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Class IC antiarrhythmic agents may induce acquired forms of Brugada Syndrome. We have identified a novel mutation in SCN5A, the gene that encodes the α-subunit of the human cardiac sodium channel (hNav1.5), in a patient who exhibited Brugada- type ECG changes during pharmacotherapy of atrial arrhythmias. To assess whether the novel mutation p.V1328M can cause drug induced Brugada Syndrome. Administration of pilsicainide, a class IC antiarrhythmic agent, caused Brugada- type ST elevation in a 66-year-old Japanese male who presented with paroxysmal atrial fibrillation (PAF), type I atrial flutter and inducible ventricular fibrillation (VF) during electrophysiological study. Genetic screening using direct sequencing identified a novel SCN5A variant, p.V1328M. Electrophysiological parameters of WT and p.V1328M and their effects on drug pharmacokinetics were studied using the patch-clamp method. Whole-cell sodium current densities were similar for WT and p.V1328M channels. While p.V1328M mutation did not affect the voltage-dependence of the activation kinetics, it caused a positive shift of voltage-dependent steady-state inactivation by 7 mV. The tonic block in the presence of pilsicainide was similar in WT and p.V1328M, when sodium currents were induced by a low frequency pulse protocol (q15s). On the contrary, p.V1328M mutation enhanced pilsicainide induced use-dependent block at 2 Hz. (Ki: WT, 35.8 μM; V1328M, 19.3 μM). Our study suggests that a subclinical SCN5A mutation, p.V1328M, might predispose individuals harboring it to drug-induced Brugada Syndrome.

Strategies that accurately predict outcomes in elderly heart failure (HF) patients have not been sufficiently established. In previous reports, nutritional status, ability to perform activities of daily living (ADL), and lower limb muscle strength are known prognostic factors associated with cardiac rehabilitation (CR). In the present study, we investigated which CR factors can accurately predict one-year outcomes in elderly patients with HF among the above factors. Hospitalized patients with HF over 65 years of age from January 2016 to January 2022 were retrospectively enrolled in the Yamaguchi Prefectural Grand Medical (YPGM) Center. They were consequently recruited to this single-center retrospective cohort study. Nutritional status, ADL, and lower limb muscle strength were assessed by geriatric nutritional risk index (GNRI), Barthel index (BI), and short physical performance battery (SPPB) at discharge, respectively. One year after discharge, the primary and secondary outcomes were evaluated by all-cause death or HF readmission and major adverse cardiac and cerebrovascular events (MACCE), respectively. Overall, 1,078 HF patients were admitted to YPGM Center. Of those, 839 (median age 84.0, 52% female) met the study criteria. During the follow-up of 228.0 days, 72 patients reached all-cause death (8%), 215 experienced HF readmission (23%), and 267 reached MACCE (30%: 25 HF death, six cardiac death, and 13 strokes). A multivariate Cox proportional hazard regression analysis revealed that the GNRI predicted the primary outcome (Hazard ratio [HR]: 0.957; 95% confidence interval [CI]: 0.934-0.980;  < 0.001) and the secondary outcome (HR: 0.963; 95%CI: 0.940-0.986;  = 0.002). Furthermore, a multiple logistic regression model using the GNRI most accurately predicted the primary and secondary outcomes compared to those with the SPPB or BI models. A nutrition status model using GNRI provided a better predictive value than ADL ability or lower limb muscle strength. It should be recognized that HF patients with a low GNRI at discharge may have a poor prognosis at one year.

Background Whether nonsustained ventricular tachycardia (NSVT) is a marker of increased risk of sustained ventricular tachyarrhythmias (VTAs) remains to be established in patients receiving cardiac resynchronization therapy with a defibrillator (CRT‐D) for primary prevention. Methods Among the follow‐up data of the Japan cardiac device treatment registry (JCDTR) with an implantation date between January 2011 and August 2015, information regarding a history of NSVT before the CRT‐D implantation for primary prevention had been registered in 269 patients. Outcomes were compared between two groups with and without NSVT: NSVT group (n = 179) and No NSVT group (n = 90). Results There was no significant difference with regard to age, gender, and NYHA class between the two groups. Left ventricular ejection fraction (LVEF) was 25.6% in the NSVT group and 28.0% in the No NSVT group (P = .046). The rate of appropriate therapy at 24 months was 26.0% and 18.4% in the NSVT and No NSVT groups (P = .22), respectively. Survival free from heart failure death was reduced in the NSVT group, as compared with the No NSVT group, with the rate of 90.2% vs 97.2% at 24 months (P = .030). A multivariate analysis identified a history of NSVT, anemia, and no use of angiotensin‐converting enzyme inhibitor (ACEI) or angiotensin‐receptor blocker (ARB) as predictors of heart failure death. Conclusions NSVT appears to be a surrogate marker of severe heart failure rather than a substrate for subsequent sustained VTAs in patients with CRT‐D for primary prevention.

Aims Data regarding prognostic events following catheter ablation (CA) for atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) are scarce. We conducted this study to compare the incidence of major adverse clinical events (MACE) following CA for AF between patients with HFpEF and those with systolic heart failure (HF). Methods and results This single‐centre observational study included 142 patients with HF who underwent CA for AF (median follow‐up: 4.0 [2.6, 6.3] years). The patients were grouped based on the presence of HFpEF (n = 84) and systolic HF (left ventricular ejection fraction <50%, n = 58). We compared the cumulative incidence and incidence rate of MACE, comprising all‐cause death, unplanned cardiovascular hospitalization (CVH), and HF hospitalization (HFH) between both groups and the number of HFH before and after CA in each group. Multivariate analysis was performed to identify the predictors of MACE in patients with HFpEF. The incidence of MACE was comparable between the groups (following the first procedure: HFpEF: 23%, 4.7/100 person‐years, vs. systolic HF: 28%, 6.6/100 person‐years, P = 0.18; last procedure: 20%, 4.8/100 person‐years, vs. 24%, 6.9/100 person‐years, P = 0.21). Although the incidence of HFH was lower in patients with HFpEF than in those with systolic HF (first procedure: 14%, 2.9/100 person‐years, vs. 24%, 5.7/100 person‐years, P = 0.07; last procedure: 11%, 2.5/100 person‐years, vs. 24%, 6.9/100 person‐years, P = 0.01), the incidence of CVH was higher (first procedure: 8%, 1.7/100 person‐years, vs. 5%, 1.2/100 person‐years, P = 0.74; last procedure: 6%, 1.4/100 person‐years, vs. 2%, 0.5/100 person‐years, P = 0.4). The number of HFH significantly decreased in both groups after CA (HFpEF: 1 hospitalization [the first and third quartiles: 0, 1] in pre‐CA, vs. 0 hospitalizations [0, 0] in post‐CA, P < 0.0001; systolic HF: 1 hospitalization [0, 1], vs. 0 hospitalizations [0, 0], P < 0.005). The proportion of HFH among total clinical events was significantly smaller in patients with HFpEF than in those with systolic HF (following the first procedure: 56% vs. 88%, P < 0.005; last procedure: 52% vs. 92%, P < 0.005). Conclusions CA for AF could be beneficial for patients with HFpEF, similar to those with systolic HF. However, clinical events other than HFH should be considered cautiously in such patients.

Abstract Background The choice of cardiac resynchronization therapy device, with (CRT-D) or without (CRT-P) a defibrillator, in patients with heart failure largely depends on the physician׳s discretion, because it has not been established which subjects benefit most from a defibrillator. Methods We examined the annual trend of CRT device implantations between 2006 and 2014, and evaluated the factors related to the device selection (CRT-D or CRT-P) for primary prevention of sudden cardiac death in patients with heart failure by analyzing the Japan Cardiac Device Treatment Registry (JCDTR) database from January 2011 and August 2015 (CRT-D, n =2714; CRT-P, n =555). Results The proportion of CRT-D implantations for primary prevention among all the CRT-D recipients was more than 70% during the study period. The number of CRT-D implantations for primary prevention reached a maximum in 2011 and decreased gradually between 2011 and 2014, whereas CRT-P implantations increased year by year until 2011 and remained unchanged in recent years. Multivariate analysis identified age (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.90–0.95, P <0.0001), male sex (OR 1.99, 95% CI 1.28–3.11, P <0.005), reduced left ventricular ejection fraction (LVEF) (OR 0.96, 95% CI 0.94–0.98, P <0.0001), and non-sustained ventricular tachycardia (NSVT) (OR 2.85, 95% CI 1.87–4.35, P <0.0001) as independent factors favoring the choice of CRT-D. Conclusions Younger age, male sex, reduced LVEF, and a history of NSVT were independently associated with the choice of CRT-D for primary prevention of sudden cardiac death in patients with heart failure in Japan.

Background This study aimed to investigate the correlation between left atrial low‐voltage areas (LVAs) and an arrhythmogenic superior vena cava (SVC) and the impact on the efficacy of an empiric SVC isolation (SVCI) along with a pulmonary vein isolation (PVI) of non‐paroxysmal atrial fibrillation (non‐PAF) with or without LVAs. Methods We retrospectively enrolled 153 consecutive patients with non‐PAF who underwent a PVI alone (n = 51) or empiric PVI plus an SVCI (n = 102). Left atrial voltage maps were constructed during sinus rhythm to identify the LVAs (<0.5 mV). An arrhythmogenic SVC was defined as firing from the SVC and an SVC associated with the maintenance of AF‐like rapid SVC activity. Results An arrhythmogenic SVC and LVAs were identified in 28% and 65% of patients with a PVI alone and 36% and 73% of patients with a PVI plus SVCI, respectively (P = .275 and P = .353). In the multivariate analysis a female gender, higher pulmonary artery systolic pressure (PAPs), and arrhythmogenic SVC were associated with the presence of LVAs. In the PVI plus SVCI strategy, there was no significant difference in the atrial tachyarrhythmia/AF‐free survival between the patients with and without LVAs after initial and multiple sessions (50% vs. 61%; P = .386, 73% vs. 79%; P = .530), however, differences were observed in the PVI alone group (27% vs. 61%; P = .018, 49% vs. 78%; P = .046). Conclusions The presence of LVAs was associated with an arrhythmogenic SVC. An SVCI may have the potential to compensate for an impaired outcome after a PVI in non‐PAF patients with LVAs. The LVAs was associated with an arrhythmogenic SVC in non‐PAF patients. An SVCI compensated for an impaired outcome after PVI in non‐PAF patients with LVAs.

Background: Hospitalized patients with acute decompensated heart failure (ADHF) frequently exhibit aggravating mitral regurgitation (MR). Those patients do not always undergo surgical mitral valve repair, but particularly in the elderly, they are often treated by conservative medical therapy. This study was aimed to investigate factors affecting 6-month outcomes in hospitalized patients with heart failure (HF) harboring surgically untreated MR. Methods: We screened the presence of MR in hospitalized patients with HF between September 2017 and May 2020 in the Yamaguchi Prefectural Grand Medical (YPGM) center. At the time of discharge of these patients, individuals with surgically unoperated MR, including primary and secondary origin, were consequently recruited to this single-center prospective cohort study. The patients with severe MR who undergo surgical mitral valve treatment were not included in this study. The primary endpoint was all-cause readmission or all-cause death and the secondary endpoint was HF-related endpoint at 6 months after discharge. The Cox proportional hazard regression analyses were employed to assess the predictors for the composite endpoint. Results: Overall, 489 patients with ADHF were admitted to the YPGM center. Of those, 146 patients (30% of total patients with HF) (median age 83.5 years, 69 men) were identified as harboring grade II MR or greater. Consequently, all the recruited patients were diagnosed as functional MR. During a median follow-up of 186.0 days, a total of 55 patients (38%) reached the primary or secondary endpoints (HF death and readmission in 31 patients, other in 24 patients). As a result of multivariate analysis, geriatric nutritional risk index [hazard ratio (HR) = 0.932; 95% CI = 0.887–0.979, p = 0.005], age (HR = 1.058; 95% CI = 1.006–1.112, p = 0.027), and left ventricular ejection fraction (HR = 0.971; 95% CI = 0.945–0.997, p = 0.030) were independent predictors of all-cause death or all-cause admission. Body mass index (HR = 0.793; 95% CI = 0.614–0.890, p = 0.001) and ischemic heart disease etiology (HR = 2.732; 95% CI = 1.056–7.067, p = 0.038) were also independent predictors of the HF-related endpoints. Conclusion: Malnutrition and underweight were substantial predictors of adverse outcomes in elderly patients with HF harboring surgically untreated moderate-to-severe functional MR.

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. The TRANSITION JAPAN‐ICD/WCD study explores the clinical outcomes of Japanese HFrEF patients meeting implantable cardioverter defibrillator (ICD) and wearable cardioverter defibrillator (WCD) criteria, including those who choose or decline device implantation, to assess the ICD/WCD current status after the introduction of new heart failure drugs like SGLT2i or ARNi in Japan.