Clinical Features of 544 Patients With Ruptured Aortic Aneurysm　- A Report From the Tokyo Acute Aortic Super Network Database.

BACKGROUND: Epidemiological data on ruptured aortic aneurysms from large-scale studies are scarce. The aims of this study were to: clarify the clinical course of ruptured aortic aneurysms; identify aneurysm site-specific therapies and outcomes; and determine the clinical course of patients receiving conservative therapy.Methods and Results: Using the Tokyo Acute Aortic Super Network database, we retrospectively analyzed 544 patients (mean [±SD] age 78±10 years; 70% male) with ruptured non-dissecting aortic aneurysms (AAs) after excluding those with impending rupture. Patient characteristics, status on admission, therapeutic strategy, and outcomes were evaluated. Shock or pulselessness on admission were observed in 45% of all patients. Conservative therapy, endovascular therapy (EVT), and open surgery (OS) accounted for 32%, 23%, and 42% of cases, respectively, with corresponding mortality rates of 93%, 30%, and 29%. The overall in-hospital mortality rate was 50%. The prevalence of pulselessness was highest (48%) in the ruptured ascending AA group, and in-hospital mortality was the highest (70%) in the ruptured thoracoabdominal AA group. Multivariable logistic regression analysis indicated in-hospital mortality was positively associated with pulselessness (odds ratio [OR] 10.12; 95% confidence interval [CI] 4.09-25.07), and negatively associated with invasive therapy (EVT and OS; OR 0.11; 95% CI 0.06-0.20). CONCLUSIONS: The outcomes of ruptured AAs remain poor; emergency invasive therapy is essential to save lives, although it remains challenging to reduce the risk of death.

Study Profile of the Tsuruoka Metabolomics Cohort Study (TMCS).

The Tsuruoka Metabolomics Cohort Study (TMCS) is an ongoing population-based cohort study being conducted in the rural area of Yamagata Prefecture, Japan. This study aimed to enhance the precision prevention of multi-factorial, complex diseases, including non-communicable and aging-associated diseases, by improving risk stratification and prediction measures. At baseline, 11,002 participants aged 35-74 years were recruited in Tsuruoka City, Yamagata Prefecture, Japan, between 2012 and 2015, with an ongoing follow-up survey. Participants underwent various measurements, examinations, tests, and questionnaires on their health, lifestyle, and social factors. This study used an integrative approach with deep molecular profiling to identify potential biomarkers linked to phenotypes that underpin disease pathophysiology and provide better mechanistic insights into social health determinants. The TMCS incorporates multi-omics data, including genetic and metabolomic analyses of 10,933 participants and comprehensive data collection ranging from physical, psychological, behavioral, and social to biological data. The metabolome is used as a phenotypic probe because it is sensitive to changes in physiological and external conditions. The TMCS focuses on collecting outcomes for cardiovascular disease, cancer incidence and mortality, disability, functional decline due to aging and disease sequelae, and the variation in health status within the body represented by omics analysis that lies between exposure and disease. It contains several sub-studies on aging, heated tobacco products, and women's health. This study is notable for its robust design, high participation rate (89%), and long-term repeated surveys. Moreover, it contributes to precision prevention in Japan and East Asia as a well-established multi-omics platform.

Preferred monotherapy after short-term dual antiplatelet therapy: Systematic review and network meta-analysis of randomized trials.

BACKGROUND: Randomized controlled trials (RCTs) have demonstrated the efficacy and safety of P2Y12 inhibitor monotherapy following short-term dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI). However, no studies have compared P2Y12 inhibitor and aspirin monotherapy following short-term DAPT. We aimed to compare available strategies for DAPT duration and post-DAPT antiplatelet monotherapy following PCI. METHODS: Seven DAPT strategies [ticagrelor or clopidogrel following 1-month DAPT, ticagrelor following 3-month DAPT, aspirin following 3-6 months of DAPT (reference strategy), aspirin or P2Y12 inhibitor following 6-18-months of DAPT, and DAPT for ≥18 months] were compared using a network meta-analysis. The primary efficacy outcome was defined as a composite of all-cause death, myocardial infarction, and stroke. The primary bleeding outcome was trial-defined major or minor bleeding. RESULTS: Our analysis identified 25 eligible RCTs, including 89,371 patients who underwent PCI. Overall, none of the strategies negatively affected the primary efficacy outcomes. For primary bleeding outcomes, ticagrelor following 3-month DAPT was associated with a reduced risk of primary bleeding outcomes (HR 0.73; 95 % CI 0.57-0.95). Clopidogrel following 1-month DAPT was also associated with a reduced risk of primary bleeding outcomes (HR 0.54; 95 % CI 0.34-0.85), however, the strategy was associated with an increased risk of myocardial infarction or stent thrombosis. Similar trends were observed among patients with acute coronary syndrome and high bleeding risk. CONCLUSIONS: Compared with aspirin monotherapy following short-term DAPT, ticagrelor following 3-month DAPT was associated with a reduced risk of primary bleeding outcomes without increasing any ischemic outcomes.

Practice differences and knowledge gaps in complex and high-risk interventions between Japan and the USA: A case-based discussion.

Advances in percutaneous coronary intervention (PCI) devices and techniques have expanded the pool of eligible patients for revascularization, including those with comorbidities, reduced left ventricular function, or anatomical complexity (defined as CHIP: complex and high-risk interventions in indicated patients). CHIP interventions are typically performed by selected operators who specialize in complex PCI. This review presents two cases performed in the USA, to discuss the similarities and differences in practice patterns between CHIP operators in Japan and the USA. The first case involves a 58-year-old male presenting with myocardial infarction and cardiogenic shock, and the second case involves a 51-year-old female with a history of coronary artery bypass grafting presenting with a chronic total occlusion and PCI complicated by vessel perforation. The discussion focuses on appropriate patient selection, the role of the heart team approach for decision-making, the use of hemodynamic support devices, and other relevant factors. By comparing practices in Japan and the USA, this review highlights opportunities for knowledge exchange and potential areas for improving patient outcomes.

Volume-outcome relationship in balloon aortic valvuloplasty: results of a consecutive, patient-level data analysis from a Japanese nationwide multicentre registry (J-SHD).

OBJECTIVE: Transcatheter balloon aortic valvuloplasty (BAV) remains an important alternative treatment for severe, symptomatic aortic stenosis. With increasing numbers of BAVs being performed, the need for large-scale volume-outcome relationship assessments has become evident. Here, we aimed to explain such relationships by analysing consecutive, patient-level BAV data recorded in a prospective Japanese nationwide multicentre registry. DESIGN: Prospective study. SETTING: Data of 1920 BAVs performed in 200 Japanese hospitals from January 2015 to December 2019. PARTICIPANTS: The mean patient age was 85 years, and 36.9% of procedures involved male patients. METHODS: The efficacy of BAV was assessed by reducing the mean transaortic valve gradient after the procedure. We also assessed in-hospital complication rates, including in-hospital death, bleeding, urgent surgery, distal embolism, vessel rupture and contrast-induced nephropathy. Based on the distribution of case volume (median 20, IQR 10-46), we divided the patients into high-volume (≥20) and low-volume (<20) groups. In-hospital complication risk was assessed with adjustment by logistic regression modelling. RESULTS: Indications for BAV included palliative/destination (44.2%), bridge to transcatheter aortic valve replacement (34.5%), bridge to surgical aortic valve replacement (7.4%) and salvage (9.7%). Reduction of the mean transaortic valve gradient was similar between the high-volume and low-volume groups (20 mm Hg vs 20 mm Hg, p=0.12). The proportion of in-hospital complications during BAV was 4.2%, and the incidence of complications showed no difference between the high-volume and low-volume groups (4.2% vs 4.1%, p=1.00). Rather than hospital volume, salvage procedure was an independent predictor of in-hospital complications (OR, 4.04; 95% CI, 2.03 to 8.06; p<0.001). CONCLUSION: The current study demonstrated that procedural outcomes of BAV were largely independent of its institutional volume.

Age-Stratified Prevalence and Relative Prognostic Significance of Traditional Atherosclerotic Risk Factors: A Report from the Nationwide Registry of Percutaneous Coronary Interventions in Japan.

Background The prevalence of traditional atherosclerotic risk factors (TARFs) and their association with clinical profiles or mortality in percutaneous coronary intervention remain unclear. Methods and Results The study analyzed 559 452 patients who underwent initial percutaneous coronary intervention between 2012 and 2019 in Japan. TARFs were defined as male sex, hypertension, dyslipidemia, diabetes, smoking, and chronic kidney disease. We calculated the relative importance according to R2 and machine learning models to assess the impact of TARFs on clinical profile and in-hospital mortality. The relative contribution (RC) of each TARF was defined as the average percentage of the relative importance calculated from these models. The age-specific prevalence of TARFs, except for chronic kidney disease, formed an inverted U-shape with significantly different peaks and percentages. In the logistic regression model and relative risk model, smoking was most strongly associated with acute myocardial infarction (adjusted odds ratio [OR], 1.62 [95% CI, 1.60-1.64]; RC, 47.1%) and premature coronary artery disease (adjusted unstandardized beta coefficient, 2.68 [95% CI, 2.65-2.71], RC, 42.2%). Diabetes was most strongly associated with multivessel disease (adjusted unstandardized beta coefficient, 0.068 [95% CI, 0.066-0.070], RC, 59.4%). The absence of dyslipidemia was most strongly associated with presentation of cardiogenic shock (adjusted OR, 0.62 [95% CI, 0.61-0.64], RC, 34.2%) and in-hospital mortality (adjusted OR, 0.44 [95% CI, 0.41-0.46], RC, 39.8%). These specific associations were consistently observed regardless of adjustment or stratification by age. Conclusions Our analysis showed a significant variation in the age-specific prevalence of TARFs. Further, their contribution to clinical profiles and mortality also varied widely.

Gender Differences in Long-Term Outcomes of Young Patients Who Underwent Percutaneous Coronary Intervention: Long-Term Outcome Analysis from a Multicenter Registry in Japan.

Young patients who underwent percutaneous coronary intervention (PCI) have shown worse long-term outcomes but remain inadequately investigated. We analyzed 1,186 consecutive young patients (aged ≤55 years) from the Keio Cardiovascular PCI registry who were successfully discharged after PCI (2008 to 2019) and compared them to 5,048 older patients (aged 55 to 75 years). The primary outcome was a composite of all-cause death, acute coronary syndrome, heart failure, bleeding, stroke requiring admission, and coronary artery bypass grafting within 2 years after discharge. In the young patients, the mean age was 48.4 ± 5.4 years, acute coronary syndrome cases accounted for 69.6%, and 92 (7.8%) were female. Body mass index; hemoglobin levels; and proportions of smoking, hyperlipidemia, and ST-elevation myocardial infarction were lower and dialysis or active cancer proportions were higher in young female patients than male patients. A higher number of young female than male patients reached the primary end point and all-cause death (15.2% vs 7.1%, p = 0.01; 4.3% vs 1.0%, p = 0.023), mainly because of noncardiac death (4.3% versus 0.5%, p = 0.001). After covariate adjustment, the primary end point rates were higher among young women than men (hazard ratio 2.00, 95% confidence interval 1.03 to 3.89, p = 0.042). Gender did not predict the primary end point among older patients (vs men; hazard ratio 0.84, 95% confidence interval 0.67 to 1.06, p = 0.14). In conclusion, young women showed worse outcomes during the 2-year post-PCI follow-up, but this gender difference was absent in patients aged 55 to 75 years.

One-year outcome of transcatheter aortic valve replacement for bicuspid aortic valve stenosis: a report from the Japanese Nationwide registry (J-TVT registry).

The outcome of transcatheter aortic valve replacement (TAVR) for patients with bicuspid aortic valve (BAV) remains unclear, particularly among Asian patients that are known to have different valvular morphology and lower body habitus. This study investigated patient characteristics, procedural and 1-year outcome of TAVR for BAV within national TAVR registry in Japan. The patient-level data were extracted from the J-TVT (Japanese Transcatheter Valvular Therapy) registry between August 2013 and December 2018; overall, there were 423 patients (2.5%) with BAV and 16,802 patients with tricuspid aortic valve (TAV). At baseline, patients with BAV were younger and had less arteriosclerotic comorbidities. There was no statistically significant difference between BAV and TAV groups in conversion to surgery (0.5% vs. 1.1%, p = 0.34) and 30-day mortality (0.5% vs. 1.3%, p = 0.18). Cumulative all-cause survival and survival from major adverse events were analyzed. Cox proportional hazard regression model was used to estimate the hazard ratio. All-cause mortality and major adverse event rate at 1 year were comparable between the two groups. Relative hazard for all-cause mortality for BAV compared to TAV was 1.01 (0.70-1.45; p = 0.96), and for major adverse event was 0.94 (0.69-1.27; p = 0.67). From the Japanese nationwide TAVR registry, procedural and 1-year outcome of TAVR in BAV was as favorable as TAVR in TAV.

Ischemic and Bleeding Outcomes in Patients Who Underwent Percutaneous Coronary Intervention With Chronic Kidney Disease or Dialysis (from a Japanese Nationwide Registry).

The relation between chronic kidney disease (CKD) and outcomes in patients receiving percutaneous coronary intervention (PCI) is thought to be bidirectional; these patients are at a higher risk of ischemic and bleeding events. From a Japanese nationwide PCI registry, ischemic (cardiovascular death, nonfatal myocardial infarction, or nonfatal ischemic stroke) and bleeding events (fatal or nonfatal major bleeding) 1 year after discharge among patients who had second- or newer-generation drug-eluting stent implantation were analyzed. Patients on oral anticoagulants were excluded. Patients were stratified according to their preprocedural renal function: CKD stages 1 to 2 (estimated glomerular filtration rate [eGFR] ≥60 ml/min/1.73 m2), 3 (eGFR 30 to 59), or 4 to 5 (eGFR <30), or those receiving dialysis. Overall, 23,349 patients, including 2,798 patients with CKD 3 to 5 (12.0%) and 1,464 patients on dialysis (6.3%), were investigated. One-year ischemic events were observed in 1.5%, 5.2%, 9.7%, and 5.3% in the CKD stages 1-to-2, 3, 4-to-5, and dialysis groups, respectively; patients with CKD stages 3 or 4 to 5 and those receiving dialysis were associated with higher risks of ischemic events after adjustment of covariates than were patients without CKD. Compared with ischemic events, 1-year bleeding events were low, with incidence rates of 1.5%, 2.0%, 3.4%, and 2.3%, respectively. Furthermore, the presence of CKD or dialysis was not associated with a higher risk of bleeding events after adjustment of covariates. In conclusion, in the contemporary nationwide PCI registry, the presence of CKD and dialysis was independently associated with a higher risk of ischemic events but not with bleeding events, and this suggests a need to alter the models of care delivery in these patients.

Standard modifiable cardiovascular risk factors in patients with acute coronary syndrome: A report from multicenter percutaneous coronary intervention registry.

BACKGROUND: High mortality in patients with acute coronary syndrome (ACS) without standard modifiable cardiovascular risk factors [SMuRFs (e.g. diabetes, hypertension, smoking, and dyslipidemia)] has been reported. However, details regarding their acute presentation and reasons for the excess risk remain unclear. METHOD: Patient-level data were extracted from a multicenter procedure-based registry (KiCS-PCI). We analyzed consecutive patients with ACS who underwent de novo percutaneous coronary intervention (PCI) between 2009 and 2020. The primary outcome of interest was the in-hospital mortality. RESULTS: Among the 10,523 patients with ACS, 7775 met the inclusion criteria. Patients without SMuRFs who underwent PCI [n = 529 (6.8 %)] were older [median 71 (IQR: 63-79) vs. 68 (59-76) years, p < 0.001] and more often presented with cardiogenic shock or cardiopulmonary arrest (14.6 % vs. 8.6 %, p < 0.001; 12.7 % vs. 5.3 %, p < 0.001, respectively). In patients with ST-elevation myocardial infarction (STEMI), median door-to-balloon time was significantly longer in SMuRF-less patients (90 min vs 82 min). In-hospital death was significantly higher in SMuRF-less patients [10.2 % vs. 4.1 %, p < 0.001, adjusted odds ratio, 1.81 (95%CI, 1.26-2.59); p = 0.001], whereas the rate of procedural complications showed no significant difference. When stratified by the ACS presentation pattern, the findings were consistent, although the association between SMuRF-less and the increased risk of in-hospital mortality was not statistically significant in patients with non-ST-elevation- (NSTE)-ACS. CONCLUSIONS: SMuRF-less ACS patients frequently presented with cardiopulmonary arrest and/or cardiogenic shock, leading to high in-hospital mortality. When stratified by the ACS presentation pattern, the association of SMuRF-less and the increased risk of mortality was more prominent in STEMI patients and it was not statistically significant in NSTE-ACS patients. Almost half of these patients had amendable left main trunk or left anterior descending artery disease and treating clinicians should be aware of this paradox to avoid the delay in treatment.

Clinical expert consensus document on drug-coated balloon for coronary artery disease from the Japanese Association of Cardiovascular Intervention and Therapeutics.

Drug-coated balloon (DCB) technology was developed to deliver the antiproliferative drugs to the vessel wall without leaving any permanent prosthesis or durable polymers. The absence of foreign material can reduce the risk of very late stent failure, improve the ability to perform bypass-graft surgery, and reduce the need for long-term dual antiplatelet therapy, potentially reducing associated bleeding complications. The DCB technology, like the bioresorbable scaffolds, is expected to be a therapeutic approach that facilitates the "leave nothing behind" strategy. Although newer generation drug-eluting stents are the most common therapeutic strategy in modern percutaneous coronary interventions, the use of DCB is steadily increasing in Japan. Currently, the DCB is only indicated for treatment of in-stent restenosis or small vessel lesions (< 3.0 mm), but potential expansion for larger vessels (≥ 3.0 mm) may hasten its use in a wider range of lesions or patients with obstructive coronary artery disease. The task force of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) was convened to describe the expert consensus on DCBs. This document aims to summarize its concept, current clinical evidence, possible indications, technical considerations, and future perspectives.

Impact of concomitant mitral regurgitation during transcatheter aortic valve replacement on 1-year survival outcomes.

BACKGROUND: We investigated the influence of concomitant mitral regurgitation (MR) in patients undergoing transcatheter aortic valve implantation on the 1-year outcome using Japan Transcatheter Valve Therapy (J-TVT) registry data. METHODS: The patients who underwent the transcatheter aortic valve implantation for aortic stenosis performed from August 2013 to December 2019 in Japan were included. History of previous valve surgery and dialysis patients were excluded. A total of 24,979 patients were included, and 1-year follow-up data were obtained from the registry (follow-up rate 98.5 %). Propensity-score matching, using multivariable logistic regression and 1:1 matching without replacement, was performed between the patients with grade 3-4 MR (MR 3-4 group) and those with grade 0-2 MR (MR 0-2 group). All-cause death and the composite outcome of death and/or heart failure events were compared. RESULTS: After propensity score matching, 3920 cases (1960 cases each in MR 0-2 group and MR 3-4 group) were extracted. The procedure success rate was 96.4 % in MR 0-2 and 96.0 % in MR 3-4 group (p = 0.56) and the surgical conversion rate was 0.7 % in MR 0-2 group and 0.8 % in MR 3-4 group (p = 0.58). Cox regression model showed no statistical difference in 1-year survival rate between MR 0-2 group (89.4 %) and MR 3-4 group (89.6 %) (p = 0.80). However, freedom from 1-year death and/or heart failure event was lower in MR 3-4 (86.3 %) than in MR 0-2 group (88.9 %) (p = 0.01). This trend was also found in the subgroup of New York Heart Association (NYHA) class 1-2 but not in the subgroup of NYHA class 3-4. CONCLUSIONS: One-year survival rate was not different between groups but freedom from death and/or heart failure events was lower in patients with preoperative MR grade 3-4 than in patients with preoperative MR grade 0-2 after transcatheter aortic valve replacement.

Characteristics and outcomes of patients with no standard modifiable risk factors undergoing primary revascularization for acute myocardial infarction: Insights from the nationwide Japanese percutaneous coronary intervention registry.

BACKGROUND: Identification of and therapeutic approaches to standard modifiable risk factors (SMuRFs), including hypertension, diabetes, dyslipidemia, and smoking, have led to improved survival of patients at risk for coronary events. However, recent studies have indicated that a significant proportion of patients with acute myocardial infarction (AMI) have no SMuRFs. We aimed to assess in-hospital outcomes and the prevalence of these patients using the Japanese nationwide percutaneous coronary intervention (J-PCI) registry. METHODS: The J-PCI is a procedure-based registration program in Japan. A total of 115,437 PCI procedures were performed on patients with AMI between January 2019 and December 2020. The participants were divided into 2 groups: those with at least 1 SMuRF and those without any SMuRFs. The primary outcome was in-hospital mortality. RESULTS: Of the 115,437 patients with AMI, 1,777 (1.6%) had no SMuRFs. Patients without SMuRFs were older; more likely to have left main disease; and more likely to present with heart failure, cardiogenic shock, and cardiac arrest than those with SMuRFs, resulting in higher rates of mechanical circulatory support use and impaired post-PCI coronary blood flow. In-hospital mortality was significantly higher in patients without SMuRFs than in those with SMuRFs (18.3% vs 5.3%, P < .001), irrespective of the presence or absence of ST-segment elevation. CONCLUSIONS: In Japan, where annual health checks are mandated under universal health care coverage, the vast majority of patients with AMI undergoing PCI have SMuRFs. However, although small in number, patients without SMuRFs are more likely to present with life-threatening conditions and have worse in-hospital survival.

Clinical Outcomes of Urgent or Emergency Transcatheter Aortic Valve Implantation　- Insights From the Nationwide Registry of Japan Transcatheter Valve Therapies.

BACKGROUND: Limited data are available for clinical outcomes in patients who underwent urgent or emergency transcatheter aortic valve implantation (TAVI). This study investigated in-hospital and 1-year outcomes and explored prognostic covariates in urgent/emergency TAVI using nationwide registry data.Methods and Results: Among 26,775 patients who underwent TAVI between August 2013 and December 2019, 25,495 with 1-year follow-up information were analyzed in this study. Baseline and procedural characteristics, as well as clinical adverse events, were compared between the urgent/emergency and elective TAVI groups. The primary outcome was all-cause mortality within 1 year after TAVI. Multivariable Cox regression models were constructed to identify independent predictors after urgent or emergency TAVI. Urgent or emergency TAVI was performed in 578 (2.3%) patients. The Society of Thoracic Surgeons score was significantly higher in the urgent/emergency than elective TAVI group (13.3% vs. 6.0%; P<0.001). Device success rate was comparable between the 2 groups. All-cause death-free survival within 1 year was lower in the urgent/emergency than elective TAVI group (77.2% vs. 92.2%; log rank P<0.001). Malignancy, albumin and creatinine concentrations, ejection fraction, and mean pressure gradient were associated with 1-year mortality in the urgent/emergency TAVI group. CONCLUSIONS: Despite higher surgical risk and more comorbidities, the procedure was successfully performed in patients undergoing urgent/emergency TAVI, although it should be noted that prognosis was worse than for elective TAVI.

Contrast volume and in-hospital outcomes of dialysis patients undergoing percutaneous coronary intervention.

Toxicity resulting from retained contrast media may cause adverse cardiovascular outcomes (e.g., heart failure and cardiogenic shock) for dialysis patients. However, the association between the administered contrast volume and outcomes of dialysis patients after percutaneous coronary intervention (PCI) has not been sufficiently investigated. We evaluated 953 consecutive dialysis patients (age, 67.9 ± 9.9 years; 30.1% with acute coronary syndrome) who underwent PCI between September 2008 and March 2019. Patients were divided into two groups: those with a contrast volume ≥ 200 ml and those with a contrast volume < 200 ml. The cutoff was 200 ml because 100 ml increment of contrast volume is known to raise the risk of acute kidney injury, and 200 ml is more than the average volume used at most PCI centers. The primary endpoint was a composite of in-hospital death, post-PCI cardiogenic shock and post-PCI heart failure. A multivariable logistic regression model and smooth spline curve were constructed to assess the association between contrast volume and the primary endpoint. The median contrast volume was 157 ml (interquartile range, 115-210 ml). The overall primary endpoint incidence was 6.8% (N = 65). A contrast volume ≥ 200 ml was associated with a higher risk of the primary endpoint (odds ratio 2.91; 95% confidence interval 1.42-6.05; P = 0.004). The smooth spline curve demonstrated a linear relationship between the contrast volume and primary endpoint. In conclusions, the contrast volume was associated with adverse in-hospital outcomes of dialysis patients undergoing PCI. Attention should be focused on the contrast volume used for dialysis patients undergoing PCI.

Cost-Effectiveness Analysis of Initiating Type 2 Diabetes Therapy with a Sodium-Glucose Cotransporter 2 Inhibitor Versus Conventional Therapy in Japan.

INTRODUCTION: Many patients with type 2 diabetes mellitus (T2DM) suffer from complications that impose substantial burdens on prognosis and medical costs. Accumulating evidence has demonstrated the clinical benefit of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on cardiovascular and renal complications. However, the health economic impact of SGLT2i remains unclear. The aim of this study was to evaluate the cost-effectiveness of initiating antidiabetic therapy with an SGLT2i using Japanese real-world data. METHODS: We constructed a natural history model incorporating heart failure (HF), myocardial infarction, stroke, chronic kidney disease, and end-stage renal disease (ESRD) as complications. The target population comprised patients with T2DM who newly initiated their first oral glucose-lowering drugs. By using a population-based microsimulation, we estimated the 10-year medical costs in Japanese yen (JPY) and outcomes (hospitalization for/development of complications and quality-adjusted life years [QALY]) for patients who initiated antidiabetic therapy with an SGLT2i or conventional therapy. Sensitivity analyses included a probabilistic sensitivity analysis (PSA) with 1,000,000 iterations. RESULTS: In the base-case analysis, the total medical cost per person was JPY 1,638,806 versus JPY 1,825,033 and the QALYs were 8.732 versus 8.513 for the SGLT2i strategy versus the conventional strategy, respectively. Thus, initiating treatment with an SGLT2i was dominant, more effective (QALY gain), and lower cost. When treating 10,000 patients, the SGLT2i strategy would reduce all-cause deaths by 410 (552 vs 962), HF events by 201 (897 vs 1098), and ESRD events by 16 (16 vs 32) versus the conventional strategy. The PSA revealed that the probability of dominance for initiating SGLT2i therapy was 90.5%, demonstrating the robustness of the results. CONCLUSION: Our results suggest that initiating T2DM treatment with SGLT2i, aimed at managing cardiovascular and renal complications from the early stages of diabetes, can improve the clinical outcome and reduce cost burden of T2DM.

Non-cardiovascular readmissions after transcatheter aortic valve replacement: Insights from a Japanese nationwide registry of transcatheter valve therapies.

BACKGROUND: Despite advances in technology and technique, a certain proportion of patients experience non-cardiovascular (CV) readmissions after transcatheter aortic valve replacement (TAVR). However, the actual burden and details of non-CV readmission remain uncertain. METHODS: The Japan-Transcatheter Valve Therapies (J-TVT) registry is a representative nationwide registry, and mandates complete data entry, including 1-year outcomes, for patients undergoing TAVR in Japan. We analyzed the non-CV adverse events (AEs) requiring readmission after the index TAVR procedure between 2013 and 2018. RESULTS: A total of 14,472 patients were analyzed (68.8% of women with median age of 85 years). Overall, 367 patients (2.5%) and 1050 patients (7.2%) had non-CV readmission at 30 days and 1 year, respectively. The most frequent non-CV AEs were related to respiratory (24.0%) and gastrointestinal disease (19.3%). Specifically, 79.0% of all respiratory AEs were pneumonia (infectious, interstitial, or aspiration). Of the gastrointestinal AEs, 22.1% were malignancies, and 18.5% were non-procedural-related bleeding. Age ≥90 years, male sex, body mass index <20 kg/m2, New York Heart Association functional class III/IV, atrial fibrillation/flutter, malignancy, chronic obstructive pulmonary disease, dialysis, hemoglobin level, albumin level, creatinine level, and non-transfemoral approach were independent predictors of non-CV readmission. CONCLUSIONS: In this analysis of the nationwide registry of patients undergoing TAVR, rate of non-CV readmission at 30 days and 1 year, particularly those related to respiratory and gastrointestinal conditions, were lower than those previously reported. However, caution is still needed when performing TAVR on patients susceptible to these conditions.

Practice Patterns and Outcomes of Transcatheter Aortic Valve Replacement in the United States and Japan: A Report From Joint Data Harmonization Initiative of STS/ACC TVT and J-TVT.

Background The practice pattern and outcome of medical devices following their regulatory approval may differ by country. The aim of this study is to compare postapproval national clinical registry data on transcatheter aortic valve replacement between the United States and Japan on patient characteristics, periprocedural outcomes, and the variability of outcomes as a part of a partnership program (Harmonization-by-Doing) between the 2 countries. Methods and Results The patient-level data were extracted from the US Society of Thoracic Surgeons /American College of Cardiology Transcatheter Valve Therapy (STS/ACC TVT) and the J-TVT (Japanese Transcatheter Valvular Therapy) registry, respectively, to analyze transcatheter aortic valve replacement outcomes between 2013 and 2019. Data entry for these registries was mandated by the federal regulators, and the majority of variable definitions were harmonized to allow direct data comparison. A total of 244 722 transcatheter aortic valve replacements from 646 institutions in the United States and 26 673 transcatheter aortic valve replacements from 171 institutions in Japan were analyzed. Median volume per site was 65 (interquartile range, 45-97) in the United States and 28 (interquartile range, 19-41) in Japan. Overall, patients in J-TVT were older (United States: mean-age, 80.1±8.7 versus Japan: 84.4±5.2; P<0.001), were more frequently women (45.9% versus 68.1%; P<0.001), and had higher median Society of Thoracic Surgeons Predicted Risk of Mortality (5.27% versus 6.20%; P<0.001) than patients in the United States. Japan had lower unadjusted 30-day mortality (1.3% versus 3.2%; P<0.001) and composite outcomes of death, stroke, and bleeding (17.5 versus 22.5%; P<0.001) but had higher conversion to open surgery (0.94% versus 0.56%; P<0.001). Conclusions This collaborative analysis between the United States and Japan demonstrated the feasibility of international comparison using the national registries coded under mutual variable definitions. Both countries obtained excellent outcomes, although the Japanese had lower 30-day mortality and major morbidity. Harmonization-by-Doing is one of the key steps needed to build global-level learning to improve patient outcomes.