Background: Temporal change in outcomes of heart failure patients receiving cardiac resynchronization therapy with a defibrillator (CRT-D) is unknown. Methods: We assess outcomes and underlying heart diseases of patients receiving CRT-D with analyzing database of the Japan cardiac device treatment registry (JCDTR) at the implantation year 2011-2015 and New JCDTR at the implantation year 2018-2021. Results: Proportion of nonischemic heart diseases was about 70% in both the groups (JCDTR: 69%; New JCDTR: 72%). Cardiac sarcoidosis increased with the rate of 5% in the JCDTR to 9% in the New JCDTR group. During an average follow-up of 21 months, death from any cause occurred in 167 of 906 patients in the JCDTR group (18%) and 79 of 611 patients in the New JCDTR group (13%) (adjusted hazard ratio [aHR] in the New JCDTR group, 0.72; 95% confidence interval [CI]: 0.55-0.94; p = .017). The superiority was mainly driven by reduction in the risk of noncardiac death. With regard to appropriate and inappropriate implantable cardioverter-defibrillator (ICD) therapy, there was a significant reduction in the New JCDTR group versus the JCDTR group (aHR in the New JCDTR group, 0.76; 95% CI: 0.59-0.98; p = .032 for appropriate ICD therapy; aHR in the New JCDTR group, 0.24; 95% CI: 0.12-0.50; p < .0001 for inappropriate ICD therapy). Conclusions: All-cause mortality was reduced in CRT-D patients implanted during 2018-2021 compared to those during 2011-2015, with a significant reduction in noncardiac death.
Background: Panoramic studies in patients with cardiac resynchronization therapy with a defibrillator (CRT-D) focusing on the etiology and indication are scarce. Besides, a controversy exists regarding requirement of a defibrillator in non-ischemic patients for primary prevention with CRT. Methods: Annual trends of de novo CRT-D implantations from 2011 to 2020 and outcomes of those between January 2011 and August 2015 were analyzed from the Japan cardiac device treatment registry (JCDTR) and New JCDTR database. Results: From 2011 to 2020, 8062 CRT-D recipients were registered, whose dominant indication was primary prevention of sudden cardiac death with a steady rate of about 70%. There was no significant temporal change of the proportion of non-ischemic patients being about 70% and 65% for primary and secondary prevention, respectively. Non-ischemic patients for primary prevention were associated with increased odds of appropriate ICD therapy [adjusted hazard ratio (aHR): 1.66; 95% confidence interval (CI): 1.01-2.75; p = .047] and reduced odds of any death (aHR: 0.66; 95% CI: 0.44-0.99; p = .046) as compared to ischemic patients. Conclusions: Proportion of non-ischemic etiology was much higher than that of ischemic one in the CRT-D cohort. Based on the higher odds of appropriate ICD therapy, non-ischemic patients for primary prevention appear to be prudently selected in Japan.
AIMS: The HINODE study aimed to analyse rates of mortality, appropriately treated ventricular arrhythmias (VA), and heart failure in Japanese patients and compared with those in Western patients. METHODS AND RESULTS: After treatment decisions following contemporary practice in Japan, patients were prospectively enrolled into four cohorts: (i) internal cardioverter-defibrillator (ICD), (ii) cardiac resynchronization therapy (CRT) defibrillator (CRT-D), (iii) standard medical therapy ('non-device': ND), or (iv) pacing (indicated for CRT; received pacemaker or CRT pacing). Cohorts 1-3 required a left ventricular ejection fraction ≤35%, a history of heart failure, and a need for primary prevention of sudden cardiac death based on two to five previously identified risk factors. Endpoint outcomes were adjudicated by the independent committees. ICD and CRT-D cohorts, considered as high-voltage (HV) cohorts, were pooled for Kaplan-Meier analysis and propensity-matched to Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) arm B and C patients. The study enrolled 354 patients followed for 19.6 ± 6.5 months, with a minimum of 12 months. Propensity-matched HV cohorts showed comparable VA (P = 0.61) and mortality rates (P = 0.29) for HINODE and MADIT-RIT. The ND cohort presented a high crossover rate to ICD therapy (6.1%, n = 7/115), and the CRT-D cohort showed elevated mortality rates. The pacing cohort revealed that patients implanted with pacemakers had higher mortality (26.0%) than those with CRT-Pacing (8.4%, P = 0.05). CONCLUSIONS: The mortality and VA event rates of landmark trials are applicable to patients with primary prevention in Japan. Patients who did not receive guideline-indicated CRT devices had poor outcomes.
Heart Failure , Ventricular Function, Left , Arrhythmias, Cardiac , Death, Sudden, Cardiac/epidemiology , Death, Sudden, Cardiac/prevention & control , Heart Failure/complications , Heart Failure/therapy , Humans , Japan/epidemiology , Stroke Volume , Treatment Outcome
AIM: To investigate the therapeutic effect of lenvatinib (LEN) in liver disease etiology, especially nonviral hepatocellular carcinoma (HCC). METHODS AND RESULTS: Sixty-seven patients with unresectable advanced HCC (u-HCC) treated with LEN and consisting of 26 hepatitis C virus (HCV), 19 hepatitis B virus (HBV), 11 alcohol, and 11 nonalcoholic steatohepatitis (NASH) cases were retrospectively recruited. Univariate and multivariate Cox proportional hazard models were used to determine predictive factors for survival. The objective response rate in the nonviral (alcohol and NASH) group was higher than that in the viral group (59.1% [13/22] vs. 46.7% [21/45]). Progression-free survival was significantly longer in the nonviral group than in the viral group (13.7 vs. 6.6 months; hazard ratio [HR] 0.324; 95% confidence interval [CI] 0.174-0.602; P < 0.01). Similarly, median overall survival (OS) was significantly longer in the nonviral group than in the viral group (not evaluable vs. 15.9 months; HR = 0.277; 95% CI = 0.116-0.662; P < 0.01). Multivariate analysis revealed that portal vein invasion (HR = 5.327, P = 0.0025), treatment line (HR = 0.455, P = 0.023), and etiology (HR = 0.180, P = 0.00055) were significant independent factors associated with OS in u-HCC patients treated with LEN. CONCLUSION: Our results suggest that LEN is more effective against nonviral u-HCC than against viral u-HCC.
BACKGROUND: Randomized trials in Western countries have provided evidence that prophylactic implantable cardioverter-defibrillator (ICD) therapy reduces mortality in heart failure (HF) patients with reduced left ventricular ejection fraction. However, the risk of life-threatening ventricular arrhythmias in Japanese HF patients sharing similar risk factors is still unknown. METHODS: The Heart Failure Indication and Sudden Cardiac Death Prevention Trial Japan trial (NCT03185832) is a prospective, multicenter registry designed to collect data on ventricular arrhythmia, HF events, and mortality in Japanese HF patients. Japanese patients with HF and 2-5 predefined risk factors who were indicated for cardiac device implantation based on European Society of Cardiology guidelines were enrolled in four treatment arms: implantable cardioverter-defibrillator (ICD), cardiac resynchronization therapy defibrillator (CRT-D), HF pacing (PA; Pacemaker and cardiac resynchronization pacemaker), and nondevice (ND) cohorts and followed for a minimum of 12 months. Since it is anticipated that some baseline patient characteristics and risk factors will differ significantly from those reported in predominantly Western populations, event rates will be compared to a propensity-matched population from the MADIT RIT trial. Primary endpoints are composite rates of first appropriately treated ventricular arrhythmias (VA) or/and life-threatening VA symptoms for the ICD and CRT-D cohorts. For nondevice and PA cohorts, the primary outcome is all-cause mortality. CONCLUSIONS: The Heart Failure Indication and Sudden Cardiac Death Prevention Trial Japan is a large prospective multicenter registry with defined device treatment cohorts and will provide data for risk stratification for cardiovascular events in Japanese HF patients.
BACKGROUND: The aim of this study was to clarify the current status and role of programmed ventricular stimulation in patients without sustained ventricular arrhythmias and reduced left ventricular ejection fraction (LVEF). METHODS: The follow-up data of the Japan cardiac device treatment registry (JCDTR) was analyzed in 746 patients with LVEF â¦35% and no prior history of sustained ventricular arrhythmias who underwent de novo implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy with a defibrillator (CRT-D) implantation between January 2011 and August 2015. RESULTS: Electrophysiological study (EPS) with programmed ventricular stimulation had been performed before the device implant in 118 patients (15.8%, EPS group). During the mean follow-up of 21 ± 12 months, the rate of freedom from any death and appropriate defibrillator therapy was not significantly different between EPS group (n = 118) and No EPS group (n = 628). NYHA class II-IV, and QRS duration were negatively associated with performing EPS. Among patients in the EPS group, the rate of ventricular tachycardia (VT)/ventricular fibrillation (VF) induction was 48%. The inducibility was not a predictor of appropriate defibrillator therapy, whereas BNP â§535 pg/mL and no use of amiodarone were significantly associated with a risk of the appropriate therapy. CONCLUSION: EPS for induction of VT/VF had been performed in about 16% of patients with reduced LVEF before primary prevention ICD/CRT-D implantation. Elevated BNP levels and no use of amiodarone, but not inducibility of VT/VF, appeared to be associated with appropriate defibrillator therapy in these populations.
Background: There has been no large multicenter clinical trial on the prognosis of implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy with a defibrillator (CRT-D) in Japanese patients with coronary artery disease (CAD). The aim of the present study was to compare differences in the prognoses of Japanese patients with CAD between primary and secondary prevention, and to identify potential predictors of prognosis. MethodsâandâResults: We investigated 392 CAD patients (median age 69 years, 90% male) treated with ICD/CRT-D enrolled in the Japan Implantable Devices in CAD (JID-CAD) Registry. The primary endpoint was all-cause death, and the secondary endpoint was appropriate ICD therapies. Endpoints were assessed by dividing patients into primary prevention (n=165) and secondary prevention (n=227) groups. The mean (±SD) follow-up period was 2.1±0.9 years. The primary endpoint was similar in the 2 groups (P=0.350). Conclusions: The mortality rate in Japanese patients with CAD who underwent ICD/CRT-D implantation as primary prevention was not lower than that of patients who underwent ICD/CRT-D implantation as secondary prevention, despite the lower cardiac function in the patients undergoing ICD/CRT-D implantation as primary prevention.
INTRODUCTION: Type 2 diabetes (T2DM) is associated with cardiovascular death, including sudden cardiac death due to arrhythmias. Patients with an implantable cardioverter-defibrillator (ICD) are also at high risk of developing a clinically significant ventricular arrhythmia. It has been reported that sodium-glucose cotransporter 2 (SGLT2) inhibitors can reduce cardiovascular deaths; however, the physiological mechanisms of this remain unclear. It is, however, well known that SGLT2 inhibitors increase blood ketone bodies, which have been suggested to have sympatho-suppressive effects. Empagliflozin (EMPA) is an SGLT2 inhibitor. The current clinical trial titled "Placebo-controlled, double-blind study of empagliflozin (EMPA) and implantable cardioverter-defibrillator (EMPA-ICD) in patients with type 2 diabetes (T2DM)" was designed to investigate the antiarrhythmic effects of EMPA. METHODS: The EMPA-ICD study is a prospective, multicenter, placebo-controlled, double-blind, randomized, investigator-initiated clinical trial currently in progress. A total of 210 patients with T2DM (hemoglobin A1c 6.5-10.0%) will be randomized (1:1) to receive once-daily placebo or EMPA, 10 mg, for 24 weeks. The primary endpoint is the number of clinically significant ventricular arrhythmias for 24 weeks before and 24 weeks after study drug administration, as documented by the ICD. The secondary endpoints of the study are the change from baseline concentrations in blood ketone and catecholamine 24 weeks after drug treatment. CONCLUSION: The EMPA-ICD study is the first clinical trial to assess the effect of an SGLT2 inhibitor on clinically significant ventricular arrhythmias in patients with T2DM and an ICD. TRIAL REGISTRATION: Unique trial number, jRCTs031180120 ( https://jrct.niph.go.jp/latest-detail/jRCTs031180120 ).
BACKGROUND: Trends of de novo implantation of cardiac implantable electronic devices (CIEDs) including implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy with a defibrillator (CRT-D) or pacemaker (CRT-P) in advancing age are unknown. METHODS: Analysis of data from the Japan cardiac device treatment registry (JCDTR) with an implantation date between January 2006 and December 2016 was performed focusing on advancing age of â§75 years. RESULTS: The cohort included 17 564 ICD, 9470 CRT-D and 1087 CRT-P recipients for de novo implantation. The rate of patients â§75 years of age increased from 17.1% to 20.5% in ICD implantation (P = .052), from 19.7% to 30.0% in CRT-D implantation (P < .0001), and from 40.0% to 64.0% in CRT-P implantation (P = .17). There was an apparent increase in the percentage of nonischemic patients aged â§75 years receiving ICD (10.9% in 2006 to 16.4% in 2016, P = .0008) and CRT-D (17.1% in 2006 to 27.8% in 2016, P = .0001). The implantation for primary prevention ICD (P = .059) and CRT-D (P = .012) was also associated with a temporal increase in the percentage of patients aged â§75 years. CONCLUSIONS: Proportion of patients â§75 years of age for de novo CIED implantation gradually increased from 2006 to 2016, presumably because of the growing number of nonischemic cardiomyopathy and heart failure patients requiring primary prevention of sudden cardiac death.
A 62-year-old man with Brugada syndrome underwent subcutaneous implantable cardioverter defibrillator implantation. The lead was positioned along the left sternal border and defibrillation threshold (DFT) testing was performed. However, ventricular fibrillation (VF) was not terminated with 65 J and 80 J shocks. Shock impedance was 82 ohms. We repositioned the lead to the right sternal border and performed DFT testing again, followed by the VF termination with a 65 J shock. Shock impedance was 59 ohms. The positional relationship among the lead, generator, and heart was changed by lead repositioning, which may have contributed to improved shock impedance and DFT.
BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease characterized by fibrofatty replacement and ventricular arrhythmias. ARVC is believed to be a disease of the young, with most cases being diagnosed before the age of 40 years. We report here a case of newly diagnosed ARVC in an octogenarian associated with a pathogenic variant in the plakophilin 2 gene (PKP2). CASE PRESENTATION: An 80-year-old Japanese man was referred for sustained ventricular tachycardia. His baseline electrocardiogram showed negative T waves in V1-V4. Right ventriculography showed right ventricular aneurysm. Because this case met three major criteria, ARVC was diagnosed. He was successfully treated with radiofrequency ablation and oral amiodarone. Genetic analysis identified an insertion mutation in exon 8 of PKP2 (1725_1728dupGATG), which caused a frameshift and premature termination of translation (R577DfsX5). CONCLUSIONS: To the best of our knowledge, this is the first report of newly diagnosed ARVC in an octogenarian associated with a loss-of-function PKP2 pathogenic variant. Although the late clinical presentation of ARVC is rare, it should be included in the differential diagnosis when treating older patients with ventricular tachyarrhythmias.
Arrhythmogenic Right Ventricular Dysplasia/genetics , Loss of Function Mutation , Plakophilins/genetics , Aged, 80 and over , Amiodarone/administration & dosage , Anti-Arrhythmia Agents/administration & dosage , Arrhythmogenic Right Ventricular Dysplasia/diagnosis , Arrhythmogenic Right Ventricular Dysplasia/physiopathology , Arrhythmogenic Right Ventricular Dysplasia/therapy , Catheter Ablation , Genetic Predisposition to Disease , Humans , Male , Phenotype , Risk Factors , Treatment Outcome
BACKGROUND: Implantable cardioverter defibrillators (ICDs) are being used with increasing frequency in children. Our aim was to examine the current trend of pediatric ICD implantation in Japan. MethodsâandâResults: Data was extracted from the Japanese Cardiac Device Treatment Registry (JCDTR), a nation-wide registry started in 2006. All patients aged less than 18 years who had an ICD implantation registered between 2006 and 2016 were included in the analysis. A total of 201 patients were included, with a median age of 16 years (range 1-18). The underlying cardiac diagnosis was primary electrical disease (67%), cardiomyopathy (26%) and congenital heart disease (4%), with idiopathic ventricular fibrillation (29%) and long QT syndrome (21%) being the 2 most common diagnoses. Implantation indication was primary prevention in only 30 patients (15%). There were 27 patients (13%) aged ≤12 years, with a larger proportion of patients with cardiomyopathy (33%). The indication in younger children was secondary prevention in all cases. Younger children may be under-represented in our study given the nature of the database as it is a predominantly adult cardiology database. CONCLUSIONS: In the past decade, ICD implantation has been performed in approximately 20 children per year in Japan, mostly for secondary prevention. There was no increase in the trend nor a change in age distribution.
Arrhythmias, Cardiac/therapy , Databases, Factual , Defibrillators, Implantable/trends , Registries , Adolescent , Arrhythmias, Cardiac/epidemiology , Arrhythmias, Cardiac/physiopathology , Child , Child, Preschool , Female , Humans , Male
Previous studies suggested that right ventricular pacing was associated with pacing-induced cardiac dysfunction (PICD). The purpose of this study was to investigate the clinical characteristics including the incidence of undiagnosed cardiac sarcoidosis (CS) in patients with atrioventricular block (AVB) who manifest PICD. We retrospectively investigated consecutive patients with permanent pacemaker (PPM) undergoing a first-generator replacement surgery with a new PPM or an upgrade procedure to a cardiac resynchronization therapy (CRT) device between December 1, 2011 and June 30, 2017. Patients with AVB showing normal echocardiographic findings before PPM implantation were included and divided into 2 groups: patients with post-PPM left ventricular ejection fraction (LVEF) < 40% and/or undergoing an upgrade procedure to CRT (PICD group) and patients with post-PPM LVEF ≥ 40% who underwent replacement surgery with a new PPM (no-PICD group). There were 15 and 41 patients in the PICD and no-PICD groups, respectively. A wider-paced QRS duration just after the PPM implantation and/or lower pre-PPM LVEF was observed in the PICD group. Furthermore, 46.7% of the PICD patients (7/15) satisfied the diagnostic criteria for CS according to the guideline of the Japanese Circulation Society, although no patients fulfilled these criteria before PPM implantation. In conclusion, a high incidence of CS was observed in patients with AVB who had PICD. However, none of these patients was diagnosed with CS before PPM implantation.
Atrioventricular Block/therapy , Cardiomyopathies/epidemiology , Diagnostic Errors/statistics & numerical data , Pacemaker, Artificial/adverse effects , Sarcoidosis/epidemiology , Ventricular Function, Left/physiology , Aged , Atrioventricular Block/diagnosis , Atrioventricular Block/etiology , Cardiomyopathies/complications , Cardiomyopathies/diagnosis , Female , Follow-Up Studies , Humans , Incidence , Japan/epidemiology , Male , Middle Aged , Retrospective Studies , Sarcoidosis/complications , Sarcoidosis/diagnosis
Action Potentials , Atrial Premature Complexes/physiopathology , Bundle-Branch Block/physiopathology , Heart Conduction System/physiopathology , Heart Rate , Tachycardia, Ventricular/physiopathology , Aged , Atrial Premature Complexes/diagnosis , Bundle-Branch Block/diagnosis , Cardiac Pacing, Artificial , Electrocardiography , Electrophysiologic Techniques, Cardiac , Humans , Male , Tachycardia, Ventricular/diagnosis , Time Factors
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.
