Prognostic Value of the Severity of Clinical Congestion in Patients Hospitalized for Decompensated Heart Failure: Findings From the Japanese KCHF Registry.

BACKGROUND: Congestion is a leading cause of hospitalization and a major therapeutic target in patients with heart failure (HF). Clinical practice in Japan is characterized by a long hospital stay, which facilitates more extensive decongestion during hospitalization. We herein examined the time course and prognostic impact of clinical congestion in a large contemporary Japanese cohort of HF. METHODS AND RESULTS: Peripheral edema, jugular venous pressure, and orthopnea were graded on a standardized 4-point scale (0-3) in 3787 hospitalized patients in a Japanese cohort of HF. Composite Congestion Scores (CCS) on admission and at discharge were calculated by summing individual scores. The primary outcome was a composite of all-cause death or HF hospitalization. The median admission CCS was 4 (interquartile range, 3-6). Overall, 255 patients died during the median hospitalization length of 16 days, and 1395 died or were hospitalized for HF over a median postdischarge follow-up of 396 days. The cumulative 1-year incidence of the primary outcome increased at higher tertiles of congestion on admission (32.5%, 39.3%, and 41.0% in the mild [CCS ≤3], moderate [CCS = 4 or 5], and severe [CCS ≥6] congestion groups, respectively, log-rank P < .001). The adjusted hazard ratios of moderate and severe congestion relative to mild congestion were 1.205 (95% confidence interval [CI], 1.065-1.365; P = .003) and 1.247 (95% CI, 1.103-1.410; P < .001), respectively. Among 3445 patients discharged alive, 85% had CCS of 0 (complete decongestion) and 15% had a CCS of 1 or more (residual congestion) at discharge. Although residual congestion predicted a risk of postdischarge death or HF hospitalization (adjusted hazard ratio, 1.314 [1.145-1.509]; P < .001), the admission CCS correlated with the risk of postdischarge death or HF hospitalization, even in the complete decongestion group. No correlation was observed for postdischarge death or HF hospitalization between residual congestion at discharge and admission CCS (P for the interaction = .316). CONCLUSIONS: In total, 85% of patients were discharged with complete decongestion in Japanese clinical practice. Clinical congestion, on admission and at discharge, was of prognostic value. The severity of congestion on admission was predictive of adverse outcomes, even in the absence of residual congestion. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02334891 (NCT02334891) https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017241 (UMIN000015238).

Prognostic Impact of Hyperpolypharmacy Due to Noncardiovascular Medications in Patients After Acute Decompensated Heart Failure　- Insights From the Clue of Risk Stratification in the Elderly Patients With Heart Failure (CURE-HF) Registry.

BACKGROUND: Hyperpolypharmacy is associated with adverse outcomes in older adults, but because literature on its association with cardiovascular (CV) outcomes after acute decompensated heart failure (ADHF) is sparse, we investigated the relationships among hyperpolypharmacy, medication class, and death in patients with HF.Methods and Results: We evaluated the total number of medications prescribed to 884 patients at discharge following ADHF. Patients were categorized into nonpolypharmacy (<5 medications), polypharmacy (5-9 medications), and hyperpolypharmacy (≥10 medications) groups. We examined the relationship of polypharmacy status with the 2-year mortality rate. The proportion of patients taking ≥5 medications was 91.3% (polypharmacy, 55.3%; hyperpolypharmacy, 36.0%). Patients in the hyperpolypharmacy group showed worse outcomes than patients in the other 2 groups (P=0.002). After multivariable adjustment, the total number of medications was significantly associated with an increased risk of death (hazard ratio [HR] per additional increase in the number of medications, 1.05; 95% confidence interval [CI], 1.01-1.10; P=0.027). Although the number of non-CV medications was significantly associated with death (HR, 1.07; 95% CI, 1.02-1.13; P=0.01), the number of CV medications was not (HR, 1.01; 95% CI, 0.92-1.10; P=0.95). CONCLUSIONS: Hyperpolypharmacy due to non-CV medications was associated with an elevated risk of death in patients after ADHF, suggesting the importance of a regular review of the prescribed drugs including non-CV medications.

Polypharmacy and Bleeding Outcomes After Percutaneous Coronary Intervention.

BACKGROUND: Polypharmacy was reported to be associated with major bleeding in various populations. However, there are no data on polypharmacy and its association with bleeding in patients undergoing percutaneous coronary intervention (PCI).Methods and Results: Among 12,291 patients in the CREDO-Kyoto PCI Registry Cohort-3, we evaluated the number of medications at discharge and compared major bleeding, defined as Bleeding Academic Research Consortium Type 3 or 5 bleeding, across tertiles (T1-3) of the number of medications. The median number of medications was 6, and 88.0% of patients were on ≥5 medications. The cumulative 5-year incidence of major bleeding increased incrementally with increasing number of medications (T1 [≤5 medications] 12.5%, T2 [6-7] 16.5%, and T3 [≥8] 20.4%; log-rank P<0.001). After adjusting for confounders, the risks for major bleeding of T2 (hazard ratio [HR] 1.21; 95% confidence interval [CI] 1.08-1.36; P=0.001) and T3 (HR 1.27; 95% CI 1.12-1.45; P<0.001) relative to T1 remained significant. The adjusted risks of T2 and T3 relative to T1 were not significant for a composite of myocardial infarction or ischemic stroke (HR 0.95 [95% CI 0.83-1.09; P=0.47] and HR 1.06 [95% CI 0.91-1.23; P=0.48], respectively). CONCLUSIONS: In a real-world population of patients undergoing PCI, approximately 90% were on ≥5 medications. Increasing number of medications was associated with a higher adjusted risk for major bleeding, but not ischemic events.

Polypharmacy and Clinical Outcomes in Hospitalized Patients With Acute Decompensated Heart Failure.

BACKGROUND: Polypharmacy is a common problem among patients with acute decompensated heart failure (ADHF) who often have multiple comorbidities. OBJECTIVE: The aim of this study was to define the number of medications at hospital discharge and whether it is associated with clinical outcomes at 1 year. METHODS: We evaluated the number of medications in 2578 patients with ADHF who were ambulatory at hospital discharge in the Kyoto Congestive Heart Failure Registry and compared 1-year outcomes in 4 groups categorized by quartiles of the number of medications (quartile 1, ≤ 5; quartile 2, 6-8; quartile 3, 9-11; and quartile 4, ≥ 12). RESULTS: At hospital discharge, the median number of medications was 8 (interquartile range, 6-11) with 81.5% and 27.8% taking more than 5 and more than 10 medications, respectively. The cumulative 1-year incidence of a composite of death or rehospitalization (primary outcome measure) increased incrementally with an increasing number of medications (quartile 1, 30.8%; quartile 2, 31.6%; quartile 3, 39.7%; quartile 4, 50.3%; P < .0001). After adjusting for confounders, the excess risks of quartile 4 relative to those of quartile 1 remained significant ( P = .01). CONCLUSIONS: In the contemporary cohort of patients with ADHF in Japan, polypharmacy at hospital discharge was common, and excessive polypharmacy was associated with a higher risk of mortality and rehospitalizations within a 1-year period. Collaborative disease management programs that include a careful review of medication lists and an appropriate deprescribing protocol should be implemented for these patients.

Starting Neurohormonal Antagonists in Patients With Acute Heart Failure With Mid-Range and Preserved Ejection Fraction.

BACKGROUND: The clinical benefits of neurohormonal antagonists for patients with heart failure (HF) with mid-range and preserved ejection fraction (HFmrEF and HFpEF) are uncertain.Methods and Results: This study analyzed 858 consecutive patients with HFmrEF (EF: 40-49%) or HFpEF (EF ≥50%), who were hospitalized for acute HF, and who were discharged alive, and were not taking angiotensin-converting enzyme inhibitors (ACE)-I/ angiotensin II receptor blockers (ARB) or ß-blockers at admission. The study population was classified into 4 groups according to the status of prescription of ACE-I/ARB and ß-blocker at discharge: no neurohormonal antagonist (n=342, 39.9%), ACE-I/ARB only (n=128, 14.9%), ß-blocker only (n=189, 22.0%), and both ACE-I/ARB and ß-blocker (n=199, 23.2%) groups. The primary outcome measure was a composite of all-cause death or HF hospitalization. The cumulative 1-year incidence of the primary outcome measure was 41.2% in the no neurohormonal antagonist group, 34.0% in the ACE-I/ARB only group, 28.6% in the ß-blocker only group, and 16.4% in the both ACE-I/ARB and ß-blocker group (P<0.001). Compared with the no neurohormonal antagonist group, both the ACE-I/ARB and ß-blocker groups were associated with a significantly lower risk for a composite of all-cause death or HF hospitalization (HR: 0.46, 95% CI: 0.28-0.76, P=0.002). CONCLUSIONS: In hospitalized patients with HFmrEF and HFpEF, starting both ACE-I/ARB and a ß-blocker was associated with a reduced risk of the composite of all-cause death or HF hospitalization compared with patients not starting on an ACE-I/ARB or ß-blocker.

Overview of the 84th Annual Scientific Meeting of the Japanese Circulation Society　- Change Practice!

Due to the COVID-19 pandemic, the 84thAnnual Meeting of the Japanese Circulation Society (JCS) was held in a web-based format for the first time in its history as "The Week for JCS 2020" from Monday, July 27 to Sunday, August 2, 2020. All sessions, including general abstracts, were streamed live or on-demand. The main theme of the meeting was "Change Practice!" and the aim was to organize the latest findings in the field of cardiovascular medicine and discuss how to change practice. The total number of registered attendees was over 16,800, far exceeding our expectations, and many of the sessions were viewed by far more people than at conventional face-to-face scientific meetings. At this conference, the power of online information dissemination was fully demonstrated, and the evolution of online academic meetings will be a direction that cannot be reversed in the future. The meeting was completed with great success, and we express our heartfelt gratitude to all affiliates for their enormous amount of work, cooperation, and support.

Adverse effect of switching only once low-carbohydrate diet to high-carbohydrate diet on postprandial glucose concentration in healthy women.

BACKGROUND AND OBJECTIVES: Our aim was to evaluate the acute effect of switching low-carbohydrate diet (LCD) to high-carbohydrate diet (HCD) on glycemic parameters in healthy women. METHODS AND STUDY DESIGN: Twen-ty-two women (age 21.7±4.0 years; HbA1c 5.3±0.3 %, mean±SD) wore flash glucose monitoring system and consumed test meals for 3 days from Day 4 to 6. Participants consumed identical HCD meals except LCD dinner on Day 5. The energy ratio of carbohydrate, fat, and protein were 64%, 21%, and 15% for HCD and 47%, 35%, and 18% for Day 5 with LCD dinner (19%, 59%, and 22%). RESULTS: The incremental glucose peak (IGP, both p<0.001) and incremental area under the curve for glucose (IAUC, both p<0.001) 3h of LCD dinner were all sig-nificantly lower than those of HCD dinner on Day 4 and 6. However, after consuming LCD dinner on Day 5, IGP breakfast (2.33±0.15 vs 1.71±0.15 mmo/L, p<0.01), IGP lunch (3.31±0.25 vs 2.54±0.18 mol/L, p<0.01), IAUC 3h of breakfast (210±18 vs 136±14 mmol/L×min, p<0.001), mean blood glucose (5.72±0.11 vs 5.40±0.11 mmol/L, p<0.01), and standard deviation (1.11±0.06 vs 0.88±0.04 mmol/L, p<0.01) on Day 6 were all signifi-cantly higher than those of corresponding meals before LCD dinner on Day 4, in spite of consuming all identical HCD meals. The glycemic parameters returned to the levels before consuming LCD on Day 7. CONCLUSIONS: Consuming LCD only once is enough to cause 24-h higher postprandial blood glucose concentration in subse-quent consumption of HCD in healthy women.

Tomato juice preload has a significant impact on postprandial glucose concentration in healthy women: A randomized cross-over trial.

BACKGROUND AND OBJECTIVES: Our aim was to evaluate the effect of consuming tomato juice before carbohydrate on postprandial glucose concentrations in healthy women. METHODS AND STUDY DESIGN: In this randomized controlled cross-over study, 25 healthy women (age 21.6±3.8 years, HbA1c 5.3±0.2 %, mean±SD) consumed either 200 g of tomato juice, tomato, or water (control) at 30 min before consuming 200 g of boiled white rice at 9:00 and consumed identical lunch at 13:00 for 3 days. The blood glucose concentrations were measured by selfmonitoring blood glucose at 0, 30, 45, 60, 90, 150, and 210 min pre- and post-breakfast, and at 0, 30, 60, 120, 150, and 180 min pre- and post-lunch. The concentration of postprandial glucose, incremental glucose peak (IGP), and incremental area under the curve for glucose after the test meals were compared among 3 days. RESULTS: Incremental blood glucose concentrations at 60 min (2.32±0.16 vs 2.97±0.19 mmol/L, p<0.05, mean±SEM), 90 min (2.36±0.23 vs 3.23±0.24 mmol/L, p<0.01), and IGP (2.77±0.19 vs 3.68±0.22 mmol/L, p<0.001) in consuming tomato juice 30 min before carbohydrate were all significantly lower than those of water, while IGP of consuming tomato was tended to be lower than that of water (2.82±0.19 mmolL, p=0.023). No significant difference was observed in glycaemic parameters after consuming lunch among 3 days. CONCLUSIONS: Consuming tomato juice half hour before carbohydrate ameliorates the postprandial blood glucose concentrations, although total amounts of energy and carbohydrate of tomato juice are higher than those of water.

Late-night-dinner deteriorates postprandial glucose and insulin whereas consuming dinner dividedly ameliorates them in patients with type 2 diabetes: A randomized crossover clinical trial.

BACKGROUND AND OBJECTIVES: The aims of this study is to explore the acute effect of consuming dinner at different timing on postprandial glucose and hormone in patients with type 2 diabetes. METHODS AND STUDY DESIGN: Eight patients (age 70.8±1.9 years, HbA1c 7.6±0.6 %, BMI 23.3±3.2, mean±SD) were randomly assigned in this crossover study. Patients consumed the test meals of dinner at 18:00 on the first day, and dinner at 21:00 or divided dinner (vegetable and rice at 18:00 and vegetable and the main dish at 21:00) on the second or third day. Postprandial glucose, insulin, glucagon, free fatty acid (FFA), active glucagon-like peptide-1 (GLP-1), and active glucose- dependent insulinotropic polypeptide (GIP) concentration after dinner were evaluated. RESULTS: Both incremental area under the curve (IAUC) 2h for glucose and insulin were higher in dinner at 21:00 than those in dinner at 18:00 (IAUC glucose: 449±83 vs 216±43 mmol/L×min, p<0.01, IAUC insulin:772±104 vs 527±107 µU/mL×min, p<0.01, mean±SEM). However, in divided dinner both IAUC 4h for glucose and insulin tended to be lower than those of dinner at 21:00 (IAUC glucose: 269±76 mmol/L×min, p=0.070, IAUC insulin: 552±114 µU/mL×min, p=0.070). IAUC of active GLP-1 and active GIP demonstrated no difference among different dinner regimen. CONCLUSIONS: Consuming late-night-dinner (21:00) deteriorates postprandial glucose and insulin compared with those of early-evening-dinner (18:00) whereas consuming dinner dividedly ameliorates them.

Demographics, Management, and In-Hospital Outcome of Hospitalized Acute Heart Failure Syndrome Patients in Contemporary Real Clinical Practice in Japan　- Observations From the Prospective, Multicenter Kyoto Congestive Heart Failure (KCHF) Registry.

BACKGROUND: There is a scarcity of reports on the clinical characteristics and management practice in contemporary all-comer patients with acute decompensated heart failure (ADHF). Methods and Results: The Kyoto Congestive Heart Failure (KCHF) registry is a prospective observational cohort study enrolling 4,056 consecutive patients who had hospital admission due to ADHF without any exclusion criteria between October 2014 and March 2016 in the 19 participating hospitals in Japan. Baseline characteristics, clinical presentations, management, and in-hospital outcomes were compared between heart failure (HF) with reduced left ventricular ejection fraction (LVEF; HFrEF, LVEF <40%), HF with mid-range LVEF (HFmrEF, LVEF 40-49%), and HF with preserved LVEF (HFpEF, LVEF ≥50%). Of the 4,041 patients with documented LVEF, 1,744 (43%) had HFpEF; 746 (19%), HFmrEF; and 1,551 (38%), HFrEF. The median age was 80 years (IQR, 72-86 years) in the entire population, and was higher with increasing LVEF (P<0.001). The in-hospital mortality rate was higher in the HFrEF than in the HFmrEF and HFpEF groups (9.2%, 4.8%, and 5.1%, respectively, P<0.001). CONCLUSIONS: This registry elucidated the clinical features and clinically relevant in-hospital outcomes in contemporary consecutive patients with ADHF in real-world clinical practice in Japan. When classified by LVEF, significant differences in characteristics and in-hospital outcomes existed between patients with HFrEF, HFmrEF, and HFpEF.

Subclinical myocardial damage after anthracycline chemotherapy in Japanese patients with breast cancer.

BACKGROUND: Data on the incidence, timing, and severity of myocardial damage after anthracycline-based chemotherapy (AC) in Japanese patients with breast cancer are limited. METHOD: We evaluated cancer therapy-related cardiac dysfunction (CTRCD) in Japanese women with breast cancer (n = 51) after the first AC according to the definitions of the 2022 European Society of Cardiology onco-cardiology guideline, including assessment of high-sensitivity troponin I (TnI) and B-type natriuretic peptide (BNP) levels. RESULTS: CTRCD was detected in 67 % of the patients (3.9 %, 7.8 %, 9.8 %, 43 %, 37 %, 22 %, 20 %, and 9.8 % of patients at 1 week and 1, 2, 3, 6, 9, 12, and 15 months post-AC, respectively) without significant left ventricular ejection fraction reduction (<50 %) and heart failure. Elevated TnI levels (>26 pg/mL) were found in 43 % of patients, and elevated BNP levels (≥35 pg/mL) were observed in 22 % of patients during the follow-up period. CONCLUSIONS: Approximately two-thirds of the Japanese patients in this study experienced CTRCD, which was frequently observed at 3 or 6 months post-AC. However, all patients with CTRCD were diagnosed with mild asymptomatic CTRCD. Although, these patients were diagnosed with mild asymptomatic CTRCD, careful long-term follow-up will be required.

Prognostic value of E/e' ratio and its change over time in ST-segment elevation myocardial infarction with preserved left ventricular ejection fraction in the reperfusion era.

BACKGROUND: The ratio of early diastolic mitral inflow velocity to mitral annular velocity (E/e') is a prognostic factor in patients with ST-segment elevation myocardial infarction (STEMI). However, data are lacking on long-term outcomes and longitudinal changes in E/e' in patients with preserved left ventricular ejection fraction (LVEF) in the reperfusion era. METHODS: This is a pre-specified echocardiographic substudy of a randomized controlled trial evaluating the efficacy of beta-blockers in STEMI patients with LVEF ≥40 % after primary percutaneous coronary intervention (PCI). Patients were divided into 2 groups according to E/e' at discharge: ≤14 (normal E/e' group) or > 14 (high E/e' group). The primary outcome was a composite of all-cause death, myocardial infarction, stroke, acute coronary syndrome, and heart failure hospitalization. We also assessed longitudinal changes in E/e' and conducted a landmark analysis using E/e' at 1 year after STEMI. RESULTS: There were 173 and 38 patients in the normal and high E/e' groups, respectively. During a median follow-up of 3.9 years, the primary outcome occurred in 19 patients (11.0 %) and 10 patients (26.3 %) in the normal and high E/e' groups, respectively. The cumulative incidence of the primary outcome was higher in the high E/e' group than in the normal E/e' group (21.9 % vs. 7.1 % at 3 years; log-rank p = 0.013). E/e' in the high E/e' group decreased over time (p < 0.001), but remained higher than in the normal E/e' group at 1 year after STEMI (13.7 ±â€¯5.3 vs. 8.6 ±â€¯2.3, p < 0.001). E/e' > 14 at 1 year was also associated with poor outcomes (log-rank p = 0.008). A sensitivity analysis using multivariate Cox proportional hazards regression models yielded consistent results. CONCLUSION: High E/e' at discharge is associated with poor long-term outcomes in STEMI patients with preserved LVEF after primary PCI, which may be explained by persistent high E/e' late after STEMI.

Development of interpretable machine learning models to predict in-hospital prognosis of acute heart failure patients.

AIMS: In recent years, there has been remarkable development in machine learning (ML) models, showing a trend towards high prediction performance. ML models with high prediction performance often become structurally complex and are frequently perceived as black boxes, hindering intuitive interpretation of the prediction results. We aimed to develop ML models with high prediction performance, interpretability, and superior risk stratification to predict in-hospital mortality and worsening heart failure (WHF) in patients with acute heart failure (AHF). METHODS AND RESULTS: Based on the Kyoto Congestive Heart Failure registry, which enrolled 4056 patients with AHF, we developed prediction models for in-hospital mortality and WHF using information obtained on the first day of admission (demographics, physical examination, blood test results, etc.). After excluding 16 patients who died on the first or second day of admission, the original dataset (n = 4040) was split 4:1 into training (n = 3232) and test datasets (n = 808). Based on the training dataset, we developed three types of prediction models: (i) the classification and regression trees (CART) model; (ii) the random forest (RF) model; and (iii) the extreme gradient boosting (XGBoost) model. The performance of each model was evaluated using the test dataset, based on metrics including sensitivity, specificity, area under the receiver operating characteristic curve (AUC), Brier score, and calibration slope. For the complex structure of the XGBoost model, we performed SHapley Additive exPlanations (SHAP) analysis, classifying patients into interpretable clusters. In the original dataset, the proportion of females was 44.8% (1809/4040), and the average age was 77.9 ± 12.0. The in-hospital mortality rate was 6.3% (255/4040) and the WHF rate was 22.3% (900/4040) in the total study population. In the in-hospital mortality prediction, the AUC for the XGBoost model was 0.816 [95% confidence interval (CI): 0.815-0.818], surpassing the AUC values for the CART model (0.683, 95% CI: 0.680-0.685) and the RF model (0.755, 95% CI: 0.753-0.757). Similarly, in the WHF prediction, the AUC for the XGBoost model was 0.766 (95% CI: 0.765-0.768), outperforming the AUC values for the CART model (0.688, 95% CI: 0.686-0.689) and the RF model (0.713, 95% CI: 0.711-0.714). In the XGBoost model, interpretable clusters were formed, and the rates of in-hospital mortality and WHF were similar among each cluster in both the training and test datasets. CONCLUSIONS: The XGBoost models with SHAP analysis provide high prediction performance, interpretability, and reproducible risk stratification for in-hospital mortality and WHF for patients with AHF.

Eating Vegetables First Regardless of Eating Speed Has a Significant Reducing Effect on Postprandial Blood Glucose and Insulin in Young Healthy Women: Randomized Controlled Cross-Over Study.

People with fast eating habits have been reported to have an increased risk of diabetes and obesity. To explore whether the speed of eating a test meal (tomato, broccoli, fried fish, and boiled white rice) influences postprandial blood glucose, insulin, triglyceride, and free fatty acid levels, 18 young, healthy women consumed a 671 kcal breakfast at fast speed (10 min) and slow speed (20 min) with vegetables first and slow speed (20 min) with carbohydrate first on three separate days. This study was conducted using a within-participants cross-over design in which all participants consumed identical meals of three different eating speeds and food orders. Significant ameliorations of both fast and slow eating with vegetables first regimen on postprandial blood glucose and insulin levels at 30 and 60 min were observed compared with those of slow eating with carbohydrates first. In addition, the standard deviation, large amplitude of excursion, and incremental area under the curve for blood glucose and insulin in both fast and slow eating with vegetables first were all significantly lower than those of slow eating with carbohydrate first. Interestingly, there was no significant difference between fast and slow eating on postprandial blood glucose and insulin levels as long as vegetables were consumed first, although postprandial blood glucose at 30 min was significantly lower in slow eating with vegetables first than that of fast eating with the same food order. These results suggest that food order with vegetables first and carbohydrate last ameliorates postprandial blood glucose and insulin concentrations even if the meal was consumed at fast speed.

Association of intravenous heparin administration with in-hospital clinical outcomes among hospitalized patients with acute heart failure.

BACKGROUNDS: Patients with acute heart failure (AHF) possess a high risk for thromboembolism, and thromboembolism prophylaxis using heparin has been recommended by the guidelines. METHODS: Among 4056 patients enrolled in the KCHF Registry, the current study population consisted of 2525 patients after excluding patients with acute coronary syndrome and oral anticoagulants on admission and those with mechanical circulatory supports. There were 789 patients (31%) with heparin administration within 24 h after admission, and 1736 patients (69%) without. RESULTS: The baseline characteristics included mean age: 78 ± 13 years, New York Heart Association class IV: 51%, ischemic etiology: 30%, atrial fibrillation: 31% and mean left ventricular ejection fraction: 45%. During median hospitalization length of 16 days, 161 patients had all-cause death, 34 patients developed ischemic stroke, and 48 patients developed major bleeding. Multivariable logistic regression analyses demonstrated that heparin administration compared with no heparin administration was not associated with a lower risk for all-cause death (OR: 1.39, 95%CI: 0.90-2.15; P = 0.14), nor for ischemic stroke (OR: 1.14, 95%CI: 0.53-2.43; P = 0.74), but was associated with a higher risk for major bleeding (OR: 2.88, 95%CI: 1.54-5.41; P < 0.001). CONCLUSIONS: In patients with AHF, heparin administration within 24 h after admission was not associated with a lower risk of all-cause death and ischemic stroke, but was associated with a higher risk of major bleeding during hospitalization. Our study raises questions about the routine use of heparin for thromboembolism prophylaxis in hospitalized patients with AHF. Further studies are warranted to address the utility of anticoagulant therapy in these patients.

Cardiac Rehabilitation for Patients With Stable Ischemic Heart Disease Without Revascularization　- Rationale and Design of a Single-Arm Pilot Study.

Background: Clinical practice guidelines strongly recommend optimal medical therapy (OMT), including lifestyle modification, pharmacotherapy, and exercise-based cardiac rehabilitation (CR), in patients with stable ischemic heart disease (SIHD). However, the efficacy and safety of CR in patients with SIHD without revascularization remain unclear. Methods and Results: The Prospective Registry of STable Angina RehabiliTation (Pre-START) study is a multicenter, prospective, single-arm, open-label pilot study to evaluate the efficacy and safety of CR on health-related quality of life (HRQL), exercise capacity, and clinical outcomes in Japanese patients with SIHD without revascularization. In this study, all patients will undergo guideline-based OMT and are encouraged to have 36 outpatient CR sessions within 5 months after enrollment. The primary endpoint is the change in the Seattle Angina Questionnaire-7 summary score between baseline and the 6-month visit; an improvement of ≥5 points will be defined as a clinically important change. Secondary endpoints include changes in other HRQL scores and exercise capacity between baseline and the 6-month visit, as well as clinical outcomes between enrollment and the 6-month visit. Conclusions: The Pre-START study will provide valuable evidence to elucidate the efficacy and safety of CR in patients with SIHD and indispensable information for a subsequent randomized controlled trial. The study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (ID: UMIN000045415) on April 1, 2022.