Multicenter prospective observational study to clarify the current status and clinical outcome in Japanese patients who have an indication for implantable cardioverter defibrillator (ICD) or wearable cardioverter defibrillator (WCD) (TRANSITION JAPAN-ICD/WCD study): Rationale and design of a prospective, multicenter, observational, comparative study.

Background: Despite the positive impact of implantable cardioverter defibrillators (ICDs) and wearable cardioverter defibrillators (WCDs) on prognosis, their implantation is often withheld especially in Japanese heart failure patients with reduced left ventricular ejection fraction (HFrEF) who have not experienced ventricular tachycardia (VT) or ventricular fibrillation (VF) for uncertain reasons. Recent advancements in heart failure (HF) medications have significantly improved the prognosis for HFrEF. Given this context, a critical reassessment of the treatment and prognosis of ICDs and WCDs is essential, as it has the potential to reshape awareness and treatment strategies for these patients. Methods: We are initiating a prospective multicenter observational study for HFrEF patients eligible for ICD in primary and secondary prevention, and WCD, regardless of device use, including all consenting patients. Study subjects are to be enrolled from 31 participant hospitals located throughout Japan from April 1, 2023, to December 31, 2024, and each will be followed up for 1 year or more. The planned sample size is 651 cases. The primary endpoint is the rate of cardiac implantable electronic device implementation. Other endpoints include the incidence of VT/VF and sudden death, all-cause mortality, and HF hospitalization, other events. We will collect clinical background information plus each patient's symptoms, Clinical Frailty Scale score, laboratory test results, echocardiographic and electrocardiographic parameters, and serial changes will also be secondary endpoints. Results: Not applicable. Conclusion: This study offers invaluable insights into understanding the role of ICD/WCD in Japanese HF patients in the new era of HF medication.

Comparing cryoballoon and contact-force guided radiofrequency ablation in pulmonary vein isolation for atrial fibrillation in patients with hypertrophic cardiomyopathy.

BACKGROUND: Pulmonary vein isolation (PVI) employing cryoballoon (CB) or contact force-guided radiofrequency (CF-RF) catheter ablation has been established as an effective strategy for managing atrial fibrillation (AF). However, its efficacy in hypertrophic cardiomyopathy (HCM) remains to be further explored. METHODS: This retrospective study analyzed 60 consecutive AF patients with HCM (average age 67 ± 10 years; 41 men) who were consecutively admitted to our hospital from January 2014 to December 2022 and underwent initial PVI. RESULTS: The patients were treated with CB (26 patients) or CF-RF (34 patients). Successful PVI was achieved in both groups without significant complications. In the CF-RF group, additional ablations were performed on the cavotricuspid isthmus (14.7% of patients) and the anterior line (2.9%). The CB group benefited from reduced procedural times (93 ± 31 vs. 165 ± 60 min, p < 0.05) and decreased saline irrigation requirements (77.5 ± 31.4 vs. 870 ± 281.9 mL, p < 0.0001). Using a contrast medium was exclusive to the CB group (33.8 ± 4.2 mL). In a 12-month follow-up, the atrial tachyarrhythmia recurrence-free rates in the CB and CF-RF groups were comparable (77% and 76%, respectively; p = 0.63 according to the log-rank test). Notably, pulmonary vein reconnection was prevalent in most (7 out of 8) patients requiring a secondary ablation procedure. CONCLUSION: PVI is feasible as a strategy for AF in patients with HCM employing either CB or CF-RF techniques. While the recurrence-free rates were comparable in both groups, differences were noted in procedure duration, saline usage, and the need for a contrast medium.

Complete remission of giant cell myocarditis by prednisolone monotherapy: A case with mild inflammation demonstrated by mismatch between T2-high intensity areas and late gadolinium enhancement.

Giant cell myocarditis (GCM) is a potentially lethal subtype of myocarditis. Herein, we report a case of a 22-year-old woman with GCM who was successfully treated with prednisolone monotherapy. The patient had a fever and shortness of breath and was referred to our hospital. Laboratory test results revealed elevated troponin I levels. Cardiac magnetic resonance (CMR) showed high intensity in the inferoseptal segment of the left ventricle on T2-weighted short tau inversion recovery imaging without late gadolinium enhancement (LGE), suggesting predominant edema rather than necrosis. The patient was diagnosed with GCM based on an endomyocardial biopsy, which revealed lymphocyte infiltration and multinucleated giant cells in the absence of granuloma formation. Subsequently, the patient received intravenous methylprednisolone at 1000 mg/day for 3 days followed by oral prednisolone at 30 mg/day, which normalized troponin levels. Follow-up CMR revealed improved cardiac inflammation; therefore, the patient was discharged without prescribing another immunosuppressive agent. Prednisolone was tapered and terminated three years after discharge. The patient went one year without medication and had no recurrence of GCM on follow-up. This case highlights the presence of mild GCM, successfully treated by steroid monotherapy, in which the mismatch between high-intensity T2 areas and LGE suggests mild inflammation. Learning objective: Giant cell myocarditis (GCM) is potentially lethal and usually requires multiple immunosuppressive agents. Here, we report a patient with GCM with preserved left ventricular ejection fraction. Cardiac magnetic resonance revealed focal high T2 signal intensity areas without late gadolinium enhancement, indicating myocardial edema without necrosis. The patient remained in remission with prednisolone monotherapy for 2 years. Our report indicates that "mild" GCM may be treated with prednisolone monotherapy.

Dual tachyarrhythmia: Ventricular fibrillation induced by atrial tachyarrhythmia in a patient with hypertrophic cardiomyopathy.

A patient with hypertrophic cardiomyopathy experienced cardiopulmonary arrest. An automated external defibrillator administered defibrillation for ventricular fibrillation (A). The pacemaker recorded atrial tachycardia with a rapid ventricular response before the patient collapsed (B). After a few minutes, the pacemaker records dual tachyarrhythmia, characterized by the simultaneous presence of ventricular fibrillation (VF) and atrial fibrillation (AF) (C). This case demonstrates that VF induced by atrial tachyarrhythmia could contribute to AF-related sudden cardiac death.

Landiolol, an intravenous ß1-selective blocker, is useful for dissociating a fusion of atrial activation via accessory pathway and atrioventricular node.

Introduction: During ventricular pacing, a fusion of atrial activation may occur owing to the simultaneous retrograde conduction of the atrioventricular (AV) node and accessory pathway (AP), potentially leading to an inaccurate mapping of the atrial AP insertion site. Objective: We tested the hypothesis that landiolol, an ultra-short-acting intravenous ß1-blocker, could dissociate a fusion of atrial activation. Methods: We conducted a prospective before-and-after study to investigate the effect of landiolol on retrograde conduction via the AV node and AP. We enrolled 21 consecutive patients with orthodromic AV reciprocating tachycardia who underwent electrophysiological studies at our hospital between January 1, 2018, and August 31, 2020. Results: Six patients exhibited a fusion of atrial activation. After landiolol administration (10 µg/kg/min), the effective refractory period was unchanged in AP (280 [240-290] ms vs. 280 [245-295] ms, p = .91), whereas that of the AV node was prolonged (275 [215-380] ms vs. 332 [278-445] ms, p = .03). The Wenckebach pacing rate via retrograde AV node decreased after landiolol administration (180 [140-200] beats per minute [bpm] vs. 140 [120-180] bpm, p = .02). Thus, landiolol decreased the minimum ventricular pacing rate required to dissociate a fusion of atrial activation (180 [160-200] bpm vs. 140 [128-155] bpm, p = .007). Radiofrequency catheter ablation under landiolol administration successfully eliminated AP in all patients during ventricular pacing without complications or recurrence. Conclusion: Landiolol inhibited the AV node without affecting the AP and helped dissociate a fusion of atrial activation at a lower ventricular pacing rate.

Two-Year Outcomes of Primary Prophylactic Use of Defibrillators for Ischemic and Non-Ischemic Cardiomyopathy　- Propensity Score-Matched Analysis From the Nippon Storm Study.

BACKGROUND: In 2016, the DANISH study reported negative results regarding the efficacy of implantable cardioverter-defibrillators (ICDs) in patients with non-ischemic cardiomyopathy (NICM) and reduced left ventricular ejection fraction (LVEF). In this study we determined the efficacy of using ICDs for primary prophylaxis in patients with NICM.Methods and Results: We selected 1,274 patients with underlying cardiac disease who were enrolled in the Nippon Storm Study. We analyzed the data of 451 patients with LVEF ≤35% due to NICM or ischemic cardiomyopathy (ICM) who underwent ICD implantation for primary prophylaxis (men, 78%; age, 65±12 years; LVEF, 25±6.4%; cardiac resynchronization therapy, 73%; ICM, 33%). After propensity score matching, we compared the baseline covariates between groups: NICM (132 patients) and ICM (132 patients). The 2-year appropriate ICD therapy risks were 27.7% and 12.2% in the NICM and ICM groups, respectively (hazard ratio, 0.390 [95% confidence interval, 0.218-0.701]; P=0.002). CONCLUSIONS: This subanalysis of propensity score-matched patients from the Nippon Storm Study revealed that the risk of appropriate ICD therapy was significantly higher in patients with NICM than in those with ICM.

Safety and Performance of the Micra VR Leadless Pacemaker in a Japanese Cohort　- Comparison With Global Studies.

BACKGROUND: The Micra leadless pacemaker has demonstrated favorable outcomes in global trials, but its real-world performance and safety in a Japan-specific population is unknown.Methods and Results: Micra Acute Performance (MAP) Japan enrolled 300 patients undergoing Micra VR leadless pacemaker implantation in 15 centers. The primary endpoint was the acute (30-day) major complication rate. The 30-day and 6-month major complication rates were compared to global Micra studies. All patients underwent successful implantation with an average follow-up of 7.23±2.83 months. Compared with previous Micra studies, Japanese patients were older, smaller, more frequently female, and had a higher pericardial effusion risk score. 11 acute major complications were reported in 10 patients for an acute complication rate of 3.33% (95% confidence interval: 1.61-6.04%), which was in line with global Micra trials. Pericardial effusion occurred in 4 patients (1.33%; 3 major, 1 minor). No procedure or device-related deaths occurred. Frailty significantly improved from baseline to follow-up as assessed by Japan Cardiovascular Health Study criteria. CONCLUSIONS: In a Japanese cohort, implantation of the Micra leadless pacemaker had a high success rate and low major complication rate. Despite the Japan cohort being older, smaller, and at higher risk, the safety and performance was in line with global Micra trials.

Total synthesis of (-)-domoic acid, a potent ionotropic glutamate receptor agonist and the key compound in oceanic harmful algal blooms.

The stereo-controlled total synthesis of (-)-domoic acid is described. The critical construction of the C1'-C2' Z-configuration was accomplished by taking advantage of an unsaturated lactam structure. The side chain fragment was introduced in the final stages of synthesis through a modified Julia-Kocienski reaction, aiming for its efficient derivatization.

The usefulness of balloon occlusive left ventricular lead delivery in combination with the quadripolar active fixation lead for a patient with complex coronary venous morphology.

Complex coronary vein morphology impedes the insertion of the left ventricular (LV) lead and reduces the effectiveness of cardiac resynchronization therapy (CRT). A 77-year-old woman underwent dual-chamber pacemaker implantation via the left subclavian approach for a complete atrioventricular block 17 years previously. She was hospitalized due to decompensated heart failure, and her cardiac rhythm completely depended on ventricular pacing at that time. Transthoracic echocardiography showed thinning of the ventricular septum in the basal region and pacing-induced dyssynchrony. She was clinically diagnosed with cardiac sarcoidosis with severe LV systolic dysfunction. She was referred for an upgrade to CRT. Given that prior contrast venography showed occlusion of the left subclavian vein, an additional LV lead was inserted through the right subclavian vein. Coronary venography showed a lateral vein that branched from the great cardiac vein with an acute angle and had multiple tortuosities in the peripheral branches. Since the LV lead placement was unsuccessful with the conventional method, we attempted the lead placement using the balloon occlusion technique (BOT). Lead delivery into the anatomical optimal lateral vein was successful by using BOT, and LV pacing from the most delayed basal region was achieved in combination with the active fixation LV lead. .

Effectiveness of Implantable Cardioverter Defibrillator in Patients With Non-Ischemic Heart Failure With Systolic Dysfunction　- Subanalysis of the Nippon Storm Study.

BACKGROUND: The prospective observational Nippon Storm Study aggregated clinical data from Japanese patients receiving implantable cardioverter-defibrillator (ICD) therapy. This study investigated the usefulness of prophylactic ICD therapy in patients with non-ischemic heart failure (NIHF) enrolled in the study.Methods and Results: We analyzed 540 NIHF patients with systolic dysfunction (left ventricular ejection fraction <50%). Propensity score matching was used to select patient subgroups for comparison; 126 patients were analyzed in each of the primary (PP) and secondary (SP) prophylaxis groups. The incidence of appropriate ICD therapy during follow-up in the PP and SP groups was 21.4% and 31.7%, respectively (P=0.044). The incidence of electrical storm (ES) was higher in SP than PP patients (P=0.024). Cox proportional hazard analysis revealed that increased serum creatinine in SP patients (hazard ratio [HR] 1.18; 95% confidence interval [CI] 1.02-1.33; P=0.013) and anemia in PP patients (HR 0.92; 95% CI 0.86-0.98; P=0.008) increased the likelihood of appropriate ICD therapy, whereas long-lasting atrial fibrillation in PP patients (HR, 0.64 [95% CI, 0.45-0.91], P=0.013) decreased that likelihood. CONCLUSIONS: In propensity score-matched Japanese NIHF patients, the incidence of appropriate ICD therapy and ES was significantly higher in SP than PP patients. Impaired renal function in SP patients and anemia in PP patients increased the likelihood of appropriate ICD therapy, whereas long-lasting atrial fibrillation reduced that likelihood in PP patients.

Characterization of the PRAETORIAN score in Japanese patients undergoing subcutaneous implantable cardioverter-defibrillator implantation.

BACKGROUND: The PRAETORIAN score was developed to evaluate the implant position and predict defibrillation success in patients implanted with a subcutaneous implantable cardioverter-defibrillator (S-ICD). However, usefulness of the PRAETORIAN score for Japanese patients is unknown. METHODS: We evaluated usefulness of this score, which was determined by width of sub-coil fat, sub-generator fat, and anterior positioning of the S-ICD generator by post-operative chest X-ray, in consecutive 100 Japanese S-ICD implanted patients [78 men, median age 59 (IQR 46.5-67.0) years, median body mass index (BMI) 24.2 (21.3-27.2) kg/m2]. RESULTS: The median PRAETORIAN score was 30 (30-45) and 93 patients were classified as a low risk of conversion failure. The remaining seven were at an intermediate risk. Almost all patients were classified as an optimal pulse-generator position in the second and third steps of the PRAETORIAN score. The only difference observed was in the width of sub-coil fat in the first step. To further evaluate its significance, patients were divided into the Thicker group (sub-coil fat >1 coil width, n = 19) and the Thinner group (sub-coil fat ≤1 coil width, n = 81). BMI and post-shock impedance were both higher in the Thicker group than in the Thinner group [27.1 (25.6-31.6) versus 23.1 (20.9-25.7) kg/m2, p < 0.001, and 75 (68-88) versus 63 (55-74) Ω, p = 0.003, respectively]. During the median follow-up periods of 888 (523-1418) days, 7 patients experienced appropriate shock therapy for spontaneous ventricular tachyarrhythmias, who were all at a low risk. No conversion failure was observed. Inappropriate shock (IAS) occurred in 11 patients, and there was no difference in IAS rate between the Thicker group (n = 2) and the Thinner group (n = 9) (p = 0.747 by log-rank test). CONCLUSIONS: Most Japanese patients were classified as at low risk of conversion failure. The PRAETORIAN score may be useful for the evaluation of conversion failure in Japanese S-ICD implanted patients.

Reduced Left Ventricular Ejection Fraction Is a Risk for Sudden Cardiac Death in the Early Period After Hospital Discharge in Patients With Acute Myocardial Infarction.

BACKGROUND: The incidence of sudden cardiac death (SCD) after discharge in Japanese acute myocardial infarction (AMI) patients with reduced left ventricular ejection fraction (LVEF) treated with primary percutaneous coronary intervention (PCI) remains unknown.Methods and Results:The study population included 1,429 AMI patients (199 with LVEF ≤35% and 1,230 with LVEF >35%) admitted to the Hirosaki University Hospital, treated with primary PCI within 12 h after onset, and survived to discharge. LVEF was evaluated in all patients before discharge, and the patients were followed up for a mean of 2.6±0.8 years. The Kaplan-Meier survival curves revealed LVEF ≤35% was associated with all-cause death and SCD. The incidence of SCD was 2.6% at 1 year and 3.1% at 3 years in patients with LVEF ≤35%, whereas it was 0.1% at 1 year and 0.3% at 3 years in patients with LVEF >35%. Sixty-seven percent of SCDs in patients with LVEF ≤35% occurred within 4 months after discharge, and the events became less frequent after this period. A Cox proportional hazard model indicated LVEF ≤35% as an independent predictor for all-cause death and SCD. CONCLUSIONS: The incidence of SCD was relatively low in Japanese AMI patients treated with primary PCI, even in patients with LVEF ≤35% upon discharge. Careful management of patients with reduced LVEF is required to prevent SCD, especially in the early phase after discharge.

Intracardiac conduction time as a predictor of cardiac resynchronization therapy response: Results of the BIO|SELECT pilot study.

BACKGROUND: Quadripolar left ventricular (LV) leads are capable of sensing and pacing the left ventricle from 4 different electrodes, which may potentially improve patient response to cardiac resynchronization therapy (CRT). OBJECTIVE: We measured 3 different time intervals: right ventricular (RV)-sensed to LV-sensed during intrinsic rhythm (RVs-LVs), RV-paced to LV-sensed (RVp-LVs), and LV-paced to LV-sensed (LVp-LVs, between distal [LV1] and proximal pole on a quadripolar LV lead), and assessed their association with CRT response in terms of LV end-systolic volume (LVESV) and a composite benefit index (CBI) comprising LVESV, LV ejection fraction (LVEF), brain natriuretic peptide level, and NYHA class. METHODS: A CRT-defibrillator system with quadripolar LV lead was implanted in 196 patients (mean age 69 years, mean LVEF 30%, left bundle-branch block [LBBB] 58%). Conduction intervals were measured before hospital discharge. At baseline and 7-month follow-up, echocardiographic and other components of CBI were determined. RESULTS: The mean RVs-LV1s, RVp-LV1s, and LVp-LVs delays were 68 ± 38 ms, 132 ± 34 ms, and 99 ± 31 ms, respectively. From baseline to 7 months, LVESV decreased by 17.3% ± 28.6%. The RVs-LV1s interval correlated stronger with CBI (R2 = 0.12, P < .00001) than with LVESV change (R2 = 0.05, P = .006). In contrast, RVp-LV1s did not correlate and LVp-LVs correlated only weakly with CRT response. The subgroup of patients (44%) with LBBB and RVs-LV1s above the lower quartile (≥34 ms) showed the greatest response to CRT. CONCLUSION: The RVs-LVs interval during intrinsic rhythm is relevant for CRT success, whereas RVp-LVs and LVp-LVs intervals did not predict CRT response.

Cardiac Conduction Disorders as Markers of Cardiac Events in Myotonic Dystrophy Type 1.

Background Myotonic dystrophy type 1 involves cardiac conduction disorders. Cardiac conduction disease can cause fatal arrhythmias or sudden death in patients with myotonic dystrophy type 1. Methods and Results This study enrolled 506 patients with myotonic dystrophy type 1 (aged ≥15 years; >50 cytosine-thymine-guanine repeats) and was treated in 9 Japanese hospitals for neuromuscular diseases from January 2006 to August 2016. We investigated genetic and clinical backgrounds including health care, activities of daily living, dietary intake, cardiac involvement, and respiratory involvement during follow-up. The cause of death or the occurrence of composite cardiac events (ie, ventricular arrhythmias, advanced atrioventricular blocks, and device implantations) were evaluated as significant outcomes. During a median follow-up period of 87 months (Q1-Q3, 37-138 months), 71 patients expired. In the univariate analysis, pacemaker implantations (hazard ratio [HR], 4.35; 95% CI, 1.22-15.50) were associated with sudden death. In contrast, PQ interval ≥240 ms, QRS duration ≥120 ms, nutrition, or respiratory failure were not associated with the incidence of sudden death. The multivariable analysis revealed that a PQ interval ≥240 ms (HR, 2.79; 95% CI, 1.9-7.19, P<0.05) or QRS duration ≥120 ms (HR, 9.41; 95% CI, 2.62-33.77, P < 0.01) were independent factors associated with a higher occurrence of cardiac events than those observed with a PQ interval <240 ms or QRS duration <120 ms; these cardiac conduction parameters were not related to sudden death. Conclusions Cardiac conduction disorders are independent markers associated with cardiac events. Further investigation on the prediction of occurrence of sudden death is warranted.