Excessive cardiac sympathetic nerve activity significantly contributes to chronic heart failure (CHF) and lethal arrhythmias. However, reliable dynamic markers to assess sympathetic modulation are lacking in clinical practice. The T wave peak to T wave end interval (TpTe) to Q-T end interval ratio (TpTe/QTe) has been suggested as a surrogate marker for transmural dispersion of repolarization (TDR). We hypothesized that the TpTe/QTe reflects cardiac sympathetic nerve activity based on anatomical differences in the distribution and activation of cardiac sympathetic nerves. 12-lead Electrocardiograms (ECGs) were analyzed retrospectively in two cohorts without structural heart disease: (1) Exercise study; ECGs from patients who underwent treadmill or cardiopulmonary exercise testing between 2013 and 2023 were analyzed at baseline and 1-min post-maximal exercise. (2) β-stimulator infusion study; ECGs from patients who underwent catheter ablation (CA) of premature ventricular contractions (PVCs) or paroxysmal supraventricular tachycardias (PSVT) between 2017 and 2022 were analyzed at baseline and post-isoproterenol (ISO) infusion. In the exercise study, 45 patients (35.6

IntroductionImplantable cardioverter-defibrillators (ICDs) reduce the risk of sudden cardiac death caused by ventricular tachycardia or ventricular fibrillation in patients with ischemic and non-ischemic cardiomyopathy. However, the cost-effectiveness of ICD implantation in Japanese patients with heart failure and reduced left ventricular ejection fraction remains unclear. This study aimed to evaluate the cost-effectiveness of ICD implantation in a Japanese setting.MethodsA Markov model with 1-month cycles was developed to assess the cost-effectiveness of ICD implantation compared with conventional medical therapy. The analysis was conducted from the perspective of a public healthcare payer over a 30-year time horizon. Scenario analyses accounting for waning treatment effects were performed, as along with deterministic and probabilistic sensitivity analyses (PSA).ResultsIn the base-case analysis, the incremental cost-effectiveness ratio (ICER) was US $29,838 per quality-adjusted life year (QALY). In the scenario analyses, the ICER increased to US $40,205 and $36,199 per QALY when the treatment effect began to wane after 5 and 10 years, respectively. ICD efficacy and battery longevity had the greatest influence on the ICER. PSA showed that the ICER per QALY ranged from US $19,472 at the 2.5th percentile to US $83,365 at the 97.5th percentile.ConclusionsIn the Japanese healthcare context, ICD implantation for primary prevention was found to be more cost-effective than the reference value. However, depending on several assumptions, the ICER may exceed the reference value. Sensitivity analyses highlighted the significant impact of the hazard ratio and battery longevity on cost-effectiveness. Further research is needed to identify subpopulations with significantly different cost-effectiveness outcomes.

INTRODUCTION:Decrement-evoked potentials (DEEPs) are used to identify the functional substrate during ventricular tachycardia (VT) ablation, but distinguishing arrhythmogenic from bystander DEEPs remains challenging. METHODS AND RESULTS:During substrate-based VT ablation, DEEPs were analyzed using a predefined early evaluation window and dominant initial deflection during S1 pacing and S2 extrastimulus. DEEPs exhibiting polarity change between S1 and S2 were observed at the critical ablation site, whereas DEEPs without polarity change were found at non-critical sites. Ablation at the polarity-changing DEEP site was effective. CONCLUSION:DEEP polarity behavior may help differentiate critical VT substrate from bystander regions.

Background Although the implantable cardioverter defibrillators (ICD) are the only established treatment to prevent sudden cardiac death, previous studies reported that those who receive shock therapies, whether appropriate or inappropriate, have a higher risk of death. However, the difference in the influence of shock therapies between via Transvenous-ICD (TV-ICD) and Subcutaneous-ICD (S-ICD) has not been adequately examined. We aimed to investigate the influence of shocks on myocardium in patients with TV-ICD and S-ICD.Methods We enrolled consecutive patients who received a defibrillator or transvenous pacemaker (TV-PM) implantation between November 2020 and March 2024. A total of 74 patients were included in this study and divided into three groups: patients with TV-ICD with defibrillation testing (DFT) (TV-DFT, 27 patients), those with transvenous devices implanted without DFT (TV-no DFT, 25 patients) and those with S-ICD (22 patients).Results Delta log troponin-I (the difference of serum troponin-I levels between baseline and after implantation) was significantly increased in TV-DFT group. In patients with TV-ICD (46 patients), Delta log troponin-I was significantly correlated with total shock joules. In the multivariable linear regression analysis, a value of total shock joules was independently associated with delta troponin-I.Conclusion Elevation of serum troponin-I was associated with the TV-ICD shocks and correlated with the total shock energy, but not with S-ICD shocks. Our results suggest that TV-ICD shocks are associated with greater myocardial injury compared to S-ICD shocks, and that total shock energy is an important determinant of the extent of myocardial damage.

ABSTRACT Among recipients of implantable cardioverter‐defibrillators (ICDs) or cardiac resynchronization therapy with defibrillators (CRT‐Ds), non‐ischemic etiology is predominant, accounting for more than 60% of cases in Japan, which is higher than that in the United States and other European countries. Despite recent concerns about primary prevention ICD/CRT‐D implantation for non‐ischemic patients with systolic heart failure in advanced guideline‐directed medical therapy (GDMT), ICD/CRT‐D therapy is likely effective in reducing the slope of the relationship between all‐cause death and sudden cardiac death. Two cohort studies in Japan have shown that the cumulative incidence of appropriate ICD/CRT‐D therapy is higher among non‐ischemic patients than ischemic patients receiving primary prevention ICD/CRT‐D implantation. Additionally, recent published cohort studies in the United States, Europe, and Japan reported a significant decrease in the risk of all‐cause death in primary prevention ICD/CRT‐D recipients compared to those without ICD/CRT‐D therapy. Notably, ICD/CRT‐D utilization in Japan is the lowest among the Group of Seven (G7) countries. Governmental acknowledgment of the value of primary prevention ICD/CRT‐D therapy, as well as educational activities for non‐cardiac electrophysiologists, are required to prevent a potential labor shortage and an excess of healthcare costs following out‐of‐hospital cardiac arrest (OHCA).

Background:Cardiac resynchronization therapy with defibrillator (CRT-D) improves survival, reduces hospitalization, and enhances quality of life in patients with heart failure and reduced ejection fraction (HFrEF). As heart failure prevalence increases in aging societies such as Japan, the associated clinical and economic burden continues to rise. Previous cost-effectiveness analyses conducted in multiple countries indicate that CRT-D may be cost-effective in selected patients with HFrEF. However, its cost-effectiveness within the Japanese health care system remains uncertain. Objective:This study aimed to evaluate the cost-effectiveness of CRT-D in patients with HFrEF within the Japanese health care setting. Methods:A partitioned survival model was developed with 3 health states: after treatment (follow-up), hospitalization, and death. Survival for CRT-D was estimated by reconstructing individual patient-level data from the Kaplan-Meier curve of the RAFT (Resynchronization-Defibrillation for Ambulatory Heart Failure Trial) study using the method proposed by Guyot et al followed by fitting multiple parametric models; the gamma distribution was selected for the base case analysis. Survival for optimal medical therapy (OMT), the comparator, was estimated by applying a hazard ratio from a published meta-analysis. Hospitalization rates and device longevity were derived from prior studies. Cost estimates were obtained from the JROAD-DPC (Japanese Registry Of All cardiac and vascular Disease-Diagnostic Procedure Combination) database and the Japanese medical fee schedule. Utility values were assigned according to New York Heart Association class assuming treatment-specific distributions. The analysis was conducted from the public health care payer perspective using a monthly cycle over a 20-year time horizon. Deterministic and probabilistic sensitivity analyses were performed. Additionally, scenario analyses were conducted by varying the duration of treatment effect. Results:In the base case analysis, per capita costs were ¥12,258,410 (¥1=US $0.006 as of July 7, 2026) for CRT-D and ¥640,056.90 for OMT, resulting in an incremental cost of ¥11,618,353. CRT-D generated 7.07 quality-adjusted life years (QALYs) compared with 4.75 QALYs for OMT, yielding an incremental gain of 2.32 QALYs. The incremental cost-effectiveness ratio (ICER) was ¥5,009,880 per QALY. Scenario analyses showed that, when treatment effect waned after 7.5 years, the ICER increased to ¥5,423,235 per QALY. When the time horizon was shortened to 10 years or extended to 30 years, the ICERs were ¥8,523,072 and ¥4,386,803 per QALY, respectively. Deterministic sensitivity analysis identified CRT-D efficacy (hazard ratio), discount rate, and initial treatment cost as primary ICER drivers. Probabilistic sensitivity analysis produced a median ICER of ¥5,022,618 (IQR ¥4,448,306-¥5,760,425) per QALY, with a 95% credible interval of ¥3,804,418 to ¥7,178,795. At a willingness-to-pay value of ¥5,000,000 per QALY, CRT-D had a 49.2% probability of being cost-effective. Conclusions:CRT-D demonstrated acceptable cost-effectiveness in patients with HFrEF in Japan. Treatment efficacy and initial cost were the primary determinants of economic value, emphasizing the importance of appropriate patient selection and strategies to reduce device costs.

Background:Battery longevity in high-voltage devices (HVDs), specifically implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy-defibrillators (CRT-Ds), is critical for reducing the frequency of generator replacements, minimizing procedural risks, and enhancing patient outcomes. Despite technological advancements, significant variability in battery performance remains among the major manufacturers. This study aimed to evaluate the battery longevity among ICDs and CRT-Ds from the major manufacturers implanted at a single institution and identify the factors influencing battery depletion. Methods:We conducted a retrospective analysis of 353 patients implanted with HVDs (63 Abbott, 150 Boston Scientific, 140 Medtronic) at Hokkaido University Hospital between 2012 and 2021. Kaplan-Meier curves and Cox proportional hazards models were used to analyze the device longevity, with a primary endpoint of the time to battery depletion, defined by the elective replacement indicator. A multivariate analysis adjusted for the potential confounders. Results:Boston Scientific devices exhibited a significantly longer battery life than Abbott and Medtronic devices (p < 0.001), with a 6-year replacement-free survival of 99% for ICDs and 93% for CRT-Ds. A multivariate analysis identified the device manufacturer, device type (ICD vs. CRT-D), and ventricular pacing rate as independent predictors of battery depletion (p < 0.001). Conclusion:Battery longevity differed significantly by the manufacturer, which may influence device selection. Devices with a longer battery life may help reduce the replacement frequency and could potentially contribute to improved patient outcomes and cost-effectiveness.

BACKGROUND:Ventricular arrhythmias (VAs) in chronic ischemic heart failure (HF) are associated with high mortality and often refractory to beta-blocker treatment, highlighting the need for alternative therapeutic targets. OBJECTIVE:This study investigates the role of neuropeptide Y (NPY), a neurotransmitter released during sympathoexcitation, in the pathogenesis of VAs associated with ischemic chronic HF following myocardial infarction (MI). METHODS:Using a mouse model of ischemic chronic HF after coronary ligation, we employed biochemical, electrophysiological, and calcium ion (Ca2+) imaging analyses to investigate the proarrhythmic mechanisms of NPY. RESULTS:Immunohistochemical staining revealed a significantly elevated NPY expression in both the MI and border zone, consistent with findings in human autopsy samples. In cardiomyocytes isolated from ischemic HF mice, NPY treatment increased Ca2+ waves at a dose that did not elicit this response in normal heart cardiomyocytes, an effect suppressed by NPY Y1 receptor blocker. Additionally, the NPY treatment elevated the frequency of delayed afterdepolarizations at the membrane potential level. Similarly, NPY-induced VAs that were suppressed by the NPY Y1 receptor blocker in Langendorff-perfused chronic ischemic failed hearts at a concentration that had no effect in normal hearts. CONCLUSION:We identified structural and functional changes in NPY within an chronic ischemic HF model, leading to increased arrhythmogenicity through Ca2+ mishandling. Therefore, targeting NPY signaling may offer a novel therapeutic approach for treating VAs in patients with chronic ischemic HF.

Outflow tract premature ventricular contractions (OT-PVCs) with an R wave pattern break in Lead V2 (PBV2) pose significant treatment challenges due to their refractory nature and complex anatomical origins. A 56-year-old male with drug-resistant palpitations underwent detailed electroanatomical mapping using a microcatheter to identify the earliest activation site. This precision mapping was crucial for directing the ablation strategy accurately. The “enveloped ablation” technique was employed, involving multisite, low-power ablations surrounding the critical activation site, tailored to address the unique electrical and structural characteristics of OT-PVCs with a PBV2. This case highlights the importance of accurate mapping and tailored ablation strategies in managing OT-PVCs with PBV2.

Background:Evidence supporting the benefit from primary prevention implantable cardioverter-defibrillator (ICD)/cardiac resynchronization therapy with a defibrillator (CRT-D) for heart failure with reduced ejection fraction (HFrEF) is scarce in real-world settings. Methods:We analyzed propensity score matched cohorts of patients eligible for Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) from Japan cardiac device treatment registry (JCDTR) and Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD). The former served as the defibrillator therapy group and the latter as the conventional therapy group. Results:During an average follow-up of 24 months, death occurred in 35 of 285 patients (12%) with defibrillator therapy and 65 of 285 patients (23%) with conventional therapy. Adjusted hazard ratios of all-cause death, sudden death, heart failure death, and noncardiac death in defibrillator versus conventional therapy were 0.616 (95% confidence interval [CI]: 0.402-0.943, p = 0.026), 0.274 (95% CI: 0.103-0.731, p = 0.0097), 0.362 (95% CI: 0.172-0.764, p = 0.0077) and 1.45 (95% CI: 0.711-2.949, p = 0.31). After accounting for death without appropriate defibrillator therapy as a competing risk, the cumulative incidence of first appropriate defibrillator therapy in the defibrillator therapy group was nearly identical to that of all-cause death in the conventional therapy group. Subgroup analyses indicated a lack of defibrillator benefit in patients with hypertension (p = 0.01 for interaction). Conclusions:Primary prevention ICD/CRT-D reduced the risk of all-cause mortality of patients with HFrEF eligible for SCD-HeFT compared to conventional therapy in the real-world cohort.

Pseudoaneurysms at the coronary artery bypass graft (CABG) anastomosis site are rare. Here, we report a rare case of spontaneous resolution of a pseudoaneurysm at the anastomosis site developed soon after CABG. A 66-year-old man was referred to our hospital because of chest pain with paroxysmal atrial fibrillation. Pulmonary vein isolation (PVI), atrial appendage closure, and CABG were performed under cardiopulmonary bypass. Contrast computed tomography (CT) on postoperative day (POD) 5 revealed a pseudoaneurysm at the anastomosis of the left internal mammary artery (LIMA) to the circumflex artery. However, the pseudoaneurysm spontaneously resolved after three days. Given the possibility of rupture, surgical or interventional treatment would generally be the first choice. Exceptionally, observation for days to weeks may be one of the management strategies in patients with a small pseudoaneurysm, stable vital signs, no symptoms, discontinuable antithrombotic medications, a short time after CABG, or a pseudoaneurysm at the anastomosis site. The findings in this case may serve as a reference for the determination of treatment strategies for similar cases in the future.

Background Low‐voltage areas in the left atrium predict atrial fibrillation recurrence after catheter ablation and are associated with adverse outcomes like death, heart failure, and stroke. Detecting low‐voltage areas (LVAs) typically requires invasive procedures, highlighting the need for a simple, minimally invasive marker. Vasoactive intestinal peptide (VIP), a neuropeptide released during parasympathetic stimulation, affects electrophysiological remodeling in atrial fibrillation. We hypothesized that serum VIP could serve as a biomarker for detecting LVAs in these patients. Methods and Results This prospective, cross‐sectional study was conducted at Hokkaido University Hospital between August 2021 and September 2023. We included 108 patients with atrial fibrillation scheduled for catheter ablation. Blood samples were collected during ablation to measure VIP using an ELISA. Electroanatomical mapping identified LVAs, defined as regions with bipolar voltage ≤0.5 mV and occupying >5% of the left atrial surface. Statistical analyses evaluated the relationship between VIP and LVAs. Fifty‐one patients (47%) had LVAs, with significantly higher serum VIP levels than those without (335.1 versus 247.7 pg/mL, P<0.001). VIP levels and female sex were statistically significant factors of LVAs. Adding VIP to the existing score significantly improved its discrimination (area under the curve: 0.784 versus 0.707, P<0.001). Conclusions Serum VIP levels are higher in patients with atrial fibrillation with LVAs, suggesting its potential as a noninvasive biomarker for detecting these areas and improving clinical management.