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Prolonged anticoagulation therapy is recommended for patients with intermediate-risk for recurrence of venous thromboembolism (VTE). The current study aimed to identify risk factors of VTE recurrence and major bleeding in intermediate-risk patients. The COMMAND VTE Registry is a multicenter registry enrolled consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan. The current study population consisted of 1703 patients with intermediate-risk for recurrence. The primary outcome measure was recurrent VTE during the entire follow-up period, and the secondary outcome measures were recurrent VTE and major bleeding during anticoagulation therapy. In the multivariable Cox regression model for recurrent VTE incorporating the status of anticoagulation therapy as a time-updated covariate, off-anticoagulation therapy was strongly associated with an increased risk for recurrent VTE (HR 9.42, 95% CI 5.97-14.86). During anticoagulation therapy, the independent risk factor for recurrent VTE was thrombophilia (HR 3.58, 95% CI 1.56-7.50), while the independent risk factors for major bleeding were age ≥ 75 years (HR 2.04, 95% CI 1.36-3.07), men (HR 1.52, 95% CI 1.02-2.27), history of major bleeding (HR 3.48, 95% CI 1.82-6.14) and thrombocytopenia (HR 3.73, 95% CI 2.04-6.37). Among VTE patients with intermediate-risk for recurrence, discontinuation of anticoagulation therapy was a very strong independent risk factor of recurrence during the entire follow-up period. The independent risk factors of recurrent VTE and those of major bleeding during anticoagulation therapy were different: thrombophilia for recurrent VTE, and advanced age, men, history of major bleeding, and thrombocytopenia for major bleeding. CLINICAL TRIAL REGISTRATION: Unique identifier: UMIN000021132. COMMAND VTE Registry: http://www.umin.ac.jp/ctr/index.htm ., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: We recently developed the self-management system using the HF points and instructions to visit hospitals or clinics when the points exceed the pre-specified levels. We found that the self-management system decreased the hospitalization for HF with an increase in unplanned visits and early intervention in the outpatient department. However, it is unclear whether we managed severe HF outpatients who should have been hospitalized. In this study, we aimed to compare HF severity in rehospitalized patients with regard to self-management system use., Results: We retrospectively enrolled 306 patients (153 patients each in the system user and non-user groups) using propensity scores (PS). We compared HF severity and length of readmission in rehospitalized patients in both groups. During the 1-year follow-up period, 24 system users and 43 non-system users in the PS-matched cohort were hospitalized. There were no significant differences between the groups in terms of brain natriuretic peptide levels at readmission, maximum daily intravenous furosemide dose, percentage of patients requiring intravenous inotropes, duration of hospital stay and in-hospital mortality. These results suggest that the HF severity in rehospitalized patients was not different between the two groups., (© 2021. The Author(s).)

Background: The detailed causes of death in non-ST-segment-elevation myocardial infarction (NSTEMI) have not been adequately evaluated compared to those in ST-segment elevation myocardial infarction (STEMI)., Methods: The study population was 6,228 AMI patients who underwent percutaneous coronary intervention (STEMI: 4,625 patients and NSTEMI: 1,603 patients). The primary outcome was all-cause death., Results: Within 6 months after AMI, the adjusted mortality risk was not significantly different between NSTEMI patients and STEMI patients (HR: 0.83, 95%CI: 0.67-1.03, P = 0.09). Regarding the causes of death within 6 months after AMI, mechanical complications more frequently occurred in STEMI patients than in NSTEMI patients, while proportions of post resuscitation status on arrival and heart failure were higher in in NSTEMI patients than in STEMI patients. Beyond 6 months after AMI, the adjusted mortality risk of NSTEMI relative to STEMI was not significantly different. (HR: 1.04, 95%CI: 0.90-1.20, P = 0.59). Regarding causes of death beyond 6 months after AMI, almost half of deaths were cardiovascular causes in both groups, and breakdown of causes of death was similar between NSTEMI and STEMI., Conclusion: The mortality risk within and beyond 6 months after AMI were not significantly different between STEMI patients and NSTEMI patients after adjusting confounders. Deaths due to post resuscitation status and heart failure were more frequent in NSTEMI within 6 months after AMI., Competing Interests: Dr. Shiomi reports modest honoraria from Abbott Vascular, and Boston Scientific. Dr. Morimoto reports modest honoraria from Bayer and Kowa, and modest expert witness from Boston Scientific and Sanofi. Dr. Kato reports modest honoraria from Daiichi-Sankyo, Ono Pharmaceutical, AstraZeneca, Tanabe-Mitsubishi, Bayer, Phizer, Bristol-Meyers Squibb, Boehringer ingelheim, Takeda, MSD KK, Amgen, and research fund from Ono Pharmaceutical and Abbott Japan. Dr. Ehara reports modest honoraria from Abbott Vascular, Bayer, Boston Scientific, Medtronic, and Terumo. Dr. Furukawa reports modest honoraria from Bayer, Kowa, and Sanofi. Dr. Nakagawa reports modest research grant from Abbott Vascular and Boston Scientific, and modest honoraria from Abbott Vascular, Bayer, and Boston Scientific. Dr. Kimura reports significant honoraria from Abbott Vascular, and modest honoraria from Astellas, AstraZeneca, Bayer, Boston Scientific, Kowa, and Sanofi. None of the article contents have not been published, nor under consideration for publication in any other journal before appearing in PLOS ONE.

Background: There is a paucity of data on the long-term clinical outcomes according to the severity of pulmonary embolism (PE) at initial diagnosis., Methods: The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic venous thromboembolism (VTE). After excluding 1312 patients without PE, the current study population consisted of 1715 patients with PE, who were divided into 3 groups according to the clinical severity; massive PE, sub-massive PE and low-risk PE., Results: There were 179 patients (10%) with massive PE, 742 patients (43%) with sub-massive PE, and 794 patients (46%) with low-risk PE. By the landmark analysis at 3 months, the cumulative incidences of recurrent VTE were similar among the 3 groups both within and beyond 3 months (Massive PE: 2.9%, Sub-massive PE: 4.2%, and Low-risk PE: 3.3%, P = 0.61, and 4.3%, 8.8%, and 7.8% at 5 years, P = 0.47, respectively). After adjusting confounders, the risk of massive PE relative to low-risk PE for recurrent VTE beyond 3 months remained insignificant (adjusted HR 0.54, 95% CI: 0.13-1.51, P = 0.27). Patients with massive PE at initial diagnosis more often presented as severe recurrent PE events than those with sub-massive and low-risk PE., Conclusions: In the current real-world large registry, the long-term risk of overall recurrent VTE in patients with massive PE at initial diagnosis did not significantly differ from those with sub-massive and low-risk PE beyond 3 months, although patients with massive PE at initial diagnosis more frequently developed recurrent VTE as PE with severe clinical presentation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Polypharmacy was reported to be associated with increased mortality in various populations. However, there is a scarcity of data on status of polypharmacy and association with long-term mortality in patients who underwent percutaneous coronary intervention (PCI). Among 12,291 patients who underwent first PCI in the CREDO-Kyoto PCI/CABG registry Cohort-3, we evaluated the number of medications at discharge from index PCI hospitalization, and compared long-term mortality across the 3 groups divided by the tertiles of the number of medications. The median number of medications was 6 (interquartile range: 5 to 8), and 88.0% of the patients were on >=5 medications. Most of medications were those related to cardiovascular disease. Patients taking more medications were older and more often had co-morbidities and guideline-indicated medications. The cumulative 5-year incidence of all-cause death increased incrementally with increasing number of medications (Tertile 1 [<=5]: 13.1%, Tertile 2 [6 to 7]: 13.9%, and Tertile 3 [>=8]: 18.0%, log-rank p <0.001). After adjusting confounders, the mortality risks of Tertile 2 and Tertile 3 relative to Tertile 1 were no longer significant (Tertile 2: hazard ratio 0.93; 95% confidence interval 0.84 to 1.04; p = 0.23, and Tertile 3: hazard ratio 0.91; 95% confidence interval 0.81 to 1.03; p = 0.14, respectively). In conclusion, in a real-world population of patients who underwent PCI, approximately 90% of patients were on >=5 medications. Increasing medications was associated with higher crude incidence of all-cause death, whereas adjusted mortality risks were similar regardless of the number of medications. These data might suggest that achievement of optimal medical therapy would be preferred, even if it might increase the number of medications used., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background It remains controversial whether long-term clinical impact of newly diagnosed atrial fibrillation (AF) in the acute phase of acute myocardial infarction (AMI) is different from that of prior AF diagnosed before the onset of AMI. Methods and Results The current study population from the CREDO-Kyoto AMI (Coronary Revascularization Demonstrating Outcome Study in Kyoto Acute Myocardial Infarction) Registry Wave-2 consisted of 6228 patients with AMI who underwent percutaneous coronary intervention. The baseline characteristics and long-term clinical outcomes were compared according to AF status (newly diagnosed AF: N=489 [7.9%], prior AF: N=589 [9.5%], and no AF: N=5150 [82.7%]). Median follow-up duration was 5.5 years. Patients with newly diagnosed AF and prior AF had similar baseline characteristics with higher risk profile than those with no AF including older age and more comorbidities. The cumulative 5-year incidence of all-cause death was higher in newly diagnosed AF and prior AF than no AF (38.8%, 40.7%, and 18.7%, P <0.001). The adjusted hazard ratios (HRs) for mortality of newly diagnosed AF and prior AF relative to no AF remained significant with similar magnitude (HR, 1.31; 95% CI, 1.12-1.54; P <0.001, and HR, 1.32; 95% CI, 1.14-1.52; P <0.001, respectively). The cumulative 5-year incidence of stroke decreased in the order of newly diagnosed AF, prior AF and no AF (15.5%, 12.9%, and 6.3%, respectively, P <0.001). The higher adjusted HRs of both newly diagnosed AF and prior AF relative to no AF were significant for stroke, with a greater risk of newly diagnosed AF than that of prior AF (HR, 2.05; 95% CI, 1.56-2.69; P <0.001, and HR, 1.33; 95% CI, 1.00-1.78; P =0.048, respectively). The higher stroke risk of newly diagnosed AF compared with prior AF was largely driven by the greater risk within 30 days. The higher adjusted HRs of newly diagnosed AF and prior AF relative to no AF were significant for heart failure hospitalization (HR, 1.73; 95% CI, 1.35-2.22; P <0.001, and HR, 2.23; 95% CI, 1.82-2.74; P <0.001, respectively) and major bleeding (HR, 1.46; 95% CI, 1.23-1.73; P <0.001, and HR, 1.36; 95% CI, 1.15-1.60; P <0.001, respectively). Conclusions Newly diagnosed AF in AMI had risks for mortality, heart failure hospitalization, and major bleeding higher than no AF, and comparable to prior AF. The risk of newly diagnosed AF for stroke might be higher than that of prior AF.

Background: The clinical significance of the discrepancy between left ventricular hypertrophy (LVH) by echocardiography and ECG remains to be elucidated., Methods: After excluding patients who presented with pacemaker placement, QRS duration ≥120 ms and cardiomyopathy and moderate to severe valvular disease, we retrospectively analysed 3212 patients who had undergone both scheduled transthoracic echocardiography (echo) and ECG in a hospital-based population. Cornell product >2440 mm · ms was defined as ECG-based LVH; left ventricular mass index >115 g/m 2 for men and >95 g/m 2 for women was defined as echo-based LVH. The study population was categorised into four groups: patients with both ECG-based and echo-based LVH (N=131, 4.1%), those with only echo-based LVH (N=156, 4.9%), those with only ECG-based LVH (N=409, 12.7%) and those with no LVH (N=2516, 78.3%)., Results: The cumulative 3-year incidences of a composite of all-cause death and major adverse cardiovascular events were 32.0%, 33.8%, 19.2% and 15.7%, respectively. After adjusting for confounders, the HRs relative to that in no LVH were 1.63 (95% CI 1.16 to 2.28), 1.68 (95% CI 1.23 to 2.30) and 1.09 (95% CI 0.85 to 1.41) in patients with both ECG-based and echo-based LVH, those with only echo-based LVH, and those with only ECG-based LVH, respectively., Conclusions: Echo-based LVH without ECG-based LVH was associated with a significant risk of adverse clinical events, and the risk was comparable to that in patients with both echo-based and ECG-based LVH., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The treatment of coronary artery disease has substantially changed over the past two decades. However, it is unknown whether and how much these changes have contributed to the improvement of long-term outcomes after coronary revascularization. We assessed trends in the demographics, practice patterns and long-term outcomes in 24,951 patients who underwent their first percutaneous coronary intervention (PCI) (n = 20,106), or isolated coronary artery bypass grafting (CABG) (n = 4,845) using the data in a series of the CREDO-Kyoto PCI/CABG Registries (Cohort-1 [2000 to 2002]: n = 7,435, Cohort-2 [2005 to 2007]: n = 8,435, and Cohort-3 [2011 to 2013]: n = 9,081). From Cohort-1 to Cohort-3, the patients got progressively older across subsequent cohorts (67.0 ± 10.0, 68.4 ± 9.9, and 69.8 ± 10.2 years, p trend < 0.001). There was increased use of PCI over CABG (73.5%, 81.9%, and 85.2%, p trend < 0.001) and increased prevalence of evidence-based medications use over time. The cumulative 3-year incidence of all-cause death was similar across the 3 cohorts (9.0%, 9.0%, and 9.3%, p = 0.74), while cardiovascular death decreased over time (5.7%, 5.1%, and 4.8%, p = 0.03). The adjusted risk for all-cause death and for cardiovascular death progressively decreased from Cohort-1 to Cohort-2 (HR:0.89, 95%CI:0.80 to 0.99, p = 0.03, and HR:0.80, 95%CI:0.70 to 0.92, p = 0.002, respectively), and from Cohort-2 to Cohort-3 (HR:0.86, 95%CI:0.78 to 0.95, p = 0.004, and HR:0.77, 95%CI:0.67-0.89, p < 0.001, respectively). The risks for stroke and repeated coronary revascularization also improved over time. In conclusions, we found a progressive and substantial reduction of adjusted risk for all-cause death, cardiovascular death, stroke, and repeated coronary revascularization over the past two decades in Japan., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Patients undergoing percutaneous coronary intervention (PCI) often develop atrial fibrillation (AF). We investigated the clinical effects of AF status on in-hospital mortality and complications in patients with PCI using a recent large-scale nationwide dataset., Methods: Using a claims-based dataset from 1022 hospitals in Japan for the time period between 2012 and 2016, patients with PCI were identified and classified into 3 groups according to AF status: no AF, prevalent AF before admission, and incident AF after admission. In-hospital mortality, complications, and medical costs were compared in crude and propensity-matched cohorts., Results: In 659,525 hospitalized patients undergoing PCI, prevalent AF and incident AF were observed in 6.0% and 1.3% patients, respectively; the AF rates increased over 5 years. A greater proportion of older patients and patients with comorbidities had both of these categories of AF; undergoing PCI for acute coronary syndrome was common in incident AF. Both prevalent AF and incident AF were associated with worse crude outcomes and complications during hospitalization. In propensity-matched cohorts, incident AF was associated with a higher in-hospital mortality rate, longer length of stay, higher direct costs, and higher rate of complications, including stroke and acute kidney injury, compared with prevalent AF. These outcomes, except length of in-hospital stay, did not change for either AF status over 5 years., Conclusions: Prevalent AF and incident AF in patients undergoing PCI were both associated with deteriorating crude outcomes and complications; in particular, incident AF was associated with worse adjusted outcomes and complications. Further efforts are needed to improve patient outcomes in an aging society in which the incidence of AF is increasing., (© 2021 The Authors.)

Background: Although diabetes mellitus (DM) is a common comorbidity of aortic stenosis (AS), clinical evidence about the long-term effect of DM on patients with AS is insufficient.Methods and Results:Data were acquired from CURRENT AS, a large Japanese multicenter registry that enrolled 3,815 patients with severe AS. Patients without initial valve replacement were defined as the conservative group; among them, 621 (23.4%) had DM, whereas 1997 did not. The DM group was further divided into 2 groups according to insulin treatment (insulin-treated DM, n=130; non-insulin treated DM, n=491). The primary outcome was a composite of aortic valve (AV)-related death and heart failure (HF) hospitalization. Secondary outcomes were AV-related death, HF hospitalization, all-cause death, cardiovascular death, sudden death, and surgical or transcatheter AV replacement during follow up. As a result, DM was associated with higher risk for the primary outcome (52.8% vs. 42.9%, P<0.001), with a statistically significant adjusted hazard ratio (HR 1.33, 95% confidence interval: 1.14-1.56, P<0.001). All secondary outcomes were not significantly different between DM and non-DM patients after adjusting for confounding factors, except for HF hospitalization. Insulin use was not associated with higher incidence of primary or secondary outcome., Conclusions: In initially conservatively managed patients with AS, DM was independently associated with higher risk for a composite of AV-related death or HF hospitalization; however, insulin use was not associated with poor outcomes.

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.

While the prognostic impact of QRS axis deviation has been assessed, it has never been investigated in patients without conduction block. Thus, we evaluated the prognostic impact of QRS-axis deviation in patients without conduction block. We retrospectively analyzed 3353 patients who had undergone both scheduled transthoracic echocardiography and electrocardiography in 2013 in a hospital-based population, after excluding patients with a QRS duration of ≥ 110 ms, pacemaker placement, and an QRS-axis - 90° to - 180° (northwest axis). The study population was categorized into three groups depending on the mean frontal plane QRS axis as follows: patients with left axis deviation (N = 171), those with right axis deviation (N = 94), and those with normal axis (N = 3088). The primary outcome was a composite of all-cause death and major adverse cardiovascular events. The cumulative 3-year incidence of the primary outcome measure was significantly higher in the left axis deviation group (26.4% in the left axis deviation, 22.7% in the right axis deviation, and 18.4% in the normal axis groups, log-rank P = 0.004). After adjusting for confounders, the excess risk of primary outcome measure remained significant in the left axis deviation group (hazard ratio [HR] 1.44; 95% confidence interval [CI] 1.07-1.95; P = 0.02), while the excess risk of primary outcome measure was not significant in the right axis deviation group (HR 1.22; 95% CI 0.76-1.96; P = 0.41). Left axis deviation was associated with a higher risk of a composite of all-cause death and major adverse cardiovascular events in hospital-based patients without conduction block in Japan.

There is a scarcity of data comparing long-term clinical outcomes between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with three-vessel coronary artery disease (3VD) in the new-generation drug-eluting stents era. CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who had undergone first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. We identified 2525 patients with 3VD (PCI: n = 1747 [69%], and CABG: n = 778 [31%]). The primary outcome measure was all-cause death. Median follow-up duration was 5.7 (interquartile range: 4.4 to 6.6) years. The cumulative 5-year incidence of all-cause death was significantly higher in the PCI group than in the CABG group (19.8% vs 13.2%, log-rank p = 0.001). After adjusting confounders, the excess risk of PCI relative to CABG for all-cause death remained significant (HR, 1.45; 95% CI, 1.14 to 1.86; p = 0.003), which was mainly driven by the excess risk for non-cardiovascular death (HR, 1.88; 95% CI, 1.30 to 2.79; p = 0.001), while there was no excess risk for cardiovascular death between PCI and CABG (HR, 1.19; 95% CI, 0.87 to 1.64; p = 0.29). There was significant excess risk of PCI relative to CABG for myocardial infarction (HR, 1.77; 95% CI, 1.19 to 2.69; p = 0.006), whereas there was no excess risk of PCI relative to CABG for stroke (HR, 1.24; 95% CI, 0.83 to 1.88; p = 0.30). In conclusion, in the present study population reflecting real-world clinical practice in Japan, PCI compared with CABG was associated with significantly higher risk for all-cause death, while there was no excess risk for cardiovascular death between PCI and CABG., Competing Interests: Declaration of Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this study., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The majority of acute pulmonary embolism (PE) is caused by thrombus developed from leg veins. However, impact of concomitant deep venous thrombosis (DVT) on clinical outcomes has not been fully evaluated in patients with acute PE., Methods: The COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic venous thromboembolism (VTE) in Japan. The current study population consisted of 655 acute PE patients who underwent lower extremities ultrasound examination at diagnosis for the assessment of concomitant DVT status., Results: There were 424 patients with proximal DVT (64.7%), 162 patients with distal DVT (24.7%), and 69 patients with no DVT (10.5%). The cumulative 90-day incidence of all-cause death was higher in proximal DVT patients than in distal DVT and no DVT patients (7.9%, 2.5%, and 1.4%, p = 0.01). Regarding the causes of death, the cumulative 90-day incidence of PE-related death was low, and not significantly different across the 3 groups (1.4%, 0.6%, and 1.7%, p = 0.62). The most frequent cause of death was cancer in proximal and distal DVT patients. There were no significant differences in 90-day rates of recurrent VTE and major bleeding, regardless of the status of concomitant DVT (2.9%, 3.2%, and 2.2%, p = 0.79, and 1.5%, 4.4%, and 4.9%, p = 0.46, respectively)., Conclusions: Acute PE with proximal DVT at diagnosis was associated with a higher risk for short-term mortality than in patients without DVT, while the risk for short-term mortality was not significantly different between distal DVT patients and patients without DVT., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: To evaluate changes in demographics, clinical practices and long-term clinical outcomes of patients with ST segment-elevation myocardial infarction (STEMI) before and beyond 2010., Design: Multicentre retrospective cohort study., Setting: The Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) AMI Registries Wave-1 (2005-2007, 26 centres) and Wave-2 (2011-2013, 22 centres)., Participants: 9001 patients with STEMI who underwent coronary revascularisation (Wave-1: 4278 patients, Wave-2: 4723 patients)., Primary and Secondary Outcome Measures: The primary outcome was all-cause death at 3 years. The secondary outcomes were cardiovascular death, cardiac death, sudden cardiac death, non-cardiovascular death, non-cardiac death, myocardial infarction, definite stent thrombosis, stroke, hospitalisation for heart failure, major bleeding, target vessel revascularisation, ischaemia-driven target vessel revascularisation, any coronary revascularisation and any ischaemia-driven coronary revascularisation., Results: Patients in Wave-2 were older, more often had comorbidities and more often presented with cardiogenic shock than those in Wave-1. Patients in Wave-2 had shorter onset-to-balloon time and door-to-balloon time, were more frequently implanted drug-eluting stents, and received guideline-directed medication than those in Wave-1. The cumulative 3-year incidence of all-cause death was not significantly different between Wave-1 and Wave-2 (15.5% and 15.7%, p=0.77). The adjusted risk of all-cause death in Wave-2 relative to Wave-1 was not significant at 3 years (HR 0.92, 95% CI 0.83 to 1.03, p=0.14), but lower beyond 30 days (HR 0.86, 95% CI 0.75 to 0.98, p=0.03). The adjusted risks of Wave-2 relative to Wave-1 were significantly lower for definite stent thrombosis (HR 0.59, 95% CI 0.43 to 0.81, p=0.001) and for any coronary revascularisation (HR 0.75, 95% CI 0.69 to 0.81, p<0.001), but higher for major bleeding (HR 1.34, 95% CI 1.20 to 1.51, p=0.005)., Conclusions: We could not demonstrate improvement in 3-year mortality risk from Wave-1 to Wave-2, but we found reduction in mortality risk beyond 30 days. We also found risk reduction for definite stent thrombosis and any coronary revascularisation, but an increase in the risk of major bleeding from Wave-1 to Wave-2., Competing Interests: Competing interests: All authors have completed the Unified Competing Interest form and declare the following: HSh reports personal fees from Abbott Vascular, Boston Scientific and Daiichi Sankyo. TM reports lecturer's fees from Bayer, Daiichi Sankyo, Japan Lifeline, Kyocera, Mitsubishi Tanabe, Novartis and Toray; the manuscript fees from Bristol-Myers Squibb and Kowa; serving on advisory boards for Asahi Kasei, Boston Scientific, Bristol-Myers Squibb and Sanofi. ETK reports grant from Ono Pharmaceutical and reports personal fees from Daiichi Sankyo, AstraZeneca, Bristol-Myers Squibb, Tanabe-Mitsubishi Pharma, Ono Pharmaceutical, MSD KK and Pfizer. NE reports personal fees from Abbott Vascular, Medtronic, Terumo, Bayer, Boston Scientific, Daiichi-Sankyo, Edwards Lifescience, Pfizer, Bristol Myers Squibb, Takeda and Boehringer Ingelheim. YF reports personal fees from Daiichi Sankyo, Bayer, Sanofi, Kowa, Pfizer, Bristol-Myers Squibb, Otsuka Parmaceutical, Sumitomo Dainippon Pharma, Takeda and Ono Pharmaceutical. YN reports grant from Abbott Vascular and Boston Scientific, and reports personal fees from Abbott Vascular, Bayer, Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo. TKi reports personal fees from Abbott Vascular, MSD, Eisai, Edwards Lifescience, Ono Pharmaceutical, Tsumura, Medical Review, Kowa, Sanofi, Daiichi Sankyo, Takeda Pharmaceutical, Pharmaceuticals and Medical Devices Agency, Abiomed, Bayer, Bristol-Myers Squibb, Boston Scientific, Lifescience, Toray, Astellas Amgen Biopharma, Astellas, AstraZeneca, Otsuka Parmaceutical, OrbusNeich, MSD Life Science Foundation, Public Health Research Foundation, Chugai Pharmaceutical, Boehringer Ingelheim, Japan Society for the Promotion of Science, Interscience, Philips, Kowa Pharmaceutical, Mitsubishi Tanabe Pharma, Terumo, Novartis Pharma and Sumitomo Dainippon Pharma., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate patient characteristics and long-term outcomes in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) in the past two decades., Design: Multicenter retrospective study., Setting: The Coronary REvascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) percutaneous coronary intervention (PCI)/coronary artery bypass grafting (CABG) Registry Cohort-2 (2005-2007) and Cohort-3 (2011-2013)., Participants: 3254 patients with NSTEACS who underwent first coronary revascularisation., Primary and Secondary Outcome Measures: The primary outcome was all-cause death. The secondary outcomes were cardiovascular death, cardiac death, sudden cardiac death, non-cardiovascular death, non-cardiac death, myocardial infarction, definite stent thrombosis, stroke, hospitalisation for heart failure, major bleeding, any coronary revascularisation and target vessel revascularisation., Results: Patients in Cohort-3 were older and more often had heart failure at admission than those in Cohort-2. The prevalence of PCI, emergency procedure and guideline-directed medical therapy was higher in Cohort-3 than in Cohort-2. In patients who received PCI, the prevalence of transradial approach, drug-eluting stent use and intravascular ultrasound use was higher in Cohort-3 than in Cohort-2. There was no change in 3-year adjusted mortality risk from Cohort-2 to Cohort-3 (HR 1.00, 95% CI 0.83 to 1.22, p=0.97). Patients in Cohort-3 compared with those in Cohort-2 were associated with lower adjusted risks for stroke (HR 0.65, 95% CI 0.46 to 0.92, p=0.02) and any coronary revascularisation (HR 0.76, 95%CI 0.66 to 0.87, p<0.001), but with higher risk for major bleeding (HR 1.25, 95% CI 1.06 to 1.47, p=0.008). The unadjusted risk for definite stent thrombosis was lower in Cohort-3 than in Cohort 2 (HR 0.29, 95% CI 0.11 to 0.67, p=0.003)., Conclusions: In the past two decades, we did not find improvement for mortality in patients with NSTEACS. We observed a reduction in the risks for definite stent thrombosis, stroke and any coronary revascularisation, but an increase in the risk for major bleeding., Competing Interests: Competing interests: HS reports personal fees from Abbott Vascular, Boston Scientific and Daiichi Sankyo. TM reports lecturer’s fees from Bayer, Daiichi Sankyo, Japan Lifeline, Kyocera, Mitsubishi Tanabe, Novartis and Toray; the manuscript fees from Bristol-Myers Squibb and Kowa; served advisory boards for Asahi Kasei, Boston Scientific, Bristol-Myers Squibb and Sanofi. NE reports personal fees from Abbott Vascular, Medtronic, Terumo, Bayer, Boston Scientific, Daiichi-Sankyo, Edwards Lifescience, Pfizer, Bristol Myers Squibb, Takeda and Boehringer Ingelheim. YF reports personal fees from Daiichi Sankyo, Bayer, Sanofi, Kowa, Pfizer, Bristol-Myers Squibb, Otsuka Parmaceutical, Sumitomo Dainippon Pharma, Takeda and Ono Pharmaceutical. YN reports grant from Abbott Vascular and Boston Scientific, and reports personal fees from Abbott Vascular, Bayer, Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo. TK reports personal fees from Abbott Vascular, MSD, Eisai, Edwards Lifescience, Ono Pharmaceutical, Tsumura, Medical Review, Kowa, Sanofi, Daiichi Sankyo, Takeda Pharmaceutical, Pharmaceuticals and Medical Devices Agency, Abiomed, Bayer, Bristol-Myers Squibb, Boston Scientific, Lifescience, Toray, Astellas Amgen Biopharma, Astellas, AstraZeneca, Otsuka Parmaceutical, OrbusNeich, MSD Life Science Foundation, Public Health Research Foundation, Chugai Pharmaceutical, Boehringer Ingelheim, Japan Society for the Promotion of Science, Interscience, Philips, Kowa Pharmaceutical, Mitsubishi Tanabe Pharma, Terumo, Novartis Pharma and Sumitomo Dainippon Pharma., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To perform self-care in patients with heart failure (HF), we developed and implemented a new HF point self-care system, which was characterized by 1) the way weight and HF symptoms were scored ("Heart Failure Points") and 2) the timing of consultations defined for both patients and health care providers. We examined the association between the induction of the new system and 1-year outcomes in patients hospitalized for HF., Methods: We retrospectively enrolled 569 consecutive patients into our study who were admitted for HF treatment at our hospital: 275 patients between November 2011 and October 2013 (before the induction of the self-management system) and 294 patients between November 2015 and October 2017 (after the induction). We sought to compare the clinical outcomes between patients using the self-management system and those not using the system after propensity-score (PS) matching. The primary outcome measure was a composite of all-cause death or HF rehospitalization., Results: The cumulative 1-year incidence of the primary outcome measure in the use group (n = 153) was significantly lower than that in the non-use group (n = 153) (24.5% vs. 34.9%, respectively; p = 0.031; hazard ratio: 0.62; 95% confidence interval: 0.40-0.96), mainly due to a reduction in HF hospitalization., Conclusions: The induction of the new self-care system was associated with better 1-year outcomes in patients hospitalized for HF. This system may help patients with HF to achieve more efficient self-care., (Copyright © 2020. Published by Elsevier Ltd.)

Two randomized control trials demonstrated that transcatheter aortic valve implantation was associated with 1-2 year clinical outcomes comparable or even superior to surgical aortic valve replacement (SAVR) in low surgical risk patients with severe aortic stenosis (AS). However, no previous study has reported the clinical outcomes after SAVR in Japanese patients with low surgical risk. From 3815 consecutive patients enrolled in the CURRENT AS registry, we retrieved 220 patients who underwent SAVR in reference to the inclusion and exclusion criteria of the PARTNER 3 trial. Age and surgical risk score in the current study population were comparable to those in the PARTNER 3 trial (Age: 75 years versus 74 years, and STS-PROM score: 2.3 versus 1.9). The cumulative incidence of a composite all-cause death or stroke was comparable between the current study population and the SAVR patients in the PARTNER 3 trial both at 30-day (2.3% versus 3.3%), and at 1-year (4.1% versus 4.9%). The clinical outcomes of SAVR in low surgical risk patients with severe AS selected from a real world Japanese registry according to the inclusion and exclusion criteria of the PARTNER 3 trial was favorable and numerically comparable to those of SAVR patients in the PARTNER 3 trial.

Objectives: To examine the association of a high C-reactive protein (CRP) level at discharge from an acute decompensated heart failure (ADHF) hospitalisation with the 1-year clinical outcomes., Design: A post-hoc subanalysis of a prospective cohort study of patients hospitalised for ADHF (using the Kyoto Congestive Heart Failure (KCHF) registry) between October 2014 and March 2016 with a 1-year follow-up., Setting: A physician-initiated multicentre registry enrolled consecutive hospitalised patients with ADHF for the first time at 19 secondary and tertiary hospitals in Japan., Participants: Among the 4056 patients enrolled in the KCHF registry, the present study population consisted of 2618 patients with an available CRP value both on admission and at discharge and post-discharge clinical follow-up data. We divided the patients into two groups, those with a high CRP level (>10 mg/L) and those with a low CRP level (≤10 mg/L) at discharge from the index hospitalisation., Primary and Secondary Outcome Measures: The primary outcome measure was all-cause death after discharge from the index hospitalisation. The secondary outcome measures were heart failure hospitalisations, cardiovascular death and non-cardiovascular death., Results: The high CRP group and low CRP group included 622 patients (24%) and 1996 patients (76%), respectively. During a median follow-up period of 468 days, the cumulative 1-year incidence of the primary outcome was significantly higher in the high CRP group than low CRP group (24.1% vs 13.9%, log-rank p<0.001). Even after a multivariable analysis, the excess mortality risk in the high CRP group relative to the low CRP group remained significant (HR, 1.43; 95% CI, 1.19 to 1.71; p<0.001). The excess mortality risk was consistent regardless of the clinically relevant subgroup factors., Conclusions: A high CRP level (>10 mg/L) at discharge from an ADHF hospitalisation was associated with an excess mortality risk at 1 year. TRIAL REGISTRATION DETAILS: https://clinicaltrials.gov/ct2/show/NCT02334891 (NCT02334891) https://upload.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000017241 (UMIN000015238)., 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: The effect of body weight (BW) on bleeding and ischemic events has not been adequately evaluated in real-world percutaneous coronary intervention (PCI) practice.Methods and Results:12,690 consecutive patients undergoing first PCI in the CREDO-Kyoto registry cohort-2 were divided into 3 groups according to tertiles of BW stratified by sex (male; Tertile 1 [<60.0 kg], 2 [60.0-68.0 kg], and 3 [>68.0 kg], and female; Tertile 1 [<47.9 kg], 2 [47.9-55.8 kg], and 3 [>55.8 kg]). Cumulative 5-year incidences of the primary bleeding (GUSTO moderate/severe) and ischemic (myocardial infarction/ischemic stroke) endpoints increased incrementally with decrease in BW in both strata (male Tertiles 1, 2, and 3: 13.7%, 10.3%, and 8.0%, P<0.001, and 13.9%, 11.3%, and 10.2%, P<0.001; female Tertiles 1, 2, and 3: 17.9%, 12.9%, and 10.1%, P<0.001, and 17.9%, 12.9%, and 10.1%, P<0.001). Compared with Tertile 3, the adjusted risks of Tertile 1 for the primary bleeding and ischemic endpoints remained significant in the female stratum (hazard ratio (HR): 1.45, 95% confidence interval (CI): 1.14-1.87, P=0.003, and HR:1.49, 95% CI:1.13-1.95, P=0.004), but not in the male stratum (HR:1.10, 95% CI:0.92-1.32, P=0.31, and HR:1.06, 95% CI:0.90-1.27, P=0.47)., Conclusions: Cumulative incidences of bleeding and ischemic events increased incrementally as BW decreased in both men and women. The adjusted risks of underweight relative to overweight for bleeding and ischemic events were significant only in women.

Objective: We aimed to evaluate the association of the prognostic impact of coronary revascularisation with physician-referred non-invasive diagnostic imaging tests (single photon emission CT (SPECT) vs coronary CT angiography) for coronary artery disease., Design: A post hoc analysis of a subgroup from the patient cohort recruited for the Japanese Coronary-Angiography or Myocardial Imaging for Angina Pectoris Study., Setting: Multiple centres in Japan., Participants: From the data of 2780 patients with stable angina, enrolled prospectively between January 2006 and March 2008 in Japan, who had undergone physician-referred non-invasive imaging tests, 1205 patients with SPECT as an initial strategy and 625 with CT as an initial strategy were analysed. We assessed the effect of revascularisation (within 90 days) in each diagnostic imaging stratum and the interaction between the two strata., Primary and Secondary Outcome Measures: Major adverse cardiac events (MACEs), including death, myocardial infarction, hospitalisation for heart failure and late revascularisation, were followed up for 1 year. The χ 2 test, Student's t-test, Kaplan-Meier analysis, log-rank test and multivariable Cox proportional hazard model were used in data analysis., Results: A total of 210 (17.4%) patients in the SPECT stratum and 149 (23.8%) in the CT stratum underwent revascularisation. Although in each stratum, the cumulative 1 year incidence of MACEs was significantly higher in patients who underwent revascularisation than in those who did not (SPECT stratum: 9.1 vs 1.2%, log-rank p<0.0001; CT stratum: 6.1 vs 0.8%, log-rank p=0.0001), there was no interaction between the risk of revascularisation and the imaging strata (SPECT stratum: adjusted HR (95% CI), 4.25 (1.86-9.72); CT stratum: 4.13 (1.16-14.73); interaction: p=0.97)., Conclusion: The association of revascularisation with the outcomes of patients with suspected coronary artery disease was not different between SPECT-first and CT-first strategies in a physician-referred fashion., 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.)

A 74-year-old woman, with a history of aortic valve replacement and open mitral commissurotomy due to rheumatic aortic and mitral stenosis, presented with dyspnea. She developed severe tricuspid regurgitation (TR), requiring tricuspid valve replacement (TVR). Despite an uneventful postoperative course, she was readmitted for dyspnea 2 months later. Trans-thoracic echocardiogram revealed severe mitral regurgitation (MR), despite mild MR at the time of TVR, which has not been previously reported. The main MR mechanism was increased left ventricular preload due to improved TR. Increased diuresis has controlled her congestive heart failure, but her MR remained moderate., (© 2020 Wiley Periodicals LLC.)

Background: There are no data comparing transcatheter aortic valve implantation (TAVI) with surgical aortic valve replacement (SAVR) outcomes in real clinical practice in Japan., Methods and results: We combined 2 independent registries, the K-TAVI Registry (a 6-center prospective registry of consecutive patients who underwent TAVI) and the CURRENT AS Registry (a large, 27-center registry of 3,815 consecutive patients with severe aortic stenosis [AS]). In the K-TAVI Registry, 338 patients underwent TAVI with SAPIEN XT balloon-expandable valves from October 2013 to January 2016, whereas in the CURRENT AS Registry 237 patients with severe AS underwent SAVR from January 2003 to December 2011. Propensity score matching was conducted, with final cohort comprising 306 patients. The cumulative 2-year incidence of all-cause death and heart failure (HF) hospitalization did not differ significantly between the TAVI and SAVR groups (13.7% vs. 12.4% [P=0.81] and 7.9% vs 3.9% [P=0.13], respectively). After adjusting for residual confounders, there were no significant differences between the TAVI and SAVR groups in the risk for all-cause death (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.35-1.58; P=0.43) or HF hospitalization (HR 1.27; 95% CI 0.40-4.59; P=0.69)., Conclusions: These findings from 2 independent Japanese registries suggest that the 2-year risk of all-cause mortality and HF does not differ significantly between TAVI and SAVR groups in real-world practice in Japan.

Aims: Early aortic valve replacement (AVR) might be beneficial in selected high-risk asymptomatic patients with severe aortic stenosis (AS), considering their poor prognosis when managed conservatively. This study aimed to develop and validate a clinical scoring system to predict AS-related events within 1 year after diagnosis in asymptomatic severe AS patients., Methods and Results: We analysed 1274 asymptomatic severe AS patients derived from a retrospective multicentre registry enrolling consecutive patients with severe AS in Japan (CURRENT AS registry), who were managed conservatively and completed 1-year follow-up without AVR. From a randomly assigned derivation set (N = 849), we developed CURRENT AS risk score for the AS-related event (a composite of AS-related death and heart failure hospitalization) within 1 year using a multivariable logistic regression model. The risk score comprised independent risk predictors including left ventricular ejection fraction <60%, haemoglobin ≤11.0 g/dL, chronic lung disease (2 points), diabetes mellitus, haemodialysis, and any concomitant valve disease (1 point). The predictive accuracy of the model was good with the area under the curve of 0.79 and 0.77 in the derivation and validation sets (N = 425). In the validation set, the 1-year incidence of AS-related events was much higher in patients with score ≥2 than in patients with score ≤1 (Score 0: 2.2%, Score 1: 1.9%, Score 2: 13.4%, Score 3: 14.3%, and Score ≥4: 22.7%, P < 0.001)., Conclusion: The CURRENT-AS risk score integrating clinical and echocardiographic factors well-predicted the risk of AS-related events at 1 year in asymptomatic patients with severe AS and was validated internally., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Severe primary mitral regurgitation [degenerative MR (DMR)] is associated with poor outcomes, including cardiac death and hospitalization due to worsening heart failure. However, little information is available regarding the characteristics of moderate DMR and their impacts on prognostic outcome. The aim of the present study was to investigate the prognosis and its determinants in patients with moderate DMR., Methods: We retroactively reviewed 13,700 consecutive patients who underwent transthoracic echocardiography and selected those with moderate DMR but without other underlying cardiac diseases. We assessed the characteristics and event-free rate of patients with moderate DMR compared with those of age- and gender-matched patients with mild or no MR., Results: The cohort included 182 (1%) patients with moderate DMR, and these were compared with 182 age- and gender-matched patients with mild or no MR. During the follow-up period of 1376 ± 652 days, 30 patients (8%) met the composite endpoint defined as cardiac death or hospitalization due to worsening heart failure. Kaplan-Meier analysis showed that patients with moderate DMR were significantly associated with a poor outcome compared to patients with mild or no MR (log-rank test p < 0.0001). Cox proportional hazard ratio revealed that moderate DMR and paroxysmal atrial fibrillation (PAF) were the independent predictors of the composite endpoint., Conclusions: Patients with moderate DMR and concomitant PAF had a significantly worse outcome compared to those with mild or no MR. Active surveillance and some intervention for patients with PAF and moderate DMR may be required., (Copyright © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

The high controlling nutritional status (CONUT) score that represents poor nutritional status has been acknowledged to have prognostic implications in chronic heart failure. We aimed to investigate its role in acute decompensated heart failure (ADHF). Using the data from an multicenter registry that enrolled 4056 consecutive patients hospitalized for ADHF in Japan between 2014 and 2016, we analyzed 2466 patients in whom data on the components of the CONUT score at hospital presentation were available. The decrease of lymphocyte count and total cholesterol was assigned with 0, 1, 2, and 3 points and the decrease of albumin was assigned with 0, 2, 4, and 6 points according to the severity. We defined low CONUT score as 0-4 (N = 1568) and high CONUT score as 5-9 (N = 898). The patients in the high CONUT score group were older and more likely to have a smaller body mass index than those in the low CONUT score group. The high CONUT score group was associated with higher rate of death and infection during the index hospitalization compared to the low CONUT score group (9.0% versus 4.4%, and 21.9% versus 12.7%, respectively). After adjusting for confounders, the excess risk of high relative to low CONUT score for mortality and infection was significant (OR: 1.61, 95%CI: 1.05-2.44, and OR: 1.66, 95%CI: 1.30-2.12, respectively). The effect was incremental according to the score. High CONUT score was associated with higher risk for in-hospital mortality and infection in an incremental manner in patients hospitalized for ADHF.

The prognostic impact of left atrial size in patients without systolic dysfunction nor atrial fibrillation (AF) has not been fully elucidated in Japan. We retrospectively analyzed data obtained from 4444 consecutive patients who had undergone both scheduled transthoracic echocardiography and electrocardiography in 2013 in our hospital. Those who presented with a history of myocardial infarctions, severe and moderate valvular diseases, low ejection fraction (< 50%), and documented AF, and without data on LA volume index (LAVI) or tissue Doppler early diastolic mitral annular velocity were excluded. We defined high LAVI as a value > 34 ml/m 2 . The primary outcome measure was a composite of all-cause death and major adverse cardiac events. A total of 2792 patients were categorized into two groups: 2627 with normal LAVI (94.1%), 165 with high LAVI (5.9%). The median age of patients in the normal and high LAVI groups were 67, and 77 years, respectively (p < 0.001). Prevalence of diabetes mellitus, hypertension, and chronic kidney disease, and left ventricular mass index was higher in the high-LAVI group than normal-LAVI group. After adjusting for confounders, the excess 3-year risk of primary outcome of high-LAVI related to normal-LAVI was significant (hazard ratio 1.44; 95% confidence interval 1.03-1.97, p = 0.032). High-LAVI should be considered a marker of a worse long-term follow-up in patients without systolic dysfunction nor AF.

Background: This study aimed to evaluate the effect of the initial aortic valve replacement (AVR) strategy relative to a conservative strategy on long-term outcomes stratified by age among asymptomatic patients with severe aortic stenosis (AS).Methods and Results:Among 1,808 asymptomatic severe AS patients in the CURRENT AS registry, there were 1,166 patients aged ≥75 years (initial AVR: n=124, and conservative: n=1,042), and 642 patients with age <75 years (initial AVR: n=167, and conservative: n=475). Median follow-up interval was 1,280 (interquartile range [IQR]: 1,012-1,611) days, and 1461 (IQR: 1,132-1,886) days in patients aged ≥ and <75 years, respectively. The favorable effect of the initial AVR strategy relative to conservative strategy for heart failure (HF) hospitalization was seen regardless of the age stratum (≥75 years: adjusted hazard ratio [HR] 0.13, 95% confidence interval [CI] 0.05-0.34, and <75 years: HR 0.37, 95% CI 0.14-0.99, interaction P=0.35). However, the lower mortality risk of the initial AVR strategy relative to conservative strategy was significant in patients aged ≥75 years, but not in patients <75 years, with significant interaction (HR 0.35, 95% CI 0.20-0.61, and HR 0.69, 95% CI 0.41-1.16, interaction P=0.016)., Conclusions: The benefit of initial AVR in reducing HF hospitalization in asymptomatic patients with severe AS was consistently seen regardless of age. The magnitude of mortality benefit of initial AVR was greater in super-elder patients than in non-super-elder patients.

Background: Atrial fibrillation (AF) is the most common arrhythmia in patients undergoing percutaneous coronary intervention (PCI)., Hypothesis: Large administrative data may provide further insight into temporal trends in the prevalence and burden of AF in patients who underwent PCI., Methods: Using the National Inpatient Sample database in the U.S., AF patients ≥18 years who underwent PCI between 2005 and 2014 and were identified by the International Classification of Diseases, ninth revision, Clinical Modification, were examined. In-hospital mortality, morbidity, resource use, and medical costs were evaluated in crude and propensity-matched analyses., Results: Among an estimated 6 272 232 hospitalizations, of patients undergoing PCI, AF prevalence was 9.9% and steadily increased from 8.6% to 12.0% between 2005 and 2014 (P < .001); there was also a greater proportion of comorbidities. There was a marked increase in AF prevalence among those aged ≥65 years and those undergoing elective PCIs. AF was independently associated with higher in-hospital mortality and higher rates of transient ischaemic attack/stroke, bleeding complications, and non-home discharge. Excessive in-hospital mortality, stroke rate, gastrointestinal bleeding, blood transfusion, length of stay, and costs among AF hospitalizations were consistently observed throughout the study period., Conclusion: AF becomes more prevalent in patients undergoing PCI, possibly due to a higher comorbidity, particularly in elderly patients with non-acute indications. Less favorable trends in mortality, bleeding, and stroke among AF patients who underwent PCI were consistent over time. Continuous efforts are needed to improve outcomes and manage strategies for AF patients undergoing PCI., (© 2019 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

Objectives: The aim of this study was to investigate the prognostic impact of the decline in left ventricular ejection fraction (LVEF) at 1-year follow-up in patients with severe aortic stenosis (AS) managed conservatively., Background: No previous study has explored the association between LVEF decline during follow-up and clinical outcomes in patients with severe AS., Methods: Among 3,815 patients with severe AS enrolled in the multicenter CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry in Japan, 839 conservatively managed patients who underwent echocardiography at 1-year follow-up were analyzed. The primary outcome measure was a composite of AS-related deaths and hospitalization for heart failure., Results: There were 91 patients (10.8%) with >10% declines in LVEF and 748 patients (89.2%) without declines. Left ventricular dimensions and the prevalence of valve regurgitation and atrial fibrillation or flutter significantly increased in the group with declines in LVEF. The cumulative 3-year incidence of the primary outcome measure was significantly higher in the group with declines in LVEF than in the group with no decline (39.5% vs. 26.5%; p < 0.001). After adjusting for confounders, the excess risk of decline in LVEF over no decline for the primary outcome measure remained significant (hazard ratio: 1.98; 95% confidence interval: 1.29 to 3.06). When stratified by LVEF at index echocardiography (≥70%, 60% to 69%, and <60%), the risk of decline in LVEF on the primary outcome was consistently seen in all the subgroups, without any interaction (p = 0.77)., Conclusions: Patients with severe AS with >10% declines in LVEF at 1 year after diagnosis had worse AS-related clinical outcomes than those without declines in LVEF under conservative management. (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis Registry; UMIN000012140)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to evaluate the association of isolated tricuspid regurgitation (TR) with long-term outcome in patients with preserved left ventricular ejection fraction (LVEF). Methods and Results: We retrospectively analyzed 3,714 patients who had undergone both scheduled transthoracic echocardiography and electrocardiography in 2013 in a hospital-based population, after excluding severe and moderate left-side valvular disease and LVEF <50%. We classified patients into 2 groups: moderate to severe TR (n=53) and no moderate to severe TR (n=3,661). Next, we generated a propensity score (PS)-matched cohort: the moderate to severe TR group and the no moderate to severe TR group (n=41 in each group). The primary outcome was a composite of all-cause death and major adverse cardiac events. In the moderate to severe TR group, patients were older, and more likely to have higher left atrial volume index and E/e' than those in the no moderate to severe TR group. In the PS-matched cohort, cumulative 3-year incidence of the primary outcome was 61.5% in the moderate to severe TR group and 24.3% in the no moderate to severe TR group (log-rank P=0.043; hazard ratio, 2.86; 95% CI: 1.37-6.37). Conclusions: Isolated moderate to severe TR is associated with poor clinical outcome in patients with preserved LVEF., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2019, THE JAPANESE CIRCULATION SOCIETY.)

Introduction: We developed a novel, reliable and easy method that retains stability of the repositioned flap and vestibular expansion., Method: The conventionally elevated mucosal flap is secured to the desired depth of the vestibule by the pressure created by the polyvinyl chloride 6Fr suction catheter which is fixed to the alveolar bone with cortical bone screws passing through the inner lumen of the tube. The keratinized free flap is placed on the periosteum conventionally, and horizontal mattress suturing is performed for immobilization, with the suture running through the inner lumen of the tube transversally., Conclusion: This simple method gives us great benefit on the vestibuloplasty., Competing Interests: Conflict of interestNone., (© The Association of Oral and Maxillofacial Surgeons of India 2019.)

Ventricular and extraventricular response to pressure overload may be a common process in aortic stenosis and hypertension. We aimed to evaluate the association of a newly defined staging classification characterizing the extent of cardiac damage, originally developed for aortic stenosis, with long-term outcomes in patients with hypertension. We retrospectively analyzed 1639 patients with hypertension who had undergone both scheduled transthoracic echocardiography and electrocardiography in 2013 in a Japanese hospital, after excluding severe and moderate aortic stenosis, aortic regurgitation, mitral stenosis, previous myocardial infarction, or cardiomyopathy. We classified patients according to the presence or absence of cardiac damage as detected on echocardiography as follows: stage 0, no cardiac damage (n=858; 52.3%); stage 1, left ventricular damage (n=358; 21.8%); stage 2, left atrial or mitral valve damage (n=360; 22.0%); or stage 3 and 4, pulmonary vasculature, tricuspid valve, or right ventricular damage (n=63; 3.8%). The primary outcome was a composite of all-cause death and major adverse cardiac events. Cumulative 3-year incidence of the primary outcome was 15.5% in stage 0, 20.7% in stage 1, 31.8% in stage 2, and 60.6% in stage 3. After adjusting for confounders, the stage was incrementally associated with higher risk of the primary outcome (per 1-stage increase: hazard ratio, 1.46 [95% CI, 1.31-1.61]; P <0.001). The staging classification characterizing the extent of cardiac damage, originally developed for aortic stenosis, was associated with long-term outcomes in patients with hypertension in a stepwise manner.

Objective: We aimed to evaluate the association of the severity of left ventricular (LV) diastolic dysfunction with long-term outcomes in patients with normal ejection fraction., Design: Retrospective study., Setting: A single centre in Japan., Participants: We included 3576 patients who underwent both scheduled transthoracic echocardiography and ECG between 1 January and 31 December 2013, in a hospital-based population after excluding valvular diseases or low ejection fraction (<50%) or atrial fibrillation and categorised them into three groups: septal tissue Doppler early diastolic mitral annular velocity (e')≥7 (without relaxation disorder, n=1593), e'<7 and early mitral inflow velocity (E)/e'≤14 (with relaxation disorder and normal LV end-diastolic pressure, n=1337) and e'<7 and E/e'>14 (with relaxation disorder and high LV end-diastolic pressure, n=646)., Primary and Secondary Outcome Measures: The primary outcome measure was a composite of all-cause death and major adverse cardiac events (MACE). The secondary outcome measure were all-cause death and MACE, separately., Results: The cumulative 3-year incidences of the primary outcome measures were significantly higher in the e'<7 and E/e'≤14 (19.0%) and e'<7 and E/e'>14 group (23.4%) than those for the e'≥7 group (13.0%; p<0.001). After adjusting for confounders, the excess 3-year risk of primary outcome for the groups with e'<7 and E/e'≤14 related to e'≥7 (HR: 1.24; 95% CI 1.02 to 1.52) and e'<7 and E/e'>14 related to e'<7 (HR: 1.57; 95% CI 1.28 to 1.94) were significant. The severity of diastolic dysfunction was associated with incrementally higher risk for primary outcomes (p<0.001)., Conclusion: The severity of LV diastolic dysfunction using e'<7 and E/e'>14 was associated with the long-term prognosis in patients with normal ejection fraction in an incremental fashion., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Normal findings of cardiac scintigraphy predict good outcomes. However, a paucity of the data exists for elderly patients 85 years or older. In the present study, we aimed to demonstrate the association between the abnormal findings of cardiac scintigraphy and the risk of all cause death in patients 85 years or older., Methods: We enrolled 143 consecutive patients 85 years or older with known or suspected coronary artery disease who underwent stress scintigraphy under adenosine or an exercise test and a 99m Technetium (Tc)-labeled tracer or thallium 201 ( 201 Tl), dual tracer rest scintigraphy using 201 Tl and 123 I-β-methyl iodophenyl pentadecanoic acid ( 123 I-BMIPP), or 123 I-BMIPP single tracer scintigraphy. Ischemia was defined by an induced perfusion abnormality according to a provocation test with recovery at rest or decreased uptake of 123 I-BMIPP despite normal perfusion at rest. Infarction was defined by perfusion abnormalities assessed by images at rest on 201 Tl or 99m Tc-labeled tracer. We defined these findings as abnormal when at least one of these aforementioned characteristics was observed., Results: Patients in the abnormal findings group (N = 62) were more likely to have undergone prior coronary angiography and to have decreased ejection fraction than those in the normal findings group (N = 81). The median follow-up duration was 797 days (interquartile range, 635-1045 days), with follow-up rates of 90% at 1 year and 73% at 2 years. The 2-year mortality rate were significantly higher in the abnormal findings group than in the normal findings group (26.8% vs. 10.9%; p = 0.01). The risk of abnormal findings relative to normal findings remained significant for the mortality (adjusted hazard ratio, 5.99; 95% CI, 1.37-42.8; P = 0.015)., Conclusion: Abnormal myocardial scintigraphy findings were associated with the increased risk for mortality, even for patients 85 years or older.

Background: Because cardiovascular function and hemodynamics markedly change during pregnancy, our aim was to elucidate left ventricular (LV) diastolic function in pregnant women.Methods and Results:We prospectively collected the data of 397 pregnant women treated between 2012 and 2013. We evaluated their LV systolic and diastolic functions via echocardiography during the 3rd trimester (28-30 weeks' gestation) and within 4 days of delivery. Additionally, we analyzed the cardiac geometry: relative wall thickness and LV mass index (LVMI). Diastolic dysfunction was defined as early diastolic mitral annulus velocity (e') <7 cm/s and peak early filling velocity (E)/e' ratio >15. The pregnant women were 33.7±5.0 years old and the prevalence of hypertensive disorders in pregnancy (HDP) was 4.0%. LV systolic function was preserved in all pregnant women. However, diastolic function significantly decreased after delivery (mean e': 12.6 vs. 11.6 cm/s, P<0.0001; median E/e' ratio: 6.4 vs. 7.3, P<0.0001). Diastolic function after delivery was associated with the prevalence of HDP (P=0.035) and was correlated with age (R=-0.17, P=0.0009) and LVMI (R=-0.30, P<0.0001). However, these changes in diastolic function remained within the normal range and only 1 woman (1/397, 0.3%) had LV diastolic dysfunction after delivery., Conclusions: LV diastolic function decreased after delivery in pregnant women but was within the normal range.

Background: Transcatheter aortic valve implantation (TAVI) is criticized by some as an expensive treatment in super-elder patients with limited life expectancy. However, there is a knowledge gap regarding the magnitude of clinical benefit provided by TAVI in comparison with conservative management in patients with severe aortic stenosis (AS) in real clinical practice, which would be important in the decision making for TAVI., Methods: We combined two independent registries, namely CURRENT AS and K-TAVI registries. CURRENT AS was a multicenter registry enrolling 3815 consecutive patients with severe AS irrespective to treatment modalities between January 2003 and December 2011. K-TAVI was a multicenter, prospective registry including 449 consecutive patients with severe AS, who underwent TAVI with SAPIEN XT balloon-expandable valves between October 2013 and June 2016. In these 2 registries, 449 patients received TAVI and 894 patients were managed with conservative strategy. We conducted propensity score matching and finally obtained a cohort of 556 patients (278 patients for each group) for the analysis. The primary outcome measures were all-cause death and heart failure (HF) hospitalization at 2-year., Results: The cumulative 2-year incidences of all-cause death and HF hospitalization were significantly lower in the TAVI group than in the conservative group (16.8% versus 36.6%, P<0.001, and 10.7% versus 37.2%, P<0.001). After adjusting the residual confounders, TAVI reduced the risks of all-cause death (HR, 0.46; 95%CI, 0.32-0.69; P = 0.0001) and HF hospitalizations (HR, 0.25; 95%CI, 0.16-0.40; P<0.0001) compared with conservative strategy. There was no difference in the cumulative incidence of non-cardiovascular death between the 2 groups., Conclusions: TAVI in the early Japanese experience was associated with striking risk reduction for all-cause death as well as HF hospitalization as compared with the historical cohort of patients with severe AS who were managed conservatively just before introduction of TAVI in Japan., Competing Interests: The authors have declared that no competing interests exist.

Background: There has not been a previous report on the long-term outcomes of those patients who refuse aortic valve replacement (AVR) despite physicians' recommendations.Methods and Results:Among 3,815 consecutive patients with severe aortic stenosis (AS) enrolled in the CURRENT AS registry, the study population comprised 2,005 symptomatic patients, who were subdivided into 3 groups by their treatment strategy and the reasons for conservative strategy (Initial AVR group: n=905; Patient rejection group: n=256; Physician judgment group, n=844). The primary outcome measure was a composite of aortic valve-related death and heart failure hospitalization. Patients in the patient rejection group as compared with those in the physician judgment group were younger, and had less comorbidities, and lower surgical risk scores. The cumulative 5-year incidence of the primary outcome measure in the patient rejection group was markedly higher than that in the initial AVR group, and was similar to that in the physician judgment group (60.7%, 19.0%, and 66.4%, respectively)., Conclusions: Patient rejection was the reason for non-referral to AVR in nearly one-quarter of the symptomatic patients with severe AS who were managed conservatively. The dismal outcome in patients who refused AVR was similar to that in patients who were not referred to AVR based on physician judgment despite less comorbidities and lower surgical risk scores in the former than in the latter.

Background The contemporary incidence of and reasons for early readmission after infective endocarditis ( IE ) are not well known. Therefore, we analyzed 30-day readmission demographics after IE from the US Nationwide Readmission Database. Methods and Results We examined the 2010 to 2014 Nationwide Readmission Database to identify index admissions for a primary diagnosis of IE with survival at discharge. Incidence, reasons, and independent predictors of 30-day unplanned readmissions were analyzed. In total, 11 217 patients (24.8%) were nonelectively readmitted within 30 days among the 45 214 index admissions discharged after IE . The most common causes of readmission were IE (20.5%), sepsis (8.7%), complications of device/graft (8.1%), and congestive heart failure (7.6%). In-hospital mortality and the valvular surgery rates during the readmissions were 8.1% and 9.1%, respectively. Discharge to home or self-care, undergoing valvular surgery, aged ≥60 years, and having private insurance were independently associated with lower rates of 30-day readmission. Length of stay of ≥10 days, congestive heart failure, diabetes mellitus, renal failure, chronic pulmonary disease, peripheral artery disease, and depression were associated with higher risk. The total hospital costs of readmission were $48.7 million per year (median, $11 267; interquartile range, $6021-$25 073), which accounted for 38.6% of the total episodes of care (index+readmission). Conclusions Almost 1 in 4 patients was readmitted within 30 days of admission for IE . The most common reasons were IE , other infectious causes, and cardiac causes. A multidisciplinary approach to determine the surgical indications and close monitoring are necessary to improve outcomes and reduce complications in in-hospital and postdischarge settings.

Background: Some epidemiological studies have demonstrated the association between psoriasis vulgaris and coronary artery disease (CAD). However, there is a lack of specific data regarding the association between psoriasis vulgaris and myocardial infarction (MI), the more severe and critical presentation of CAD, in the Japanese population., Methods and Results: We retrospectively analyzed 113,065 patients of all ages at our hospital from January 1, 2011 to January 1, 2013. We extracted the data of patients with psoriasis vulgaris, diabetes mellitus, dyslipidemia, or MI (acute, sub-acute, or old), including sex and age from the electronic medical record database. The prevalence of MI in patients with hypertension, dyslipidemia, diabetes mellitus, and psoriasis vulgaris were 4.8% (794/16,476), 5.0% (459/9236), 4.6% (531/11,555), and 2.7% (32/1197), respectively. Multivariate analysis showed that psoriasis vulgaris was significantly associated with MI [adjusted odds ratio (OR): 1.87; 95% confidence interval (CI): 1.26-2.68; p=0.0022]. In a subgroup analysis of 24,069 patients who had one or more comorbidities including diabetes mellitus, dyslipidemia, and hypertension, psoriasis vulgaris was still independently associated with MI after adjusting for sex and age (adjusted OR, 1.49; 95% CI: 1.02-2.18; p=0.0358) in adults., Conclusion: Psoriasis vulgaris was significantly associated with MI in a Japanese hospital-based population., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Atrial fibrillation (AF) can lead to a decrease in stroke volume (SV) despite a preserved left ventricular ejection fraction (LVEF). However, no previous studies have evaluated the prognostic importance of the decreased SV in patients with AF and concomitant heart failure with preserved ejection fraction (HFpEF)., Methods: We retrospectively studied the cases of 1520 consecutive patients who had undergone right heart catheterization. HFpEF (New York Heart Association functional class ≥II and LVEF ≥50%) was observed in 574 patients. We selected 47 patients with persistent AF with a heart rate of 40-110bpm and HFpEF without other underlying heart diseases., Results: Among a total of 47 patients, 16 (34%) had normal SV [SV index (SVI) >35ml/m 2 and 31 (66%) patients had low SV (SVI≤35ml/m 2 )]. During the follow-up period of 1115±305 days, 14 patients (30%) met the composite endpoint defined as cardiac death and admission due to worsening heart failure. Cox proportional hazard ratio analysis showed that SVI was a predictor of the endpoint, independently of the cardiac index and other parameters. Kaplan-Meyer analysis showed that low SVI was significantly associated with a poor prognosis, with an event-free rate of 58% at the mean follow-up period of 991 days (log-rank p=0.02). In the multiple regression analysis, a high systemic vascular resistance index and a high heart rate were independent determinants of low SVI., Conclusions: Our findings suggest that low SV had a significant impact on prognosis in patients with AF despite the preserved LVEF. The SVI depended on the heart rate and SVRI., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objectives: We sought to evaluate the prognostic impact of the B-type natriuretic peptide (BNP) levels in patients with asymptomatic severe aortic stenosis (AS), who were not referred for aortic valve replacement (AVR)., Methods: We used data from a Japanese multicentre registry, the Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis Registry, which enrolled 3815 consecutive patients with severe AS. Of those, 387 asymptomatic patients who were not referred for AVR without left ventricular dysfunction and very severe AS were subdivided into four groups based on their BNP levels (BNP<100 pg/mL, n=201; 100≤BNP<200 pg/mL, n=94; 200≤BNP<300 pg/mL, n=42 and BNP>300 pg/mL, n=50)., Results: The cumulative 5-year incidence of AS-related events (aortic valve-related death or heart failure hospitalisation) was incrementally higher with increasing BNP level (14.2%, 29.6%, 46.3% and 47.0%, p<0.001). After adjusting for confounders, the risk for AS-related events was incrementally greater with increasing BNP levels (HR: 1.97, 95% CI: 0.97 to 3.98, p=0.06; HR: 3.59, 95% CI: 1.55 to 8.32, p=0.03 and HR: 7.38, 95% CI: 3.21 to 16.9, p<0.001, respectively). Notably, asymptomatic patients with BNPlevels of <100 pg/mL had an event rate of only 2.1% at 1 year., Conclusions: Increased BNP level was associated with a higher risk for AS-related adverse events in patients with asymptomatic severe AS with normal left ventricular ejection fraction who were not referred for AVR. Asymptomatic patients with BNP levels of <100 pg/mL had relatively low event rate, who might be safely followed with watchful waiting strategy., Trail Registration Number: UMIN000012140., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Tricuspid regurgitation (TR) has been reported to be associated with worse survival in various heart diseases, but there are few data in aortic stenosis (AS)., Methods and Results: In the Contemporary Outcomes after Surgery and Medical Treatment in Patients with Severe Aortic Stenosis (CURRENT AS) Registry enrolling 3815 consecutive patients with severe AS, there were 628 patients with moderate or severe TR (TR group) and 3187 patients with no or mild TR (no TR group). The study patients were subdivided into the initial aortic valve replacement (AVR) stratum (n = 1197) and the conservative stratum (n = 2618) according to treatment strategy. The primary outcome measure was a composite of aortic valve-related death or hospitalization due to heart failure. The 5-year freedom rate from the primary outcome measure was significantly lower in the TR group than in the no TR group (49.1% vs. 67.3%, P < 0.001). Even after adjusting for confounders, the excess risk of TR relative to no TR for the primary outcome measure remained significant [hazard ratio (HR): 1.25, 95% confidence interval (CI): 1.06-1.48; P = 0.008]. The trend for the excess adjusted risk in the TR group was consistent in the initial AVR and the conservative strata (HR 1.55, 95% CI: 0.97-2.48; P = 0.07; HR 1.22, 95% CI: 1.02-1.46; P = 0.03, respectively). In the initial AVR stratum, the 5-year freedom rate from the primary outcome measure was not different between the two groups with (n = 56) or without (n = 91) concomitant tricuspid annuloplasty (61.5% vs. 72.1%, P = 0.48)., Conclusion: The presence of clinically significant TR concomitant with severe AS is associated with a poor long-term outcome, regardless of the initial treatment strategy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Background: Using the normal values for the East Asian population, we evaluated age- and body size-adjusted left ventricular end-diastolic dimension (LVEDD) and its prognostic impact in a hospital-based population in Japan. Methods and Results: We retrospectively analyzed data obtained from 4,444 consecutive patients who had undergone both transthoracic echocardiography and electrocardiography at Kitano Hospital in 2013. Those who presented with a history of previous episodes of myocardial infarction and severe or moderate valvular disease or with low ejection fraction (<50%) were excluded from the analysis. We calculated LVEDD adjusted by age and body surface area. A total of 3,474 patients were categorized into 3 groups: 401 with large adjusted LVEDD, 2,829 with normal adjusted LVEDD, and 244 with small adjusted LVEDD. Mean patient age in the large, normal, and small adjusted LVEDD groups was 66.6±18.4, 65.6±15.7, and 62.1±15.5 years, respectively (P<0.001). After adjusting for confounding factors, the excess adjusted 3-year risk of primary outcome of large adjusted LVEDD relative to normal LVEDD was significant (HR, 1.40; 95% CI: 1.08-1.78). The risk for primary outcomes of small adjusted LVEDD relative to normal adjusted LVEDD was significantly lower (HR, 0.55; 95% CI: 0.34-0.85)., Conclusions: Adjusted large LVEDD has a deleterious impact on long-term mortality, whereas small LVEDD carried a significantly lower risk.

Prognostic impact of anemia complicating severe aortic stenosis (AS) remains unclear. We assessed the impact of anemia on cardiovascular and bleeding outcomes in 3403 patients enrolled in the CURRENT AS registry. 835 patients (25%) had mild (hemoglobin 11.0-12.9 g/dl for men/11.0-11.9 g/dl for women) and 1282 patients (38%) had moderate/severe anemia (Hb ≤ 10.9 g/dl) at diagnosis of severe AS. Mild and moderate/severe anemia were associated with significantly increased risks relative to no anemia (hemoglobin ≥13.0 g/dl for men/≥12.0 g/dl for women) for the primary outcome measure (aortic valve-related death or heart failure hospitalization) in the entire population [hazard ratio (HR): 1.30; 95% confidence interval (CI): 1.07-1.57 and HR: 1.56; 95%CI: 1.31-1.87, respectively] and in the conservative management stratum (HR: 1.73; 95%CI: 1.40-2.13 and HR: 2.05; 95%CI: 1.69-2.47, respectively). Even in the initial aortic valve replacement stratum, moderate/severe anemia was associated with significantly increased risk for the primary outcome measure (HR: 2.12; 95%CI: 1.44-3.11). Moreover, moderate/severe anemia was associated with significantly increased risk for major bleeding while under conservative management (HR: 1.93; 95%CI: 1.21-3.06). These results warrant further study to explore whether better management of anemia would lead to improvement of clinical outcomes.

Background: We aimed to investigate the values and the changes of brain natriuretic peptide (BNP) and cardiac troponin in pregnant women., Methods and Results: We prospectively collected the data of 405 pregnant women who were treated at Japanese general hospital between 2012 and 2013. We analyzed their laboratory data and echocardiographic findings during the third trimester (28-30 weeks' gestation) and within 4 days of delivery. In addition, we evaluated the factors associated with elevation of BNP and cardiac troponin I (cTnI) levels. The pregnant women were 33.8 ± 5.0 years old and the prevalence of pregnancy induced hypertension (PIH) and placental abnormality was 4.2% and 2.5%, respectively. BNP levels increased after delivery (13.2 pg/mL vs. 23.5 pg/mL; P <0.001), correlated with increased left ventricular diastolic dimension (P = 0.035), left atrial dimension (P <0.001), and decreased hemoglobin (P <0.001). Moreover, cTnI levels increased to over 0.015 ng/mL after delivery in 4.0% of pregnant women. In multivariate analysis, PIH (OR: 18.71, P = 0.003), placental abnormality (OR: 26.78, P = 0.007), and decreased hemoglobin after delivery (OR: 2.59, P <0.001) were the factors associated with elevated cTnI., Conclusions: BNP levels increased in association with cardiac chamber enlargement and decreased hemoglobin after delivery. Additionally, the factors affecting elevated cTnI levels were related to labor and delivery., Competing Interests: The authors have declared that no competing interests exist.

Background Data are scarce on the role of aortic valve area (AVA) to identify those patients with asymptomatic severe aortic stenosis (AS) who are at high risk of adverse events. We sought to explore the prognostic impact of AVA in asymptomatic patients with severe AS in a large observational database. Methods and Results Among 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the present study included 1309 conservatively managed asymptomatic patients with left ventricular ejection fraction ≥50%. The study patients were subdivided into 3 groups based on AVA (group 1: AVA >0.80 cm 2 , N=645; group 2: 0.8 cm 2 ≥AVA >0.6 cm 2 , N=465; and group 3: AVA ≤0.6 cm 2 , N=199). The prevalence of very severe AS patients (peak aortic jet velocity ≥5 m/s or mean aortic pressure gradient ≥60 mm Hg) was 2.0%, 5.8%, and 26.1% in groups 1, 2, and 3, respectively. The cumulative 5-year incidence of AVR was not different across the 3 groups (39.7%, 43.7%, and 39.9%; P=0.43). The cumulative 5-year incidence of the primary outcome measure (a composite of aortic valve-related death or heart failure hospitalization) was incrementally higher with decreasing AVA (24.1%, 29.1%, and 48.1%; P<0.001). After adjusting for confounders, the excess risk of group 3 and group 2 relative to group 1 for the primary outcome measure remained significant (hazard ratio, 2.21, 95% CI, 1.56-3.11, P<0.001; and hazard ratio, 1.34, 95% CI, 1.01-1.78, P=0.04, respectively). Conclusions AVA ≤0.6 cm 2 would be a useful marker to identify those high-risk patients with asymptomatic severe AS, who might benefit from early AVR. Clinical Trial Registration URL: www.umin.ac.jp . Unique identifier: UMIN000012140.

Background: Despite recommendations in the guidelines and consensus documents, there has been no randomized controlled trial evaluating oral anticoagulation (OAC) alone without antiplatelet therapy (APT) in patients with atrial fibrillation and stable coronary artery disease beyond 1 year after coronary stenting., Methods: This study was a prospective, multicenter, open-label, noninferiority trial comparing OAC alone to combined OAC and single APT among patients with atrial fibrillation beyond 1 year after stenting in a 1:1 randomization fashion. The primary end point was a composite of all-cause death, myocardial infarction, stroke, or systemic embolism. The major secondary end point was a composite of the primary end point or major bleeding according to the International Society on Thrombosis and Haemostasis classification. Although the trial was designed to enroll 2000 patients during 12 months, enrollment was prematurely terminated after enrolling 696 patients in 38 months., Results: Mean age was 75.0±7.6 years, and 85.2% of patients were men. OAC was warfarin in 75.2% and direct oral anticoagulants in 24.8% of patients. The mean CHADS 2 score was 2.5±1.2. During a median follow-up interval of 2.5 years, the primary end point occurred in 54 patients (15.7%) in the OAC-alone group and in 47 patients (13.6%) in the combined OAC and APT group (hazard ratio, 1.16; 95% CI, 0.79-1.72; P=0.20 for noninferiority, P=0.45 for superiority). The major secondary end point occurred in 67 patients (19.5%) in the OAC-alone group and in 67 patients (19.4%) in the combined OAC and APT group (hazard ratio, 0.99; 95% CI, 0.71-1.39; P=0.016 for noninferiority, P=0.96 for superiority). Myocardial infarction occurred in 8 (2.3%) and 4 (1.2%) patients, whereas stroke or systemic embolism occurred in 13 (3.8%) and 19 (5.5%) patients, respectively. Major bleeding occurred in 27 (7.8%) and 36 (10.4%) patients, respectively., Conclusions: This randomized trial did not establish noninferiority of OAC alone to combined OAC and APT in patients with atrial fibrillation and stable coronary artery disease beyond 1 year after stenting. Because patient enrollment was prematurely terminated, the study was underpowered and inconclusive. Future larger studies are required to establish the optimal antithrombotic regimen in this population., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01962545.

Background: Readmissions after in-hospital cardiopulmonary resuscitation (ICPR) are common and contribute to increased health care utilization and costs. This study aimed to estimate the burden and patterns of 30-day readmission after ICPR from the US Nationwide Readmission Database (NRD)., Methods: Using International Classification of Diseases-Ninth Revision-Clinical Modification codes, patients who underwent ICPR in the 2014 NRD were included. The incidence, predictors, causes, and costs of 30-day readmission were analyzed with discharge weights to obtain national estimates., Results: Among the 27,278 index admissions that survived to hospital discharge after ICPR, 5439 (20.0%) were readmitted within 30 days. Length of stay (LOS) ≥11 days during index hospitalization, chronic pulmonary disease, congestive heart failure, renal failure, discharge from the teaching metropolitan hospital, Medicare insurance, depression, and diabetes were independent predictors of 30-day readmission. The most common causes of readmission among the 5439 cases were sepsis (13.7%), heart failure (10.9%), and respiratory failure (6.4%). The estimated median costs of readmission were $10,498 (interquartile range, $5797-21,364), which accounted for 25.7% of the total episodes of care (index + readmission). The median LOS of readmission was 5 (3-9) days., Conclusions: Thirty-day readmissions after ICPR were associated with patient comorbidities and significant cost burden. Recognition of these predictors and individualization of care would allow for the provision of appropriate interventions, and reduce readmissions and healthcare costs., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Background: There is no large-scale study comparing postoperative mortality after aortic valve replacement (AVR) for asymptomatic severe aortic stenosis (AS) between initial treatment with AVR vs. eventual AVR after conservative management. Methods and Results: We analyzed data from a multicenter registry enrolling 3,815 consecutive patients with severe AS. Of 1,808 asymptomatic patients, 286 patients initially underwent AVR (initial AVR group), and 377 patients were initially managed conservatively and eventually underwent AVR (AVR after watchful waiting group). Mortality after AVR was compared between the 2 groups. Subgroup analysis according to peak aortic jet velocity (Vmax) at diagnosis was also conducted. There was no significant difference between the 2 groups in 5-year overall survival (OS; 86.0% vs. 84.1%, P=0.34) or cardiovascular death-free survival (DFS; 91.3% vs. 91.1%, P=0.61), but on subgroup analysis of patients with Vmax ≥4.5 m/s at diagnosis, the initial AVR group was superior to the AVR after watchful waiting group in both 5-year OS (88.4% vs. 70.6%, P=0.003) and cardiovascular DFS (91.9% vs. 81.7%, P=0.023)., Conclusions: Asymptomatic severe AS patients who underwent AVR after watchful waiting had a postoperative survival rate similar to those who initially underwent AVR. In a subgroup of patients with Vmax ≥4.5 m/s at diagnosis, however, the AVR after watchful waiting group had worse postoperative survival rate than the initial AVR group.