Search

In patients with acute myocardial infarction (MI), heart failure (HF) is one of the most common complications that is associated with a significant burden of mortality and healthcare resources. The clinical benefits of key HF drugs, the so-called "4 pillars" or "fantastic 4", namely β-blockers, mineralocorticoid receptor antagonists, angiotensin receptor-neprilysin inhibitor, and sodium-glucose cotransporter 2 inhibitors, have been established in patients with HF with reduced ejection fraction, whereas the effects of these drugs are not comprehensively appreciated in patients with acute MI. This review summarizes current evidence on pharmacological and device-based interventions for preventing HF after acute MI.

This is the first consensus statement of the Joint Committee on Renal Denervation of the Japanese Society of Hypertension (JSH)/Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT)/Japanese Circulation Society (JCS). The consensus is that the indication for renal denervation (RDN) is resistant hypertension or "conditioned" uncontrolled hypertension, with high office and out-of-office blood pressure (BP) readings despite appropriate lifestyle modification and antihypertensive drug therapy. "Conditioned" uncontrolled hypertension is defined as having one of the following: 1) inability to up-titrate antihypertensive medication due to side effects, the presence of complications, or reduced quality of life. This includes patients who are intolerant of antihypertensive drugs; or 2) comorbidity at high cardiovascular risk due to increased sympathetic nerve activity, such as orthostatic hypertension, morning hypertension, nocturnal hypertension, or sleep apnea (unable to use continuous positive airway pressure), atrial fibrillation, ventricular arrythmia, or heart failure. RDN should be performed by the multidisciplinary Hypertension Renal Denervation Treatment (HRT) team, led by specialists in hypertension, cardiovascular intervention and cardiology, in specialized centers validated by JSH, CVIT, and JCS. The HRT team reviews lifestyle modifications and medication, and the patient profile, then determines the presence of an indication of RDN based on shared decision making with each patient. Once approval for real-world clinical use in Japan, however, the joint RDN committee will update the indication and treatment implementation guidance as appropriate (annually if necessary) based on future real-world evidence.

Background: This prospective ANAFIE Registry substudy investigated the relationship between the echocardiographic parameters of left atrial (LA) structure and function and clinical outcomes at 2 years among atrial fibrillation (AF) patients aged ≥75 years., Methods and results: Outcomes of 1,474 elderly non-valvular AF (NVAF) patients who underwent transthoracic echocardiography at baseline were analyzed by categories of maximum LA volume index (max. LAVi) and LA emptying fraction (LAEF) total. Baseline mean±standard deviation LAEF total and max. LAVi were 28.2±14.9% and 54.2±25.9 mL/m 2 , respectively. Proportions of oral anticoagulant (OAC), direct OAC, and warfarin use were 92.7%, 68.7%, and 24.0%, respectively. Patients with LAEF total ≤45.0% (n=1,213) vs. >45.0% (n=224) were at higher risk of cardiovascular events (hazard ratio [HR]: 2.19, P=0.021) and heart failure (HF) hospitalization (HR: 2.25, P=0.045). Risk of all-cause death was higher with max. LAVi >48.0 mL/m 2 (n=656) vs. ≤48.0 mL/m 2 (n=621) (HR: 1.69, P=0.048). Subgroups with abnormal LA function and structure had increased incidence of cardiac/cardiovascular events and HF hospitalization. No significant interaction was observed between echocardiographic parameters and OAC type., Conclusions: Elderly Japanese patients with NVAF and LAEF total ≤45.0% were at higher risk of cardiovascular events and HF hospitalization, and those with max. LAVi >48.0 mL/m 2 were at higher risk of all-cause death.

Background: This study investigated whether the chronic use of adaptive servo-ventilation (ASV) reduces all-cause mortality and the rate of urgent rehospitalization in patients with heart failure (HF)., Methods and results: This multicenter prospective observational study enrolled patients hospitalized for HF in Japan between 2019 and 2020 who were treated either with or without ASV therapy. Of 845 patients, 110 (13%) received chronic ASV at hospital discharge. The primary outcome was a composite of all-cause death and urgent rehospitalization for HF, and was observed in 272 patients over a 1-year follow-up. Following 1:3 sequential propensity score matching, 384 patients were included in the subsequent analysis. The median time to the primary outcome was significantly shorter in the ASV than in non-ASV group (19.7 vs. 34.4 weeks; P=0.013). In contrast, there was no significant difference in the all-cause mortality event-free rate between the 2 groups., Conclusions: Chronic use of ASV did not impact all-cause mortality in patients experiencing recurrent admissions for HF.

The 87 th Annual Meeting of the Japanese Circulation Society (JCS2023) was held in March 2023 in Fukuoka, Japan, marking the first in-person gathering after the COVID-19 pandemic. With the theme of "New Challenge With Next Generation" the conference emphasized the development of future cardiovascular leaders and technologies such as artificial intelligence (AI). Notable sessions included the Mikamo Lecture on heart failure and the Mashimo Lecture on AI in medicine. Various hands-on sessions and participatory events were well received, promoting learning and networking. Post-event surveys showed high satisfaction among participants, with positive feedback on face-to-face interactions and the overall experience. JCS2023, attended by 17,852 participants, concluded successfully, marking a significant milestone in post-pandemic meetings, and advancing cardiovascular medicine.

Background: Lower systolic blood pressure (SBP) is known to be associated with poor prognosis in heart failure (HF). We evaluated the efficacy and safety of sacubitril/valsartan according to baseline SBP tertiles in Japanese patients from the PARALLEL-HF study., Methods and results: In all, 223 patients were stratified into tertiles according to baseline SBP (≤114 mmHg: n=75; >114 and ≤130 mmHg: n=76; and >130 mmHg: n=72). Patients with lower SBP (≤114 mmHg) had the highest median N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations at baseline (P=0.0184). No significant difference was observed between sacubitril/valsartan and enalapril for the composite outcome of cardiovascular death and HF hospitalization across SBP tertiles (P-interaction=0.2682). Although the P-interaction value was not significant (0.2106), a greater reduction in NT-proBNP with sacubitril/valsartan compared with enalapril was observed in patients with SBP >130 mmHg (P=0.0076). The incidence of hypotension-related events and reduction or discontinuation of treatment due to hypotension-related events was higher in the lower SBP subgroup, and these events were more frequent in the sacubitril/valsartan than enalapril group., Conclusions: The efficacy of sacubitril/valsartan compared with enalapril was consistent across baseline SBP tertiles in Japanese patients from the PARALLEL-HF study. Hypotension-related events were more common in patients treated with sacubitril/valsartan with lower SBP.

Background: The PARALLEL-HF study assessed the efficacy and safety of sacubitril/valsartan vs. enalapril in Japanese patients with chronic heart failure with reduced ejection fraction (HFrEF). This open-label extension (OLE) assessed long-term safety with sacubitril/valsartan., Methods and results: This study enrolled 150 patients who received sacubitril/valsartan 50 or 100 mg, b.i.d., in addition to optimal background heart failure (HF) therapy. A dose level of sacubitril/valsartan 200 mg, b.i.d., was targeted by Week 8. At OLE baseline, higher concentrations of B-type natriuretic peptide (BNP) and urine cGMP, and lower concentrations of N-terminal pro B-type natriuretic peptide (NT-proBNP), were observed in the sacubitril/valsartan core group (patients who received sacubitril/valsartan in both the core and extension study) than in the enalapril core group (patients who received enalapril in the core study and were then transitioned to sacubitril/valsartan). The mean exposure to study drug was 98.9%. There was no trend of worsening of HF at Month 12. No obvious changes in cardiac biomarkers were observed, whereas BNP and urine cGMP increased and NT-proBNP decreased in the enalapril core group, which was evident at Weeks 2-4 and sustained to Month 12., Conclusions: Long-term sacubitril/valsartan at doses up to 200 mg, b.i.d., has a positive risk-benefit profile; it was safe and well tolerated in Japanese patients with chronic HFrEF.

Background: This sub-analysis of the ANAFIE Registry, a prospective, observational study of >30,000 Japanese non-valvular atrial fibrillation (NVAF) patients aged ≥75 years, assessed the prevalence of direct oral anticoagulant (DOAC) under-dose prevalence, identified the factors of under-dose prescriptions, and examined the relationship between DOAC dose and clinical outcomes., Methods and results: Patients, divided into 5 groups by DOAC dose (standard, over-, reduced, under-, and off-label), were analyzed for background factors, cumulative incidences, and clinical outcome risk. Endpoints were stroke/systemic embolic events (SEE), major bleeding, and all-cause death during the 2-year follow-up. Of 18,497 patients taking DOACs, 20.7%, 3.8%, 51.6%, 19.6%, and 4.3%, were prescribed standard, over-, reduced, under-, and off-label doses. Factors associated with under-dose use were female sex, age ≥85 years, reduced creatinine clearance, history of major bleeding, polypharmacy, antiplatelet agents, heart failure, dementia, and no history of catheter ablation or cerebrovascular disease. After confounder adjustment, under-dose vs. standard dose was not associated with the incidence of stroke/SEE or major bleeding but was associated with a higher mortality rate. Patients receiving an off-label dose showed similar tendencies to those receiving an under-dose; that is, they showed the highest mortality rates for stroke/SEE, major bleeding, and all-cause death., Conclusions: Inappropriate low DOAC doses (under- or off-label dose) were not associated with stroke/SEE or major bleeding but were associated with all-cause death.

Background: The present study aimed to clarify the regional variations in clinical practice and the prognosis of patients with heart failure with reduced ejection fraction (HFrEF) in Japan using the Japanese Registry of Acute Decompensated Heart Failure (JROADHF)., Methods and results: We recruited data of hospitalized patients with HFrEF (n=4,329) from the JROADHF. The patients were divided into 6 groups based on the region of Japan where they were hospitalized: Hokkaido-Tohoku (n=504), Kanto (n=958), Chubu (n=779), Kinki (n=902), Chugoku-Shikoku (n=446), and Kyushu (n=740). We compared the patients' characteristics, including etiology of HF and prognosis after discharge. The age of the patients was lowest in the Kanto and Kinki regions. In contrast, there were no differences in the prevalence of comorbidities, levels of B-type natriuretic peptide, or left ventricular EF among the 6 groups. Post-discharge cardiospecific prognosis, specifically, the composite of cardiac death or HF hospitalization, cardiac death, and HF hospitalization, was comparable among the 6 regions., Conclusions: There were no differences in cardiospecific prognosis in patients with HFrEF among the 6 regions in Japan.

Background: Previous studies on mortality in atrial fibrillation (AF) included a limited number of elderly patients receiving direct oral anticoagulants (DOACs). This subanalysis of the ANAFIE Registry evaluated 2-year mortality according to causes of death of elderly non-valvular AF (NVAF) patients in the DOAC era., Methods and results: The ANAFIE Registry was a multicenter prospective observational study. Mean patient age was 81.5 years and 57.3% of patients were male. Of the 32,275 patients completing the study, 2,242 died. The most frequent causes of death were cardiovascular (CV) death (32.4%), followed by infection (17.1%) and malignancy (16.1%). Incidence rates of CV-, malignancy-, and infection-related death were 1.20, 0.60, and 0.63 per 100 person-years, respectively. Patients aged ≥85 years showed increased proportions of non-CV and non-malignancy deaths and a decreased proportion of malignancy deaths compared with patients aged <85 years. The incidence of death due to congestive heart failure/cardiogenic shock, infection, and renal disease was higher in patients aged ≥85 than those aged <85 years. Compared with warfarin, DOACs were associated with a significantly lower risk of death by intracranial hemorrhage, ischemic stroke, and renal disease., Conclusions: This subanalysis described the mortality according to causes of death of Japanese elderly NVAF patients in the DOAC era. Our results imply that a more holistic approach to comorbid conditions and stroke prevention are required in these patients.

Background: Little is known about nationwide temporal trends in the clinical characteristics and treatment of dilated cardiomyopathy (DCM) in Japan., Methods and results: We collected data regarding demographics, echocardiography, and treatment of DCM between 2003 to 2013 from Clinical Personal Records, a national registry organized by the Japanese Ministry of Health, Labour, and Welfare. Among the 40,794 DCM patients screened, 27,702 with left ventricular ejection fraction (LVEF) <50% and age ≥18 years were enrolled in this study and divided into 3 groups according to registration year: Group 1, 2003-2005 (10,006 patients); Group 2, 2006-2010 (11,252 patients); and Group 3, 2011-2013 (6,444 patients). Over time, there were decreases in age at registration (mean [±SD] 58.6±13.0 vs. 56.8±13.8 vs. 56.2±13.8 years; P<0.001) and LVEF (33.5±10.0% vs. 31.1±9.9% vs. 29.2± 9.7%; P<0.001), and an increase in patients with New York Heart Association Class III-IV (28.2% vs. 35.2% vs. 41.0%; P<0.001). The use of β-blockers (59.1% vs. 79.3% vs. 87.8%; P<0.001) and mineralocorticoid receptor antagonists (30.6% vs. 35.8% vs. 39.7%; P<0.001) increased over time. In multivariate analysis, male sex, systolic blood pressure, chronic kidney disease, hemoglobin, and registration year were positively associated, whereas age and LVEF were negatively associated, with β-blocker prescription., Conclusions: Although the clinical characteristics of DCM changed, the implementation of optimal medical therapy for DCM increased from 2003 to 2013 in Japan.

Background: This All Nippon AF in the Elderly (ANAFIE) Registry sub-analysis evaluated the impact of polypharmacy on 2-year outcomes in a large, elderly (aged ≥75 years) Japanese population with non-valvular atrial fibrillation (NVAF)., Methods and results: The ANAFIE Registry was a multicenter, prospective, observational study with a 24-month follow-up period. Of 32,275 enrolled NVAF patients, 31,419 were grouped by the number of prescribed concomitant medications (other than oral anticoagulants [OACs]): 0-4 [38.8%], 5-8 [43.3%], and ≥9 [17.9%]). Patients receiving more concomitant medications were older, had poor renal function, and suffered more comorbidities than those receiving fewer concomitant medications. Several patient background factors, including diabetes mellitus, myocardial infarction, and chronic kidney disease, were significantly correlated with an increased number of concomitant medications. With increasing medications, OAC prescription rates decreased, but the warfarin prescription rate increased, and the cumulative incidence rates of stroke/systemic embolic events (SEE), major bleeding, gastrointestinal bleeding, fracture/falls, cardiovascular events, cardiovascular death, and all-cause death significantly increased (each, P<0.05). In multivariate analysis, increasing medications was independently associated with increases in these events, except for stroke/SEE. There were no significant interactions between the number of medications and anticoagulant treatment with direct OAC or warfarin concerning the incidence of these events., Conclusions: Polypharmacy was frequent among elderly patients with NVAF who were older with more comorbidities, and was independently associated with a higher incidence of extracranial events.

Background: Echocardiographic data on the cardiac structure and function in elderly patients with atrial fibrillation (AF) and heart failure (HF) are limited. This subcohort study of the ANAFIE Registry analyzed echocardiographic parameters to identify cardiac structural and functional characteristics., Methods and results: Of 32,726 subjects in the ANAFIE population, 1,494 (4.6%) were entered as the echocardiography subcohort. Half of the patients, including those with persistent and permanent AF, older age (≥80 years), and CHADS 2 score ≥2, had left atrial (LA) volume index ≥48 mL/m 2 , indicating severe LA enlargement. LA enlargement significantly correlated with impaired LA reservoir function, regardless of age and CHADS 2 score. Types of AF and rhythm were strongly related to LA volume and reservoir function (P<0.0001). Moderate-to-severe mitral and tricuspid regurgitation were significantly more common, and the early diastolic mitral inflow velocity to mitral annulus velocity ratio was significantly higher among patients with than without HF history (all, P<0.0001)., Conclusions: In this subcohort, LA enlargement correlated with impaired LA reservoir function. Elderly patients with non-valvular AF and a history of HF had LA enlargement and dysfunction, increased LV mass index, low LV ejection fraction, and high heart rate.

Background: Data on outcomes for patients with atrial fibrillation (AF) and active cancer are scarce. The effect of active cancer on thrombosis and bleeding risks in elderly (≥75 years) patients with non-valvular AF (NVAF) enrolled in the All Nippon AF In the Elderly (ANAFIE) Registry were prospectively analyzed., Methods and results: In this subanalysis of the ANAFIE Registry, a prospective, multicenter, observational study conducted in Japan, we compared the incidence rates of clinical outcomes between active cancer and non-cancer groups. Relationships between primary outcomes and anticoagulation status were evaluated. Of the 32,725 patients enrolled in the Registry, 3,569 had active cancer at baseline; 92.0% of active cancer patients received anticoagulants (23.7%, warfarin; 68.2%, direct oral anticoagulants [DOACs]). Two-year probabilities of stroke/systemic embolic events (SEE) were similar in the cancer (3.33%) and non-cancer (3.16%) groups. Patients with cancer had greater incidences of major bleeding (2.86% vs. 2.04%), all-cause death (10.95% vs. 6.77%), and net clinical outcomes (14.63% vs. 10.00%) than those without cancer. In patients without cancer, DOACs were associated with a decreased risk of stroke/SEE, major bleeding, all-cause death, and net clinical outcome compared with warfarin. No between-treatment differences were observed in patients with active cancer., Conclusions: Active cancer had no effect on stroke/SEE incidence in elderly NVAF patients, but those with cancer had higher incidences of major bleeding events and all-cause death than those without cancer.

Background: The usefulness of electrocardiographic (ECG) voltage criteria for diagnosing hypertrophic cardiomyopathy (HCM) in pediatric patients is poorly defined., Methods and results: ECGs at the 1st grade (mean [±SD] age 6.6±0.3 years) were available for 11 patients diagnosed with HCM at around the 7th grade (13.2±0.3 years). ECGs were available for another 64 patients diagnosed with HCM in the 1st (n=15), 7th (n=32), and 10th (n=17) grades. Fifty-one voltage criteria were developed by grade and sex using 62,841 ECGs from the general population. Voltage criteria were set at the 99.95th percentile (1/2,000) point based on the estimated prevalence of childhood HCM (2.9 per 100,000 [1/34,483]) to decrease false negatives. Conventional criteria were from guidelines for school-aged children in Japan. Of 11 patients before diagnosis, 2 satisfied conventional criteria in 1st grade; 5 (56%) of the remaining 9 patients fulfilled 2 voltage criteria (R wave in limb-lead I [RI]+S wave in lead V3 [SV3] and R wave in lead V3 [RV3]+SV3). Robustness analysis for sensitivity showed RV3+SV3 was superior to RI+SV3. For all patients after diagnosis, RI+SV4 was the main candidate. However, conventional criteria were more useful than voltage criteria., Conclusions: Early HCM prediction was possible using RV3+SV3 in >50% of patients in 1st grade. Voltage criteria may help diagnose prediagnostic or early HCM, and prevent tragic accidents, although further prospective studies are required.

Background: The high mortality of acute myocardial infarction (AMI) with cardiogenic shock (i.e., Killip class IV AMI) remains a challenge in emergency cardiovascular care. This study aimed to examine institutional factors, including the number of JCS board-certified members, that are independently associated with the prognosis of Killip class IV AMI patients., Methods and results: In the Japanese registry of all cardiac and vascular diseases-diagnosis procedure combination (JROAD-DPC) database (years 2012-2016), the 30-day mortality of Killip class IV AMI patients (n=21,823) was 42.3%. Multivariate analysis identified age, female sex, admission by ambulance, deep coma, and cardiac arrest as patient factors that were independently associated with higher 30-day mortality, and the numbers of JCS board-certified members and of intra-aortic balloon pumping (IABP) cases per year as institutional factors that were independently associated with lower mortality in Killip class IV patients, although IABP was associated with higher mortality in Killip classes I-III patients. Among hospitals with the highest quartile (≥9 JCS board-certified members), the 30-day mortality of Killip class IV patients was 37.4%., Conclusions: A higher numbers of JCS board-certified members was associated with better survival of Killip class IV AMI patients. This finding may provide a clue to optimizing local emergency medical services for better management of AMI patients in Japan.

Background: With aging population, the prevalence and incidence of heart failure (HF) have been increasing worldwide. However, the characteristics and outcomes of patients with HF in an era of aging are not well established in Japan., Methods and results: The Japanese Registry Of Acute Decompensated Heart Failure (JROADHF), a retrospective, multicenter, nationwide registry, was designed to study the clinical characteristics and outcomes of patients hospitalized with HF throughout Japan in 2013. One hundred and twenty-eight hospitals were selected by cluster random sampling and 13,238 hospitalized patients with HF were identified by medical record review. Demographics, medical history, severity, treatment, and in-hospital and long-term outcome data were collected from the Diagnostic Procedure Combination and medical charts. Data were analyzed using univariate and multivariate logistic regression or Cox regression analysis. The mean age of registered patients was 78.0±12.5 years and 52.8% were male. Elderly patients (age >75 years) accounted for 68.9%, and HF with preserved ejection fraction (HFpEF) accounted for 45.1%. Median length of hospital stay was 18 days and in-hospital mortality was 7.7%. The median follow-up period was 4.3 years, and the incidence rates for cardiovascular death and rehospitalization for HF were 7.1 and 21.1 per 100 person-years, respectively., Conclusions: A contemporary nationwide registry demonstrated that hospitalized HF patients were very elderly, HFpEF was common, and their prognosis was still poor in Japan.

Background: Infective endocarditis (IE) in patients with adult congenital heart disease (ACHD) remains a diagnostic challenge due to difficulties in detecting endocardial lesions by echocardiography. 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) has shown good diagnostic performance in prosthetic valve IE. This study aimed to assess its additional diagnostic value in ACHD-associated IE and to characterize its advantages., Methods and results: Overall, 22 patients with ACHD and clinical suspicion of IE were retrospectively studied. 18 F-FDG PET/CT was performed in addition to conventional assessment based on the modified Duke criteria. The final IE diagnosis was determined by an expert team during a 3-month clinical course, resulting in 18 patients diagnosed with IE. Seven patients (39%) were diagnosed with definite IE only by initial echocardiography. An 18 F-FDG PET/CT assessment revealed endocardial involvement in the other 9 patients, resulting in the diagnosis of definite IE in 16 in total (88%). Right-sided endocardial lesions were more common (n=12, 67%) but rarely identified by echocardiography, whereas 18 F-FDG PET/CT revealed right-sided lesions in 9 patients. A negative 18 F-FDG PET/CT (n=7, 39%) assessment was associated with a native valve IE (71% vs. 0%). In 4 patients who were identified with not-IE, neither echocardiography nor 18 F-FDG PET/CT detected any suspicious cardiac involvement., Conclusions: In the diagnosis of ACHD-associated IE, characterized by right-sided IE, 18 F-FDG PET/CT assessment should be useful.

Background: Atrial fibrillation (AF) is a common arrhythmia in the elderly, and causes complications such as cardioembolic stroke. Serum high-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation, has been reported to be a risk factor for developing AF in Western countries. However, few community-based studies have examined this issue in general Asian populations., Methods and results: A total of 2,510 community-dwelling Japanese participants aged ≥40 years without a history of AF were divided into 4 groups according to the sex-specific quartiles of serum hs-CRP concentrations (Q1, lowest and Q4, highest) and followed up for 24 years. The hazard ratios and their 95% confidence intervals for the development of AF were estimated using a Cox proportional hazards model. During the follow up, 234 subjects developed AF. The risk of AF increased significantly with elevating serum hs-CRP levels after adjustment for potential confounding factors (hazard ratio [95% confidence interval], Q1, 1.00 [reference]; Q2, 1.26 [0.83-1.92]; Q3, 1.77 [1.18-2.66]; and Q4, 1.89 [1.24-2.86]; P for trend <0.001)., Conclusions: The study findings suggest that elevated serum hs-CRP levels are an independent risk factor for the development of AF in a general Japanese population.

Background: In the Prospective Comparison of angiotensin receptor neprilysin inhibitor (ARNI) With ACEi to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) study, treatment with sacubitril/valsartan reduced the primary outcome of cardiovascular (CV) death and heart failure (HF) hospitalization compared with enalapril in patients with chronic HF and reduced ejection fraction (HFrEF). A prospective randomized trial was conducted to assess the efficacy and safety of sacubitril/valsartan in Japanese HFrEF patients., Methods and results: In the Prospective comparison of ARNI with ACEi to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients (PARALLEL-HF) study, 225 Japanese HFrEF patients (New York Heart Association [NYHA] class II-IV, left ventricular ejection fraction [LVEF] ≤35%) were randomized (1 : 1) to receive sacubitril/valsartan 200 mg bid or enalapril 10 mg bid. Over a median follow up of 33.9 months, no significant between-group difference was observed for the primary composite outcome of CV death and HF hospitalization (HR 1.09; 95% CI 0.65-1.82; P=0.6260). Early and sustained reductions in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline were observed with sacubitril/valsartan compared with enalapril (between-group difference: Week 2: 25.7%, P<0.01; Month 6: 18.9%, P=0.01, favoring sacubitril/valsartan). There was no significant difference in the changes in NYHA class and Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score at Week 8 and Month 6. Sacubitril/valsartan was well tolerated with fewer study drug discontinuations due to adverse events, although the sacubitril/valsartan group had a higher proportion of patients with hypotension., Conclusions: In Japanese patients with HFrEF, there was no difference in reduction in the risk of CV death or HF hospitalization between sacubitril/valsartan and enalapril, and sacubitril/valsartan was safe and well tolerated.

Background: The latest guidelines recommend early intervention in adult atrial septal defect (ASD) patients with signs of right ventricular (RV) enlargement. However, the criteria of RV enlargement for optimal intervention remain unclear. We investigated the preoperative determinants for normalizing the RV volume after transcatheter closure of ASD in adults., Methods and results: We retrospectively analyzed 52 ASD patients who underwent transcatheter closure. Cardiac magnetic resonance imaging (CMR) measured RV volume before and 1 year after the closure. The patients were divided into normalized (postoperative RV end-systolic volume index [RVESVI] <47 mL/m 2 and end-diastolic volume index [RVEDVI] <108 mL/m 2 ) and non-normalized (postoperative RVESVI ≥47 mL/m 2 or RVEDVI ≥108 mL/m 2 ) groups. Preoperative RVESVI was significantly smaller (72 mL/m 2 vs. 80 mL/m 2 ) and RVEF was higher (56% vs. 51%) in the normalized group compared with the non-normalized group. Receiver-operating characteristic analysis for the normalization of postoperative RV volume showed that the preoperative threshold value of RVESVI was 75 mL/m 2 . In addition, multivariate analysis showed that preoperative RVESVI was an independent predictor for normalization of RV volume., Conclusions: Preoperative RVESVI is an independent predictor for normalization of RV volume at 1 year after transcatheter closure of ASD in adults. Early intervention before RVESVI reaches 75 mL/m 2 may confer optimal timing for normalizing RV volume.

Background: Ischemic preconditioning (IPC) is an effective procedure to protect against ischemia/reperfusion (I/R) injury. Hypoxia-inducible factor-1α (Hif-1α) is a key molecule in IPC, and roxadustat (RXD), a first-in-class prolyl hydroxylase domain-containing protein inhibitor, has been recently developed to treat anemia in patients with chronic kidney disease. Thus, we investigated whether RXD pretreatment protects against I/R injury., Methods and results: RXD pretreatment markedly reduced the infarct size and suppressed plasma creatinine kinase activity in a murine I/R model. Analysis of oxygen metabolism showed that RXD could produce ischemic tolerance by shifting metabolism from aerobic to anaerobic respiration., Conclusions: RXD pretreatment may be a novel strategy against I/R injury.

Background: An inverse relationship exists between hospital case volume and mortality in patients with heart failure (HF). However, hospital performance factors associated with mortality in HF patients have not been examined. We aimed to identify these using exploratory factor analysis and assess the relationship between these factors and 7-day, 30-day, and in-hospital mortality among HF patients in Japan., Methods and results: We analyzed the records of 198,861 patients admitted to 683 certified hospitals of the Japanese Circulation Society between 2012 and 2014. Records were obtained from the nationwide database of the Japanese Registry Of All cardiac and vascular Diseases-Diagnostic Procedure Combination (JROAD-DPC). Using exploratory factor analysis, 90 hospital survey items were grouped into 5 factors, according to their collinearity: "Interventional cardiology", "Cardiovascular surgery", "Pediatric cardiology", "Electrophysiology" and "Cardiac rehabilitation". Multivariable logistic regression analysis was performed to determine the association between these factors and mortality. The 30-day mortality was 8.0%. Multivariable logistic regression analysis showed the "Pediatric cardiology" (odds ratio (OR) 0.677, 95% confidence interval [CI]: 0.628-0.729, P<0.0001), "Electrophysiology" (OR 0.876, 95% CI: 0.832-0.923, P<0.0001), and "Cardiac rehabilitation" (OR 0.832, 95% CI: 0.792-0.873, P<0.0001) factors were associated with lower mortality. In contrast, "Interventional cardiology" (OR 1.167, 95% CI: 1.070-1.272, P<0.0001) was associated with higher mortality., Conclusions: Hospital factors, including various cardiovascular therapeutic practices, may be associated with the early death of HF patients.

Background: Despite the well-established benefits in patients with non-valvular atrial fibrillation (NVAF), oral anticoagulants (OAC) have been underused in elderly patients. We investigated the characteristics and status of anti-thrombotic therapy in elderly NVAF patients in Japan according to a history of stroke or of transient ischemic attack (TIA)., Methods and results: In a multicenter, prospective, observational study, 32,726 Japanese patients aged ≥75 years with NVAF were enrolled, and divided into 3 groups for the present analysis: 6,543 patients with previous ischemic stroke (IS) or TIA (2,410 women), 275 with previous hemorrhagic stroke (HS; 113 women), and the other 25,908 without previous stroke or TIA (11,470 women). Median CHADS 2 score was 5 in patients with IS/TIA, 2 in those with HS and 2 in those without stroke/TIA (P<0.05). Anti-thrombotic agents were used in 97.1% of patients with IS/TIA (OAC alone in 73.0%; antiplatelets alone in 3.7%; and both in 23.4%), 90.2% of those with HS (84.7%, 3.2%, and 12.1%, respectively), and 94.1% of those without stroke/TIA (83.4%, 2.7%, and 13.9%, respectively; P<0.05 for any anti-thrombotic choice). Of patients taking OAC, 72.2% received direct OAC (DOAC)., Conclusions: In this unique nationwide NVAF registry of >30,000 elderly patients, >90% of patients, even those with HS, received anti-thrombotic therapy, nearly always with OAC. DOAC were the major choice of OAC.

Background: Atrial fibrillation (AF) is increasing as the global population ages. Elderly AF patients (≥75 years) have a worse prognosis than younger patients, and effective management is often difficult due to multiple comorbidities. This analysis examined the age-related differences in clinical characteristics and treatment in real-world elderly Japanese AF patients., Methods and results: The ANAFIE Registry is a multicenter, prospective, observational registry of 32,726 non-valvular AF patients aged ≥75 years. The present study assessed the age-related differences in baseline clinical status and anticoagulant therapy between age groups 75-<80, 80-<85, 85-<90, and ≥90 years. The prevalence of persistent or permanent AF increased, and that of paroxysmal AF decreased, with increasing age (trend P<0.0001). The risk of stroke, based on CHADS 2 and CHA 2 DS 2 -VASc scores, and bleeding, based on HAS-BLED score, increased with age. Both warfarin and apixaban were used more often as age increased (trend P<0.0001, for each), while other anticoagulants were used less. Anticoagulant doses were significantly lower in older patients., Conclusions: Permanent/persistent AF, comorbidities, and cardiovascular and bleeding risk all increased significantly with age. Furthermore, use of warfarin and apixaban increased with age, accompanied by a decrease in other oral anticoagulant usage.

Background: This study examined the association between prehospital supraglottic airway (SGA) and/or epinephrine compared with bag-mask ventilation (BMV) and Glasgow-Pittsburgh cerebral performance category (CPC) 1 status in patients with out-of-hospital cardiac arrest (OHCA) using a large, nationwide, population-based registry dataset., Methods and results: This was a post hoc analysis of the All-Japan Utstein Registry. We included patients with OHCA of cardiac origin aged ≥18 years with resuscitation performed by emergency medical services (EMS) between January 2011 and December 2015. The primary endpoint was favorable neurological outcome (CPC 1). The patients were divided into 4 groups according to the prehospital management performed by EMS: BMV group received only basic life support (BLS); epinephrine group received BLS plus epinephrine; SGA group received BLS plus SGA; and combined group received BLS plus epinephrine and SGA. Univariate and multivariable logistic regression analyses were performed for the primary endpoint. Among the 106,434 patients with OHCA, 48,847 received only BMV, 8,958 received BLS+epinephrine, 25,467 received BLS+SGA, and 15,551 received BLS+epinephrine+SGA. Using the BMV group as the reference, multivariable analysis showed that the epinephrine, SGA, and combined groups were independently associated with a reduced incidence of favorable neurological outcomes., Conclusions: Our results indicated that compared with BLS, patients in the prehospital SGA and/or epinephrine groups had a significantly reduced incidence of CPC 1 status.

Background: The average maternal age at delivery, and thus the associated maternal risk are increasing including in women with congenital heart disease (CHD). A comprehensive management approach is therefore required for pregnant women with CHD. The present study aimed to investigate the factors determining peripartum safety in women with CHD., Methods and results: We retrospectively collected multicenter data for 217 pregnant women with CHD (age at delivery: 31.4±5.6 years; NYHA classifications I and II: 88.9% and 7.4%, respectively). CHD severity was classified according to the American College of Cardiology/American Heart Association guidelines as simple (n=116), moderate complexity (n=69), or great complexity (n=32). Cardiovascular (CV) events (heart failure: n=24, arrhythmia: n=9) occurred in 30 women during the peripartum period. Moderate or great complexity CHD was associated with more CV events during gestation than simple CHD. CV events occurred earlier in women with moderate or great complexity compared with simple CHD. Number of deliveries (multiparity), NYHA functional class, and severity of CHD were predictors of CV events., Conclusions: This study identified not only the severity of CHD according to the ACC/AHA and NYHA classifications, but also the number of deliveries, as important predictive factors of CV events in women with CHD. This information should be made available to women with CHD and medical personnel to promote safe deliveries.

Background: Increased heart rate (HR) is an independent risk factor for cardiovascular outcomes in chronic heart failure (HF). Ivabradine, anI f inhibitor, improved outcomes in patients with HF and reduced ejection fraction (HFrEF) in the SHIFT study. We evaluated its efficacy and safety in Japanese HFrEF patients in a randomized, double-blind, placebo-controlled phase III study: the J-SHIFT study. The main objective was to confirm a hazard ratio of <1 in the primary composite endpoint of cardiovascular death or hospital admission for worsening HF., Methods and results: Patients with NYHA functional class II-IV, left ventricular EF ≤35%, and resting HR ≥75 beats/min in sinus rhythm under optimal medical therapy received ivabradine (n=127) or placebo (n=127). Mean reduction in resting HR was significantly greater in the ivabradine group (15.2 vs. 6.1 beats/min, P<0.0001). However, symptomatic bradycardia did not occur. A total of 26 (20.5%) patients in the ivabradine group and 37 (29.1%) patients in the placebo group had the primary endpoint event (hazard ratio 0.67, 95% CI 0.40-1.11, P=0.1179) during median follow-up of 589 days. Mild phosphenes were reported in 8 (6.3%) patients in the ivabradine group and 4 (3.1%) patients in the placebo group (P=0.3760)., Conclusions: The J-SHIFT study supported the efficacy and safety of ivabradine for Japanese HFrEF patients, in accord with the SHIFT study.

Background: The purpose of this study was to clarify the implementation rate of multidisciplinary heart failure (HF) care and cardiac rehabilitation (CR) in Japan, as well as the relationship between implementation rates and characteristics of the facility.Methods and Results:Survey participants were cardiologists who are members of the Japan Heart Failure Society and belonged to 1 of 845 medical institutions that are members of the Japan Heart Failure Society, as of April 2016. A total of 288 institutions (34.1%) returned the questionnaire. The percentages of hospitals implementing multidisciplinary HF care were 78.5% for inpatients and 32.6% for outpatients with HF. Inpatient and outpatient CR for HF had implementation rates of 80.4% and 56.5%, respectively. In addition, very few HF patients (7.3%, 3,741/51,323 patients) received outpatient CR. Both the presence of nurses certified in chronic HF care and registered CR instructors on staff were consistently associated with implementation of multidisciplinary HF care, and Japanese Circulation Society training hospitals, lower number of hospital beds, and presence of registered CR instructors on staff were consistently associated with implementation of CR., Conclusions: This first nationwide survey demonstrated that the implementation rates of multidisciplinary care and CR for HF, especially for outpatients, are low in Japan. Skilled healthcare professionals are expected to play important roles in the widespread implementation of this type of HF care in Japan.