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[Display omitted] A graphical abstract containing the most significant findings of this study was developed and attached to the submission. Cardiac sarcoidosis (CS) is a potentially serious form of infiltrative cardiomyopathy. Despite scarce evidence, immunosuppressive treatment is generally recommended, but local routines may vary significantly. We sought to survey the clinical practices in the treatment of CS, with the aim that the results may suggest future research priorities. We conducted a web-based survey focused on treatment-naive patients with CS. We subclassified CS according to the presence/absence of overt cardiac presentation (clinically manifest/silent) and to the presence/absence of active inflammation (metabolically active/inactive by fluorodeoxyglucose positron emission tomography). The survey was developed jointly by the authors and administered to expert clinicians (n = 79) involved in CS treatment. An agreement threshold was set at 70%. A total of 62 of 79 respondents (78.5%) from 12 countries completed the survey. The agreement threshold was reached for: (1) always treating clinically manifest, metabolically active CS, 57 of 62 (91.9%), (2) never treating clinically silent, metabolically inactive CS, 44 of 62 (71.0%), (3) not requiring histopathologic confirmation of sarcoidosis before treatment initiation, (49 of 62, 79.0%), (4) using fluorodeoxyglucose positron emission tomography for assessing treatment indication (44 of 62, 71.0%) and treatment response (44 of 62, 71.0%), and (5) using prednisone as a first-line agent (100%), although respondents were divided on monotherapy (69.4%) or combination with methotrexate 25.8%. The approach to particular scenarios, tapering, and duration of treatment showed the greatest variation in response. In conclusion, in this survey of clinical practice, important aspects of CS treatment reached the agreement threshold, whereas others showed a great degree of clinical equipoise.

Aims Contemporary estimates of heart failure (HF) prevalence in Japan are scarce. We aimed to estimate HF prevalence and trends in Japan using nationally representative, large administrative claims databases. Methods and results This retrospective analysis used data from the Japan Medical Data Center (JMDC) (age ≤74 years) and the Medical Data Vision (MDV) (all ages) databases (study period: 1 January 2014–31 December 31 2019). We calculated HF prevalence using crude and sex‐/age‐standardized models (weighting based on Japanese census data, 2014–2019). Among 8 954 313 individuals aged ≤74 years from JMDC, and 27 920 174 of all ages from MDV, the cumulative 6 year (2014–2019) crude and sex‐/age‐standardized prevalence of HF per 1000 persons (95% confidence intervals) in Japan was 21.80 [21.70, 21.89] and 41.79 [30.25, 56.11] using JMDC and 65.09 [65.00, 65.18] and 60.95 [46.94, 77.62], respectively, using MDV. We observed an increasing yearly trend in crude HF prevalence per 1000 persons: 11.12 in 2014 and 14.69 in 2019 for JMDC; 58.09 and 77.18, respectively, for MDV. There was an overall increasing trend of comorbidities over time (2014–2019) among HF patients, especially in type 2 diabetes, malignant cancer, chronic kidney disease, and atrial fibrillation. From 2014 to 2019, the percentage of patients in JMDC with type 2 diabetes increased from 15.4% to 20.8% and 23.4% to 31.5% in MDV; malignant cancer frequency increased from 16.5% to 20.1% in JMDC and 18.8% to 23.9% in MDV; frequency of chronic kidney disease increased from 14.8% to 17.7% in JMDC and 18.2% to 22.7% in MDV; and frequency of atrial fibrillation increased from 13.6% to 15.6% in JMDC and 23.8% to 29.0% in MDV. Conclusions We estimated that the prevalence of HF in Japan was 2.2–3.7% for patients aged ≤74 during the period 2014–2019 using the JMDC database, while the prevalence for patients of all ages was 6.5% using the MDV database.

Aims Epidemiological and outcome studies on patients in Japan with heart failure (HF) categorized by left ventricular ejection fraction (LVEF) are currently limited. The aim of this non‐interventional database study was to provide further information on these patients. Methods and results Administrative claims data and electronic medical records from hospitals participating in the Voluntary Hospitals in Japan (VHJ) organization were used. Patients hospitalized with a primary diagnosis of HF between 1 April 2017 and 30 March 2020 were categorized by baseline LVEF on echocardiogram: HF with reduced EF (HFrEF, LVEF <40%); HF with preserved EF (HFpEF, LVEF ≥50%); and HF with mildly reduced EF (HFmrEF, 40% to <50% LVEF). Patients were evaluated for baseline characteristics, pre‐admission diagnosis, prescription drugs, length of hospitalization, HF treatment cost, overall cost of hospitalization, and in‐hospital prescription. An exploratory analysis compared post‐hospitalization mortality and re‐hospitalization rates. In total, 10 646 hospitalized patients from 17 VHJ hospitals were enrolled. Of these, 7212 were included in the analysis set and categorized into HFpEF (3183, 44.1%), HFmrEF (1280, 17.7%), and HFrEF (2749, 38.1%) groups based on baseline LVEF. Beta‐blocker use increased during hospitalization, with a mean (95% confidence interval [CI]) of 23.3% (22.3–24.3) of patients receiving these agents before admission versus 69.4% (68.3–70.5) at discharge. Administration of diuretics, angiotensin converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs) showed a similar trend. Differences in treatments were observed between HF categories at discharge, with a higher proportion (95% CI) of ACE inhibitor use in the HFrEF group (40.6% [38.7–42.4]) versus HFmrEF (27.5% [25.1–30.0]) and HFpEF (20.6% [19.2–22.1]) groups (P < 0.0001), and more ARB use in the HFmrEF and HFpEF groups (32.5% [29.9–35.1] and 31.2% [29.6–32.9], respectively) versus HFrEF (25.1% [23.5–26.8]; P < 0.0001). Mean (standard deviation [SD]) length of hospitalization was 22.2 (23.3) days, and the median (interquartile range) was 17 (11‐25) days. Estimated average cost of HF treatment per patient during index hospitalization was 300 090 yen with HFrEF treatment costing the most. Average total healthcare expenditure during hospitalization was 1 225 650 yen per index hospitalization per patient, with HFrEF also the most expensive. During a mean (SD) observation period of 324 (304) days, ~21% of patients in each group required re‐hospitalization for HF, and 625 patients (8.7%) died. Conclusions The proportion of patients in each HF category was largely consistent with existing data. Discharge medications indicated high prescription of guideline‐directed therapy. This study provides real‐world data on patients with HF in Japan that can help inform future clinical decision‐making.

Malnutrition is becoming one of the most important determinants of worse clinical outcomes in patients with acute heart failure (AHF). However, appropriate tools for evaluating the nutritional status in patients aged ≥65 years with AHF remain unclear. We examined 490 consecutive patients aged ≥65 years with AHF. They were divided into 2 groups according to Geriatric Nutritional Risk Index (GNRI; cut-off value = 92). During a median period of 189 days, the mortality rate was significantly higher in the lower GNRI group than the higher GNRI group (p <0.001). In multivariate analyses, lower GNRI was an independent determinant of adverse events (HR 0.92, 95% CI 0.88 to 0.95, p <0.001). The GNRI showed the best prognostic value (C-statistic: 0.70) among other nutritional indexes. Adding GNRI to an existing outcome prediction model for mortality in AHF significantly increased the C-statistic from 0.68 to 0.74 (p = 0.017). The net reclassification improvement afforded by GNRI was 60% overall, 27% for events, and 33% for nonevents (p <0.001). In conclusion, lower GNRI on admission was independently associated with worse clinical outcomes in patients aged ≥65 years with AHF, and it was superior to other nutritional parameters. Furthermore, the assessment of nutritional status using GNRI is very helpful for risk stratification.

Although the risk of thromboembolism is increased in heart failure (HF) patients irrespective of atrial fibrillation (AF), especially during the acute decompensated phase, the effects of intravenous anticoagulants for these patients remain unclear. We sought to investigate the current practice and effects of intravenous anticoagulant therapy in acute HF (AHF) patients with sinus rhythm. We analyzed a nationwide prospective cohort from April 2012 to March 2016. We extracted 309,015 AHF adult patients. After application of the exclusion criteria, we divided the 92,573 study population into non-heparin [n = 70,621 (76.3%)] and heparin [n = 21,952 (23.7%)] groups according to the use of intravenous heparin for the first 2 consecutive days after admission. Multivariable logistic regression analyses demonstrated that heparin administration was not associated with in-hospital mortality (OR 0.97, 95% CI 0.91–1.03) and intracranial hemorrhage (OR 1.18, 95% CI 0.78–1.77), while heparin administration was significantly associated with increased incidence of ischemic stroke (OR 1.49, 95% CI 1.29–1.72) and venous thromboembolism (OR 1.62, 95% CI 1.14–2.30). In conclusion, intravenous heparin administration was not associated with favorable in-hospital outcomes in AHF patients with sinus rhythm. Routine additive use of intravenous heparin to initial treatment might not be recommended in AHF patients.

Abbreviations ACC American College of Cardiology ACT activated clotting time ADL activities of daily living AF atrial fibrillation AHA American Heart Association BMI body mass index BMS bare metal stent CCI Charlson comorbidity index CCr creatinine clearance CFAE complex fractionated atrial electrogram CKD chronic kidney disease CLBBB complete left bundle branch block CLS closed loop stimulation CMR cardiac magnetic resonance CO cardiac output COPD chronic obstructive pulmonary disease CRT cardiac resynchronization therapy CRT-D cardiac resynchronization therapy defibrillator CRT-P cardiac resynchronization therapy pacemaker CSP conduction system pacing CT computed tomography DBP diastolic blood pressure DDD/DDDR dual chamber pacing, dual chamber sensing, and pacemaker activation or inhibition on a sensed event / rate-modulated pacing DOAC direct oral anticoagulant ECG electrocardiogram eGFR estimated glomerular filtration rate EPS electrophysiological study EV-ICD extra vascular-implantable cardioverter defibrillator FAAM fractionated signal areas in the atrial muscle FDA US Food and Drug Administration FIRM focal impulse and rotor modulation FNNC filamin C FXa factor Xa HBP His bundle pacing HFpEF heart failure with preserved ejection fraction HFrEF heart failure with reduced ejection fraction HRS Heart Rhythm Society ICD implantable cardioverter defibrillator ILAM isochronal late activation map INR international normalized ratio LBBA left bundle branch area LBBAP left bundle branch area pacing LBBB left bundle branch block LGE late gadolinium enhancement LMNA lamin A/C LVA low-voltage areas LVAD left ventricular assist device LVEF left ventricular ejection fraction MMSE mini-mental state examination MRI magnetic resonance imaging MRSA methicillin-resistant Staphylococcus aureus NCDR National Cardiovascular Data Registry NSAIDs non-steroidal anti-inflammatory drugs NSVT non-sustained ventricular tachycardia NYHA New York Heart Association PCI percutaneous coronary intervention PCWP pulmonary capillary wedge pressure PFA pulsed field ablation PLN phospholamban PVC premature ventricular contraction PVI pulmonary vein isolation PVS pulmonary vein stenosis QOL quality of life RBM20 RNA binding motif protein 20 RCT randomized controlled trial RVP right ventricular pacing SBP systolic blood pressure SCD sudden cardiac death S-ICD subcutaneous implantable cardioverter defibrillator SPRM Seattle proportional risk model SUV standard uptake value V6RWPT R wave peak time in lead V6 VDD atrial-synchronized ventricular pacing (ventricle pacing, dual chamber sensing, and pacemaker activation or inhibition on a sensed event) VOM vein of Marshall VOM-EI ethanol injection into the vein of Marshall VF ventricular fibrillation VT ventricular tachycardia VVI/VVIR ventricular demand pacing (ventricle pacing, ventricle sensing, and pacemaker inhibition on a sensed event) / rate-modulated pacing 6MWD 6-minute walking distance 18F-FDG-PET 18F-fluorodeoxyglucose-positron emission tomography TABLE OF CONTENTS Foreword 2 I. Implantable Cardiac Electrical Devices 3 1. The importance of comprehensive management, which includes not only drug therapy but also the identification and intervention of various modifiable risk factors, is now recognized worldwide. Since the publication of the Guidelines for the Nonpharmacologic Treatment of Arrhythmias in 2000, guidelines for catheter ablation, pacemaker and implantable cardioverter-defibrillator (ICD) therapy, and arrhythmia surgery have been revised in 2006 and 2011.4 In addition, the atrial fibrillation catheter ablation technique has become common practice due to remarkable progress in medical engineering technology and the establishment of treatment techniques and surgical procedures, diversifying the nonpharmacological treatment of arrhythmia. Level A Demonstrated in multiple randomized interventional clinical trials or meta-analysis Level B Demonstrated in a single randomized intervention clinical trial or a large non-randomized intervention clinical trial Level C Consensus among experts and/or small clinical trials (including backward-looking studies and registries) Clinical Questions The Japanese Circulation Society guidelines have introduced a format in which clinical questions (CQs) are set, a systematic review is conducted using the GRADE system, and recommendations are clearly indicated. Because this is a focused update, we did not establish a systematic review group independent of the guideline writing committee members, and instead, we developed 2 CQs that occur in daily practice. [...]in promoting shared decision-making, providing information to citizens and patients is crucial, and this focus update guideline includes six topics related to arrhythmia treatment.

Left atrial (LA) structural remodelling develops in rheumatic heart disease (RHD) according to the disease severity of the mitral valve and the presence of atrial fibrillation. Sustained active inflammation has been previously reported in the LA of patients with RHD, suggesting a direct role of cell-mediated immunity in the pathogenesis of LA remodelling. Dendritic cells (DCs) have a major antigen-presenting role, and are known as crucial modulators of innate and adaptive immunity. We investigated whether DCs are involved in the pathogenesis of LA remodelling in RHD. Immunohistochemical analyses were performed using antibodies to CD11c, CD209 and CD80 as markers of myeloid DCs, migratory-active DCs, mature DCs and infiltrated inflammatory cells including T lymphocytes (CD3) and M1 (CD68; pro-inflammatory profile) and M2 (CD163; pro-resolution profile) macrophages. Furthermore, tenascin-C, an extracellular matrix (ECM) protein that appears during ECM remodelling and inflammatory response, was examined. Infiltrated myeloid DCs, migratory-active DCs, mature DCs and other inflammatory infiltrates including T lymphocytes and M1 and M2 macrophages, were significantly higher in the RHD group than the non-RHD group. The positive area fraction for tenascin-C was significantly higher in the RHD group than in the non-RHD group. Our histological findings suggest that inflammation may persist long after a bout of rheumatic fever, ultimately leading to ECM remodelling. We identified and quantitatively assessed several subsets of DCs and other immunocompetent cells, and our results indicated that activation of DCs has some role in persistence of LA inflammation in patients with chronic RHD.

Background Pre- and post-procedural hemodynamic changes which could affect adverse outcomes in aortic stenosis (AS) patients who undergo transcatheter aortic valve replacement (TAVR) have not been well investigated. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) enables accurate analysis of blood flow dynamics such as flow velocity, flow pattern, wall shear stress (WSS), and energy loss (EL). We sought to examine the changes in blood flow dynamics of patients with severe AS who underwent TAVR. Methods We examined 32 consecutive severe AS patients who underwent TAVR between May 2018 and June 2019 (17 men, 82 ± 5 years, median left ventricular ejection fraction 61%, 6 self-expanding valve), after excluding those without CMR because of a contraindication or inadequate imaging from the analyses. We analyzed blood flow patterns, WSS and EL in the ascending aorta (AAo), and those changes before and after TAVR using 4D flow CMR. Results After TAVR, semi-quantified helical flow in the AAo was significantly decreased (1.4 ± 0.6 vs. 1.9 ± 0.8, P  = 0.002), whereas vortical flow and eccentricity showed no significant changes. WSS along the ascending aortic circumference was significantly decreased in the left ( P  = 0.038) and left anterior ( P  = 0.033) wall at the basal level, right posterior ( P  = 0.011) and left ( P  = 0.010) wall at the middle level, and right ( P  = 0.012), left posterior ( P  = 0.019) and left anterior ( P  = 0.028) wall at the upper level. EL in the AAo was significantly decreased (15.6 [10.8–25.1 vs. 25.8 [18.6–36.2]] mW, P  = 0.012). Furthermore, a significant negative correlation was observed between EL and effective orifice area index after TAVR (r = − 0.38, P  = 0.034). Conclusions In severe AS patients undergoing TAVR, 4D flow CMR demonstrates that TAVR improves blood flow dynamics, especially when a larger effective orifice area index is obtained.