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There has been no previous report evaluating the long impact of atrial fibrillation (AF) on the clinical outcomes stratified by the initial management [conservative or aortic valve replacement (AVR)] strategies of severe aortic stenosis (AS).We analyzed 3815 patients with severe AS enrolled in the CURRENT AS registry. Patients with AF were defined as those having a history of AF when severe AS was found on the index echocardiography. The primary outcome measure was a composite of aortic valve-related death or hospitalization for heart failure.The cumulative 5-year incidence of the primary outcome measure was significantly higher in patients with AF than in those without AF (44.2 % versus 33.2 %, HR 1.54, 95 % CI 1.35-1.76). After adjusting for confounders, the risk of AF relative to no AF remained significant (HR 1.34, 95 % CI 1.16-1.56). The magnitude of excess adjusted risk of AF for the primary outcome measure was greater in the initial AVR stratum (N = 1197, HR 1.95, 95 % CI 1.36-2.78) than in the conservative stratum (N = 2618, HR 1.26, 95 % CI 1.08-1.47) with a significant interaction (p = 0.04). In patients with AF, there was a significant excess adjusted risk of paroxysmal AF (N = 254) relative to chronic AF (N = 528) for the primary outcome measure (HR 1.34, 95 % CI 1.01-1.78).In patients with severe AS, concomitant AF was independently associated with worse clinical outcomes regardless of the initial management strategies. In those patients with conservative strategy, paroxysmal AF is stronger risk factor than chronic AF.

BACKGROUND: The relationship between very low on-treatment low-density lipoprotein cholesterol (LDL-C) level and cardiovascular event risk is still unclear in patients receiving the same doses of statins.Methods and Results: From the REAL-CAD study comparing high-dose (4 mg/day) with low-dose (1 mg/day) pitavastatin therapy in patients with stable coronary artery disease, 11, 105 patients with acceptable statin adherence were divided into 3 groups according to the on-treatment LDL-C level at 6 months (

It is unknown whether beneficial effects of higher-dose statins on cardiovascular events are different according to the thrombotic risk in patients with chronic coronary syndrome (CCS).Methods and Results: The Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study is a randomized trial comparing 4 mg and 1 mg pitavastatin in patients with CCS. This study categorized 12,413 patients into 3 strata according to the CREDO-Kyoto thrombotic risk score: low-risk (N=9,434; 4 mg: N=4,742, and 1 mg: N=4,692), intermediate-risk (N=2,415; 4 mg: N=1,188, and 1 mg: N=1,227); and high-risk (N=564; 4 mg: N=269, and 1 mg: N=295). The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina. Cumulative 4-year incidence of the primary endpoint was significantly higher in the high-risk stratum than in the intermediate- and low-risk strata (11.0%, 6.3%, and 4.5%, P0.0001). In the low-risk stratum, the cumulative 4-year incidence of the primary endpoint was significantly lower in the 4 mg than in the 1 mg group (4.0% and 4.9%, P=0.02), whereas in the intermediate- and high-risk strata, it was numerically lower in the 4 mg than in the 1 mg group. There was no significant treatment-by-subgroup interaction for the primary endpoint (P-interaction=0.77).High-dose pitavastatin therapy compared with low-dose pitavastatin therapy was associated with a trend toward lowering the risk for cardiovascular events irrespective of the thrombotic risk in patients with CCS.

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

There is a scarcity of data on incidence, risk factors, especially clinical severity, and long-term prognostic impact of periprocedural stroke after coronary revascularization in contemporary real-world practice. Among 14,867 consecutive patients undergoing first coronary revascularization between January 2011 and December 2013 (percutaneous coronary intervention [PCI]: N = 13258, and coronary artery bypass grafting [CABG]: N = 1609) in the Coronary Revascularization Demonstrating Outcome Study in Kyoto PCI/CABG registry Cohort-3, we evaluated the details on periprocedural stroke. Periprocedural stroke was defined as stroke within 30 days after the index procedure. Incidence of periprocedural stroke was 0.96% after PCI and 2.13% after CABG (log-rank p0.001). Proportions of major stroke defined by modified Rankin Scale ≥2 at hospital discharge were 68% after PCI, and 77% after CABG. Independent risk factors of periprocedural stroke were acute coronary syndrome (ACS), carotid artery disease, advanced age, heart failure, and end-stage renal disease after PCI, whereas they were ACS, carotid artery disease, atrial fibrillation, chronic obstructive pulmonary disease, malignancy, and frailty after CABG. There was excess long-term mortality risk of patients with periprocedural stroke relative to those without after both PCI and CABG (hazard ratio 1.71 [1.25 to 2.33], and hazard ratio 4.55 [2.79 to 7.43]). In conclusion, incidence of periprocedural stroke was not negligible not only after CABG, but also after PCI in contemporary real-world practice. Majority of patients with periprocedural stroke had at least mild disability at hospital discharge. ACS and carotid artery disease were independent strong risk factors of periprocedural stroke after both PCI and CABG. Periprocedural stroke was associated with significant long-term mortality risk after both PCI and CABG.

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

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%, P0.001, and 13.9%, 11.3%, and 10.2%, P0.001; female Tertiles 1, 2, and 3: 17.9%, 12.9%, and 10.1%, P0.001, and 17.9%, 12.9%, and 10.1%, P0.001). 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).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.

BACKGROUND The transradial approach is reportedly associated with reduced bleeding complications and mortality after percutaneous coronary intervention (PCI). It is unknown whether the clinical benefits of transradial vs. transfemoral PCI differ between high bleeding risk (HBR) and non-HBR patients.Methods and Results:After excluding patients with acute myocardial infarction, dialysis, and a transbrachial approach from the 13,087 patients undergoing first PCI in the CREDO-Kyoto Registry Cohort-2, 6,828 patients were eligible for this study. Patients were divided into 2 groups according to bleeding risk based on Academic Research Consortium HBR criteria, and then divided into a further 2 groups according to access site, radial or femoral: HBR-radial, n=1,054 (38.3%); HBR-femoral, n=1,699 (61.7%); non-HBR-radial, n=1,682 (41.3%); and non-HBR-femoral, n=2,393 (58.7%). In the HBR group, the 30-day incidence and adjusted risk for major bleeding (1.9% vs. 4.7% [P

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.

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.

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

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 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)

Visual Abstract, Highlights • KUS121 was developed to selectively inhibit the adenosine triphosphatase activity of valosin-containing protein without affecting other cellular functions of valosin-containing protein. • KUS121 preserved adenosine triphosphate levels, reduced endoplasmic reticulum stress, and suppressed cell death in H9C2 rat cardiomyoblast cells, treated with tunicamycin or hydrogen peroxide, or cultured in glucose-free medium. • In murine ischemia and reperfusion injury models, KUS121 treatment after reperfusion attenuated the infarcted size and preserves cardiac function by maintaining adenosine triphosphate levels and reducing ER stress. • In porcine ischemia and reperfusion injury models, intracoronary administration of KUS121 also attenuated the infarcted area in a dose-dependent manner. • These results indicated that KUS121 is a promising novel therapeutic agent for myocardial infarction., Summary No effective treatment is yet available to reduce infarct size and improve clinical outcomes after acute myocardial infarction by enhancing early reperfusion therapy using primary percutaneous coronary intervention. The study showed that Kyoto University Substance 121 (KUS121) reduced endoplasmic reticulum stress, maintained adenosine triphosphate levels, and ameliorated the infarct size in a murine cardiac ischemia and reperfusion injury model. The study confirmed the cardioprotective effect of KUS121 in a porcine ischemia and reperfusion injury model. These findings confirmed that KUS121 is a promising novel therapeutic agent for myocardial infarction in conjunction with primary percutaneous coronary intervention.

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 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.

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] There are limited data on the long-term stent-related adverse events as related to the duration of dual antiplatelet therapy (DAPT) in second-generation (G2) drug-eluting stents (DES) compared with first-generation (G1) DES. [Objectives] This study sought to compare the long-term stent-related outcomes of G2-DES with those of G1-DES. [Methods] The study group consisted of 15, 009 patients who underwent their first coronary revascularization with DES from the CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Grafting) Registry Cohort-2 (first-generation drug-eluting stent [G1-DES] period; n = 5, 382) and Cohort-3 (second-generation drug eluting stent [G2-DES] period; n = 9, 627). The primary outcome measures were definite stent thrombosis (ST) and target vessel revascularization (TVR). [Results] The cumulative 5-year incidences of definite ST and TVR were significantly lower in the G2-DES group than in the G1-DES group (0.7% vs 1.4%; P < 0.001; and 16.2% vs 22.1%; P < 0.001, respectively). The lower adjusted risk of G2-DES relative to G1-DES for definite ST and TVR remained significant (HR: 0.53; 95% CI: 0.37-0.76; P < 0.001; and HR: 0.74; 95% CI: 0.68-0.81; P < 0.001, respectively). In the landmark analysis that was based on the DAPT status at 1 year, the lower adjusted risk of on-DAPT status relative to off-DAPT was significant for definite ST beyond 1 year in the G1-DES stratum (HR: 0.42; 95% CI: 0.24-0.76; P = 0.004) but not in the G2-DES stratum (HR: 0.66; 95% CI: 0.26-1.68; P = 0.38) (Pinteraction = 0.14). [Conclusions] G2-DES compared with G1-DES were associated with a significantly lower risk for stent-related adverse events, including definite ST and TVR. DAPT beyond 1 year was associated with a significantly lower risk for very late ST of G1-DES but not for that of G2-DES.

Heavy coronary calcification hinders successful stent implantation, and cutting balloons can be used for post-dilation after stent deployment. However, evidence regarding its use is limited to case reports. Therefore, this study aimed to investigate in-stent dilation in circumferential coronary calcifications using Wolverine cutting balloons, compared with conventional non-compliance (NC) balloons. Circumferential coronary calcification models were designed based on the patient’s intravascular ultrasound images. Three-dimensional printed models were subjected to bench tests and software analysis was performed using the finite-element method (FEM). As a result, the bench test showed that higher balloon pressure was needed to dilate the models with stent implantation, either using Wolverine (17.1 ± 2.7 atm) or NC Emerge (18.9 ± 1.8 atm), while lower pressure was needed in models without stents using Wolverine [11.7 ± 2.9 atm, analysis of variance (ANOVA) p

Due to the COVID-19 pandemic, the 84

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

Heavy calcification is one of the factors that hinder the success of coronary angioplasty, and a cutting balloon is used for such lesions. This study aimed to explore the optimal method of dilation of highly calcified lesions using a cutting balloon. Calcification models were developed from patient computed tomography and intravascular ultrasound data, and were constructed using three-dimensional printers. The lesions were dilated using a Wolverine™ cutting balloon and NC Emerge™ noncompliant balloon catheter, and the success rate of dilation and maximum dilation pressure were compared. The maximum first principal stresses in calcified lesions were also evaluated by computer simulation using the finite element method. In the bench test, the dilation success rate of the Wolverine™ cutting balloon was higher and the maximum dilation pressure required was lower (p

Background Patients with severe aortic stenosis (AS) might be at high risk for adverse cardiovascular events at the time of non-cardiac surgery.Methods and Results:The current study population included 348 patients who underwent elective non-cardiac surgery under general or spinal anesthesia during the follow up of 3,815 patients in the CURRENT AS (Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis) registry. There were 187 patients with untreated severe AS at time of surgery (untreated severe AS group) and 161 patients who had undergone aortic valve replacement (AVR) before surgery (prior AVR group), including 23 patients with prophylactic AVR. The primary outcome measure was 30-day mortality after non-cardiac surgery. At 30 days after non-cardiac surgery, 8 patients (4.3%) died in the untreated severe AS group, while no patients died in the prior AVR group (P=0.008). The causes of death were cardiovascular in 6 out of 8 patients. Mortality at 30 days was higher in untreated severe AS patients with AS-related symptoms before surgery than in those without AS-related symptoms (7.2% vs. 3.1%). Higher surgical risk estimates of the non-cardiac surgery incrementally increased the risk of 30-day mortality in patients with untreated severe AS, though the difference was not statistically significant (low-risk: 0%, intermediate-risk: 4.3%, and high-risk: 6.6 %, P=0.46). Conclusions Symptomatic and asymptomatic severe AS might be associated with higher risk of 30-day mortality if untreated before elective intermediate- and high-risk non-cardiac surgery, while no patient with prior AVR died after elective non-cardiac surgery.

BACKGROUND Three-dimensional (3D) printed models have been recently introduced for diagnosis and preprocedural planning for percutaneous interventions or surgery in cardiovascular disease. CASE REPORT We treated a 71-year-old woman with angina. Although we performed coronary angiography, we could not engage the catheters for the left coronary artery (LCA). Then, we withdrew the catheter and examined her anatomy using coronary computed tomographic angiography (CCTA). The CCTA revealed that the LCA originated from the noncoronary cusp (NCC). Because anomalous LCA originating from the NCC is a rare congenital anomaly, percutaneous coronary intervention was considered difficult. We decided to use a 3D-printed model, which enabled us to clearly see the anatomy and simulation before the actual procedure, which went smoothly according to the preprocedural planning using the 3D printed model. 3D printed modeling is feasible for use in reproducing coronary artery anatomy and enhancing understanding of coronary abnormalities. CONCLUSIONS Use of 3D-printed models is a useful new option that can help visualize the anatomy and perform preprocedural planning for complex cases.

It is unknown whether there is a threshold of creatine kinase (CK) or CK-MB affecting the subsequent mortality for post-discharge myocardial infarction (PDMI) after percutaneous coronary intervention. Current study sought to evaluate the impact of PDMI. The study population included 30,051 patients with successful coronary stenting and discharged alive in the pooled patient-level database of 4 Japanese studies (j-Cypher registry, CREDO-Kyoto PCI/CABG registry cohort-2, RESET, and NEXT). During 4.4 ± 1.4 year follow-up, 915 patients experienced PDMI (cumulative 5-year incidence of 3.6%). Among 466 patients with available peak CK ratio (peak CK/upper limit of normal), peak CK ratio (

Background: Clinical profiles of acute heart failure (AHF) complicating severe aortic stenosis (AS) remain unclear. Methods and Results: From a Japanese multicenter registry enrolling consecutive patients with severe AS, 3, 813 patients were categorized into the 3 groups according to the symptom of heart failure (HF); No HF (n=2, 210), chronic HF (CHF) (n=813) and AHF defined as hospitalized HF at enrolment (n=790). Median follow-up was 1, 123 days with 93% follow-up rate at 2 years. Risk factors for developing AHF included age, female sex, lower body mass index, untreated coronary artery stenosis, anemia, history of HF, left ventricular ejection fraction

OBJECTIVES The present study aimed to develop a swine coronary bifurcation model. BACKGROUND In human coronary bifurcation lesion, atherosclerotic plaques are usually observed in the lateral wall, whereas the flow divider regions are spared. There is currently no suitable coronary bifurcation animal model, on which a new stent can be tested. METHODS We developed a novel directional heat injury catheter, which comprised of a non-compliant balloon catheter (diameter: 3.0mm, length: 15mm), and two electrode cables, that were attached to either side of the balloon catheter. The technique was performed on 4 healthy pigs, and assessed in 7 lesions. We inflated the balloon at the main bifurcation branch, following which a high frequency generator was used to transmit heat to the opposite side of the electrode, towards the bifurcation carina (duration: 5min, frequency: 2 times). We performed a post-angiography 28days after the pre-angiography, to observe the distribution of neointima. The neointimal area was divided into the carina side and the opposite side of carina, and the 2 sides were compared. RESULTS The neointimal area at the opposite side of the carina was significantly larger than the carina side (1.51±0.40mm2 vs. 0.95±0.27mm2, p

The incidence of heart failure (HF) hospitalization and its impact on long-term outcomes have not been well evaluated in contemporary patients with ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI). The Coronary Revascularization Demonstrating Outcome Study in Kyoto Acute Myocardial Infarction (AMI) Registry is a multicenter registry enrolling 5,429 consecutive patients with AMI undergoing PCI from 2005 to 2007. The present study population consisted of 3,682 patients with STEMI who underwent primary PCI within 24 hours of symptom onset and discharged alive. The incidence of HF hospitalization was 4.4%/year during the first year after the index STEMI, which attenuated to approximately 1.0%/year beyond 1 year to 5 years with the median follow-up period of 1,956 days. The independent risk factors for HF hospitalization within 1 year included older age, previous myocardial infarction, HF at STEMI, left ventricular dysfunction, anterior AMI, and onset-to-balloon time3 hours, use of β blocker, and nonuse of statin at discharge. By the landmark analysis at 1 year, the cumulative incidences of all-cause death and HF hospitalization beyond 1 year and up to 5 years were significantly higher in patients with HF hospitalization within 1 year of STEMI than in patients without (36.3% vs 10.1%, p0.001, and 40.4% vs 4.3%, p0.001, respectively). Even after adjusting for confounders, HF hospitalization within 1 year remained independently associated with a higher risk for death and HF hospitalization beyond 1 year (hazard ratio 1.64, 95% CI 1.02 to 2.52, p = 0.04 and HR 5.72, 95% CI 3.46 to 9.22, p0.001, respectively). In conclusion, HF hospitalization within 1 year was independently associated with a higher risk for all-cause death and HF hospitalization beyond 1 year.

Background:There is discordance regarding the effect of symptom status before aortic valve replacement (AVR) on long-term outcome after AVR in severe aortic stenosis (AS). Methods and Results:The CURRENT AS registry is a multicenter retrospective registry enrolling 3, 815 consecutive patients with severe AS. Among 1, 196 patients managed with the initial AVR strategy, long-term clinical outcomes were compared between the symptomatic patients (n=905), and asymptomatic patients (n=291). Median follow-up interval was 1337 days with a 91% follow-up rate at 2 years. AVR was performed in 886 patients (98%) in the symptomatic group and in 287 patients (99%) in the asymptomatic group. Symptomatic patients were older and more often had comorbidities than asymptomatic patients with similar echocardiographic AS severity. The cumulative 5-year incidences of all-cause death and heart failure (HF) hospitalization were significantly higher in symptomatic patients than in asymptomatic patients (25.6% vs. 15.4%, P=0.001, and 14.2% vs. 3.8%, P

Although transcatheter aortic valve replacement (TAVR) is an excellent alternative procedure for high-risk patients with severe symptomatic aortic stenosis, it is often associated with life-threatening complications. We report on the emergency or elective use of veno-arterial extracorporeal membrane oxygenation (ECMO) to manage these complications. Between December 2013 and February 2016, 46 patients underwent TAVR at our institution. Of these, 4 patients required emergency ECMO support and another 3 patients were electively placed on ECMO support at the start of the procedure. The mean age of the ECMO patients was 87.3 ± 3.6 years and all were female. The Society of Thoracic Surgeons-predicted risk of mortality score in these patients was 12.2 ± 6.2%. TAVR with ECMO was completed through the transapical approach in 6 patients, and the transfemoral approach in 1 patient. The arterial access route for ECMO was the femoral artery in 5, the external iliac artery in 1, and the subclavian artery in 1. Indications for the use of emergency ECMO were hemodynamic instability in 2, cardiogenic shock in 2, while indications for elective ECMO were severe pulmonary hypertension, impaired left ventricular function and a combination of these. There was no 30-day mortality, and the 1-year survival rate was 83.3% with no significant difference compared to patients without ECMO support. The use of ECMO in very high-risk patients undergoing TAVR may increase safety and contribute to excellent outcomes. Although ECMO support is rarely needed in TAVR, a well-prepared treatment strategy by the heart team is mandatory.

Background The ACC/AHA guidelines introduced a new classification of severe aortic stenosis (AS) mainly based on maximum jet velocity (Vmax) and mean pressure gradient (mPG), but not on aortic valve area (AVA). However, prognostic value of this new classification has not yet been fully evaluated. Methods and results We studied 1512 patients with asymptomatic severe AS enrolled in the CURRENT AS registry in whom surgery was not initially planned. Patients were divided into 2 groups: Group 1 (N=122) comprised patients who met the recommendation for surgery; high-gradient (HG)-AS (Vmax≥4.0m/s or mPG≥40mmHg) with ejection fraction (EF) 2 (N=892). The excess risk of Group 1 relative to Group 2 for the primary outcome measure (a composite of aortic valve-related death or heart failure hospitalization) was significant (adjusted HR: 1.92, 95%CI: 1.37–2.68, P Conclusion Trans-aortic valve gradient in combination with EF was a good prognostic marker in patients with asymptomatic AS. However, patients with LGrEF-AS had extremely poor prognosis when managed conservatively.

Background Transcatheter aortic valve implantation (TAVI) is an established therapy for patients who are inoperable or at high risk for open heart surgery. The retrograde transfemoral approach is the most widely used and is the first choice in TAVI. However, existence of peripheral vascular disease or a small iliofemoral artery often limits the application of the transfemoral approach. Transvenous antegrade transseptal TAVI is an attractive option, but has already been abandoned due to its technical complexities. Methods and results We have previously described a novel technique to simplify antegrade transseptal balloon aortic valvuloplasty, which utilizes a custom-made Inoue balloon catheter with two stylets. The technique is named as the looped Inoue balloon technique, and its feasibility and efficacy were proven in an animal model and a clinical case. We applied this technique to TAVI. The present study aimed to assess the feasibility of the looped Inoue balloon technique for TAVI in two healthy pigs. The valve implantation was successful in both pigs, although the pigs died soon after the implantation (2 and 24 h). The causes of death were access site bleeding (Case 1) and migration of the prosthetic valve (Case 2). Conclusions Although several improvements and further studies are required, the study results indicate that antegrade TAVI using the looped Inoue balloon technique is feasible.

Background Few studies have evaluated the prevalence and clinical outcomes of ad hoc percutaneous coronary intervention (PCI), performing diagnostic coronary angiography and PCI in the same session, in stable coronary artery disease (CAD) patients.Methods and Results:From the CREDO-Kyoto PCI/CABG registry cohort-2, 6,943 patients were analyzed as having stable CAD and undergoing first PCI. Ad hoc PCI and non-ad hoc PCI were performed in 1,722 (24.8%) and 5,221 (75.1%) patients, respectively. The cumulative 5-year incidence and adjusted risk for all-cause death were not significantly different between the 2 groups (15% vs. 15%, P=0.53; hazard ratio: 1.15, 95% confidence interval: 0.98-1.35, P=0.08). Ad hoc PCI relative to non-ad hoc PCI was associated with neutral risk for myocardial infarction, any coronary revascularization, and bleeding, but was associated with a trend towards lower risk for stroke (hazard ratio: 0.78, 95% confidence interval: 0.60-1.02, P=0.06). Conclusions Ad hoc PCI in stable CAD patients was associated with at least comparable 5-year clinical outcomes as with non-ad hoc PCI. Considering patients' preference and the cost-saving, the ad hoc PCI strategy might be a safe and attractive option for patients with stable CAD, although the prevalence of ad hoc PCI was low in the current study population.

We report a case of a 39-year-old man with inferior vena cava (IVC) thrombus after withdrawal of IVC filter. He complained of 1-week history of swelling in his right leg, and computed tomography (CT) demonstrated occlusive thrombus in right femoral and popliteal veins. Venous thrombectomy was attempted after IVC filter placement. The filter was withdrawn without IVC filter-associated thrombus and the patient was discharged on warfarin. On day 21 after discharge, he complained of progressive swelling and CT revealed a significant amount of thrombus in IVC where the filter had been placed. Despite adequate anticoagulant therapy, CT showed increased thrombus extending from infra-renal IVC to common iliac vein. Systemic work-up for the risk factors of venous thromboembolism revealed the presence of hyperhomocysteinemia (total homocysteine 83.1 μmol/L; normal range 5–15 μmol/L) due to unbalanced diet with deficiency of folic acid and vitamin B12. Four weeks after administration of folic acid, vitamin B6/B12 as the treatment of hyperhomocysteinemia in addition to warfarin, swelling of his leg improved with significant resolution of thrombus by CT. CT also demonstrated a severe stenosis of the IVC just below the renal veins. At 6 months, he complained of mild post-thrombotic sequelae with no evidence of recurrent IVC thrombus.

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.

Background: The optimal cutoff value of fractional flow reserve (FFR) derived from coronary computed tomography angiography (FFR CT ) remains unclear. Methods: The current study population consisted of 93 patients with 139 vessels, who had suspected coronary artery disease by computed tomography angiography and underwent invasive FFR. We evaluated diagnostic performance of FFR CT according to different FFR CT cutoff values and FFR CT ranges with invasive FFR ≤0.80 as the reference standard. Results: In per-vessel analysis, median invasive FFR was 0.85 (interquartile range, 0.75–0.90), and 57 out of 139 vessels (41%) showed hemodynamically significant stenosis (≤0.80). Median FFR CT was 0.77 (interquartile range, 0.66–0.84; mean difference [invasive FFR-FFR CT ], 0.06±0.11). Per-vessel accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 73%, 95%, 59%, 61%, and 94% for the cutoff value of FFR CT ≤0.80, 81%, 86%, 78%, 73%, and 89% for FFR CT ≤0.75, and 83%, 74%, 89%, 82%, and 83% for FFR CT ≤0.70, respectively. Per-vessel accuracy across the different ranges of FFR CT ≤0.60, 0.61 to 0.70, 0.71 to 0.80, 0.81 to 0.90, and >0.90 with the cutoff value of FFR CT ≤0.80 were 95%, 74%, 32%, 93%, and 100%, respectively. Setting a gray zone of FFR CT 0.71 to 0.80 provided high positive predictive value (82%; n=42/51) in the range of FFR CT ≤0.70 and high negative predictive value (94%; n=48/51) in FFR CT >0.80. Conclusions: This study suggested that referral to invasive coronary angiography should be considered individually in the range of FFR CT 0.71 to 0.80, whereas dichotomous decision could be made in FFR CT ≤0.70 and >0.80. Future prospective studies evaluating clinical outcomes are needed to establish optimal FFR CT -based diagnostic algorithm.

It has not been yet adequately addressed whether the addition of the nonstatin LDL-C (low-density lipoprotein cholesterol)-lowering agents on top of statins has the same magnitude of risk reduction in the cardiovascular events as compared with more-intensive statin therapy.We performed a systematic review and meta-analysis of RCTs (randomized controlled trials) comparing more- versus less-intensive lipid-lowering therapy (LLT) on clinical outcomes in patients with atherosclerotic cardiovascular risk. We included 23 studies involving 133 037 patients (more-intensive LLT: 67 691 patients and less-intensive LLT: 65 346 patients). We evaluated 3 types of more- versus less-intensive LLT including more versus less statins (57 672 patients), combination therapy of ezetimibe versus statins alone (20 688 patients), or a PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor with statins versus statins alone (54 677 patients). The odds for major adverse cardiovascular events (MACE; equivalent to the composite of coronary heart death, nonfatal myocardial infarction, stroke, or coronary revascularization) were significantly lower in the more-intensive LLT group compared with the less-intensive LLT group in the entire study population (odds ratio, 0.84; 95% CI, 0.79-0.88; P0.001), and in all the 3 categories of more-intensive LLT strategies (more-intensive statin therapy: odds ratio, 0.83; 95% CI, 0.76-0.90; P0.001, ezetimibe: odds ratio, 0.90; 95% CI, 0.85-0.96; P0.001, and PCSK9 inhibitors: odds ratio, 0.81; 95% CI, 0.73-0.90; P0.001) with numerically greater relative odds reduction by more-intensive statin therapy and PCSK9 inhibitors than by ezetimibe. Odds reduction for MACE per 20 mg/dL LDL-C reduction was also different across the 3 types of more-intensive LLT (more-intensive statin therapy: 17.4%, ezetimibe: 11.0%, and PCSK9 inhibitors: 6.6%).In this meta-analysis, more-intensive LLT as compared with less-intensive LLT was associated with significant odds reduction for MACE in the entire study population and in all the 3 categories of more-intensive LLT such as more-intensive statin therapy, ezetimibe, and PCSK9 inhibitors. However, overall odds reduction for MACE and odds reduction for MACE per 20 mg/dL LDL-C reduction were different across the 3 types of more-intensive LLT. Registration: URLs: https://www.crd.york.ac.uk/PROSPERO/ and http://www.umin.ac.jp/ctr. Unique identifiers: PROSPERO: CRD42018081196, and UMIN-CTR: R000036229.

Background: It has not been yet adequately addressed whether the addition of the nonstatin LDL-C (low-density lipoprotein cholesterol)-lowering agents on top of statins has the same magnitude of risk reduction in the cardiovascular events as compared with more-intensive statin therapy. Methods and Results: We performed a systematic review and meta-analysis of RCTs (randomized controlled trials) comparing more- versus less-intensive lipid-lowering therapy (LLT) on clinical outcomes in patients with atherosclerotic cardiovascular risk. We included 23 studies involving 133 037 patients (more-intensive LLT: 67 691 patients and less-intensive LLT: 65 346 patients). We evaluated 3 types of more- versus less-intensive LLT including more versus less statins (57 672 patients), combination therapy of ezetimibe versus statins alone (20 688 patients), or a PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor with statins versus statins alone (54 677 patients). The odds for major adverse cardiovascular events (MACE; equivalent to the composite of coronary heart death, nonfatal myocardial infarction, stroke, or coronary revascularization) were significantly lower in the more-intensive LLT group compared with the less-intensive LLT group in the entire study population (odds ratio, 0.84; 95% CI, 0.79–0.88; P P P P Conclusions: In this meta-analysis, more-intensive LLT as compared with less-intensive LLT was associated with significant odds reduction for MACE in the entire study population and in all the 3 categories of more-intensive LLT such as more-intensive statin therapy, ezetimibe, and PCSK9 inhibitors. However, overall odds reduction for MACE and odds reduction for MACE per 20 mg/dL LDL-C reduction were different across the 3 types of more-intensive LLT. Registration: URLs: https://www.crd.york.ac.uk/PROSPERO/ and http://www.umin.ac.jp/ctr . Unique identifiers: PROSPERO: CRD42018081196, and UMIN-CTR: R000036229.

Fractional flow reserve (FFR) is an established method for diagnosing physiological coronary artery stenosis. A method for computing FFR using coronary computed tomography (CT) images was recently developed. However, its calculation requires off-site supercomputer analysis. Here, we report the preliminary result of a method using simple estimation of boundary conditions. The lumen boundaries of the coronary arteries were semi-automatically delineated using full width at half maximum of CT number profiles. The computational fluid dynamics (CFD) of the blood flow was performed using the boundary conditions of a fixed pressure at the coronary ostium and flow rates at each outlet. The total inflow at the coronary ostium was estimated based on the uniform wall shear stress hypothesis and corrected using a hyperemic multiplier to gain a hyperemic flow rate. The flow distribution from a parent vessel to the downstream daughter vessels was determined according to Murray's law. FFR estimated by CFD was calculated as FFRCFD = Pd/Pa. We collected patients who underwent coronary CT and coronary angiography followed by invasively measured FFR and compared FFRCFD with FFR. Sensitivity, specificity, and correlations were assessed. A total of 48 patients and 72 arteries were assessed. The correlation coefficient of FFRCFD with FFR was 0.56. The cut-off value was ≤ 0.80, sensitivity was 59.1%, and specificity was 94.0%. CFD-based FFR using simple boundary conditions for on-site clinical computation provided FFRCFD values that were moderately correlated with invasively measured FFR.

AIMS: Prediction of post-intervention fractional flow reserve (FFR) in a diffuse or sequential coronary lesion is difficult due to complex haemodynamic interactions between individual stenoses. Furthermore, the existence of a residual intra-stent pressure gradient makes the prediction difficult. We developed an equation predicting the post-intervention FFR in a diffuse/sequential lesion by considering intra-stent FFR gradient. The present study aims to validate the equation in an in vitro model and in clinical data. METHODS AND RESULTS: In the in vitro experiment, three sequential coronary stenoses were made with a collateral flow. The correlation coefficient of the predicted FFR and the actual post-intervention FFR was 0.99, and the absolute difference was 0.008±0.006 (n=50). In the clinical data analysis, the correlation coefficient was 0.41, and the absolute difference was 0.06±0.05 (n=67). We applied a fixed value of intra-stent FFR gradient and a collateral flow index so that the equation can be used in clinical practice. The correlation coefficient became 0.28 and the absolute difference became 0.06±0.06. CONCLUSIONS: In clinical practice, prediction of post-intervention FFR in a diffuse/sequential lesion is difficult even when residual intra-stent pressure gradient is considered.

AIMS: We developed a catheter simulator for percutaneous transvenous mitral commissurotomy (PTMC) based on the data from a patient with mitral valve stenosis. The simulator has the following characteristics: 1) the simulator is portable and easy to assemble and disassemble, 2) the cardiac portion is created using a 3D-printer, based on patient computed tomography data, 3) the simulator uses a foot-operated water pump to create pulsatile flow, and 4) the fossa ovalis in the atrial septum of the heart model is made of a thin polyurethane membrane and is interchangeable. We aimed to assess the effectiveness of this novel simulator for training in PTMC using the Inoue balloon in developing countries. METHODS AND RESULTS: We used this simulator for training in the National Institute of Cardiovascular Diseases in Bangladesh (13 physicians), and in Kenyatta National Hospital in Kenya (11 physicians). The effectiveness of training was evaluated by questionnaire and the procedure time in simulation. The questionnaire obtained from the trainees showed that the model scored 4.7±0.5 for realism, utility of pulsatile flow scored 4.7±0.5, simulator utility scored 4.9±0.3, and the effect of training on PTMC performance scored 4.9±0.5. The procedure time in simulation was shortened from 30.0±12.6 min (first time), to 23.4±11.9 min (second time) and to 20.4 ± 11.1 min (third time) (p

Non-invasive fractional flow reserve measured by coronary computed tomography angiography (FFRCT) has demonstrated a high diagnostic accuracy for detecting coronary artery disease (CAD) in selected patients in prior clinical trials. However, feasibility of FFRCT in unselected population have not been fully evaluated. Among 60 consecutive patients who had suspected significant CAD by coronary computed tomography angiography (CCTA) and were planned to undergo invasive coronary angiography, 48 patients were enrolled in this study comparing FFRCT with invasive fractional flow reserve (FFR) without any exclusion criteria for the quality of CCTA image. FFRCT was measured in a blinded fashion by an independent core laboratory. FFRCT value was evaluable in 43 out of 48 (89.6 %) patients with high prevalence of severe calcification in CCTA images [calcium score (CS) >400: 40 %, and CS > 1000: 19 %). Per-vessel FFRCT value showed good correlation with invasive FFR value (Spearman’s rank correlation = 0.69, P 1000), per-vessel FFRCT value showed a diagnostic performance similar to that in patients with CS ≤ 1000 (Spearman’s rank correlation = 0.81, P