Masahiko Takagi

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.

The Japanese Heart Rhythm Society established a nationwide, mandatory, multi‐center, prospective, observational registry of transvenous lead extraction (TLE) named the Japanese lead extraction registry (J‐LEX) in 2018. As of the end of 2024, a cumulative total of approximately 5400 cases has been registered across 140 participating centers since 2018. The registry includes all consecutive transvenous extractions, excluding surgical‐only cases. The indication of TLE was an infection in 54.5%, and the guideline classification was class I in 59.8% and class IIa in 21.8%. As for non‐infectious indications, TLE is performed for abandoned leads in case of lead failure or device upgrade, and for lead‐related trouble such as pain, vessel stenosis or occlusion, too many leads, tricuspid valve regurgitation, and difficulty with radiation therapy. In 2024, the TLE procedure was attempted on patients with a median age of 71.3 years, female in 32.7%, in the hybrid operating room in 73.3%, and in a standard OR with a C‐arm fluoroscope in 11.5%. The average implantation duration of the target leads was 8.5 years. Complete removal was achieved in 96.7% of the target leads, and clinical success in 97.3% of the patients. Perioperative complications were observed in 4.8% of the patients. Three patients died during a TLE operation, and 11 patients died in‐hospital (cardiac death in three patients and non‐cardiac death in eight patients).

Background: The therapeutic effects of oral anticoagulant drugs for nonvalvular atrial fibrillation (NVAF) suggest that the three factor Xa (FXa) inhibitors may have distinct safety profiles, though this is not yet fully conclusive. This study investigated the current dosing of rivaroxaban, apixaban, and edoxaban by monitoring drug plasma concentration (PC) and coagulation activity from the viewpoint of the safety. Methods and results: This multicenter clinical study monitored the drug PC and two coagulation biomarkers (fibrinogen and fibrin monomer complex [FMC]) at peak and trough timing in 268 outpatients taking rivaroxaban (n = 72), apixaban (n = 71), and edoxaban (n = 125) for NVAF. Doses were adjusted based on the dose-adjustment criteria of each drug. Referencing our previous study, peak drug PC remained below the cut-off level for predicting bleeding events except in eight patients (rivaroxaban, n = 3; apixaban, n = 2; edoxaban, n = 3) in whom bleeding events occurred. Among them, two (one each on rivaroxaban and edoxaban) had a peak drug PC below the cut-off level. Drug PCs widely varied from peak to trough, whereas FMC levels, reflecting thrombin activity, remained within the normal range (p < 0.05) than in edoxaban (32/101; 31.7%), and rivaroxaban tended to accumulate more than edoxaban. Conclusions: Although drug PC levels of once-daily FXa inhibitors widely varied from peak to trough, FMC levels were maintained within the normal range without daily variations. Rivaroxaban also tended to accumulate over time. The results indicate the low risk of thrombotic events with once-daily FXa inhibitors and its correspondence to the twice-daily regimen.

Background: The safety and effectiveness of factor-Xa (FXa) inhibitors for nonvalvular atrial fibrillation (NVAF) remains inconclusive. We investigated the current dosing of rivaroxaban, apixaban and edoxaban by monitoring drug plasma concentration (PC) and coagulation activity. Methods and Results: This multicenter clinical study monitored the drug PC levels and two coagulation biomarkers (fibrinogen: FIB, and fibrin monomer complex: FMC) at peak and trough timing in 268 outpatients receiving rivaroxaban (n = 72), apixaban (n = 71), and edoxaban (n = 125) for NVAF. Doses were adjusted according to the dose adjustment criteria of each drug. Based on our previous study, each peak drug PC remained below the cut-off level for predicting bleeding events except in eight patients (three on rivaroxaban, two on apixaban and three on edoxaban) in whom bleeding events occurred; among them, two (one each on rivaroxaban and edoxaban) had a peak drug PC below the cut-off level. Drug PCs widely varied from peak to trough, whereas FMC levels remained within the normal range (< 6.1 µg/ml) regardless of PC variation. These finding suggested that the anticoagulant effects of these drugs persisted throughout the day regardless of the drug PC levels, dosage, and frequency of dosing. Regarding the change in peak drug PC levels over time, rivaroxaban tended to accumulate more than edoxaban (p

Background: Although catheter ablation (CA) has become a standard therapeutic approach to atrial fibrillation (AF), it imposes a low but relevant risk of thromboembolic complications of around 0.5%–1%, including ischemic strokes, and has an additional risk of clinically silent cerebral embolisms (SCEs) of 10%–40%. Both cryoballoon (CB) and radiofrequency (RF) ablation are routinely used clinically worldwide, yet there are few prospective data comparing the incidence of cerebral embolism after CA of AF between CB and RF ablation.Methods: The aim of the Embo‐Abl study will be to compare the incidence of cerebral embolisms on 3 T diffusion‐weighted image magnetic resonance imaging (MRI) after CA of AF between CB and RF ablation in patients with AF in a prospective, multicenter, open‐label, controlled, randomized fashion. The primary endpoint of the Embo‐Abl study will be the occurrence of MRI‐detected SCE 1–3 days after CA. The patients will be registered and randomly assigned to either the CB or RF ablation group in a 1:1 ratio. The study cohort will include 230 patients with AF from a multicenter in Japan.Results: The results of this study are currently under investigation.Conclusion: The Embo‐Abl study will be the first to compare the incidence of periprocedural cerebral embolisms caused by CA of AF between CB and RF ablation in a prospective, multicenter, randomized, controlled fashion.

Background: Brugada syndrome (BrS) is associated with mutations in the cardiac sodium channel gene, SCN5A. However, genetic studies of patients with BrS with arrhythmic events have been limited. We sought to compare various clinical, ECG, and electrophysiological parameters according to SCN5A genotype in a large cohort of BrS probands with first arrhythmic event. Methods: Survey on Arrhythmic Events in Brugada Syndrome is a survey of 10 Western and 4 Asian countries, gathering 678 patients with BrS with first arrhythmic event. Only probands were included, and SCN5A genotype adjudicated. Patients without appropriate genetic data were excluded. Associations of genotype with clinical features were analyzed. Results: The study group comprised 392 probands: 92 (23.5%) SCN5A+ (44 pathogenic/likely pathogenic [P/LP] and 48 variants of unknown significance) and 300 (76.5%) SCN5A−. SCN5A missense variants and the patients hosting them were similar regardless of adjudication. A higher proportion of patients with P/LP were pediatric (SCN5A− (11.4% versus 3%, P =0.023). The proportion of females was higher among patients with P/LP compared with SCN5A − (18.2% versus 6.3%, P =0.013). P/LP probands were more likely to have a family history of sudden cardiac death compared with SCN5A − (41.9% versus 16.8%, P SCN5A− (87.5% versus 47%, P P P =0.009) were independent variables associated with P/LP genotype following logistic regression. Conclusions: The genetic basis of BrS has a complex relationship with gender, ethnicity, and age. Probands hosting a P/LP variant tended to experience their first arrhythmic event at a younger age and to have events triggered by fever compared with patients with SCN5A− . In addition, they were more likely to be White and to have family history of sudden cardiac death. Among females, a P/LP variant suggests an increased risk of being symptomatic. This association should be further studied on an ethnically specific basis in large prospectively collected international cohorts.

Although implantable cardioverter defibrillators (ICDs) are a powerful preventive therapy for cardiac sudden death, there are some populations in whom ICDs cannot be applied because of a lack of a definitive indication (grey‐zone patients), such as in patients during the acute phase of cardiac injury with a susceptible risk for lethal arrhythmias. In such patients, wearable cardioverter defibrillators (WCDs) provide safer bridging period during the acute phase until the final decision‐making for the ICD use and it may eliminate any inappropriate overuse of ICDs in the subacute phase. The JCS/JHRS practical guidelines provide the criteria for WCD use in Japan. Nevertheless, the evidence for that is totally limited in Japan and is dependent on the accumulation of actual real‐world data from other countries in order to be able to discuss the appropriate criteria for WCD use. This study will be conducted retrospectively and/or prospectively, and is an observational and multicenter study among Japanese institutions (J‐WCDR, Japan WCD Registry). This will provide evidence for WCD use in our own country and contribute to upcoming updates for the future guideline revisions.