditions at a family-wise error-corrected cluster-extent threshold of P<0.05 with an underlying voxel level of P<0.001. The stimulation conditions increased rCBF in the ACC (59.8±4.4 vs. 49.2±3.5 mL/100 g/min, P<0.001) and plasma noradrenaline levels (332.3±139.0 vs. 312.0±139.8 pg/mL, P=0.004) compared to the sham stimulation. A linear mixed-effects model showed a significant positive correlation between the changes in rCBF in the ACC and those in plasma noradrenaline levels (P<0.001).

Conclusions: Cardiac electrical stimulation increased both rCBF in the ACC and plasma noradrenaline levels, and the changes were correlated. The ACC may be the brain center that transfers cardiac afferent information into autonomic arousal during cardiac pacing.

Background: His bundle (HB) pacing (HBP) can achieve an ideal pattern of ventricular activation. The long-term efficacy and clinical outcomes of HBP in Japan remain unclear.

Methods and Results: This multicenter prospective observational study enrolled 115 patients undergoing HBP implantation at 8 experienced centers in Japan. Inclusion criteria comprised atrioventricular block or conduction disturbance and an anticipated ventricular pacing of ≥40% in patients scheduled for HBP implantation. All patients were followed for 3 years after implantation. The primary endpoints were all-cause mortality, hospitalization for heart failure, and upgrade to cardiac resynchronization therapy. Secondary endpoints were changes in echocardiographic parameters and laboratory biomarkers after implantation. Seventy-eight (68%) patients continued HBP after the procedure (procedural success), whereas 68 (59%) patients exhibited clinical success (HB capture threshold ≤2.5 V at 1.0 ms). Six months after implantation, echocardiographic parameters improved, and brain B-type natriuretic peptide (BNP) levels decreased substantially. Major adverse clinical events (MACE), defined as the composite of the primary endpoints, occurred in 16 (21%) patients; 18 (23%) patients discontinued HBP during the follow-up period. Multivariable analysis identified elevated BNP levels at baseline as an independent predictor of MACE.

Conclusions: HBP implantation presents technical challenges and exhibits a moderate success rate in real-world clinical practice. The high incidence of elevated HB capture thresholds and HBP abandonment mean that careful patient selection and rigorous long-term surveillance are required.

Background: In patients with pulmonary arterial hypertension, death due to ventricular arrhythmias accounts for 8–26% of total deaths, so in this study we investigated whether mitochondrial Ca²⁺uptake affects ventricular arrhythmias in right ventricular hypertrophy (RVH).

Methods and Results: A total of 70 rats were subcutaneously injected with monocrotaline (MCT-rats) or solvent; 8 mice underwent pulmonary artery banding (PAB) surgery. At 4 weeks after MCU injection or PAB surgery, trabeculae were dissected from the RVs. Levels of mitochondrial Ca²⁺, cytoplasmic Ca²⁺, and reactive oxygen species (ROS) were measured using fluorescence dyes. Mitochondrial calcium uniporter (MCU) expression was measured by Western blotting. Ca²⁺waves and arrhythmias were induced by electrical stimulation (24℃). Both MCT-rats and PAB-mice showed RVH. Ru360, an MCU inhibitor, improved arrhythmias in trabeculae from severe RVH, whereas it worsened them in trabeculae from milder RVH in MCT-rats. Depending on the degree of RVH, Ru360 decreased rhod-2 fluorescence in both MCT-rats and PAB-mice, and decreased Ca²⁺wave velocity, the 2’,7’-dichlorofluorescein fluorescence slope, and MitoSox Red fluorescence in the MCT-rats. MCU expression increased with the degree of RVH.

Conclusions: Inhibition of mitochondrial Ca²⁺uptake improved arrhythmias in severe RVH, but worsened them in milder RVH, due to differences in mitochondrial Ca²⁺uptake, ROS production, and MCU expression.

Background: Continuous anticoagulation guided by the CHA₂DS₂-VASc score is standard for atrial fibrillation (AF) but does not reflect real-time AF occurrence. We evaluated an Apple Watch-guided event-triggered anticoagulation strategy that adjusts direct oral anticoagulant (DOAC) use according to smartwatch detection.

Methods and Results: This multicenter prospective single-arm study enrolled postablation patients in sinus rhythm who were taking DOACs and had a CHA₂DS₂-VASc score ≤3. Apple Watch monitoring continued for 360 days. If no AF occurred during Days 1–30, anticoagulation was stopped on Day 31; thereafter, Apple Watch notification or electrocardiogram (ECG) evidence of AF prompted DOAC resumption through Day 360. Of 54 enrolled patients enrolled in the study, 50 comprised the analysis population (mean age 63 years; 10% female; median CHA₂DS₂-VASc score 2). Across 15,865 person-days, Apple Watch guidance reduced DOAC exposure by 94.6% compared with continuous anticoagulation. Reductions were similar for patients with CHA₂DS₂-VASc scores of 2–3 and 0–1 (95.0% and 94.0%, respectively; P=0.818). No deaths, strokes, systemic thromboembolic events, or bleeding events were observed. One device malfunction prevented ECG acquisition.

Conclusions: In this cohort, Apple Watch-guided event-triggered anticoagulation markedly reduced DOAC exposure without thromboembolic events. Given the limited sample size and low baseline thromboembolic risk, these safety findings should be interpreted cautiously. Results were similar in the prespecified analysis restricted to patients with CHA₂DS₂-VASc scores of 2–3, the group for whom postablation anticoagulation decisions are most clinically relevant.

Background: Atrial fibrillation (AF) burden and longest duration are important predictors of heart failure and embolism. However, burden-specific detection rates on 7-day Holter ECG remain unclear.

Methods and Results: Among 25,817 recordings, 2,289 cases of paroxysmal AF and 571 cases of persistent AF were identified. Low-burden AF was common, and 7-day monitoring substantially improved detection, particularly for AF burden <10% (2.6-fold increase vs. 24-h). AF burden correlated with the longest duration (r=0.79).

Conclusions: 7-day Holter monitoring improved low-burden AF detection and confirmed a strong correlation between AF burden and longest duration.