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Background: The prognostic implication of mildly reduced ejection fraction (mrEF) after acute myocardial infarction has not been clearly demonstrated. We investigated the long-term risk of cardiovascular death and its predictors in patients with mrEF following acute myocardial infarction., Methods and Results: A total of 18 668 patients who presented with acute myocardial infarction were included in 2 prospective, multicenter registries. The incidence of adverse cardiovascular events according to the left ventricular ejection fraction (EF) strata at index admission were evaluated. A score system consisting of clinical variables were developed to predict long-term cardiovascular death in the mrEF group. There were 2548 patients with reduced EF (EF ≤40%), 4266 patients with mrEF (EF 41%-49%), and 11 854 patients with preserved EF (EF ≥50%). During a median follow-up period of 37.9 months, the cardiovascular death rate was 22.3% in the reduced EF group, 10.3% in the mrEF group, and 7.3% in the preserved EF group ( P <0.001). In the mrEF group, age>65 years, hypertension, stroke, severe renal insufficiency, and Killip class ≥3 were independent predictors for cardiovascular death. Presence of >2 predictors best discriminated the high-risk patients for cardiovascular death with an area under the curve of 0.746. Incidence of cardiovascular death in the high-risk mrEF group was comparable with the rEF group, while it was lower in the low-risk mrEF group than in the pEF group., Conclusions: Patients with mrEF after acute myocardial infarction had a modest risk of cardiovascular death. Clinical predictors could help discriminate a high-risk subpopulation with cardiovascular death risks comparable with those in the reduced EF group.

Aims: Atrial fibrillation (AF) frequently coexists with heart failure with preserved ejection fraction (HFpEF), and clinical outcomes of patients with AF vary depending on its subtype. While AF progression characterized by the transition from paroxysmal AF to persistent AF is sometimes observed, the incidence and clinical impact of AF progression in patients with HFpEF remain to be explored., Methods and Results: We enrolled patients with HFpEF and paroxysmal AF from the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study. AF progression was defined as the transition from paroxysmal AF to persistent AF. A total of 718 patients (median age: 72 years, 36% were female) were enrolled. For a median follow-up of 6.0 years (interquartile range: 3.0-10.2 years), AF progression occurred in 105 patients (14.6%), with a cumulative incidence of 16.7% at 10 years. In the multivariable Cox proportional hazards model, previous hospitalization for heart failure [hazard ratio (HR) 1.74, 95% confidence interval (CI) 1.16-2.60; P = 0.007] and left atrial diameter (per 5-mm increase) (HR 1.37, 95% CI 1.20-1.55; P < 0.001) were significantly associated with AF progression. Furthermore, AF progression was significantly linked to worsening heart failure (adjusted HR 1.68, 95% CI 1.18-2.40; P = 0.004). Notably, 27 cases (26%) of worsening heart failure occurred within 1 year following AF progression., Conclusion: In patients with HFpEF, AF progression is significantly associated with adverse outcomes, particularly worsening heart failure. An increased risk is observed in the early phases following progression to persistent AF., Registration: Clinical Trials.gov Identifier: NCT00418041., Competing Interests: Conflict of interest: H.S. has received lecture fees from Bayer Yakuhin (Osaka, Japan) and Daiichi Sankyo (Tokyo, Japan). S.Y. has received lecture fees from Bristol-Meyers (Tokyo, Japan), Bayer Yakuhin (Osaka, Japan) and Daiichi Sankyo (Tokyo, Japan). T.N. has recieved Grants-in-Aid for Scientific Research (22K08092) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and personal fees from Bayer Yakuhin (Osaka, Japan), Medtronic Japan (Tokyo, Japan), and Biotronik Japan (Tokyo, Japan). The remaining authors have no conflicts of interest to be disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Age-related changes in left ventricular (LV) structure and function lower the threshold for the onset of heart failure with preserved ejection fraction (HFpEF). LV parameters change also with race; however, the racial differences in age-related changes in LV parameters with and without adjustment for body mass index (BMI), heart rate (HR), and blood pressure (BP) remain unclear., Methods and Results: We performed a subanalysis of the World Alliance Society of Echocardiography Normal Values Study, an international cross-sectional study that examined normal echocardiographic values in 15 countries. The age-related changes in 2-dimensional echocardiographic derived parameters including LV size, systolic function, and mass, were compared between healthy Japanese (n=227) and healthy White (n=98) and Black (n=69) American participants. In men, age-related changes in all parameters did not differ significantly among races. However, compared with Japanese women, White American women had a smaller body surface area (BSA)-indexed LV volume, BSA-indexed LV internal dimension at end-systole, BSA-indexed LV stroke volume, and LV mass index to BSA, and a larger LV ejection fraction with age, even after adjusting for BMI, HR, and BP., Conclusions: Age-related changes in LV structure and function, which are important for the pathophysiology of HFpEF, may differ by race. Therefore, future studies examining echocardiographic reference values for each age group in each race are needed.

The prevalence of heart failure has increased in many developed countries including Japan and the USA, due in large part to the aging of their populations. The lifetime risk of heart failure is now 20-30 % in the USA. Fortunately, there have been important advances in therapy that increase quality and length of life for those with heart failure. This review discusses the important advances in care including treatment and diagnosis and the new recommendations for this care from the recent American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Failure Society of America (HFSA) Guideline. Relevant studies that have been published since the guideline was released are also included. Of the many recommendations in the ACC/AHA/HFSA Guideline, this review focuses on the definition of heart failure, the medical treatments specific to left ventricular ejection fraction, use of devices for treatment and diagnosis, diagnosis and treatment of amyloidosis, treatment of iron deficiency, screening for asymptomatic left ventricular dysfunction, use of patient reported outcomes, and tools for implementation., Competing Interests: Declaration of competing interest There are no conflicts of interest including relationships with industry related to the content of this article., (Copyright © 2023. Published by Elsevier Ltd.)

We present a single-center retrospective analysis of 228 Japanese patients with peritoneal dialysis, in which we examined whether reduced left ventricular ejection fraction (LVEF) is a risk factor for peritonitis development. Time-dependent multivariable-adjusted Cox proportional hazards models revealed that reduced LVEF (LVEF < 50% vs. preserved LVEF ≥ 50%, hazard ratio (HR) 2.10; 95% confidence interval (CI) 1.16-3.82) was associated with peritonitis. Qualitatively, similar associations with reduced LVEF (< 50%) were observed for enteric peritonitis (adjusted HR 7.68; 95% CI 2.51-23.5) but not for non-enteric peritonitis (adjusted HR 1.15; 95% CI 0.54-2.44). Reduced LVEF is associated with a significantly higher risk of subsequent peritonitis, particularly enteric peritonitis. These results indicate that patients with reduced LVEF may be at risk of enteric peritonitis from bowel sources caused by intestinal involvement due to cardiac dysfunction., (© 2023. The Author(s).)

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: Endothelial dysfunction and increased left ventricular (LV) stiffness are associated with the incidence of heart failure with preserved ejection fraction (HFpEF). This study evaluated the association between endothelial dysfunction and LV diastolic stiffness., Methods and results: Endothelial dysfunction evaluated by flow-medicated vasodilation (FMD) and the reactive hyperemia index (RHI), which reflects endothelial dysfunction in the microvasculature, was measured in 112 subjects with hypertension in the Flow-Mediated Dilation Japan (FMD-J) study. Using transthoracic echocardiography, LV diastolic stiffness was evaluated by measuring diastolic wall strain (DWS) in the LV posterior wall. In this cross-sectional study, associations among FMD, RHI, and DWS were investigated using multiple regression analyses. The mean (±SD) age of the subjects 65±9 years, and 63% were men. DWS was significantly associated with RHI, but not FMD, on multivariate linear regression analysis (β=0.39; P<0.0001). This association was preserved in subjects without LV hypertrophy (β=0.46; P<0.0001). A DWS ≤median, suggesting increased LV diastolic stiffness, was significantly associated with RHI on multivariate logistic regression analysis (odds ratio 20.58; 95% confidence interval 4.83-87.63; P<0.0001). The receiver operating characteristic curve presented a cut-off value of 2.21 for RHI, with a sensitivity of 77% and a specificity of 71%, for DWS ≤median., Conclusions: RHI, rather than FMD, was associated with DWS. Endothelial dysfunction in the microvasculature may be associated with increased LV diastolic stiffness.

Objective: In Japan, the benefits of hospitalist physician-led care after heart failure have not been sufficiently demonstrated. We evaluated quality of care by the general internal medicine hospitalist (GIM-H) system for patients after acute heart failure and compared it with care by cardiologists., Methods: This retrospective cohort study enrolled adult patients from within a two-year period who were admitted to our institution for heart failure. Primary outcome measures were medico-economic indicators: length of hospital stay and medical costs. Secondary outcomes included readmission within 30 days of discharge, death within 30 days of admission, rate of prescription of ACEI/ARB and beta-blockers for heart failure with reduced left ventricular ejection fraction, and the percentage of patients receiving bespoke written treatment plans after discharge. This was thought to represent quality of heart failure-specific care. Outcomes between the groups were compared by adjusting for background factors using a propensity score., Results: We enrolled 404 patients, and 81 were assigned to each group after matching (mean age: 86 years, female: 64.2%, mean left ventricular ejection fraction: 53.2%). The GIM-H-treated group had a significantly shorter hospital stay (13.7 days vs. 21.8 days, P < 0.001), a significantly lower total medical cost (618,805 JPY vs. 867,857 JPY, P < 0.05) but a higher medical cost per day (48,010 JPY vs 42,813 JPY, P < 0.05) than the cardiologist-treated group. Other indicators were not significantly different., Conclusions: : GIM-H physicians in Japan are suggested to be useful and effective in care of patients with heart failure. The hospitalist system may positively impact the health economic outcomes of such 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.

Catheter-based micro-axial ventricular assist device Impella® (Abiomed, Danvers, MA) has been used in Japanese patients with drug-refractory acute heart failure (AHF) since 2017. This is the first interim analysis of the ongoing Japan Registry for Percutaneous Ventricular Assist Device (J-PVAD) to investigate the safety and efficacy of Impella support. Between October 2017 and January 2020, 823 Japanese patients, who were treated with the Impella 2.5, CP, or 5.0 pump, were enrolled. The primary endpoints were safety profiles and cumulative 30-day survival. Among them, 44.8% of patients were acute myocardial infarction with cardiogenic shock. The Impella pumps were unable to implant in 4 patients. The Impella 2.5, CP, and 5.0 pumps were used in 72.4%, 6.2%, and 16.6%, respectively, and mean support duration was 8.1 ± 10.2 days. Combination use of Impella and venoarterial extracorporeal membrane oxygenation (VA-ECMO) was applied for 387 patients (47.3%). Pump stop occurred 22 patients (2.7%). Major adverse events included hemolysis (11.2%), hemorrhage/hematoma (6.1%), peripheral ischemia (1.6%), and stroke (1.6%). The overall 30-day survival was 62.2%. Survival of patients with single Impella support was significantly higher than patients with Impella combined with VA-ECMO support (81.1% vs 49.6%; p < 0.01), who had lower blood pressure, lower left ventricular ejection fraction, and higher degree of inotropic support. Results suggest that short-term outcome of Impella support for Japanese patients was favorable with acceptable safety profiles., (© 2022. The Japanese Society for Artificial Organs.)

Background: Successful implantation of the WATCHMAN device requires an accurate understanding of left atrial appendage (LAA) anatomy and orifice dimensions. Racial differences are observed in LAA size when comparing Asians with non-Asians., Methods: A total of 170 patients (123 male, 67.4 ± 9.2 years) with paroxysmal or persistent atrial fibrillation (AF) underwent transesophageal echocardiography before catheter ablation or cardioversion (September 2018 to September 2019). As per the recommendations of the WATCHMAN device, the maximal LAA ostial diameters were measured at multiplane angles of 0°, 45°, 90°, and 135°., Results: The majority of patients (121/170, 71%) had an LAA orifice size within 17-25 mm. Fifteen (8.8%) patients had undersized (< 17 mm) and eight (0.5%) had oversized (> 31 mm) LAA. One patient in this population had no LAA. LAA size was significantly larger in patients with persistent AF than in those with paroxysmal AF (23.3 ± 4.2 mm vs. 20.0 ± 3.0 mm, p < 0.001) and in male patients than in female patients (22.4 ± 4.2 vs. 20.9 ± 3.7 mm, p = 0.03). LAA orifice dimension was significantly correlated with CHADS 2 score, the left atrial volume (LAV), E/e', and the left ventricular ejection fraction. Persistent AF, body mass index, and LAV were independently associated with LAA orifice dimension in multivariate analysis., Conclusion: This study demonstrated the distribution of LAA orifice dimension in the Japanese AF patients. This finding should be used as a reference to understand the racial characteristics of LAA size for the WATCHMAN procedure., (© 2022. Japanese Society of Echocardiography.)

Aims: This study evaluated the prognosis and prognostic factors of patients with cardiac sarcoidosis (CS), an underdiagnosed disease., Methods and Results: Patients from a retrospective multicentre registry, diagnosed with CS between 2001 and 2017 based on the 2016 Japanese Circulation Society or 2014 Heart Rhythm Society criteria, were included. The primary endpoint was a composite of all-cause death, hospitalization for heart failure, and documented fatal ventricular arrhythmia events (FVAE), each constituting exploratory endpoints. Among 512 registered patients, 148 combined events (56 heart failure hospitalizations, 99 documented FVAE, and 49 all-cause deaths) were observed during a median follow-up of 1042 (interquartile range: 518-1917) days. The 10-year estimated event rates for the primary endpoint, all-cause death, heart failure hospitalizations, and FVAE were 48.1, 18.0, 21.1, and 31.9%, respectively. On multivariable Cox regression, a history of ventricular tachycardia (VT) or fibrillation [hazard ratio (HR) 2.53, 95% confidence interval (CI) 1.59-4.00, P < 0.001], log-transformed brain natriuretic peptide (BNP) levels (HR 1.28, 95% CI 1.07-1.53, P = 0.008), left ventricular ejection fraction (LVEF) (HR 0.94 per 5% increase, 95% CI 0.88-1.00, P = 0.046), and post-diagnosis radiofrequency ablation for VT (HR 2.65, 95% CI 1.02-6.86, P = 0.045) independently predicted the primary endpoint., Conclusion: Although mortality is relatively low in CS, adverse events are common, mainly due to FVAE. Patients with low LVEF, with high BNP levels, with VT/fibrillation history, and requiring ablation to treat VT are at high risk., Competing Interests: Conflict of interest: Y.M. received an honorarium from Otsuka Pharmaceutical Co. and Novartis Japan. Other authors have nothing to declare., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background In the population with cardiac sarcoidosis (CS), approximately one third lacks extracardiac involvement and is considered to have isolated CS. Recently, the Japanese Circulation Society updated the diagnostic criteria for CS, providing a methodology for diagnosing isolated CS. We aimed to assess the characteristics of isolated CS diagnosed using a multimodal imaging approach according to the updated Japanese Circulation Society guidelines. Methods and Results We retrospectively identified 161 consecutive patients who underwent 18F-fluorodeoxyglucose positron emission tomography for suspected CS between 2012 and 2019. According to the guidelines, patients were classified as having CS with extracardiac involvement, isolated CS, or no CS. We compared the characteristics of multimodality imaging and the prevalence of major adverse cardiovascular events. The Japanese Circulation Society criteria classified 28 patients (17%) as having CS with 4 (2%) with histological confirmation, 21 (13%) as isolated CS, and 112 (70%) as no CS. Compared with CS, isolated CS showed higher left ventricular volume and reduced left ventricular ejection fraction ( P <0.01 for all). During the median follow-up period of 522 days, 24 patients had major adverse cardiovascular events. Isolated CS (hazard ratio, 3.35; [95% CI, 1.08-10.39], P =0.036) was independently associated with major adverse cardiovascular events after adjusting for reduced left ventricular ejection fraction and steroid. In the subgroup of 41 patients with serial 18F-fluorodeoxyglucose positron emission tomography evaluation, only updated CS criteria were associated with improvement in myocardial inflammation on 18F-fluorodeoxyglucose positron emission tomography. Conclusions Isolated CS detected using the updated Japanese Circulation Society guidelines was associated with poor event-free survival and should be managed with caution.

Objectives: To evaluate the procedural results and in-hospital outcomes of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) in patients with reduced left ventricular ejection fraction (LVEF)., Background: While the technical success of general CTO-PCI has improved, CTO-PCI patients with reduced LVEF remain at high-risk for adverse events., Methods: The data of 820 patients with LVEF ≤ 35% (Group 1), 1816 patients with LVEF = 35%-50% (Group 2), and 5503 patients with LVEF ≥ 50% (Group 3), registered in the Japanese CTO-PCI Expert Registry from January 2014 to December 2019, were retrospectively analyzed. The primary endpoint was in-hospital major adverse cardiac or cerebrovascular events (MACCEs), including death, myocardial infarction, stent thrombosis, stroke, and emergent revascularization. Secondary endpoints included procedural details, guidewire success, and technical success., Results: There were no differences in guidewire and technical success rates between the groups. In-hospital MACCEs was significantly higher in Group 1 (Group 1 vs. Group 2 vs. Group 3: 3.4% vs. 1.7% vs. 1.5%, p = 0.001) and was especially driven by death (1.3% vs. 0.3% vs. 0.1%, p < 0.001) and stroke (0.7% vs. 0.2% vs. 0.2%, p = 0.007). Multivariate analysis showed that LVEF ≤ 35% (odds ratio [OR]; 1.58, 95% confidence interval [CI]; 1.04-2.41, p = 0.03) and New York Heart Association (NYHA) class ≥ 3 (OR; 2.01, 95% CI; 1.03-3.93, p = 0.04) were predictors of in-hospital MACCEs., Conclusions: In-hospital MACCEs were significantly higher in patients with LVEF ≤ 35%. LVEF ≤;35% and NYHA class ≥ 3 were predictors of in-hospital MACCEs after CTO-PCI., (© 2022 Wiley Periodicals LLC.)

Background: Tafamidis has emerged as an effective treatment for patients with wild-type transthyretin cardiac amyloidosis (ATTRwt CA). The early experience of tafamidis treatment for Japanese patients with ATTRwt CA is reported here., Methods and results: Over the past 2 years, in 82 patients with ATTRwt CA (mean age of 81.7±6.0 years), tafamidis treatment was initiated for 38 patients. The remaining 44 patients were not administered tafamidis. The most frequent reason for non-administration of tafamidis was advanced heart failure and the second most reason was the patient's frailty. In patients who received tafamidis treatment, there was no discontinuation of tafamidis due to adverse events, the rate of cardiovascular-related hospitalizations per year was 0.19, and the 1-year survival rate was 92%. In the patients who continued tafamidis for 12-18 months, there was no significant deterioration from baseline for high-sensitivity cardiac troponin T level, plasma B-type natriuretic peptide level, left ventricular ejection fraction, inter-ventricular septum wall thickness, or value of left ventricular longitudinal strain., Conclusions: Tafamidis treatment was introduced for approximately half of the study patients with ATTRwt CA in real-world practice. Tafamidis is likely to be safe and may maintain the status of disease severity in the short-term in selected Japanese patients with ATTRwt CA. Further research is needed to determine appropriate patient selection for tafamidis treatment and efficacy of tafamidis in the long term.

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., (© 2022 Guidant Europe NV as part of Boston Scientific Corp. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objectives: Microscopic polyangiitis (MPA) affects various organs. However, echocardiographic findings of MPA are unclear. We aimed to evaluate the echocardiographic features of acute-phase MPA in Japanese patients., Methods: This single-centre retrospective study included 15 patients with MPA who underwent echocardiography within 2 weeks of commencing steroid therapy for induction or reinduction. The echocardiography parameters of thetients were compared with those of 30 age- and sex-matched controls., Results: No significant differences in left ventricular (LV) diameter, LV ejection fraction, or e' were observed between the two groups. However, the MPA group showed a significantly higher left atrial (LA) diameter and LA volume index, as well as higher early diastolic filling velocity, diastolic pulmonary venous flow velocity, and trans-tricuspid pressure gradient, and a shorter deceleration time (DCT). Serum C-reactive protein levels were positively correlated with E wave, E/A, and DCT. These results may indicate that increased LV stiffness, rather than impairment of LV relaxation, contributed to LV diastolic function, resulting in LA enlargement., Conclusions: Patients with acute-phase MPA had LA dilatation associated with LV diastolic dysfunction. This finding indicates the importance of cardiac assessment in patients with MPA, especially in patients with a strong inflammatory reaction., (© Japan College of Rheumatology 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study examined quality indicators (QIs) for heart failure (HF) in patients' referral documents (PRDs).We conducted a nationwide questionnaire survey to identify information that general practitioners (GPs) would like hospital cardiologists (HCs) to include in PRDs and that HCs actually include in PRDs. The percentage of GPs that desired each item included in PRDs was converted into a deviation score, and items with a deviation score of ≥ 50 were defined as QIs. We rated the quality of PRDs provided by HCs based on QI assessment.We received 281 responses from HCs and 145 responses from GPs. The following were identified as QIs: 1) HF cause; 2) B-type natriuretic peptide (BNP) or N-terminal pro-BNP concentration; 3) left ventricular ejection fraction or echocardiography; 4) body weight; 5) education of patients and their families on HF; 6) physical function, and 7) functions of daily living. Based on QI assessment, only 21.7% of HCs included all seven items in their PRDs. HCs specializing in HF and institutions with many full-time HCs were independently associated with including the seven items in PRDs.The quality of PRDs for HF varies among physicians and hospitals, and standardization is needed based on QI assessment.

Background: While there are a variety of surgical options for hypertrophic cardiomyopathy, there are small number of reports of transapical septal myectomy. Furthermore, the characteristics and incidence of anomalous structures in the left ventricle in hypertrophic cardiomyopathy patients which can be identified with imaging studies are not clear., Methods: We studied hypertrophic cardiomyopathy patients who underwent transapical septal myectomy from July 2013 to December 2019. We evaluated the frequency and characteristics of anomalous structures in the left ventricle which had been identified by preoperative examinations and studied their postoperative results., Results: A total of 59 patients was included. The median age was 40 years. Sixteen patients (27.4%) were in New York Heart Association Functional Classification III or IV. The median peak intraventricular gradient at rest was 65 mmHg. By preoperative imaging studies, anomalous structures were detected in 56 cases (94.9%), of which 88% were successfully resected with myectomy. There were two perioperative deaths, while one late death caused by acute myocardial infarction occurred. The estimated 5-year survival rate was 95%. The intraventricular gradient had significantly decreased at the time of discharge, and no reoperation for recurrent obstruction was conducted. The left ventricular ejection fraction had significantly decreased after the operation, was however within the normal range. Left atrium volume index and tricuspid regurgitant velocity significantly improved., Conclusions: Patients receiving transapical septal myectomy restored good hemodynamics from early postoperative period and showed improved subjective symptoms and good mid-term results. With multimodal imaging studies, we could accurately identify anomalous structures in hypertrophic cardiomyopathy patients and reliably treat them by transapical septal myectomy.

Background: Heart failure in elderly people causes physical and cognitive dysfunction and often requires long-term care insurance (LTCI); however, among patients with left ventricular (LV) systolic dysfunction, the incidence and risk factors of future LTCI requirements need to be elucidated., Methods and results: The study included 1,852 patients aged ≥65 years with an echocardiographic LV ejection fraction (LVEF) ≤50%; we referred to their LTCI data and those of 113,038 community-dwelling elderly people. During a mean 1.7-year period, 332 patients newly required LTCI (incidence 10.7 per 100 person-years); the incidence was significantly higher than that for the community-dwelling people (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.32-1.64). On multivariate analysis, the risk factors at the time of echocardiography leading to future LTCI requirement were atrial fibrillation (HR, 1.588; 95% CI, 1.279-1.971), history of stroke (HR, 2.02; 95% CI, 1.583-2.576), osteoporosis (HR, 1.738; 95% CI, 1.253-2.41), dementia (HR, 2.804; 95% CI, 2.075-3.789), hypnotics (HR, 1.461; 95% CI, 1.148-1.859), and diuretics (HR, 1.417; 95% CI, 1.132-1.773); however, the LVEF was not a risk factor (HR, 0.997; 95% CI, 0.983-1.011)., Conclusions: In elderly patients with LV systolic dysfunction, the incidence of LTCI requirement was more common than that for community-dwelling people; its risk factors did not include LVEF, but included many other non-cardiac comorbidities and therapies, suggesting the need for interdisciplinary cooperation to prevent disabilities.

Purpose: In the era of COVID-19, those special settings or indications for which standard transthoracic echocardiography (TTE) can safely produce benefits or advantages over minimized ultrasound imaging procedures need to be identified. Thus, the purpose of this study was to conduct a retrospective analysis with offline comprehensive conventional measurement of bilateral heart function and develop an appropriate prognostic model for in-hospital death., Methods: We performed a retrospective analysis of 37 consecutive patients with COVID-19, confirmed by real-time reverse-transcriptase polymerase chain reaction assay, who had undergone clinically indicated standard two-dimensional echocardiographic studies in intensive care wards. Offline comprehensive measurement was also performed. We further integrated the echocardiographic findings as paired evidence of vital organ involvement (possible respiratory distress assessed using right ventricular functional parameters, possible myocardial injury assessed using increased wall thickness, effusion or asynergy) and circulatory failure (suspected low flow status assessed using stroke volume index, suspected congestion assessed using elevated right or left atrial pressure). We evaluated its value for in-hospital death along with other echocardiographic findings., Results: The most common features included a normal-sized left atrium and left ventricle with preserved left ventricular ejection fraction, despite deteriorated left ventricular flow volume. Less frequent findings, such as abnormalities in the right heart and left ventricular abnormalities suggesting myocarditis, were observed. Although the single echocardiographic parameters failed to show predictive values for in-hospital death, integration of the echocardiographic findings suggested predictive value (p = 0.04, odds ratio: 12.28)., Conclusion: Standard TTE at the bedside with offline comprehensive conventional measurement may provide prognostic information that is valuable for the management of patients with COVID-19., (© 2021. The Japan Society of Ultrasonics in Medicine.)

Background: Although limited walking ability at discharge is a known risk factor for adverse outcomes in older patients with heart failure (HF), the association between pre-admission limitations and adverse outcomes is unknown. Therefore, we evaluated the prevalence of a pre-admission limitation in walking ability and its relationship with post-discharge outcomes among patients with HF with reduced, mid-range, and preserved left-ventricular ejection fraction (HFrEF, HFmrEF, and HFpEF)., Methods: We followed 2042 patients aged ≥65 years (HFrEF, n = 668; HFmrEF, n = 360; HFpEF, n = 1014) from a multicenter cohort study in Japan. A limitation in walking ability was defined as the necessity of any assistance or a walking aid. Adverse outcomes were defined as the composite of HF rehospitalization and all-cause death within 2 years after discharge., Results: During 2978.0 person-years of follow-up, 563 patients were rehospitalized due to HF exacerbation and 103 patients died. In HFrEF, HFmrEF, and HFpEF groups, the prevalence of a pre-admission limitation in walking ability was 12.1%, 18.6%, and 21.1%, respectively, the crude hazard ratios [95% confidence interval] of a pre-admission limitation in walking ability were 2.46 [1.79-3.39], 1.34 [0.87-2.06], and 1.94 [1.53-2.47], and the adjusted hazard ratios were 2.21 [1.58-3.16], 1.19 [0.75-1.89], and 1.39 [1.06-1.82], respectively., Conclusions: A pre-admission limitation in walking ability is a predictor of post-discharge HF rehospitalization or all-cause death among patients with HFrEF and HFpEF, but not among patients with HFmrEF. Shortly after admission, information regarding pre-admission functional limitations should be obtained to better understand the risk of post-discharge adverse outcomes., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Some cardiac abnormalities could be a substrate for potential embolic source in cryptogenic stroke (CS). We evaluated whether cardiac and echocardiographic markers were associated with CS in patients with incidental patent foramen ovale (PFO) as defined using the Risk of Paradoxical Embolism (RoPE) score., Materials and Methods: Among 677 patients enrolled in a multicenter observational CS registry, 300 patients (44%) had PFOs detected by transesophageal echocardiography. They were classified into probable PFO-related stroke (RoPE score>6, n = 32) and stroke with incidental PFO (RoPE score≤6, n = 268) groups, and clinical characteristics, laboratory findings, cardiac and echocardiographic markers (i.e. brain natriuretic peptide, left atrial [LA] diameter, ejection fraction, early transmitral flow velocity/early diastolic tissue Doppler imaging velocity [E/e'], LA appendage flow velocity, spontaneous echo contrast, atrial septal aneurysm, substantial PFO, and aortic arch plaques), stroke recurrence, and excellent outcome (modified Rankin scale score <2) at discharge were compared. Risk factors for low RoPE scores were determined using multiple logistic regression analysis., Results: Higher brain natriuretic peptide levels (p = 0.032), LA enlargement (p < 0.001), higher E/e' (p = 0.001), lower LA appendage flow velocity (p < 0.001), non-substantial PFO (p = 0.021), and aortic arch plaques (p = 0.002) were associated with the low RoPE score group. Patients with high RoPE scores had excellent outcomes (58% versus 78%, p = 0.035). LA enlargement (age- and sex-adjusted odds ratio, 1.15; 95 % confidence interval, 1.00-1.32; p = 0.039) was an independent predictor of low RoPE scores., Conclusions: Abnormal cardiac substrate could be associated with CS occurrence in a subset of patients with PFO. Patients with CS who had incidental PFO may be at risk of cardioembolism., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Complicated pathophysiology makes it difficult to identify the prognosis of heart failure with preserved ejection fraction (HFpEF). While plasma osmolality has been reported to have prognostic importance, mainly in heart failure with reduced ejection fraction (HFrEF), its prognostic meaning for HFpEF has not been elucidated., Methods: We prospectively studied 960 patients in PURSUIT-HFpEF, a multicenter observational study of acute decompensated HFpEF inpatients. We divided patients into three groups according to the quantile values of plasma osmolality on admission. During a follow-up averaging 366 days, we examined the primary composite endpoint of cardiac mortality or heart failure re-admission using Kaplan-Meier curve analysis and Cox proportional hazard testing., Results: 216 (22.5%) patients reached the primary endpoint. Kaplan-Meier curve analysis revealed that the highest quantile of plasma osmolality on admission (higher than 300.3 mOsm/kg) was significantly associated with adverse outcomes (Log-rank P = 0.0095). Univariable analysis in the Cox proportional hazard model also revealed significantly higher rates of adverse outcomes in the higher plasma osmolality on admission (hazard ratio [HR] 7.29; 95% confidence interval [CI] 2.25-23.92, P = 0.0009). Multivariable analysis in the Cox proportional hazard model also showed that higher plasma osmolality on admission was significantly associated with adverse outcomes (HR 5.47; 95% CI 1.46-21.56, P = 0.0113) independently from other confounding factors such as age, gender, comorbid of atrial fibrillation, hypertension history, diabetes, anemia, malnutrition, E/e', and N-terminal pro-B-type natriuretic peptide elevation., Conclusions: Higher plasma osmolality on admission was prognostically important for acute decompensated HFpEF inpatients.

Dilated cardiomyopathy (DCM) is a primary myocardial disease, the pathology of which is left ventricular or biventricular dilation and impaired myocardial contractility. The clinical and pathological diagnosis of DCM is difficult, and other cardiac diseases must be ruled out. Several studies have reported pathological findings that are characteristic of DCM, including cardiomyocyte atrophy, nuclear pleomorphism, and interstitial fibrosis, but none of these findings are DCM-specific. In this study, we examined the morphological differences in the intercalated discs (ICDs) between three groups of patients, a DCM group, a chronic heart failure group, and a control group. A total of 22 autopsy cases, including five DCM cases, nine CHF cases and eight control cases, were retrieved from the archives of the Department of Pathology at Akita University, Japan. The morphological differences were examined using multiple methods: macroscopic examination, light microscopy, immunohistochemistry, electron microscopy, and gene expression analyses. We observed disorganized ICDs, clearly illustrated by N-cadherin immunostaining in the DCM group. "Reduction of N-cadherin immunostaining intensity" and "ICD scattering" was DCM-specific. The results suggest that disorganized ICDs contribute to the development of DCM, and that N-cadherin immunostaining is useful for determining the presence of disorganized ICDs and for the pathological diagnosis of DCM.

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.

Aims: There is currently no gold standard in evaluating frailty in patients with heart failure (HF), and the prognostic value of frailty according to the Canadian Study of Health and Aging Clinical Frailty Scale (CFS) on mortality in patients with HF is still unknown., Methods and Results: Among consecutive 596 patients after their discharge from HF in Kokura Memorial Hospital (Kitakyushu, Japan) during 2015, their frailty at discharge was assessed according to CFS. Patients were classified into three groups: low (N = 232, 38.9%), intermediate (N = 230, 38.6%), and high (N = 134, 22.5%). The primary endpoint was defined as 2 year all-cause death. The mean age was 76.6 ± 10.1 years, and 55.3% were men in entire cohort. There were significant differences in age, living environment, and dementia among low, intermediate, and high CFS groups. Left ventricular ejection fraction (LVEF) and co-morbidities such as severe renal failure and severe anaemia tended to increase with frailty severity, while body mass index (BMI) and albumin level tended to decrease with frailty severity. Two year cumulative incidences of all-cause death for the three groups were 12.8%, 25.4%, and 52.7% (P < 0.001), respectively. This significant difference in the risk for all-cause death among the CFS groups was driven by the risk for cardiac (8.6%, 14.2%, and 31.0%, respectively, P < 0.001) and non-cardiac death (4.6%, 13.0%, and 31.4%, respectively, P < 0.001). The multivariate analysis showed that high frailty was independently associated with all-cause death (intermediate CFS group: adjusted hazard ratio, 1.43, 95% confidence interval, 0.86-2.36, P = 0.16; high CFS group: adjusted hazard ratio, 3.90, 95% confidence interval, 2.32-6.55, P < 0.001), and this result was consistent, irrespective of stratification based on age, sex, BMI, and LVEF without significant interaction., Conclusions: The simple CFS tool was successful in predicting the risk for all-cause death in patients with HF, and frailty according to CFS was independently associated with all-cause death irrespective of stratification based on age, sex, BMI, and LVEF without significant interaction. The CFS is a valuable prognostic tool in clinical settings., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Collagen disease is an important cause of aortic regurgitation (AR). Although aortic valve surgery is recommended for patients with AR and depressed left ventricular (LV) function, there have been few reports about risk factors for LV dysfunction in patients with AR concomitant with collagen disease., Methods and Results: We conducted this study at Kumamoto University Hospital in Japan. A total of 41 patients who had moderate to severe AR and concomitant collagen disease between January 2014 and December 2019 were enrolled. With regard to baseline characteristics, there were no significant differences in the type of collagen disease or El Khoury class between patients with preserved LV function and those with reduced LV function. B-type natriuretic peptide (375.2 [257.9-3852.6]pg/ml vs. 64.0 [33.3-133.6]pg/ml, p < 0.01), C-reactive protein (CRP) levels (2.00 [1.24-9.14]mg/dl vs. 0.19 [0.06-0.52]mg/dl, p < 0.01) and neutrophil-to-lymphocyte ratio (7.94 [3.30-9.98] vs. 3.94 [1.83-5.58], p < 0.05) were significantly higher, and hemoglobin level (10.7 ± 1.6 g/dl vs. 12.2 ± 1.8 g/dl, p < 0.05) was significantly lower in patients with reduced LV function than in those with preserved LV function. There were no significant differences in any variables associated with severity and features of AR. Multivariable logistic regression analysis showed that high CRP levels (≥1.0 mg/dl) were independently and significantly associated with LV dysfunction in patients with AR and collagen disease, even after adjusting for the severity of AR (odds ratio: 95.7; 95% confidence interval: 4.6-1990.4, p < 0.01)., Conclusions: Uncontrolled inflammation, represented as high CRP levels, is an important marker for LV dysfunction in patients with AR and collagen disease., Competing Interests: Disclosures None., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: An increase in the rate of relative poverty and the number of welfare recipients is a serious social problem in Japan. A recent overseas survey demonstrated that lack of health insurance was associated with increased in-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study is to investigate the clinical features of STEMI patients who receive welfare public assistance in Japan., Methods: We enrolled 525 STEMI patients who were hospitalized in our hospital from 2010 to 2019. We divided patients into groups of patients receiving welfare public assistance (WPA group, N = 67) and groups of patients not receiving welfare public assistance (non-WPA group, N = 458). Patient characteristics, clinical outcome, and cardiac function on transthoracic echocardiography were compared., Results: WPA group were younger than non-WPA group (61.2 ± 10.9 years VS 64.5 ± 13.3 years, p = 0.03). The prevalence of smoking was higher in WPA group compared to non-WPA group (91.0% VS 81.1% p = 0.04) and high-density lipoprotein cholesterol value of WPA group was lower than in non-WPA group (43.2 ± 9.9 mg/dl vs 47.1 ± 12.8 mg/dl, p = 0.005). Ventricular arrhythmia on admission was significantly more frequent in WPA group (11.9% VS 4.8%, p = 0.02). In acute and chronic phase, left ventricular ejection fraction in WPA group was lower than non-WPA group (in acute phase 46.6 ± 10.7% vs 53.3 ± 8.6% p = 0.001, in chronic phase 48.7 ± 10.1% vs 55.3 ± 9.4%, p = 0.008)., Conclusion: STEMI patients receiving welfare public assistance had poorer control of coronary risk, increased risk of fatal arrhythmia, and reduced systolic function than those not receiving welfare public assistance. It is necessary to have a system that can strengthen lifestyle management, such as diet and smoking cessation for the purpose of improving the prognosis of welfare recipients after AMI., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

In this document, we propose a universal definition of heart failure (HF) as a clinical syndrome with symptoms and/or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion. We also propose revised stages of HF as: At risk for HF (Stage A), Pre-HF (Stage B), Symptomatic HF (Stage C) and Advanced HF (Stage D). Finally, we propose a new and revised classification of HF according to left ventricular ejection fraction (LVEF). This includes HF with reduced ejection fraction (HFrEF): symptomatic HF with LVEF ≤40%; HF with mildly reduced ejection fraction (HFmrEF): symptomatic HF with LVEF 41-49%; HF with preserved ejection fraction (HFpEF): symptomatic HF with LVEF ≥50%; and HF with improved ejection fraction (HFimpEF): symptomatic HF with a baseline LVEF ≤40%, a ≥10 point increase from baseline LVEF, and a second measurement of LVEF > 40%., (© 2021 European Society of Cardiology and Elsevier, Inc.)

Objective Our aim was to investigate the impact of the sodium glucose cotransporter type 2 (SGLT2) inhibitor on the left ventricular (LV) diastolic function in type 2 diabetes mellitus (T2DM) patients with chronic heart failure (HF) complicating cardiovascular risk factors. Methods We analyzed data from our previous prospective multicenter study, in which we investigated the effect of dapagliflozin on the LV diastolic function of T2DM patients with stable HF at five institutions in Japan. Patients who had been taking at least 1 antidiabetic drug other than SGLT2 inhibitors started treatment with dapagliflozin. Echocardiography was performed at baseline and six months after the administration of dapagliflozin. Cardiovascular risk factors other than T2DM were age, gender, hypertension, dyslipidemia, history of cardiovascular events and overweight. Results The LV diastolic function, defined as the ratio of the mitral inflow E to the mitral e' annular velocities (E/e'), significantly decreased from 9.3 to 8.5 by six months after the administration of dapagliflozin (p=0.020) as previously reported. A multivariate logistic regression analysis showed that dyslipidemia was the only independent determinant of improvement in the E/e' after the administration of dapagliflozin among cardiovascular risk factors. Furthermore, the relative change in the E/e' from baseline to six months after the administration of dapagliflozin for HF patients with preserved ejection fraction (HFpEF) and dyslipidemia was significantly larger than that for HFpEF patients without dyslipidemia (-15.2% vs. 29.6%, p=0.014), but no such finding was observed in non-HFpEF patients. Conclusion SGLT2 inhibitors may exert a more beneficial effect on the LV diastolic function for T2DM patients with stable HF, especially those with complicating dyslipidemia, than existing treatments.

Background: Heart failure (HF) is a risk factor for adverse post-procedural outcome after revascularization; however, it is unclear how left ventricular systolic dysfunction (LVSD) and clinical HF symptoms affect percutaneous coronary intervention (PCI) outcomes. We investigated the characteristics and long-term outcomes of patients with clinical HF or LVSD after PCI., Methods: This was a Japanese multicenter registry study of adult patients receiving PCI. Among 4689 consecutive patients who underwent PCI at 15 hospitals from January 2009 to December 2012, we analyzed 2634 (56.2%) with documented left ventricular ejection fraction (LVEF). They were divided into four groups based on clinical HF (symptoms or HF hospitalization) and LVEF [≥35% and <35% (HF due to LVSD)]. The primary outcome was major adverse cardiovascular events (MACE), comprising all-cause death, acute coronary syndrome, HF hospitalization, performance of coronary artery bypass grafting, and stroke within 2 years after the initial PCI., Results: Our findings revealed 354 patients (13.4%) with HF (clinical HF, n = 173, 48.9%; LVSD, n = 132, 37.3%; both, n = 49; 13.8%). The incidence of MACE was higher in patients with clinical HF or LVSD, and was largely due to higher non-cardiac death and HF hospitalization. After adjustment, clinical HF (hazard ratio 2.16, 95% confidence interval; 1.49-3.14) and lower LVEF (per 10%, hazard ratio 0.89, 95% confidence interval; 0.81-0.99) were independently associated with higher MACE risk., Conclusions: Clinical HF and LVSD were independently associated with adverse long-term clinical outcomes, particularly with non-cardiac death and HF readmission, in patients treated with PCI., (Copyright © 2020. Published by Elsevier Ltd.)

Objective The incidence of chronic heart failure (CHF) is likely to keep increasing in Japan as the population ages, placing increased burdens on medical facilities, particularly on the limited numbers of rural hospitals. We explored the appropriateness of CHF treatment in rural areas in Japan. Methods We compared rates of adherence to therapeutic guidelines for CHF between residents with a left ventricular ejection fraction <35% living in urban areas (n = 207) and those in rural areas (n = 180). Treatments included pharmacological [beta-blockers, angiotensin-converting enzyme inhibitors (ACEi)/angiotensin II receptor blocker (ARB), mineralocorticoid receptor antagonist (MRA) and anticoagulants for atrial fibrillation] and non-pharmacological [implantable cardioverter defibrillator (ICD)/cardiac resynchronization therapy (CRT), cardiac rehabilitation and HF education] approaches. Patients This study included 387 patients with CHF, prior myocardial infarction or cardiomyopathy, and a left ventricular ejection fraction (LVEF) <35% as determined by echocardiography. Results The respective rates of treatments administered in urban and rural areas were as follows: beta-blockers, 91.3% vs. 61.7% (p<0.05); ACEi/ARB, 86.5% vs. 68.3% (p<0.05); MRA, 74.4% vs. 59.4% (p<0.01); anticoagulants, 100% vs. 86.5%, (p<0.05); ICD/CRT, 45.4% vs. 5.0% (p<0.05); cardiac rehabilitation, 32.4% vs. 13.3% (p<0.05) and HF education, 33.3% vs. 32.8% (p=0.75). Conclusion Regional disparities in treatment for CHF persist, even in Japan. Improvements in the use of guideline-directed treatment in rural areas might improve the outcomes for CHF patients.

Introduction: A better long-term quality of life after umbilical cord blood transplantation (CBT) is observed compared with transplants from other alternative donors, whereas graft failure and relapses after CBT are still major issues. To minimise graft failure and relapse after CBT, intensification of conditioning by the addition of high-dose cytosine arabinoside (CA) and concomitant continuous use of granulocyte-colony stimulating factor (G-CSF) are reported to convey a significantly better survival after CBT in some retrospective studies. To confirm the effect of G-CSF plus CA combination, in addition to the standard conditioning regimen, cyclophosphamide (CY)/total body irradiation (TBI), we design a randomised controlled study comparing CA/CY/TBI with versus without G-CSF priming (G-CSF combined conditioned cord blood transplantation [G-CONCORD] study)., Methods and Analysis: This is a multicentre, open-label, randomised phase III study that aimed to compare G-CSF+CA/CY/TBI as a conditioning regimen for CBT with CA/CY/TBI. Patients with acute myeloid leukaemia or myelodysplastic syndrome, aged 16-55 years, are eligible. The target sample size is 160 and the registration period is 4 years. The primary endpoint is the 2-year disease-free survival rate after CBT. The secondary endpoints are overall survival, relapse, non-relapse mortality, acute and chronic graft-versus-host disease, engraftment rate, time to neutrophil recovery, short-term adverse events, incidence of infections and causes of death.This study employs a single one-to-one web-based randomisation between the with-G-CSF versus without-G-CSF groups after patient registration. Combination of high-dose CA and CY/TBI in both groups is used for conditioning., Ethics and Dissemination: The study protocol was approved by the central review board, Nagoya University Certified Review Board, after the enforcement of the Clinical Trials Act in Japan. The manuscripts presenting data from this study will be submitted for publication in quality peer-reviewed medical journals. Study findings will be disseminated via presentations at national/international conferences and peer-reviewed journals., Trial Registration Numbers: UMIN000029947 and jRCTs041180059., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Increased body mass index (BMI) is a major risk factor for heart failure with preserved ejection fraction (HFpEF), and HFpEF is more prevalent in elderly females than males. We hypothesized that there may be gender differences in the association between BMI and echocardiographic left ventricular (LV) diastolic parameters., Methods: We enrolled 456 subjects (243 males) without overt cardiac diseases, all of whom underwent a health checkup. Early (E) and late (A) diastolic transmitral flow velocity, early diastolic mitral annular velocity (e'), and left atrial (LA) volume index were measured by echocardiography to assess LV diastolic function. To examine gender differences in the association between BMI and LV diastolic function, we analyzed the interaction effects of gender on the association between BMI and echocardiographic LV diastolic parameters., Results: Although there were significant gender differences in the association between BMI and E/A and e' in the crude model (interaction effect 0.037 and 0.173, respectively; P = .006 and .022, respectively), these differences were not statistically significant after adjustment for factors related to LV diastolic function. On the other hand, there were significant associations between BMI and LV diastolic parameters in each gender, even after adjustment., Conclusions: Our findings suggest there is no gender difference in the association between BMI and echocardiographic LV diastolic parameters. However, the association between BMI and LV diastolic parameters was significant in both genders. Controlling body weight might be beneficial for both women and men to prevent progression of LV diastolic dysfunction and development of HFpEF., (© 2020 Wiley Periodicals LLC.)

Background: Recent accumulating evidence reveals that the right ventricular (RV)-pulmonary artery (PA) uncoupling is associated with poor outcome in patients with heart failure (HF), RV dysfunction, and pulmonary hypertension. However, the prognostic utility of RV-PA uncoupling in HF with preserved ejection fraction (HFpEF) remains elusive. In this study, we aim to investigate the associations of RV-PA uncoupling with outcomes of HFpEF inpatients., Methods: We prospectively studied 655 patients, registered in PURSUIT-HFpEF (The Prospective Multicenter Obervational Study of Patients with Heart Failure with Preserved Ejection Fraction), a multicenter observational study of Japanese HFpEF inpatients. We assigned registered patients based on the determined value of tricuspid annular plane systolic excursion/pulmonary artery systolic pressure ratio that can predict primary outcome as an indicator of RV-PA uncoupling., Results: Univariable Cox regression testing revealed that RV-PA uncoupling was associated with the primary endpoint of all-cause death, HF rehospitalization, and cerebrovascular events (hazard ratio [HR] 1.77 [95% CI, 1.34-2.32], P <0.0001) and the secondary endpoints of all-cause death and HF rehospitalization (HR 2.75 [95% CI, 1.77-4.33], P <0.0001, HR 1.63 [95% CI, 1.18-2.26], P =0.0036, respectively). Multivariable analysis also showed that RV-PA uncoupling was significantly associated with primary endpoint and all-cause death independent of age, sex, atrial fibrillation, renal dysfunction, elevated E/e', and elevated NT-proBNP (N-terminal pro-B-type natriuretic peptide) (HR 1.38 [95% CI, 1.01-1.88], P =0.0413, HR 1.85 [95% CI, 1.14-3.01], P =0.0129, respectively)., Conclusions: Prospective study of a hospitalized cohort revealed that RV-PA uncoupling was independently associated with adverse outcomes in acute decompensated patients with HFpEF. Registration: URL: https://upload.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000024414. Unique identifier: UMIN000021831.

Takotsubo syndrome (TTS) is a complex and still poorly recognized heart disease with a wide spectrum of possible clinical presentations. Despite its reversibility, it is associated with serious adverse in-hospital events and high complication rates during follow-up. Multimodality imaging is helpful for establishing the diagnosis, guiding therapy, and stratifying prognosis of TTS patients in both the acute and post-acute phase. Echocardiography plays a key role, particularly in the acute care setting, allowing for the assessment of left ventricular (LV) systolic and diastolic function and the identification of the typical apical-midventricular ballooning pattern, as well as the circumferential pattern of wall motion abnormalities. It is also useful in the early detection of complications (i.e. LV outflow tract obstruction, mitral regurgitation, right ventricular involvement, LV thrombi, and pericardial effusion) and monitoring of systolic function recovery. Left ventriculography allows the evaluation of LV function and morphology, identifying the typical TTS patterns when echocardiography is not available or wall motion abnormalities cannot be properly assessed with ultrasound. Cardiac magnetic resonance provides a more comprehensive depiction of cardiac morphology and function and tissue characterization and offers additional value to other imaging modalities for differential diagnosis (myocardial infarction and myocarditis). Coronary computed tomography angiography has a substantial role in the diagnostic workup of patients with acute chest pain and a doubtful TTS diagnosis to rule out other medical conditions. It can be considered as a non-invasive appropriate alternative to coronary angiography in several clinical scenarios. Although the role of nuclear imaging in TTS has not yet been well established, the combination of perfusion and metabolic imaging may provide useful information on myocardial function in both the acute and post-acute phase., (The article has been co-published with permission in the European Heart Journal Cardiovascular Imaging and Journal of Echocardiography. All rights reserved. © The Author(s) 2020. The articles are identical except for minor stylistic and spelling differences in keeping with each journal’s style. Either citation can be used when citing this article.)

Background: Exercise-based cardiac rehabilitation (CR) improves health-related quality of life and exercise capacity in patients with heart failure (HF). However, CR efficacy in patients with HF who are elderly, frail, or have HF with preserved ejection fraction remains unclear. We examined whether participation in multidisciplinary outpatient CR is associated with long-term survival and rehospitalization in patients with HF, with subgroup analysis by age, sex, comorbidities, frailty, and HF with preserved ejection fraction., Methods: This multicenter retrospective cohort study was performed in patients hospitalized for acute HF at 15 hospitals in Japan, 2007 to 2016. The primary outcome (composite of all-cause mortality and HF rehospitalization after discharge) and secondary outcomes (all-cause mortality and HF rehospitalization) were analyzed in outpatient CR program participants versus nonparticipants., Results: Of the 3277 patients, 26% (862) participated in outpatient CR. After propensity matching for potential confounders, 1592 patients were included (n=796 pairs), of which 511 had composite outcomes (223 [14%] all-cause deaths and 392 [25%] HF rehospitalizations, median 2.4-year follow-up). Hazard ratios associated with CR participation were 0.77 (95% CI, 0.65-0.92) for composite outcome, 0.67 (95% CI, 0.51-0.87) for all-cause mortality, and 0.82 (95% CI, 0.67-0.99) for HF-related rehospitalization. CR participation was also associated with numerically lower rates of composite outcome in patients with HF with preserved ejection fraction or frail patients., Conclusions: Outpatient CR participation was associated with substantial prognostic benefit in a large HF cohort regardless of age, sex, comorbidities, frailty, and HF with preserved ejection fraction.

Aims: This study aims to investigate the prognostic impact of mineralocorticoid receptor antagonists (MRAs) on cardiovascular events in patients hospitalized for acute decompensated heart failure with preserved ejection fraction (HFpEF; defined as left ventricular ejection fraction ≥45%)., Methods and Results: A prospective multicentre cohort study was conducted in Nagano prefecture, Japan, between July 2014 and December 2018 that contained 518 consecutive HFpEF patients hospitalized for acute decompensated heart failure (HF). The primary outcome was a composite of cardiovascular death and HF readmission. We compared the incidence of cardiovascular events between patients who were prescribed with MRAs and those who were not in a propensity score matched cohort using a Cox proportional hazards regression model with a propensity score derived from 23 baseline variables. For sensitivity analysis, we conducted Cox proportional hazards regression models for the primary outcome adjusting for 16 clinically relevant variables in the crude cohort. The median age was 83 years, and 53% were female. The median left ventricular ejection fraction was 61%. During a median follow-up of 553 days, the primary outcome occurred in 192 (37%) patients. MRAs were used in 255 (49%) patients. After analysis, a matched cohort consisting of 370 patients was created. After propensity score matching, the baseline characteristics were well balanced between the two groups. The incidence of the primary outcome was significantly lower in MRA users than in non-users [32% (59/185) vs. 49% (90/185); hazard ratio (HR) 0.669, 95% confidence interval (CI) 0.482-0.929, P = 0.016]. The incidence of cardiovascular death was also significantly lower in the MRA users [11% (21/185) vs. 22% (41/185); HR, 0.563; 95% CI, 0.333-0.953; P = 0.032]. The risk of HF readmission tended to be lower in the MRA users [29% (54/185) vs. 41% (75/185); HR, 0.738; 95% CI, 0.520-1.048; P = 0.089]. MRA use was also associated with a lower risk of the primary outcome after Cox proportional hazards analysis adjusting for 16 clinically relevant variables in the crude cohort (HR, 0.710; 95% CI 0.507-0.995; P = 0.047)., Conclusions: Mineralocorticoid receptor antagonist use was significantly associated with a lower risk of the primary composite outcome of cardiovascular death and HF readmission in patients hospitalized for acute decompensated HFpEF. The incidence of cardiovascular mortality was also significantly lower in these patients., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: The high surgical risk in redo cardiac surgery is largely attributed to adhesions around the epicardium and the great vessels. BAX602 is an adhesion prevention reagent composed of two synthetic polyethylene glycols. Spraying BAX602 over the epicardium and the great vessels reportedly contributes to adhesion prevention after pediatric cardiac surgery. The present study aims to evaluate the safety and effectiveness of BAX602 spray in patients undergoing extracorporeal ventricular assist device implantation surgery to treat refractory congestive heart failure., Methods and Design: This investigator-initiated, multicenter, pivotal, two-arm, open-label, randomized trial will include a total of 30 patients. The primary outcome measure is the severity of adhesions, which will be evaluated during re-sternotomy surgery performed 2-12 weeks after the primary extracorporeal ventricular assist device implantation surgery. The adhesion severity will be evaluated at five predefined sites using a four-grade adhesion evaluation score (0 = no adhesion; 1 = filmy and avascular adhesion; 2 = dense/vascular adhesion; 3 = cohesive adhesion). This measure will be summarized in two ways to evaluate the effect of BAX602: (1) the total score of the severity of adhesions at all five sites (ranging from 0 to 15), and (2) the total number of sites with dense/vascular or cohesive adhesions (ranging from 0 to 5)., Ethics and Dissemination: The study findings will be disseminated at regional, national, and international conferences and through peer-reviewed scientific journals., Trial Registration: The trial was registered in the UMIN Clinical Trials Registry (UMIN-CTR: UMIN000038998) on 6 January 2020.

Aims: The association between sex and long-term outcome in patients hospitalized for acute decompensated heart failure (ADHF) has not been fully studied yet in Japanese population. The aim of this study was to determine differences in baseline characteristics and management of patients with ADHF between women and men and to compare 1-year outcomes between the sexes in a large-scale database representing the current real-world clinical practice in Japan., Methods and Results: Kyoto Congestive Heart Failure registry is a prospective cohort study enrolling consecutive patients hospitalized for ADHF in Japan among 19 centres. Baseline characteristics, clinical presentation, management, and 1-year outcomes were compared between men and women. A total of 3728 patients who were alive at discharge constituted the current study population. There were 1671 women (44.8%) and 2057 men. Women were older than men [median (IQR): 83 (76-88) years vs. 77 (68-84) years, P < 0.0001]. Hypertensive and valvular heart diseases were more prevalent in women than in men (28.0% vs. 22.5%, P = 0.0001; and 26.9% vs. 14.0%, P < 0.0001, respectively), whereas ischaemic aetiology was less prevalent in women than in men (20.0% vs. 32.5%, P < 0.0001). Women less often had reduced left ventricular ejection fraction (<40%) than men (27.5% vs. 45.1%, P < 0.0001). The cumulative incidence of all-cause death or hospitalization for heart failure was not significantly different between women and men (33.6% vs. 34.3%, P = 0.71), although women were substantially older than men. After multivariable adjustment, the risk of all-cause death or hospitalization for heart failure was significantly lower among women (adjusted hazard ratio: 0.84, 95% confidence interval: 0.74-0.96, P = 0.01)., Conclusions: Women with heart failure were older and more often presented with preserved EF with a non-ischaemic aetiology and were associated with a reduced adjusted risk of 1-year mortality compared with men in the Japanese population., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: Age-related changes in cardiac morphology and function have not been unknown in the elderly. The Japanese eLderly data Of Normal echocardioGraphy (J-LONG) study is a prospective multicenter cohort study and aimed to investigate the echocardiographic data in the healthy Japanese elderly., Methods: Thirty domestic facilities participated in this study, and 130 healthy subjects (57 men, 73 women, 79.6 ± 4.7 years, range 75-98 years, interquartile range 76-82 years) were enrolled in this cohort. Echocardiographic and clinical data sets were obtained in each facility, and total analyses were performed in the University of Tsukuba., Results: Almost all cardiac morphological data were significantly larger in men than those in women. However, corrected data by body surface area (BSA) were similar or closer between genders. As a gender difference, the negative correlation between BSA and age was observed in women only (r = - 0.46, p < 0.001), showing the independent determinant of women's left ventricular end-diastolic volume (LVEDV) was age (β = - 0.29, p = 0.01), but not BSA. In men, LVEDV was significantly correlated with BSA (β = 0.42, p = 0.001), but not with age (p = 0.10). Also, women had higher LV ejection fraction (70 ± 7.1 vs. 68 ± 4.9%, p = 0.02), lower E/A (0.67 ± 0.16 vs. 0.75 ± 0.21, p = 0.02), and higher E/e' (10 ± 2.7 vs. 8.9 ± 2.5, p = 0.03) as compared to men., Conclusions: The J-LONG study suggested that correction by the physique was needed to interpret echocardiographic data of the elderly. Also, gender differences and age-related changes in cardiac morphology and function were observed, and further studies are needed to confirm the clinical significance.

Since mitral valve (MV) complex (MVC) longitudinally bridges left ventricular (LV) base end and its middle, insufficient MVC longitudinal tissue length (TL) elongation relative to whole LV myocardial longitudinal TL elongation could limit LV-base-longitudinal-TL elongation, leading to predominant LV-base-transverse-TL elongation, constituting LV spherical remodeling. In 30 patients with dilated cardiomyopathy (DCM), 30 with aortic regurgitation (AR), and 30 controls, LV sphericity, LV-apex- or base-transverse- and longitudinal-TL, MVC-longitudinal-TL, and whole-LV-longitudinal-TL were measured by three-dimensional (3D) echocardiography. Ratio of each measure versus mean normal value (i.e., LV-apex-transverse-TL ratio) was considered to express the directional and regional tissue elongation. [LV-base-longitudinal-TL ratio/global-LV-TL ratio] and [MVC-longitudinal-TL ratio/whole-LV-longitudinal-TL ratio] were obtained as the degree of LV-base-longitudinal-TL or MVC-longitudinal-TL elongation relative to the whole LV elongation. LV-apex-transverse-, LV-apex-longitudinal-, and LV-base-transverse-TL ratios were significantly increased (1.27 to 1.42, P < 0.01) in both DCM and AR, while the LV-base-longitudinal-TL ratio was not increased in DCM [1.04 ± 0.19, not significant (ns)] and only modestly increased in AR (1.12 ± 0.21, P < 0.01). Whole-LV-longitudinal-TL ratio was significantly increased in both DCM and AR (1.22 ± 0.18 and 1.20 ± 0.16, P < 0.01), while MVC-longitudinal-TL ratio was not or only modestly increased in both groups (1.07 ± 0.15, ns, and 1.12 ± 0.17, P = 0.02, respectively). Multivariable analysis revealed that LV sphericity was independently related to a reduced [LV-base-longitudinal-TL ratio/global-LV-TL ratio] (standard β = -0.42, P < 0.01), which was further related to a reduced [MVC-longitudinal-TL ratio/whole-LV-longitudinal-TL ratio] (standard β = 0.72, P < 0.01). These are consistent with the hypothesis that relatively less MVC-longitudinal-TL elongation in the process of primary LV myocardial tissue elongation may limit LV-base-longitudinal-TL elongation, contributing to LV spherical remodeling. NEW & NOTEWORTHY Left ventricular (LV) spherical remodeling is associated with poor prognosis and less-effective cardiac performance, which commonly develops in dilated cardiomyopathy. However, its mechanism remains unclear. We hypothesized and subsequently clarified that less mitral valve complex (MVC) tissue longitudinal elongation relative to whole LV myocardial tissue longitudinal elongation is related to disproportionately less LV base longitudinal versus transverse myocardial tissue elongation, constituting spherical remodeling. This study suggests modification of MVC tissue elongation could be potential therapeutic targets.

Background: The number of hospitalized patients with heart failure (HF) is increasing as a result of the increase in the elderly population in Japan. We evaluated changes in the characteristics and outcomes of HF patients hospitalized in the 2000s to the 2010s and discharged alive based on left ventricular ejection fraction (LVEF)., Methods: Pooled patient data were obtained from The Heart Institute of Japan Heart Failure studies (HIJ-HF I: 2001-2 and HIJ-HF II: 2013-4). We studied patients discharged alive from pooled data based on LVEF < 40% (HFrEF), 40-49% (HFmrEF), and ≥50% (HFpEF). The primary outcome was death from any cause, and the secondary outcomes were cardiac death and rehospitalization due to worsened HF., Results: The proportion of HFpEF increased (35%-43%, p < 0.01), and the median ages of patients with HFmrEF (72-76 years, p < 0.01) or HFpEF (72-80 years, p < 0.01) increased from HIJ-HF I to HIJ-HF II. The use of angiotensin II receptor blockers, beta-blockers, statins, amiodarone, and erythropoietin increased, but nitrate and digoxin usage decreased. The adjusted survival rate and cardiac death-free rate were not significantly different between the 2000s and 2010s in any LVEF group, and the incidence of rehospitalization due to worsened HF was reduced in patients discharged alive from HIJ-HF I to HIJ-HF II [HFrEF: hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.51-0.89; HFmrEF: HR 0.89, 95% CI 0.68-1.16; and HFpEF: HR 0.77, 95% CI 0.61-0.97] with no significant interaction by LVEF groups., Conclusion: Our study demonstrated that age, the proportion of HFpEF, and guideline-recommended drug therapy use increased among hospitalized Japanese HF patients from the 2000s to the 2010s. The adjusted survival rate was not improved in any LVEF group, although the incidence of rehospitalization due to worsened HF was reduced., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

A growing body of evidence suggests that mitral regurgitation (MR) is associated with higher mortality in heart failure patients with reduced ejection fraction. However, prognostic impact of MR on heart failure patients with preserved ejection fraction (HFpEF) has not been fully examined. The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, prospective registration of consecutive Japanese hospitalized HFpEF patients with LVEF ≥ 50%. Severe valvular heart disease was excluded from this cohort. We divided the consecutive 341 patients into two groups based on the severity of MR at discharge: no or mild MR group (n = 317) and moderate MR group (n = 24). Compared with no or mild MR group, moderate MR group showed larger left ventricular end-diastolic diameter (52 [48-59] vs. 46 [42-50] mm, P < 0.001), left ventricular systolic diameter (35 [30-37] vs. 29 [26-34] mm, P = 0.006), left atrial diameter (49 [46-56] vs. 45 [40-50] mm, P < 0.001), and higher tricuspid regurgitation peak gradient (33 [25-40] vs. 27 [21-33] mmHg, P = 0.012). In contrast, levels of plasma B-type natriuretic peptide and left ventricular ejection fraction were comparable between the two groups. In the follow-up period (median 738 days), there were 57 all-cause deaths. In the Kaplan-Meier analysis, all-cause mortality was higher in moderate MR group than in no or mild MR group (log-rank P = 0.023). In the Cox proportional hazard analysis, moderate MR at discharge was a predictor of all-cause mortality (hazard ratio 2.256, 95% confidence interval 1.035-4.917, P = 0.041). Moderate MR at discharge is associated with adverse prognosis in hospitalized patients with HFpEF.

The prognostic significance of resting heart rate (HR) in atrial fibrillation (AF) patients with heart failure with reduced ejection fraction (HFrEF) is unclear, and there are no recommendations about the optimal HR in patients with HF in the current guidelines. Thus, we aimed to identify the relationship between resting HR and mortality in AF patients with HFrEF. A prospective multicenter cohort study was conducted between July 2014 and December 2018. We enrolled consecutive 144 AF patients with HFrEF (mean age 75 years, 34% female). The primary endpoint was all-cause death. We compared the outcomes between the high HR group (HR > 81 beats per minute [bpm], interquartile range [IQR] of HR ≥ 67%, n = 50), and the low HR group (HR ≤ 81 bpm, IQR of HR < 67%, n = 94). During a median follow-up of 538 days, the primary endpoint occurred in 41 (28.5%) patients. In Kaplan-Meier analysis, high HR was associated with a progressively increased risk of mortality (log-rank test, p = 0.034). After multivariate Cox regression analysis, high HR predicted all-cause death after adjusting for age, sex, hemoglobin, estimated glomerular filtration rate, LVEF, use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, digoxin, amiodarone, and calcium channel blockers (hazard ratio, 1.979; 95% confidence interval, 1.005-3.898; p = 0.048). Resting HR > 81 bpm at discharge had a significantly higher risk of death compared with HR ≤ 81 bpm in AF patients with HFrEF.

A prolonged QRS duration (QRSd) is promising for a response to cardiac resynchronization therapy (CRT). The variation in human body sizes may affect the QRSd. We hypothesized that conduction disturbances may exist in Japanese even with a narrow (< 130 ms)-QRS complex; such patients could be CRT candidates. We investigated the relationships between QRSd and sex and body size in Japanese. We retrospectively analyzed the values of 338 patients without heart failure (HF) (controls) and 199 CRT patients: 12-lead electrocardiographically determined QRSd, left ventricular diastolic and systolic diameters (LVDd and LVDs), body surface area (BSA), body mass index (BMI), and LVEF. We investigated the relationships between the QRSd and BSA, BMI, and LVD. The men's and women's BSA values were 1.74 m 2 and 1.48 m 2 in the controls (p < 0.0001), and 1.70 m 2 and 1.41 m 2 in the CRT patients (p < 0.0001). The men's and women's QRSd values were 96.1 ms and 87.4 ms in the controls (p < 0.0001), and 147.8 ms and 143.9 ms in the CRT group (p = 0.4633). In the controls, all body size and LVD variables were positively associated with QRSd. The CRT response rate did not differ significantly among narrow-, mid-, and wide-QRS groups (83.6%, 91.3%, 92.4%). An analysis of the ROC curve provided a QRS cutoff value of 114 ms for CRT responder. The QRSd appears to depend somewhat on body size in patients without HF. The CRT response rate was better than reported values even in patients with a narrow QRSd (< 130 ms). When patients are considered for CRT, a QRSd > 130 ms may not be necessary, and the current JCS guidelines appear to be appropriate.

Compared to the general population, elderly patients with cardiovascular disease have a higher prevalence of sarcopenia, and it shows an association with increased mortality risk. Although several studies have indicated that atherosclerosis may cause sarcopenia in community dwelling elderly subjects, the association between sarcopenia and atherosclerosis is not clear in patients with ischemic heart disease (IHD). The present study was performed to examine the association between muscle function and atherosclerosis in elderly patients with IHD. We reviewed the findings of 321 consecutive patients ≥ 65 years old with IHD. Three measures of muscle function were examined, i.e., gait speed, quadriceps isometric strength, and handgrip strength, just before hospital discharge. In addition, we measured intima-media thickness (IMT) as a parameter of arteriosclerosis. To investigate the association between sarcopenia and atherosclerosis, patients were divided into Group H (high), Group M (middle), and Group L (low) according to the tertiles of muscle function, and IMT was compared between the three groups. In addition, we considered the association between IMT thickening and muscle function. The mean age of the study population was 74.1 ± 6.0 years and 73.2% of the patients were men. IMT was compared between groups stratified according to gait speed and quadriceps isometric strength, and the results indicated that IMT was significantly lower in Group H than in Groups L and M (p < 0.05). In addition, gait speed and quadriceps isometric strength were associated with IMT thickening (p < 0.05). Parameters reflecting muscle function of the lower limbs are associated with atherosclerosis in patients with IHD.

Background: During these 2 decades (1999-2019), many therapeutic strategies have been developed in the field of heart transplant (HTx) to improve post-HTx outcomes. In the present study, 116 consecutive HTx adults between 1999 and 2019 were retrospectively reviewed to evaluate the influences of a therapeutic modification on post HTx outcomes., Methods and results: Patient survival, functional status and hemodynamics after HTx and modification of therapeutic strategies were reviewed. The overall cumulative survival rate at 10 and 20 years post-HTx was 96.4 and 76.7%, respectively. There were no significant differences in survival rate or exercise tolerance after HTx between extracorporeal and implantable continuous flow-LVAD. Post-HTx patient survival in patients, irrespective of the donor risk factors such as donor age, low LVEF, history of cardiac arrest, was equivalent across cohorts, while longer TIT and higher inotrope dosage prior to procurement surgery were significant risk factors for survival. In 21 patients given everolimus (EVL) due to renal dysfunction, serum creatinine significantly decreased 1 year after initiation. In 22 patients given EVL due to transplant coronary vasculopathy (TCAV), maximum intimal thickness significantly decreased 3 years after initiation., Conclusions: The analysis of a 20-year single-center experience with HTx in Japan shows encouraging improved results when several therapeutic modifications were made; for example, proactive use of donor hearts declined by other centers and the use of EVL in patients with renal dysfunction and TCAV.

Background: The therapeutic strategy for giant cell myocarditis (GCM) remains controversial, so we reviewed the clinical status of Japanese patients with GCM., Methods and results: We retrospectively reviewed 6 consecutive patients with GCM requiring percutaneous mechanical circulatory support (p-MCS), with 3 further requiring ventricular assist devices. One patient died during p-MCS. Cardiac function improved in the other 5 with immunosuppressive therapy, but only 3 patients treated with dual immunosuppressants, including cyclosporine (CyA), achieved >1-year survival., Conclusions: The prognosis of patients with fulminant GCM is poor, but a treatment that combines MCS and early administration of CyA-based immunosuppressants will be useful.