Edoxaban for 12 Months Versus 3 Months in Patients With Cancer With Isolated Distal Deep Vein Thrombosis (ONCO DVT Study): An Open-Label, Multicenter, Randomized Clinical Trial.

BACKGROUND: The optimal duration of anticoagulation therapy for isolated distal deep vein thrombosis in patients with cancer is clinically relevant, but the evidence is lacking. The prolonged anticoagulation therapy could have a potential benefit for prevention of thrombotic events; however, it could also increase the risk of bleeding. METHODS: In a multicenter, open-label, adjudicator-blinded, randomized clinical trial at 60 institutions in Japan, we randomly assigned patients with cancer with isolated distal deep vein thrombosis, in a 1-to-1 ratio, to receive either a 12-month or 3-month edoxaban treatment. The primary end point was a composite of a symptomatic recurrent venous thromboembolism (VTE) or VTE-related death at 12 months. The major secondary end point was major bleeding at 12 months, according to the criteria of the International Society on Thrombosis and Haemostasis. The primary hypothesis was that a 12-month edoxaban treatment was superior to a 3-month edoxaban treatment with respect to the primary end point. RESULTS: From April 2019 through June 2022, 604 patients were randomized, and after excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group. The mean age was 70.8 years, 28% of the patients were men, and 20% of the patients had symptoms of deep vein thrombosis at baseline. The primary end point of a symptomatic recurrent VTE event or VTE-related death occurred in 3 of the 296 patients (1.0%) in the 12-month edoxaban group and in 22 of the 305 patients (7.2%) in the 3-month edoxaban group (odds ratio, 0.13; 95% CI, 0.03-0.44). The major secondary end point of major bleeding occurred in 28 of the 296 patients (9.5%) in the 12-month edoxaban group and in 22 of the 305 patients (7.2%) in the 3-month edoxaban group (odds ratio, 1.34; 95% CI, 0.75-2.41). The prespecified subgroups did not affect the estimates on the primary end point. CONCLUSIONS: In patients with cancer with isolated distal deep vein thrombosis, 12 months was superior to 3 months for an edoxaban treatment with respect to the composite outcome of a symptomatic recurrent VTE or VTE-related death. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03895502.

The effect of an initial catheter ablation with an adjunctive ethanol infusion into the vein of Marshall on persistent atrial fibrillation.

INTRODUCTION: Some previous studies have reported that a first-step ethanol infusion into the vein of Marshall (EIVOM) with touch-up radiofrequency (RF) ablation can facilitate mitral isthmus (MI) block and improves the ablation outcomes in persistent atrial fibrillation (PeAF) patients. However, the effect of an initial RF ablation with an adjunctive EIVOM has not been fully investigated. METHODS: This study enrolled 233 PeAF patients undergoing pulmonary vein isolation and linear ablation including an MI, roof line, and cavotricuspid isthmus ablation. An EIVOM was performed when endocardial ablation with or without coronary sinus ablation failed to create MI block. RESULTS: Bidirectional MI block was achieved in 224 patients (96.1%). Among them, MI block was obtained by only RF ablation in 174/224 patients (77.7%) (RF group) and an adjunctive EIVOM was needed in 50/224 (22.3%) (EIVOM group). During the follow-up, 113 (64.9%) RF group patients were free from AF/atrial tachycardia compared to 41 (82.0%) EIVOM group patients (log-rank p = .045). In a multivariate Cox regression analysis, an adjunctive EIVOM was associated with a lower recurrence rate (hazard ratio = 0.39, 95% confidence interval = 0.17-0.78, p = .006). CONCLUSION: An initial RF ablation with an adjunctive EIVOM strategy improved MI ablation's acute success rate and was associated with better clinical outcomes.

Effective growth hormone replacement with once-weekly somapacitan in Japanese children with growth hormone deficiency: Results from REAL4, a phase 3 clinical trial.

OBJECTIVE: Somapacitan is a long-acting growth hormone (GH) derivative developed for the treatment of GH deficiency (GHD). This study evaluates the efficacy and tolerability of somapacitan in Japanese children with GHD after 104 weeks of treatment and after switch from daily GH. DESIGN: Subanalysis on Japanese patients from a randomised, open-labelled, controlled parallel-group phase 3 trial (REAL4, NCT03811535). PATIENTS AND MEASUREMENTS: Thirty treatment-naïve patients were randomised 2:1 to somapacitan (0.16 mg/kg/week) or daily GH (0.034 mg/kg/day) up to Week 52, after which all patients received somapacitan. Height velocity (HV; cm/year) at Weeks 52 and 104 were the primary measurements. Additional assessments included HV SD score (SDS), height SDS, bone age, insulin-like growth factor-I (IGF-I) SDS, and observer-reported outcomes. RESULTS: At Week 52, observed mean HV was similar between treatment groups (10.3 vs. 9.8 cm/year for somapacitan and daily GH, respectively). Similar HVs between groups were also observed at Week 104: 7.4 cm/year after continuous somapacitan treatment (soma/soma) and 7.9 cm/year after 1-year somapacitan treatment following switch from daily GH (switch). Other height-related endpoints supported continuous growth. IGF-I SDS increased in both groups with mean IGF-I SDS within -2 and +2 during the study. Somapacitan was well tolerated, one mild injection site reaction was reported, with no reports of injection site pain. Patient preference questionnaires showed that most patients and their caregivers (90.9%) who switched treatment at Week 52 preferred once-weekly somapacitan over daily GH treatment. CONCLUSIONS: Somapacitan showed sustained efficacy in Japanese children with GHD over 104 weeks and for 52 weeks after switching from daily GH. Somapacitan was well tolerated and preferred over daily GH.

Rationale and study design of the GOREISAN for heart failure (GOREISAN-HF) trial: A randomized clinical trial.

BACKGROUND: The decongestion strategy using loop diuretics is essential for improving signs and symptoms of heart failure (HF). However, chronic use of loop diuretics in HF has been linked to worsening renal function and adverse clinical outcomes in a dose-dependent manner. Goreisan, a traditional Japanese herbal medicine, has a long history of use in Japan for regulating body fluid homeostasis and has been recognized as causing less adverse outcomes such as dehydration in contrast to loop diuretics in clinical practice. Therefore, we designed the GOREISAN-HF trial to evaluate the long-term effects of a new decongestion strategy adding Goreisan to usual care in patients with HF and volume overload. METHODS: The GOREISAN-HF trial is an investigator-initiated, multicenter, pragmatic, randomized, comparative effectiveness trial in which we will enroll 2,192 patients hospitalized for HF at 68 hospitals in Japan. All study participants will be randomly assigned to either a decongestion strategy that adds Goreisan at a dose of 7.5 g daily on top of usual care or usual care alone. Investigators have the flexibility to change the existing diuretic regimen in both groups. The primary end point is the improvement rate of cardiac edema at 12-month follow-up, and the co-primary end point is a composite of all-cause death or hospitalization up to the end of the planned follow-up period. Secondary end points include longitudinal changes in patient-reported outcomes, loop diuretics dose, and renal function. CONCLUSIONS: The GOREISAN-HF is the first large-scale randomized pragmatic trial to assess the efficacy and safety of a new congestion control strategy adding Goreisan to usual care in patients with HF and volume overload. REGISTRATION NUMBER: NCT04691700.

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).

Sex Differences in Clinical Outcomes After Percutaneous Coronary Intervention.

BACKGROUND: There is a scarcity of studies comparing the clinical outcomes after percutaneous coronary intervention (PCI) for women and men stratified by the presentation of acute coronary syndromes (ACS) or stable coronary artery disease (CAD).Methods and Results: The study population included 26,316 patients who underwent PCI (ACS: n=11,119, stable CAD: n=15,197) from the CREDO-Kyoto PCI/CABG registry Cohort-2 and Cohort-3. The primary outcome was all-cause death. Among patients with ACS, women as compared with men were much older. Among patients with stable CAD, women were also older than men, but with smaller difference. The cumulative 5-year incidence of all-cause death was significantly higher in women than in men in the ACS group (26.2% and 17.9%, log rank P<0.001). In contrast, it was significantly lower in women than in men in the stable CAD group (14.2% and 15.8%, log rank P=0.005). After adjusting confounders, women as compared with men were associated with significantly lower long-term mortality risk with stable CAD but not with ACS (hazard ratio [HR]: 0.75, 95% confidence interval [CI]: 0.69-0.82, P<0.001, and HR: 0.92, 95% CI: 0.84-1.01, P=0.07, respectively). There was a significant interaction between the clinical presentation and the mortality risk of women relative to men (interaction P=0.002). CONCLUSIONS: Compared with men, women had significantly lower adjusted mortality risk after PCI among patients with stable CAD, but not among those with ACS.

Abdominal Aortic Aneurysm Shrinkage up to 2 Years Following Endovascular Repair with PEmbolization for Preventing Type 2 Endoleak: A Retrospective Single Center Study.

BACKGROUND: The aim of the present study was to evaluate the efficacy of preemptive embolization of aneurysm side branches that cause type 2 endoleak (T2EL). METHODS: We performed a retrospective review of consecutive patients who underwent endovascular aneurysm repair (EVAR) in our facility between April 2009 and April 2019. All the patients underwent the preemptive embolization for preventing T2EL since April 2014. The patients were divided into the nonembolization group (between April 2009 and May 2014) or the embolization group (between April 2014 and April 2019). We used a support wire to improve a success rate of the preemptive embolization. The aneurysm sac shrinkage (≧5 mm), freedom from all-cause death and aneurysm-related death, T2EL-related reinterventions, aneurysm sac enlargement (≧5 mm), and complications related to the endovascular procedure were compared between the 2 groups. RESULTS: Two-hundred patients with abdominal aortic aneurysm were included. They were divided into the nonembolization group (N = 103) and the embolization group (N = 97). We successfully embolized 89% of all the patent aneurysm side branches in the embolization group. The characteristics of the 2 groups were similar except for hypertension, patent lumbar arteries, and the use of Zenith, Excluder, and Endurant. The preemptive embolization group showed better aneurysm sac shrinkage (73% vs. 42%; P < 0.0001), no aneurysm sac enlargement (0% vs. 5%; P < 0.05), and lower T2EL-related reintervention rate (hazard ratio, 0.11; 95% confidence interval, 0.0061-0.60; P < 0.01) up to 2 years after EVAR. There were no significant differences in freedom from all-cause death, aneurysm-related death, and complications between the 2 groups. CONCLUSIONS: The present study showed the high success rate of preemptive embolization of aneurysm side branches resulting in better anatomical changes in the aneurysm sac and lower T2EL-related intervention rate in the embolization group up to 2 years after EVAR.

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.

Developing Multidisciplinary Management of Heart Failure in the Super-Aging Society of Japan.

The Japanese population is rapidly aging because of its long life expectancy and low birth rate; additionally, the number of patients with heart failure (HF) is increasing to the extent that HF is now considered a pandemic. According to a recent HF registry study, Japanese patients with HF have both medical and care-related problems. Although hospitalization is used to provide medical services, and institutionalization is used to provide care for frail older adults, it can be difficult to distinguish between them. In this context, multidisciplinary management of HF has become increasingly important in preventing hospital readmissions and maintaining a patient's quality of life. Academia has promoted an increase in the number of certified HF nurses and educators. Researchers have issued numerous guidelines or statements on topics such as cardiac rehabilitation, nutrition, and palliative care, in addition to the diagnosis and treatment of acute and chronic HF. Moreover, the Japanese government has created incentives through various medical and long-term care systems adjustments to increase collaboration between these two fields. This review summarizes current epidemiological registries that focus not only on medical but also care-related problems and the 10 years of multidisciplinary management experience in Japanese medical and long-term care systems.

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.

Bleeding Outcomes After Percutaneous Coronary Intervention in the Past Two Decades in Japan　- From the CREDO-Kyoto Registry Cohort-2 and Cohort-3.

BACKGROUND: Optimal intensity is unclear for P2Y12receptor blocker therapy after percutaneous coronary intervention (PCI) in real-world clinical practice.Methods and Results: From the CREDO-Kyoto Registry, the current study population consisted of 25,419 patients (Cohort-2: n=12,161 and Cohort-3: n=13,258) who underwent their first PCI. P2Y12receptor blocker therapies were reduced dose of ticlopidine (200 mg/day), and global dose of clopidogrel (75 mg/day) in 87.7% and 94.8% of patients in Cohort-2 and Cohort-3, respectively. Cumulative 3-year incidence of GUSTO moderate/severe bleeding was significantly higher in Cohort-3 than in Cohort-2 (12.1% and 9.0%, P<0.0001). After adjusting 17 demographic factors and 9 management factors potentially related to the bleeding events other than the type of P2Y12receptor blocker, the higher bleeding risk in Cohort-3 relative to Cohort-2 remained significant (hazard ratio (HR): 1.52 95% confidence interval (CI) 1.37-1.68, P<0.0001). Cohort-3 compared with Cohort-2 was not associated with lower adjusted risk for myocardial infarction/ischemic stroke (HR: 0.96, 95% CI: 0.87-1.06, P=0.44). CONCLUSIONS: In this historical comparative study, Cohort-3 compared with Cohort-2 was associated with excess bleeding risk, which might be at least partly explained by the difference in P2Y12receptor blockers.

Effects of Acute Coronary Syndrome and Stable Coronary Artery Disease on Bleeding and Ischemic Risk After Percutaneous Coronary Intervention.

BACKGROUND: Data evaluating the effects of acute coronary syndrome (ACS) relative to stable coronary artery disease (CAD) on bleeding risk after percutaneous coronary intervention (PCI) are scarce.Methods and Results:From the CREDO-Kyoto Registry Cohort-3, 13,258 patients undergoing first PCI (5,521 ACS; 7,737 stable CAD) were identified. Patients were further stratified according to ACS presentation and Academic Research Consortium High Bleeding Risk (HBR): ACS/HBR: n=2,502; ACS/no-HBR: n=3,019; stable CAD/HBR: n=3,905; and stable CAD/no-HBR: n=3,832. The primary bleeding endpoint was Bleeding Academic Research Consortium 3/5 bleeding, whereas the primary ischemic endpoint was myocardial infarction (MI)/ischemic stroke. Compared with stable CAD, ACS was associated with a significantly higher adjusted risk for bleeding (hazard ratio [HR] 1.85; 95% confidence interval [CI] 1.68-2.03; P<0.0001), with a markedly higher risk within 30 days (HR 4.24; 95% CI 3.56-5.06; P<0.0001). Compared with the stable CAD/no-HBR group, the ACS/HBR, no-ACS/HBR, and ACS/no-HBR groups were associated with significantly higher adjusted risks for bleeding, with HRs of 3.05 (95% CI 2.64-3.54; P<0.0001), 1.89 (95% CI 1.66-2.15; P<0.0001), and 1.69 (95% CI 1.45-1.98; P<0.0001), respectively. There was no excess adjusted risk of the ACS relative to stable CAD group for MI/ischemic stroke (HR 1.07; 95% CI 0.94-1.22; P=0.33). CONCLUSIONS: Bleeding risk after PCI depended on both ACS presentation and HBR, with a significant effect of ACS within 30 days.

Application of the Modified High Bleeding Risk Criteria for Japanese Patients in an All-Comers Registry of Percutaneous Coronary Intervention　- From the CREDO-Kyoto Registry Cohort-3.

BACKGROUND: The prevalence of and expected bleeding event rate in patients with the Japanese version of high bleeding risk (J-HBR) criteria are currently unknown in real-world percutaneous coronary intervention (PCI) practice.Methods and Results:We applied the J-HBR criteria in the multicenter CREDO-Kyoto registry cohort-3 that enrolled 13,258 consecutive patients who underwent first PCI. The J-HBR criteria included Japanese-specific major criteria such as heart failure, low body weight, peripheral artery disease and frailty in addition to the Academic Research Consortium (ARC)-HBR criteria. There were 8,496 patients with J-HBR, and 4,762 patients without J-HBR. The J-HBR criteria identified a greater proportion of patients with HBR than did ARC-HBR (64% and 48%, respectively). Cumulative incidence of the Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding was significantly higher in the J-HBR group than in the no-HBR group (14.0% vs. 4.1% at 1 year; 23.1% vs. 8.4% at 5 years, P<0.0001). Cumulative 5-year incidence of BARC 3/5 bleeding was 25.1% in patients with ARC-HBR, and 23.1% in patients with J-HBR. Cumulative incidence of myocardial infarction or ischemic stroke was also significantly higher in the J-HBR group than in the no-HBR group (6.9% vs. 3.6% at 1 year; 13.2% vs. 7.1% at 5 years, P<0.0001). CONCLUSIONS: The J-HBR criteria successfully identified those patients with very high bleeding risk after PCI, who represented 64% of patients in this all-comers registry.

A model six-month workshop for developing systematic review protocols at teaching hospitals: action research and scholarly productivity.

BACKGROUND: Research engagement contributes to the improvement of patient care. A systematic review is a suitable first scholarly activity because it entails summarization of publicly available data and usually requires neither rigorous ethical review nor research funding. METHODS: This study aimed to develop a model workshop for healthcare staff to acquire skills in creating systematic review protocols based on their own clinical questions at teaching hospitals. We used an action research method to create a model workshop at four hospitals in Japan from April 2015 to March 2017. To improve the program, we solicited reflections using participant questionnaires for each lecture and examined the quality of homework submitted by participants after each lecture. We administered a revised final version of the workshop at five hospitals from April 2016 to March 2017. We evaluated the participants' scholarly productivity related to these workshops. The observation period was a minimum of 2 years following the workshops. RESULTS: Most participants had never developed a formal clinical research protocol and voluntarily participated in the workshop. The action research was developed and implemented at nine teaching hospitals in Japan, including one university hospital. The study developed a model nine-step workshop curriculum: 1) Research question development, 2) Search strategy development, 3) Search strategy brush-up, 4) Exclusion and inclusion criteria development, 5) Risk of bias assessment planning, 6) Meta-analysis planning, 7) Subgroup and sensitivity analysis planning, 8) Planning the presentation of results, and 9) Presentation protocols. A total of 233 participants, including medical doctors and other health professionals, produced 414 research questions. Seventy-nine participants (34%) completed the workshop, and 47 review teams accomplished systematic review protocols. The participants published 13 peer-reviewed articles as a result of the workshop. CONCLUSIONS: We developed a structured scholarly productive model workshop for healthcare staff working at hospitals. We found healthcare staff with clinical subspecialties were able to develop an unexpectedly high number of research questions through this workshop. Medical teachers at hospitals with prior systematic review experience could teach how to develop systematic review protocols using this model. Further research is needed to increase the academic productivity of such workshops. TRIAL REGISTRATION: UMIN (https://www.umin.ac.jp/ctr/), UMIN000017107 (4/15/2015), UMIN000025580 (1/10/2017).

The Effects of an Oral Nutritional Supplement with Whey Peptides and Branched-Chain Amino Acids for Cardiac Rehabilitation of Patients with Chronic Heart Failure.

The aim of the present study was to determine whether the addition of an oral nutritional supplement with whey peptides and branched-chain amino acids for cardiac rehabilitation improves cardiopulmonary function, skeletal muscle function, and metabolism in CHF patients.In this randomized, parallel-group comparative pilot study, 20 CHF patients were randomly assigned to the nutrition group (n = 10) or the control group (n = 10). At baseline and 12 weeks, we performed physical examinations, motor function evaluation, clinical laboratory tests, nutritional status assessment, and echocardiography. The primary outcome was exercise tolerance, as determined by the cardiopulmonary stress test (CPX), 6-minute walking test (6MWT), and brain natriuretic peptide (BNP) levels.During follow-up, body weight, body mass index, total muscle mass, and total lean mass did not change significantly in either group. The total fat mass significantly increased in the nutrition group (14.3 ± 5.4 kg versus 16.1 ± 5.5 kg, P < 0.001) but did not change in the control group, and the difference in the changes in total fat mass between groups was significant (-0.26 ± 0.96 kg versus 1.49 ± 0.63 kg, P < 0.001). The peakVO2 and 6-minute walk test (6 MWT) significantly increased in the nutrition group (14.6 ± 3.4 mL/minute/kg versus 15.8 ± 3.8 mL/minute/kg, P = 0.029; 346.9 ± 103.1 m versus 382.7 ± 102.1 m, P = 0.048; respectively) but did not change in the control group. The changes in peakVO2 and 6MWT did not significantly differ between the groups.The oral nutritional supplement for the treatment of CHF was effective for cardiac rehabilitation in terms of fat mass and exercise capacity.The present study demonstrated that oral nutritional supplements with whey peptides and branched-chain amino acid (BCAA) for cardiac rehabilitation in patients with chronic heart failure (CHF) increased fat mass and exercise capacity. We conclude that whey peptides and BCAA supplementation may be a useful treatment for CHF patients.

Risk Factors for Major Bleeding During Anticoagulation Therapy in Cancer-Associated Venous Thromboembolism　- From the COMMAND VTE Registry.

BACKGROUND: Patients with cancer-associated venous thromboembolism (VTE) are at high risk for recurrent VTE and are recommended to receive prolonged anticoagulation therapy if they are at a low risk for bleeding. However, there are no established risk factors for bleeding during anticoagulation therapy.Methods and Results:The COMMAND VTE Registry is a multicenter retrospective registry enrolling 3,027 consecutive patients with acute symptomatic VTE among 29 Japanese centers. The present study population consisted of 592 cancer-associated VTE patients with anticoagulation therapy. We constructed a multivariable Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the potential risk factors for major bleeding. During a median follow-up period of 199 days, major bleeding occurred in 72 patients. The cumulative incidence of major bleeding was 5.8% at 3 months, 13.8% at 1 year, 17.5% at 2 years, and 28.1% at 5 years. The most frequent major bleeding site was gastrointestinal tract (47%). Terminal cancer (adjusted HR, 4.17; 95% CI, 2.22-7.85, P<0.001), chronic kidney disease (adjusted HR, 1.89; 95% CI 1.06-3.37, P=0.031), and gastrointestinal cancer (adjusted HR, 1.78; 95% CI, 1.04-3.04, P=0.037) were independently associated with an increased risk of major bleeding. CONCLUSIONS: Major bleeding events were common during anticoagulation therapy in real-world cancer-associated VTE patients. Terminal cancer, chronic kidney disease, and gastrointestinal cancer were the independent risk factors for major bleeding.

Nationwide Survey of Multidisciplinary Care and Cardiac Rehabilitation for Patients With Heart Failure in Japan　- An Analysis of the AMED-CHF Study.

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

Clinical Characteristics and Outcomes of Venous Thromboembolisms According to an Out-of-Hospital vs. In-Hospital Onset　- From the COMMAND VTE Registry.

BACKGROUND: Differences in the clinical characteristics and outcomes of venous thromboembolisms (VTEs) based on different clinical situations surrounding the onset might be important for directing appropriate treatment strategies, but have not yet been appropriately evaluated. Methods and Results: The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive patients with acute symptomatic VTEs in Japan between January 2010 and August 2014. We divided the study population into 3 groups: Out-of-hospital onset (n=2,308), In-hospital onset with recent surgery (n=310), and In-hospital onset without recent surgery (n=374). Active cancer was most prevalent in the In-hospital onset without recent surgery group, and least in the Out-of-hospital onset group (Out-of-hospital onset group: 20%, In-hospital onset with recent surgery group: 26%, and In-hospital onset without recent surgery group: 38%, P<0.001). The cumulative 5-year incidence of recurrent VTEs did not significantly differ across the 3 groups (11.4%, 5.8%, and 8.7%, respectively; P=0.11). The cumulative 5-year incidences of major bleeding and all-cause death were highest in the In-hospital onset without recent surgery group (11.1%, 8.5%, and 23.3%, P<0.001; 26.8%, 24.9%, and 48.4%, P<0.001, respectively). CONCLUSIONS: In the real-world VTE registry, the clinical characteristics and long-term outcomes substantially differed according to the clinical situation of VTE onset, suggesting the need for different treatment strategies for VTEs in different clinical settings.

Thrombolysis with tissue plasminogen activator in patients with acute pulmonary embolisms in the real world: from the COMMAND VTE registry.

There is still uncertainty about the optimal usage of thrombolysis for acute pulmonary embolisms (PEs), leading to a widely varying usage in the real world. The COMMAND VTE Registry is a multicenter retrospective registry enrolling consecutive patients with acute symptomatic venous thromboembolisms (VTEs) in Japan. The present study population consisted of 1549 patients with PEs treated with tissue plasminogen activator (t-PA) thrombolysis (N = 180, 12%) or without thrombolysis (N = 1369). Thrombolysis with t-PA was implemented in 33% of patients with severe PEs, and 9.2% of patients with mild PEs with a wide variation across the participating centers. Patients with t-PA thrombolysis were younger, and less frequently had active cancer, history of major bleeding, and anemia. At 30 days, t-PA thrombolysis as compared to no thrombolysis was associated with similar mortality rates (5.0% vs. 6.9%, P = 0.33), but a lower adjusted mortality risk (OR 0.41; 95% CI 0.18-0.90, P = 0.03), while it was associated with a trend for higher rates of major bleeding (5.6% vs. 2.9%, P = 0.06) and a significantly higher adjusted risk for major bleeding (OR 2.39; 95% CI 1.06-5.36, P = 0.03). In patients with severe PEs, the mortality rates at 30 days were significantly lower in the t-PA thrombolysis group than no thrombolysis group (15% vs. 37%, P = 0.006). In the present real-world VTE registry in Japan, t-PA thrombolysis was not infrequently implemented, not only in patients with severe PEs, but also in patients with mild PEs. A substantial mortality risk reduction might be suggested with t-PA thrombolysis in patients with severe PEs.

Possible associations between palliative care conferences and positive outcomes when performing palliative care for patients with end-stage heart failure: a nationwide cross-sectional questionnaire survey.

Palliative care for end-stage heart failure should be provided by a multidisciplinary team. However, the influence of each occupational category on patients receiving palliative care for end-stage heart failure remains unclear. Thus, this study investigated the relationships between palliative care conferences and positive outcomes of palliative care for end-stage heart failure patients. We sent questionnaires to all cardiology training hospitals authorized by the Japanese Circulation Society (n = 1004); of these, responses from the directors at 554 institutions were analyzed. We divided the responding institutions into two groups according to their implementation of palliative care conferences for patients with end-stage heart failure. The institutions that had held such conferences (n = 223) had a larger number of hospital beds, beds in the cardiovascular department, and patients admitted to the cardiovascular department, compared with institutions that had not held these conferences (n = 321). The usage rates of opioids, non-steroidal anti-inflammatory drugs, and sedatives were significantly higher in institutions that held these conferences. Multivariate analysis revealed that nutritionists and medical social workers had greater involvement in the improvement of mental symptoms and ensuring that patients could stay where they wished, respectively. The presence of palliative care physicians, physical therapists, or pharmacists was associated with multiple positive outcomes. This study indicated that there are possible associations between palliative care conferences and positive outcomes when performing palliative care for patients with end-stage heart failure.