村松 崇

Slow-flow or no-reflow phenomenon is a common procedural complication during percutaneous coronary intervention (PCI). Given the presence of fragile plaque or thrombotic materials, we hypothesized that long-time predilatation using a perfusion balloon in conjunction with intracoronary nicorandil administration reduces the risk of slow-flow or no-reflow in patients presenting with acute coronary syndrome (ACS). Subjects were patients presenting with ACS who underwent PCI between April 2020 and April 2022. We retrospectively investigated the incidence of slow-flow or no-reflow during the procedure as well as in-hospital outcomes in comparison between the cases undergoing 3-min predilatation using a perfusion balloon in conjunction with intracoronary nicorandil administration followed by DES implantation (PB group) and those with direct stenting (DS group). Among 439 ACS patients, 36 patients in the PB group and 51 patients in the DS group were examined. Mean age was 70 years and 78.2% was male. Distal protection devices were more frequently used in the DS group than in the PB group (31.3% vs. 11.1%, p = 0.02). The incidence rate of slow-flow or no-reflow was significantly lower in the PB group than in the DS group (2.8% vs. 23.5%; p < 0.01). Six cases (11.7%) in the DS group required intra-aortic balloon pumping (IABP), while none in the PB group required (p < 0.01). In-hospital clinical outcomes did not differ between the two groups. Prolonged perfusion balloon predilatation in conjunction with intracoronary nicorandil administration was safe and feasible. This novel strategy could be an attractive alternative to conventional direct stenting for ACS patients.

The CHA2DS2 -VASc score is a vital clinical tool for evaluating thromboembolic risk in patients with atrial fibrillation (AF). This study investigated the efficacy of the CHA2DS2 -VASc score in a cohort of 737 heterogeneous patients (mean age: 63 years) receiving care in cardiac intensive care units (CICUs), with a creatinine-based estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m2 upon admission and discharge. Incident chronic kidney disease (CKD) was defined as the emergence of a new-onset eGFR<60 mL/min/1.73 m2, accompanied by a decline of >5 mL/min/1.73 m2 compared to that at discharge. The primary endpoint was the incidence of CKD, and the secondary endpoints included all-cause mortality, cardiovascular events, and progression to end-stage kidney disease. In this cohort, 210 (28 %) patients developed CKD. Multivariate analyses revealed that CHA2DS2 -VASc score was a significant independent predictor of incident CKD, regardless of the presence of AF. Integration of CHA2DS2 -VASc scores with eGFR enhanced the predictive accuracy of incident CKD, as evidenced by the improved C-index, net reclassification improvement, and integrated discrimination improvement values (all p < 0.05). Over the 12-month follow-up period, a composite endpoint was observed in 61 patients (8.3 %), with elevated CHA2DS2 -VASc scores being independently associated with this endpoint. In conclusion, CHA2DS2-VASc scores have emerged as robust predictors of both CKD incidence and adverse outcomes. Their inclusion substantially refined the 12-month risk stratification of patients with preserved renal function hospitalized in the CICUs.

OBJECTIVES: Evaluation of in-stent restenosis (ISR), especially for small stents, remains challenging during computed tomography (CT) angiography. We used deep learning reconstruction to quantify stent strut thickness and lumen vessel diameter at the stent and compared it with values obtained using conventional reconstruction strategies. METHODS: We examined 166 stents in 85 consecutive patients who underwent CT and invasive coronary angiography (ICA) within 3 months of each other from 2019-2021 after percutaneous coronary intervention with coronary stent placement. The presence of ISR was defined as percent diameter stenosis ≥ 50% on ICA. We compared a super-resolution deep learning reconstruction, Precise IQ Engine (PIQE), and a model-based iterative reconstruction, Forward projected model-based Iterative Reconstruction SoluTion (FIRST). All images were reconstructed using PIQE and FIRST and assessed by two blinded cardiovascular radiographers. RESULTS: PIQE had a larger full width at half maximum of the lumen and smaller strut than FIRST. The image quality score in PIQE was higher than that in FIRST (4.2 ± 1.1 versus 2.7 ± 1.2, p < 0.05). In addition, the specificity and accuracy of ISR detection were better in PIQE than in FIRST (p < 0.05 for both), with particularly pronounced differences for stent diameters < 3.0 mm. CONCLUSION: PIQE provides superior image quality and diagnostic accuracy for ISR, even with stents measuring < 3.0 mm in diameter. CLINICAL RELEVANCE STATEMENT: With improvements in the diagnostic accuracy of in-stent stenosis, CT angiography could become a gatekeeper for ICA in post-stenting cases, obviating ICA in many patients after recent stenting with infrequent ISR and allowing non-invasive ISR detection in the late phase. KEY POINTS: • Despite CT technology advancements, evaluating in-stent stenosis severity, especially in small-diameter stents, remains challenging. • Compared with conventional methods, the Precise IQ Engine uses deep learning to improve spatial resolution. • Improved diagnostic accuracy of CT angiography helps avoid invasive coronary angiography after coronary artery stenting.

BACKGROUND: The geographical disparity in the pathophysiological pattern of coronary artery disease (CAD) among patients undergoing percutaneous coronary intervention (PCI) is unknown. OBJECTIVES: To elucidate the geographical variance in the pathophysiological characteristics of CAD. METHODS: Physiological indices derived from angiography-based fractional flow reserve pullbacks from patients with chronic coronary syndrome enrolled in the ASET Japan (n = 206) and ASET Brazil (n = 201) studies, which shared the same eligibility criteria, were analysed. The pathophysiological patterns of CAD were characterised using Murray law-based quantitative flow ratio (μQFR)-derived indices acquired from pre-PCI angiograms. The diffuseness of CAD was defined by the μQFR pullback pressure gradient index. RESULTS: Significant functional stenoses pre-PCI (μQFR ≤0.80) were more frequent in ASET Japan compared to ASET Brazil (89.9% vs. 67.5%, p < 0.001), as were rates of a post-PCI μQFR <0.91 (22.1% vs. 12.9%, p = 0.013). In the multivariable analysis, pre-procedural μQFR and diffuse disease were independent factors for predicting a post-PCI μQFR <0.91, which contributed to the different rates of post-PCI μQFR ≥0.91 between the studies. Among vessels with a post-PCI μQFR <0.91, a consistent diffuse pattern of CAD pre- and post-PCI occurred in 78.3% and 76.7% of patients in ASET Japan and Brazil, respectively; only 6.3% (Japan) and 10.0% (Brazil) of vessels had a major residual gradient. Independent risk factors for diffuse disease were diabetes mellitus in ASET Japan, and age and male gender in Brazil. CONCLUSIONS: There was geographic disparity in pre-procedural angiography-based pathophysiological characteristics. The combined pre-procedural physiological assessment of vessel μQFR and diffuseness of CAD may potentially identify patients who will benefit most from PCI.

OBJECTIVE: To examine the clinical outcomes of optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) in patients presenting with ST-segment elevation myocardial infarction (STEMI). METHODS: We retrospectively investigated 533 consecutive patients who underwent primary PCI for STEMI between June 2016 and December 2020. The primary endpoint was a target lesion failure (TLF; defined as a composite of cardiac death, target vessel myocardial infarction, or target lesion revascularization). Propensity score (PS) matching was performed to allow direct comparison of OCT-guided and intravascular ultrasound (IVUS)-guided PCI. RESULTS: Patients in the OCT group (n=166) were younger than those in the IVUS group (n=367) and had a significantly higher left ventricular ejection fraction and estimated glomerular filtration rate. Killip class IV and left main stem disease were more common in the IVUS group. The median peak creatine kinase level was comparable between the two groups (1953 U/L vs 1603 U/L). A significantly larger amount of contrast was used in the OCT group (200 mL vs 165 mL; p<0.001). The cumulative incidence of TLF during a median follow-up of 2.2 years did not differ significantly between OCT and IVUS groups (9.6% vs 13.6%; p=0.221) but cardiac mortality was significantly higher in the IVUS group (8.7% vs 3.6%; p=0.047). After PS matching (n=161 in each group), there was no significant between-group difference in TLF or any other clinical outcome measures. CONCLUSIONS: OCT-guided PCI demonstrated clinical outcomes in patients with STEMI that were comparable to those of IVUS-guided PCI despite considerable differences in background characteristics.

The renal angina index (RAI) is a validated scoring tool for predicting acute kidney injury (AKI). We investigated the efficacy of the RAI in 2436 heterogeneous patients (mean age, 70 years) treated in cardiac intensive care units (CICUs). The RAI was calculated from creatinine and patient condition scores. AKI was diagnosed by the Kidney Disease: Improving Global Outcome criteria. The primary and secondary endpoints were the development of severe AKI and all-cause mortality, respectively. Four hundred thirty-three patients developed AKI, 87 of them severe. In multivariate analyses, the RAI was a significant independent predictor of severe AKI. During the 12-month follow-up period, 210 patients suffered all-cause death. Elevated RAI was independently associated with all-cause mortality, as was NT-proBNP (p < 0.001). The RAI is a potent predictor not only of severe AKI but also of adverse outcomes and substantially improved the 12-month risk stratification of patients hospitalized in CICUs.

BACKGROUND: Even with intracoronary imaging-guided stent optimisation, suboptimal haemodynamic outcomes post-percutaneous coronary intervention (PCI) can be related to residual lesions in non-stented segments. Preprocedural assessment of pathophysiological coronary artery disease (CAD) patterns could help predict the physiological response to PCI. AIMS: The aim of this study was to assess the relationship between preprocedural pathophysiological haemodynamic patterns and intracoronary imaging findings, as well as their association with physiological outcomes immediately post-PCI. METHODS: Data from 206 patients with chronic coronary syndrome enrolled in the ASET-JAPAN study were analysed. Pathophysiological CAD patterns were characterised using Murray law-based quantitative flow ratio (μQFR)-derived indices acquired from pre-PCI angiograms. The diffuseness of CAD was defined by the pullback pressure gradient (PPG) index. Intracoronary imaging in stented segments after stent optimisation was also analysed. RESULTS: In the multivariable analysis, diffuse disease - defined by the pre-PCI μQFR-PPG index - was an independent factor for predicting a post-PCI μQFR <0.91 (per 0.1 decrease of PPG index, odds ratio 1.57, 95% confidence interval: 1.07-2.34; p=0.022), whereas the stent expansion index (EI) was not associated with a suboptimal post-PCI μQFR. Among vessels with an EI ≥80% and post-PCI μQFR <0.91, 84.0% of those vessels had a diffuse pattern preprocedure. There was no significant difference in EI between vessels with diffuse disease and those with focal disease. The average plaque burden in the stented segment was significantly larger in vessels with a preprocedural diffuse CAD pattern. CONCLUSIONS: A physiological diffuse pattern preprocedure was an independent factor in predicting unfavourable immediate haemodynamic outcomes post-PCI, even after stent optimisation using intracoronary imaging. Preprocedural assessment of CAD patterns could identify patients who are likely to exhibit superior immediate haemodynamic outcomes following PCI.

BACKGROUND: Coronary computed tomography angiography (CTA) followed by computed tomography angiography-derived fractional flow reserve (FFRCT) is now commonly used for the management of chronic coronary syndrome (CCS). CTA-verified high-risk plaque (HRP) characteristics have also been reported to be associated with a greater likelihood of adverse cardiac events but have not been used for management decisions. OBJECTIVES: The aim of this study was to evaluate clinical outcomes based on a combination of point-of-care computed tomography angiography-derived fractional flow reserve (POC-FFRCT) and the presence of HRP in CCS patients initially treated medically or with revascularization based on invasive coronary angiography findings. METHODS: CTA was performed as the initial test in 5,483 patients presenting with CCS between September 2015 and December 2020 followed by invasive coronary angiography and revascularization as necessary. POC-FFRCT assessment and HRP characterization were obtained subsequently in 745 consecutive patients. We investigated how HRP and POC-FFRCT, which were not available during the original clinical decision making, correlated with the endpoint defined as a composite of cardiac death, acute coronary syndrome, and a need for unplanned revascularization. RESULTS: Cardiac events occurred in 20 patients (2.7%) during a median follow-up of 744 days. The event rate was significantly higher in patients with POC-FFRCT <0.80 compared with POC-FFRCT ≥0.8 (5.4 vs 0.5 per 100 vessel years; log-rank P < 0.0001) and in patients with HRP compared to those without HRP (3.6 vs 0.8 per 100 vessel years; log-rank P = 0.0001). POC-FFRCT <0.80 and the presence of HRP were the independent predictors of cardiac events (HR: 16.67; 95% CI: 2.63-105.39; P = 0.002) compared with POC-FFRCT ≥0.8 and absent HRP. For the vessels with POC-FFRCT <0.80 and HRP, a significantly higher rate of adverse events was observed in patients who did not undergo revascularization compared with those revascularized (16.4 vs 1.4 per 100 vessel years; log-rank P = 0.006). CONCLUSIONS: POC-FFRCT <0.80 and the presence of HRP were the independent predictors of cardiac events, and revascularization of HRP lesions with abnormal POC-FFRCT was associated with a lower event rate.

BACKGROUND: Left ventricular (LV) global longitudinal strain (GLS) has emerged as a more sensitive index than LV ejection fraction (LVEF) for detecting subclinical LV dysfunction. We examined whether changes in GLS values are associated with the long-term prognosis of patients with a preserved LVEF and acute decompensated heart failure (HF). METHODS: We studied 100 consecutive patients (mean age: 71 years) who were hospitalized for HF with preserved ejection fraction (HFpEF) and had a preserved LVEF (≥ 50%) in both the acute and stable phases. We performed two-dimensional speckle-tracking echocardiography in the acute (GLS-acute) and stable (GLS-stable) phases at a median of 2 and 347 days after admission, respectively, and calculated the rate of change of the absolute value of GLS-stable with respect to that of GLS-acute. An improved GLS was defined as a rate of change in GLS ≥ 16%, and a non-improved GLS was a rate of change < 16%. The primary endpoint was the occurrence of major cardiovascular events (MACE). RESULTS: During a mean follow-up period of 1218 days, MACE occurred in 26 patients, including 8 all-cause deaths and 18 readmissions for HF. The rate of change in GLS for patients with MACE was lower than compared to those without MACE (10.6% vs 26.0%, p < 0.001). Multivariate Cox regression analyses indicated the rate of change in GLS was an independent predictor of MACE (p < 0.001). A non-improved GLS was correlated with a high risk of MACE. CONCLUSION: Changes in GLS values could be useful for the long-term risk stratification of patients hospitalized for HFpEF and persistently preserved LVEF.

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.

BACKGROUND: P2Y12 inhibitor monotherapy without aspirin immediately after percutaneous coronary intervention (PCI) has not been tested in East Asian patients, so in this study we aimed to assess the safety and feasibility of reduced dose (3.75 mg/day) prasugrel monotherapy in Japanese patients presenting with chronic coronary syndrome (CCS).Methods and Results: ASET-JAPAN is a prospective, multicenter, single-arm pilot study that completed enrolment of 206 patients from 12 Japanese centers in September 2022. Patients with native de-novo coronary lesions and a SYNTAX score <23 were treated exclusively with biodegradable-polymer platinum-chromium everolimus-eluting stent(s). Patients were loaded with standard dual antiplatelet therapy (DAPT) and following successful PCI and optimal stent deployment, they received low-dose prasugrel (3.75 mg/day) monotherapy for 3 months. The primary ischemic endpoint was a composite of cardiac death, spontaneous target-vessel myocardial infarction, or definite stent thrombosis. The primary bleeding endpoint was Bleeding Academic Research Consortium (BARC) type 3 or 5. At 3-month follow-up, there were no primary bleeding or ischemic events, or any stent thrombosis. CONCLUSIONS: This pilot study showed the safety and feasibility of prasugrel monotherapy in selected low-risk Japanese patients with CCS. This "aspirin-free" strategy may be a safe alternative to traditional DAPT following PCI.

The Acetyl Salicylic Elimination Trial (ASET) Japan pilot study is a multicentre, single-arm, open-label, proof-of-concept study with a stopping rule based on the occurrence of definite stent thrombosis. This study aims to demonstrate the feasibility and safety of low-dose prasugrel monotherapy following percutaneous coronary intervention (PCI) in Japanese patients presenting with chronic coronary syndromes (CCS) or non-ST-elevation acute coronary syndromes (NSTE-ACS). Four hundred patients with a SYNTAX score <23 requiring PCI due to CCS or NSTE-ACS will be screened and considered eligible for the study. The enrolment is planned in two phases: 1) 200 patients presenting with CCS, followed by 2) 200 patients presenting with NSTE-ACS. After optimal PCI with implantation of a SYNERGY (Boston Scientific) stent, patients will be enrolled and loaded with prasugrel 20 mg, followed by a maintenance dose of prasugrel 3.75 mg once daily without aspirin continued for 3 months in Phase 1 (CCS patients), and for 12 months in Phase 2 (NSTE-ACS patients). After these follow-up periods, prasugrel will be replaced by standard antiplatelet therapy according to local practice. The primary endpoint is a composite of cardiac death, target vessel myocardial infarction, or definite stent thrombosis after the index procedure. The primary bleeding endpoint is any Bleeding Academic Research Consortium type 3 or 5 bleeding occurring within 3 months of the index PCI for CCS patients, or 12 months for NSTE-ACS patients. The ASET Japan study is designed to demonstrate the feasibility and safety of reduced-dose prasugrel monotherapy after PCI in East Asian patients with acute and chronic coronary syndromes.

BACKGROUND: This study compares the efficacy of coronary computed tomography angiography (CCTA) and near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) in patients with significant coronary stenosis for predicting periprocedural myocardial injury during percutaneous coronary intervention (PCI). METHODS: We prospectively enrolled 107 patients who underwent CCTA before PCI and performed NIRS-IVUS during PCI. Based on the maximal lipid core burden index for any 4-mm longitudinal segments (maxLCBI4mm) in the culprit lesion, we divided the patients into two groups: lipid-rich plaque (LRP) group (maxLCBI4mm ≥ 400; n = 48) and no-LRP group (maxLCBI4mm < 400; n = 59). Periprocedural myocardial injury was a postprocedural cardiac troponin T (cTnT) elevation of ≥5 times the upper limit of normal. RESULTS: The LRP group had a significantly higher cTnT (p = 0.026), lower CT density (p < 0.001), larger percentage atheroma volume (PAV) by NIRS-IVUS (p = 0.036), and larger remodeling index measured by both CCTA (p = 0.020) and NIRS-IVUS (p < 0.001). A significant negative linear correlation was found between maxLCBI4mm and CT density (rho = -0.552, p < 0.001). Multivariable logistic regression analysis identified maxLCBI4mm [odds ratio (OR): 1.006, p = 0.003] and PAV (OR: 1.125, p = 0.014) as independent predictors of periprocedural myocardial injury, while CT density was not an independent predictor (OR: 0.991, p = 0.22). CONCLUSION: CCTA and NIRS-IVUS correlated well to identify LRP in culprit lesions. However, NIRS-IVUS was more competent in predicting the risk of periprocedural myocardial injury.

UNLABELLED: There have been few case reports on fatal outcomes in patients with acute myocarditis after mRNA coronavirus disease 2019 (COVID-19) vaccination. In most cases of myocarditis after mRNA COVID-19 vaccination, the myocarditis is mild, and the prognosis is good. Here we report an autopsy case of fulminant myocarditis following mRNA COVID-19 vaccination. LEARNING OBJECTIVE: The global distribution of the mRNA coronavirus disease 2019 vaccine requires consideration of appropriate treatment for postvaccination myocarditis. Eosinophil-mediated immunological injury to cardiomyocytes can be involved in the cause of fulminant inflammation from the pathological findings of postvaccination myocarditis.

It remains unclear whether the acute-phase ambulation program (AAP) improves the prognosis of heart failure (HF) patients. We examined the association between the initiation of AAP and the prognosis of patients with worsening HF. We enrolled 560 consecutive patients admitted due to worsening HF from March 2019 to April 2021. Our hospital introduced AAP in May 2020, but we did not perform AAP until April 2020. We retrospectively compared cardiac events within 180 days after discharge between patients admitted before April 2020 (conventional group) and after May 2020 (AAP group). Primary endpoints were all-cause mortality and readmission for worsening HF. The Kaplan-Meier survival curves showed a significantly lower event rate in the AAP group in HF readmission or the primary endpoint (p = 0.020 and p = 0.014). The occurrence of the primary endpoint was associated with age, history of HF, systolic blood pressure, medications including renin-angiotensin system inhibitors or angiotensin receptor blocker, hemoglobin, NT-proBNP, and AAP participation. After adjusting for these parameters and sex, participation in AAP was an independent factor associated with a reduced risk of primary endpoint occurrence (hazard ratio of 0.62 (0.41-0.95), p = 0.028). The AAP for patients with acute HF might lead to improved short-term prognosis and should be considered for implementation.

Aims: We examined in-hospital outcomes of patients that required mechanical circulatory support (MCS), such as intra-aortic balloon pumping (IABP), Impella®, or veno-arterial extracorporeal membrane oxygenation (VA-ECMO), for elective percutaneous coronary interventions (PCIs). Methods and results: The J-PCI is a prospective Japanese nationwide multicentre registry sponsored by the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) and designed to collect clinical variables and in-hospital outcome data on consecutive patients undergoing PCI. Of the 253 228 patients registered between January 2018 and December 2018, 1627 patients (0.6%) undergoing elective PCI under MCS at 551 sites were analyzed. The mean age of the patients was 74 years, and 25.2% of the patients were females. Multivessel disease and left main disease were observed in 59.0% and 19.7% of the patients, respectively. Majority of patients were treated with IABP alone (86.2%), followed by IABP plus VA-ECMO (6.0%) and Impella alone (3.9%). In-hospital mortality was reported in 134 patients (8.2%). Cardiac death was more common than non-cardiac death (6.8% vs. 1.5%). About 34.6% of the patients receiving VA-ECMO died during hospitalization, whereas 7.2% and 5.3% of patients receiving Impella and IABP died, respectively (P < 0.01). The proportion of patients with VA-ECMO or Impella who had major bleeding requiring blood transfusion was higher than that of patients with IABP (14.1% vs. 13.0% vs. 2.8%). Conclusion: In the setting of elective PCI, in-hospital mortality of patients requiring MCS was considerably high. VA-ECMO or Impella was associated with a higher risk of major bleeding than IABP.

Primary Percutaneous Coronary Intervention (PCI) has significantly contributed to reducing the mortality of patients with ST-segment elevation myocardial infarction (STEMI) even in cardiogenic shock and is now the standard of care in most of Japanese institutions. The Task Force on Primary PCI of the Japanese Association of Cardiovascular Interventional and Therapeutics (CVIT) society proposed an expert consensus document for the management of acute myocardial infarction (AMI) focusing on procedural aspects of primary PCI in 2018. Updated guidelines for the management of AMI were published by the European Society of Cardiology (ESC) in 2017 and 2020. Major changes in the guidelines for STEMI patients included: (1) radial access and drug-eluting stents (DES) over bare-metal stents (BMS) were recommended as a Class I indication, (2) complete revascularization before hospital discharge (either immediate or staged) is now considered as Class IIa recommendation. In 2020, updated guidelines for Non-ST-Elevation Myocardial Infarction (NSTEMI) patients, the followings were changed: (1) an early invasive strategy within 24 h is recommended in patients with NSTEMI as a Class I indication, (2) complete revascularization in NSTEMI patients without cardiogenic shock is considered as Class IIa recommendation, and (3) in patients with atrial fibrillation following a short period of triple antithrombotic therapy, dual antithrombotic therapy (e.g., DOAC and single oral antiplatelet agent preferably clopidogrel) is recommended, with discontinuation of the antiplatelet agent after 6 to 12 months. Furthermore, an aspirin-free strategy after PCI has been investigated in several trials those have started to show the safety and efficacy. The Task Force on Primary PCI of the CVIT group has now proposed the updated expert consensus document for the management of AMI focusing on procedural aspects of primary PCI in 2022 version.

INTRODUCTION: The optimal antithrombotic strategy for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) is uncertain. For patients with non-AF, many trials are now evaluating short 1-month dual antiplatelet therapy. In patients with AF undergoing PCI, in contrast, short dual therapy (P2Y12 inhibitor +direct oral anticoagulant (DOAC)) has not yet been evaluated. METHODS AND ANALYSIS: The OPTIMA-AF trial (OPTIMAl antiplatelet therapy in combination with direct oral anticoagulants in patients with non-valvular Atrial Fibrillation undergoing percutaneous coronary intervention with everolimus-eluting stent) is an investigator-initiated, open-label, nationwide, multicentre, prospective, randomised controlled trial. The primary objective is to compare the efficacy and safety of short dual therapy (1-month DOAC +P2Y12 inhibitor followed by DOAC monotherapy) against long dual therapy (12-month DOAC +P2Y12 inhibitor followed by DOAC monotherapy) in the treatment of AF subjects undergoing PCI. The primary efficacy endpoint is a composite of death or thromboembolic events (myocardial infarction, definite stent thrombosis, stroke or systemic embolism) at 365 days; and the primary safety endpoint is bleeding (International Society on Thrombosis and Haemostasis major or clinically relevant non-major bleeding) at 365 days. This trial is intended to show the non-inferiority of short dual therapy versus long dual therapy in terms of the primary efficacy endpoint and show superiority in terms of the primary safety endpoint. A total of 1090 subjects will be randomised in a 1:1 ratio at approximately 60 sites. ETHICS AND DISSEMINATION: This study received approval from the Certified Review Board of Osaka University (a certified research ethics committee by the Japanese Clinical Research Act). The findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: Japan Registry of Clinical Trials: jRCTs051190053; Pre-results.

AIM: We investigated the relationship between small dense low-density cholesterol (sdLDL-C) and risk of major adverse cardiovascular events (MACE) in patients treated with high- or low-dose statin therapy. METHODS: This was a prospective case-cohort study within the Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study, a randomized trial of high- or low-dose (4 or 1 mg/d pitavastatin, respectively) statin therapy, in patients with stable coronary artery disease (CAD). Serum sdLDL-C was determined using an automated homogenous assay at baseline (randomization after a rule-in period, ＞1 month with 1 mg/d pitavastatin) and 6 months after randomization, in 497 MACE cases, and 1543 participants randomly selected from the REAL-CAD study population. RESULTS: High-dose pitavastatin reduced sdLDL-C by 20% than low-dose pitavastatin (p for interaction ＜0.001). Among patients receiving low-dose pitavastatin, baseline sdLDL-C demonstrated higher MACE risk independent of LDL-C (hazard ratio [95% confidence interval], 4th versus 1st quartile, 1.67 [1.04-2.68]; p for trend=0.034). High-dose (versus low-dose) pitavastatin reduced MACE risk by 46% in patients in the highest baseline sdLDL-C quartile (＞34.3 mg/dL; 0.54 [0.36-0.81]; p=0.003), but increased relative risk by 40% in patients with 1st quartile (≤ 19.5 mg/dL; 1.40 [0.94-2.09]; p=0.099) and did not alter risk in those in 2nd and 3rd quartiles (p for interaction=0.002). CONCLUSIONS: These findings associate sdLDL-C and cardiovascular risk, independent of LDL-C, in statin-treated CAD patients. Notably, high-dose statin therapy reduces this risk in those with the highest baseline sdLDL-C.

The outbreak of coronavirus disease 19 (COVID-19) has had a great impact on medical care. During the COVID-19 pandemic, the rate of hospital admissions has been lower and the rate of in-hospital mortality has been higher in patients with acute coronary syndrome (ACS) in Western countries. However, in Japan, it is unknown whether the COVID-19 pandemic has affected the incidence of ACS. In the study, eleven hospitals in the Tokai region participated. Among enrolled hospital, we compared the incidence of ACS during the COVID-19 pandemic (April and May, 2020) with that in equivalent months in the preceding year as the control. During the study period; April and May 2020, 248 patients with ACS were admitted. Compared to April and May 2019, a decline of 8.1% [95% confidence interval (CI) 5.2-12.1; P = 0.33] in admissions for ACS was observed between April and May 2020. There was no significant difference in the strategy for revascularization and in-hospital deaths between 2019 and 2020. In conclusion, the rate of admission for ACS slightly decreased during the COVID-19 pandemic, compared to the same months in the preceding year. Moreover, degeneration of therapeutic procedures for ACS did not occur.

The prognostic role of D-dimer in different types of heart failure (HF) is poorly understood. We investigated the prognostic value of D-dimer on admission, both independently and in combination with the Get With The Guidelines-Heart Failure (GWTG-HF) risk score and N-terminal pro-B-type natriuretic peptide (NT-proBNP), in patients with preserved left ventricular ejection fraction (LVEF) and acute decompensated HF (HFpEF) or reduced LVEF (HFrEF). Baseline D-dimer levels were measured on admission in 1670 patients (mean age: 75 years) who were hospitalized for worsening HF. Of those patients, 586 (35%) were categorized as HFpEF (LVEF ≥ 50%) and 1084 as HFrEF (LVEF < 50%). During the 12-month follow-up period after admission, 360 patients died. Elevated levels (at least the highest tertile value) of D-dimer, GWTG-HF risk score, and NT-proBNP were all independently associated with mortality in all HFpEF and HFrEF patients (all p < 0.05). Adding D-dimer to a baseline model with a GWTG-HF risk score and NT-proBNP improved the net reclassification and integrated discrimination improvement for mortality greater than the baseline model alone in all populations (all p < 0.001). The number of elevations in D-dimer, GWTG-HF risk score, and NT-proBNP were independently associated with a higher risk of mortality in all study populations (HFpEF and HFrEF patients; all p < 0.001). The combination of D-dimer, which is independently predictive of mortality, with the GWTG-HF risk score and NT-proBNP could improve early prediction of 12-month mortality in patients with acute decompensated HF, regardless of the HF phenotype.

The aim of the present study was to examine the association of myocardial mass verified by computed tomography (CT) and invasive fractional flow reserve (FFR)-verified myocardial ischemia, or subsequent therapeutic strategy for the targeted vessels after FFR examination. We examined 333 vessels with intermediate stenoses in 297 patients (mean age 69.0 ± 9.5, 228 men) undergoing both coronary CT angiography and invasive FFR, and reviewed the therapeutic strategy after FFR. Of 333 vessels, FFR ≤ 0.80 was documented in 130 (39.0%). Myocardial volume supplied by the target vessel (MVT) was larger in those with FFR-verified ischemia than those without (53.4 ± 19.5 vs. 42.9 ± 22.2 cm3, P < 0.001). Addition of MVT to a model including patient characteristics (age, gender), visual assessment (≥ 70% stenosis, high-risk appearance), and quantitative CT vessel parameters [minimal lumen area (MLA), plaque burden at MLA, percent aggregate plaque volume] improved C-index (from 0.745 to 0.778, P = 0.020). Furthermore, of 130 vessels with FFR ≤ 0.80, myocardial volume exposed to ischemia (MVI) was larger in the vessels with early revascularization after FFR examination than those without (37.2 ± 20.0 vs. 26.8 ± 15.0 cm3, P = 0.003), and was independently associated with early revascularization [OR = 1.03, 95% confidence interval (1.02-1.11), P < 0.001]. Using an on-site CT workstation, MVT identified coronary arteries with FFR-verified ischemia easily and non-invasively, and MVI was associated with subsequent therapeutic strategy after FFR examinations.

BACKGROUND: The impact of chronic kidney disease (CKD) on long-term outcomes following acute myocardial infarction (AMI) in the era of modern primary PCI with optimal medical therapy is still in debate.Methods and Results:A total of 3,281 patients with AMI were enrolled in the J-MINUET registry, with primary PCI of 93.1% in STEMI. CKD stage on admission was classified into: no CKD (eGFR ≥60 mL/min/1.73 m2); moderate CKD (60>eGFR≥30 mL/min/1.73 m2); and severe CKD (eGFR <30 mL/min/1.73 m2). While the primary endpoint was all-cause mortality, the secondary endpoint was major adverse cardiac events (MACE), defined as a composite of all-cause death, cardiac failure, myocardial infarction (MI) and stroke. Of the 3,281 patients, 1,878 had no CKD, 1,073 had moderate CKD and 330 had severe CKD. Pre-person-days age- and sex-adjusted in-hospital mortality significantly increased from 0.014% in no CKD through 0.042% in moderate CKD to 0.084% in severe CKD (P<0.0001). Three-year mortality and MACE significantly deteriorated from 5.09% and 15.8% in no CKD through 16.3% and 38.2% in moderate CKD to 36.7% and 57.9% in severe CKD, respectively (P<0.0001). C-index significantly increased from the basic model of 0.815 (0.788-0.841) to 0.831 (0.806-0.857), as well as 0.731 (0.708-0.755) to 0.740 (0.717-0.764) when adding CKD stage to the basic model in predicting 3-year mortality (P=0.013; net reclassification improvement [NRI] 0.486, P<0.0001) and MACE (P=0.046; NRI 0.331, P<0.0001) respectively. CONCLUSIONS: CKD remains a useful predictor of in-hospital and 3-year mortality as well as MACE after AMI in the modern PCI and optimal medical therapy era.

BACKGROUND: Clinical implications of online 3-dimensional optical frequency domain imaging (3D-OFDI)-guided stenting for bifurcation lesions have not been investigated in the randomized controlled trials. The purpose of this study was to determine whether online 3D-OFDI-guided stenting is superior to angiography-guided percutaneous coronary intervention (PCI) in terms of incomplete stent apposition at the bifurcation segment. METHODS: The OPTIMUM trial (Online 3-Dimensional Optical Frequency Domain Imaging to Optimize Bifurcation Stenting Using UltiMaster Stent) was a randomized, multicenter clinical trial. Eligible patients had an angiographically significant stenosis in the bifurcation lesion treated with a provisional single stent strategy using the Ultimaster sirolimus eluting stent. Patients were randomly allocated to either online 3D-OFDI-guided or angiography-guided PCI. Patients randomized to 3D-OFDI guidance underwent online 3D-OFDI assessment after rewiring into the jailed side branch after stenting and proximal optimization technique, while in the angiography guidance arm, rewiring was performed using conventional fluoroscopic/angiographic guidance. The primary end point of this trial was the postprocedural average percentage of malapposed struts per lesion assessed by OFDI in the confluence zone of the main and side branches. RESULTS: Between June 8, 2017 and September 26, 2018, 110 patients with 111 bifurcation lesions were randomized at 4 Japanese centers. Of these, 56 patients with 57 lesions were treated with 3D-OFDI-guided PCI, whereas 54 patients with 54 lesions were treated with angiography-guided PCI. In the 3D-OFDI guidance arm, the feasibility of online 3D-OFDI was 98.2%. The average percentage of incomplete stent apposition per lesion at bifurcation was lower in the 3D-OFDI guidance arm than that in the angiography guidance arm (19.5±15.8% versus 27.5±14.2%, P=0.008). The superiority of the 3D-OFDI guidance arm was also confirmed in the strut level analysis (odds ratio: 0.54 [95% CI, 0.36-0.81]; P=0.003). CONCLUSIONS: Online 3D-OFDI-guided bifurcation PCI was superior to angiography-guided bifurcation PCI in terms of acute incomplete stent apposition at bifurcation. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02972489.

BACKGROUND: Given the characteristic differences between intravascular ultrasound (IVUS) and optical frequency domain imaging (OFDI), their approach to therapeutic guidance during percutaneous coronary interventions (PCIs) and arterial healing response after stenting may also vary. METHODS: MISTIC-1 (The Multimodality Imaging Study in Cardiology cohort 1) is a multicenter, randomized-controlled, noninferiority trial that compared imaging end points between OFDI- and IVUS-guided PCI. Patients with stable coronary artery disease were randomly assigned to either OFDI- or IVUS-guided PCI using a Biolimus A9-eluting stent according to a prespecified protocol for imaging guidance. Stent sizing was based on external elastic lamina in IVUS-guided PCI while lumen up-size in OFDI-guided PCI. Postprocedural OFDI was investigated regardless of randomization, while operators in IVUS-guided PCI arm were blinded to the images. The primary end point was in-segment minimum lumen area assessed using OFDI at 8 months, while the secondary end point was a composite of cardiovascular mortality, target-vessel myocardial infarction, or target-lesion revascularization (device-oriented composite end point). Patients were followed up to 3 years after the index procedure. RESULTS: A total of 109 patients (mean age 70 years, male 78%) with 126 lesions were enrolled. Postprocedural minimum stent area was 6.31±1.89 and 6.72±2.08 mm2 in OFDI and IVUS group, respectively (P=0.26). At the 8-month follow-up, in-segment minimum lumen area was 4.56±1.94 and 4.13±1.86 mm2 in OFDI and IVUS group, respectively (Pnon-inferiority <0.001). Both groups had comparable neointimal healing score (median 0.16 [interquartile range, 0.00-3.14] versus 0.90 [0.00-3.30], respectively; P=0.43). The incidence rate of device-oriented composite end point at 3 years was 7.4% and 7.3% in OFDI and IVUS group, respectively (hazard ratio, 1.05 [95% CI, 0.26-4.18]; P=0.95). CONCLUSIONS: OFDI-guided PCI was not inferior to IVUS-guided PCI in terms of in-segment minimum lumen area at 8 months. Although a small sample size was acknowledged, OFDI could be an alternative to IVUS when considering intracoronary imaging-guided PCI in selected populations with coronary artery diseases. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03292081.

Myocardial perfusion imaging (MPI) using Single Photon Emission Computed Tomography has been established as a standard noninvasive tool for risk stratification of coronary artery disease (CAD). We evaluated the diagnostic performance of on-site workstation-based computed tomography-derived fractional flow reserve (CT-FFR) in comparison with MPI using invasive fractional flow reserve (invasive FFR) as a gold standard. We enrolled 97 patients with suspected CAD. Diagnostic performance of CT angiography (CTA), and CT-FFR was compared in 105 lesions of 97 patients. Invasive FFR ≤ 0.8 was detected in 38 (36%) lesions. Diagnostic performance of CT-FFR was improved compared with CTA (AUC 0.83 vs. 0.60, p < 0.0001). The lesions with both CTA and MPI findings (n = 47), invasive FFR ≤ 0.8 was detected in 19 (40.4) lesions. CT-FFR (AUC 0.81, 95% CI 0.72-0.94) significantly improved diagnostic performance compared with CTA-50% (AUC 0.59, p = 0.00019) and MPI (AUC 0.64, p = 0.0082). In lesions with ≥ 50% on CTA (n = 42), diagnostic accuracy of CT-FFR (AUC 0.81) was significantly superior to MPI (AUC 0.64, p = 0.0239). In conclusions, CT-FFR improved diagnostic accuracy to detect invasive FFR ≤ 0.8 compared with luminal stenosis on CTA and ischemia on MPI. Patients with ≥ 50% stenosis on CTA would be the candidates for CT-FFR.

We prospectively investigated the prognostic value of urinary liver-type fatty-acid-binding protein (L-FABP) levels on hospital admission, both independently and in combination with serum creatinine-defined acute kidney injury (AKI), to predict long-term adverse outcomes in 1119 heterogeneous patients (mean age; 68 years) treated at medical (non-surgical) cardiac intensive care units (CICUs). Patients with stage 5 chronic kidney disease were excluded from the study. Of these patients, 47% had acute coronary syndrome and 38% had acute decompensated heart failure. The creatinine-defined AKI was diagnosed according to the "Kidney Disease: Improving Global Outcomes" criteria. The primary endpoint was a composite of all-cause death or progression to end-stage kidney disease, indicating the initiation of maintenance dialysis therapy or kidney transplantation. Creatinine-defined AKI occurred in 207 patients, with 44 patients having stage 2 or 3 disease. During a mean follow-up period of 41 months after enrollment, the primary endpoint occurred in 242 patients. Multivariate Cox regression analyses revealed L-FABP levels as independent predictors of the primary endpoint (p < 0.001). Adding L-FABP to a baseline model with established risk factors further enhanced reclassification and discrimination beyond that of the baseline model alone, for primary-endpoint prediction (both; p < 0.01). On Kaplan-Meier analyses, increased L-FABP (≥4th quintile value of 9.0 ng/mL) on admission or presence of creatinine-defined AKI, correlated with an increased risk of the primary endpoint (p < 0.001). Thus, urinary L-FABP levels on admission are potent and independent predictors of long-term adverse outcomes, and they might improve the long-term risk stratification of patients admitted at medical CICUs, when used in combination with creatinine-defined AKI.

OBJECTIVES: We sought to examine associations between plaque characteristics by intravascular ultrasound (IVUS) and detectability of external elastic lamina (EEL) by optical frequency domain imaging (OFDI) in human coronary arteries. BACKGROUND: It is often challenging to detect EEL which represents vessel size by light-based imaging modalities due to light intensity attenuation through atherosclerotic plaque. METHODS: IVUS and OFDI prior to stent implantation were sequentially investigated per protocol. We identified corresponding cross-sections by minimum lumen area (MLA) or just distally to side branches as anatomical landmarks. Plaque characterization was determined by integrated backscatter IVUS analysis. We categorized detectable EEL arc by OFDI into four groups: 0≤ and <1 quadrant (group 1), 1≤ and <2 quadrants (group 2), 2≤ and <3 quadrants (group 3), or 3≤ and <4 quadrants (group 4). RESULTS: We prospectively studied 103 vessels in 93 patients with stable coronary artery disease. Corresponding 711 cross-sections were analyzed. Cross-sections with detectable EEL arc <2 quadrants (group 1 or 2) were observed in 86.1% of MLA sites but only in 29.3% of non-MLA sites (p < .05). Percentage plaque area (%PA) appeared to be the strongest predictor to detect EEL arc <2 quadrants with the cut-off of 60.3% (AUC 0.90; sensitivity 79.8%, specificity 85.5%). Lipid pool and calcification remained statistically significant in predicting detectable EEL arc <2 quadrants after adjustment with %PA. CONCLUSIONS: Presence of large plaque burden, lipid pool, and calcification significantly predicts the detectability of EEL by OFDI assessment. Locations with detectable EEL arc <2 quadrants should thus be avoided for optimal stent landing zone.

BACKGROUND: The early prediction of acute kidney injury (AKI) can facilitate timely intervention and prevent complications. We aimed to understand the predictive value of urinary liver-type fatty-acid binding protein (L-FABP) levels on admission to medical (non-surgical) cardiac intensive care units (CICUs) for AKI, both independently and in combination with serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. METHODS: We prospectively investigated the predictive value of L-FABP and NT-proBNP for AKI in a large, heterogeneous cohort of patients treated in medical CICUs. Baseline urinary L-FABP and serum NT-proBNP were measured on admission. AKI was diagnosed according to the Kidney Disease: Improving Global Outcomes criteria. We studied 1273 patients (mean age, 68 years), among whom 46% had acute coronary syndromes, 38% had acute decompensated heart failure, 5% had arrhythmia, 3% had pulmonary hypertension, 2% had acute aortic syndrome, 2% had infective endocarditis, and 1% had Takotsubo cardiomyopathy. RESULTS: Urinary L-FABP levels correlated with serum NT-proBNP levels (r = 0.17, p < 0.0001). AKI occurred in 224 patients (17.6%), including 48 patients with stage 2 or 3 disease. Patients who developed AKI had higher one-week and 6-month mortality than those who did not develop AKI (p = 0.0002 and p = 0.003, respectively). In the multivariate logistic analysis, both L-FABP (p < 0.0001) and NT-proBNP (p = 0.006) were independently associated with the development of AKI. Adding L-FABP and NT-proBNP to a baseline model that included established risk factors further improved reclassification (p < 0.001) and discrimination (p < 0.01) beyond that of the baseline model or any single biomarker individually. CONCLUSIONS: Urinary L-FABP and serum NT-proBNP levels on admission are independent predictors of AKI, and when used in combination, improve early prediction of AKI in patients hospitalized at medical CICUs.

Objectives: To compare visual estimation with different quantitative coronary angiography (QCA) methods (single-vessel versus bifurcation software) to assess coronary bifurcation lesions. Background: QCA has been developed to overcome the limitations of visual estimation. Conventional QCA however, developed in “straight vessels,” has proved to be inaccurate in bifurcation lesions. Therefore, bifurcation QCA was developed. However, the impact of these different modalities on bifurcation lesion severity classification is yet unknown. Methods: From a randomized controlled trial investigating a novel bifurcation stent (Clinicaltrials.gov NCT01258972), patients with baseline assessment of lesion severity by means of visual estimation, single-vessel QCA, 2D bifurcation QCA and 3D bifurcation QCA were included. We included 113 bifurcations lesions in which all 5 modalities were assessed. The primary end-point was to evaluate how the different modalities affected the classification of bifurcation lesion severity and extent of disease. Results: On visual estimation, 100% of lesions had side-branch diameter stenosis (%DS) &gt 50%, whereas in 83% with single-vessel QCA, 27% with 2D bifurcation QCA and 26% with 3D bifurcation QCA a side-branch %DS &gt 50% was found (P &lt 0.0001). With regard to the percentage of “true” bifurcation lesions, there was a significant difference between visual estimate (100%), single-vessel QCA (75%) and bifurcation QCA (17% with 2D bifurcation software and 13% with 3D bifurcation software, P &lt 0.0001). Conclusions: Our study showed that bifurcation lesion complexity was significantly affected when more advanced bifurcation QCA software were used. “True” bifurcation lesion rate was 100% on visual estimation, but as low as 13% when analyzed with dedicated bifurcation QCA software.

While primary percutaneous coronary intervention (PCI) has significantly contributed to improve the mortality in patients with ST segment elevation myocardial infarction even in cardiogenic shock, primary PCI is a standard of care in most of Japanese institutions. Whereas there are high numbers of available facilities providing primary PCI in Japan, there are no clear guidelines focusing on procedural aspect of the standardized care. Whilst updated guidelines for the management of acute myocardial infarction were recently published by European Society of Cardiology, the following major changes are indicated; (1) radial access and drug-eluting stent over bare metal stent were recommended as Class I indication, and (2) complete revascularization before hospital discharge (either immediate or staged) is now considered as Class IIa recommendation. Although the primary PCI is consistently recommended in recent and previous guidelines, the device lag from Europe, the frequent usage of coronary imaging modalities in Japan, and the difference in available medical therapy or mechanical support may prevent direct application of European guidelines to Japanese population. The Task Force on Primary Percutaneous Coronary Intervention of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) has now proposed the expert consensus document for the management of acute myocardial infarction focusing on procedural aspect of primary PCI.