北原 秀喜

Patients with epicardial coronary vasospastic angina (VSA) may be likely to have coronary microvascular dysfunction, although mixed results have been reported. The aim of this study was to evaluate coronary microvascular function in detail using novel invasive physiologic indices, such as resistive reserve ratio (RRR) and microvascular resistance reserve (MRR). A total of 45 patients undergoing intracoronary acetylcholine (ACh) provocation test and invasive coronary circulatory evaluation using a thermodilution method were prospectively included. VSA was diagnosed as angiographic vasospasm accompanied by chest pain and/or ischemic electrocardiographic changes by intracoronary injection of ACh. Coronary circulation was assessed with physiologic indices including fractional flow reserve, resting and hyperemic mean transit time (Tmn), coronary flow reserve (CFR), basal resistance index, index of microcirculatory resistance (IMR), RRR, and MRR. Of 45 patients, 23 (51.1%) were diagnosed as having VSA. Patients with positive ACh test had longer resting Tmn (slower coronary flow velocity), higher basal resistance index, and greater RRR and MRR than those without, while fractional flow reserve, CFR, and IMR did not differ significantly between the two groups. In conclusion, although conventional measures such as CFR and IMR failed to show significant differences, RRR and MRR, novel invasive coronary physiologic indices, provided counterintuitive insights that coronary microvascular dilation function was better preserved in patients with VSA than those without.

This study sought to investigate the relationship between physiological severity and plaque vulnerability of intermediate coronary artery stenoses as assessed by fractional flow reserve (FFR) and near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). We included vessels where both FFR and NIRS-IVUS were performed. A positive FFR was defined as FFR ≤ 0.80. Lipid core burden index of the entire target vessel (TV-LCBI), maximum LCBI in 4 mm (maxLCBI4mm), and maximum plaque burden (PB) were evaluated using NIRS-IVUS. A vulnerable plaque was defined as a lipid-rich plaque (maxLCBI4mm ≥ 400) with large PB (≥ 70%). A total of 59 vessels of 45 patients were included. Median FFR value was 0.75 [interquartile 0.72, 0.82]. An FFR value of ≤ 0.80 was observed in 42 vessels (71%). TV-LCBI (correlation coefficient [CC] = - 0.331, p = 0.011), lesion length (CC = - 0.350, p = 0.007), and PB (CC = - 0.230, p = 0.080) negatively correlated with FFR value, while maxLCBI4mm did not (CC = - 0.156, p = 0.24). The prevalence of vulnerable plaques (26.2% vs. 29.4%, p > 0.99) and mean TV-LCBI, maxLCBI4mm, and PB values were not significantly different between the vessels with FFR ≤ 0.80 and those with FFR > 0.80. In multivariable logistic models, diabetes mellitus (p = 0.003) and hemoglobin A1c (p = 0.012) were associated with the presence of a vulnerable plaque. In conclusion, the results of the present study suggested that FFR may reflect total lipid burden but not necessarily plaque vulnerability. In patients with coronary artery disease and a high likelihood of rapid atherosclerosis progression, such as diabetes mellitus patients, assessing plaque vulnerability in addition to the functional severity of coronary artery lesions may help stratify better the risk of future events.

Antithrombotic therapy including antiplatelet agents and anticoagulants are prescribed for secondary prevention in patients with established cardiovascular disease. Although antithrombotic therapy is often interrupted before non-cardiac surgery with or without perioperative bridging anticoagulation, the impact on thrombotic and bleeding events remains uncertain. A total of 360 patients chronically treated with antithrombotic therapy for secondary prevention underwent elective non-cardiac surgery under general anesthesia, with the complete interruption of antithrombotic agents. The study endpoints included all-cause death, thrombotic events, and major bleeding complications after surgical procedures. Of 360 patients, 190 (52.8%) and 200 (55.6%) received antiplatelet and anticoagulation perioperatively. Atrial fibrillation (32.8%) and coronary artery disease (22.5%) were the major indications for antithrombotic regimens. Antithrombotic therapy was interrupted from 5 [2, 7] days before the surgery to 4 [2, 7] days postoperatively. Perioperative bridging therapy with unfractionated heparin was employed in 113 (31.4%) patients. During the hospitalization, one (0.3%) patient died due to non-cardiovascular causes. Thrombotic events and major bleeding occurred in two (0.6%) and eight (2.2%) patients. Bridging therapy with heparin was significantly associated with an increased risk of bleeding events (5.3% vs. 0.8%, p = 0.02). Pre-operative bridging therapy with heparin and operative duration were significantly associated with bleeding complications. In the present study, complete interruption of antithrombotic therapy resulted in a few thrombotic events in patients undergoing elective non-cardiac surgery. Bridging therapy with heparin and longer operative duration were significantly associated with post-operative bleeding complications.

Objective Oral diseases, including periodontitis and stomatitis, are highly prevalent worldwide and reportedly associated with the development of cardiovascular disease. Given the high rate of stomatitis in individuals wearing dentures, denture users may be at high risk of poor cardiovascular outcomes. We therefore investigated whether or not the use of dentures is associated with a poor clinical outcome in patients with acute myocardial infarction (MI). Methods This two-center retrospective observational study was conducted between January 2012 and March 2020. A total of 1,046 patients with acute MI who underwent primary percutaneous coronary intervention were divided into two groups according to denture use status. The primary outcomes included ischemic events (cardiovascular death, recurrent MI, and ischemic stroke) and major bleeding (Bleeding Academic Research Consortium type 3 or 5). Results Of the 1,046 patients with acute MI, 387 (37.0%) used dentures. An older age and prior MI were associated with an increased likelihood of denture use. During the mean 660-day follow-up period, ischemic and major bleeding events occurred in 169 (16.2%) and 102 (9.8%) patients, respectively. Denture use was associated with an increased risk of ischemic events, whereas no significant intergroup differences were observed in major bleeding outcomes. The results were similar among patients ≥75 years old. Conclusion More than one-third of the patients with acute MI wore dentures. Our findings suggest that denture use is significantly associated with an increased risk of ischemic events but not bleeding outcomes after acute MI.

Patients with vasospastic angina (VSA) who are resuscitated from sudden cardiac arrest (SCA) are at a high risk of recurrent lethal arrhythmia and cardiovascular events. However, the benefit of the implantable cardioverter-defibrillator (ICD) therapy in this population has not been fully elucidated. The present study aimed to analyze the prognostic impact of ICD therapy on patients with VSA and SCA. A total of 280 patients who were resuscitated from SCA and received an ICD for secondary prophylaxis were included in the present multicenter registry. The patients were divided into two groups on the basis of the presence of VSA. The primary endpoint was a composite of all-cause death and appropriate ICD therapy (appropriate anti-tachycardia pacing and shock) for recurrent ventricular arrhythmias. Of 280 patients, 51 (18%) had VSA. Among those without VSA, ischemic cardiomyopathy was the main cause of SCA (38%), followed by non-ischemic cardiomyopathies (18%) and Brugada syndrome (7%). Twenty-three (8%) patients were dead and 72 (26%) received appropriate ICD therapy during a median follow-up period of 3.8 years. There was no significant difference in the incidence of the primary endpoint between patients with and without VSA (24% vs. 33%, p = 0.19). In a cohort of patients who received an ICD for secondary prophylaxis, long-term clinical outcomes were not different between those with VSA and those with other cardiac diseases after SCA, suggesting ICD therapy may be considered in patients with VSA and those with other etiologies who were resuscitated from SCA.

BACKGROUND: Triple antithrombotic therapy, including dual antiplatelet therapy and oral anticoagulant (OAC), is recommended for a short-term period after percutaneous coronary intervention (PCI) in patients requiring anticoagulation therapy. The purpose of this study was to compare in-hospital clinical outcomes between low-dose prasugrel (3.75 mg/day) and clopidogrel, as part of triple antithrombotic therapy, using a large database in Japan. METHODS: Patients with ischemic heart disease who underwent PCI between January 2015 and December 2019, and were prescribed triple therapy with aspirin, a P2Y12 inhibitor (clopidogrel or low-dose prasugrel), and OAC (direct oral anticoagulant: DOAC or vitamin K antagonist: VKA), were selected from the Diagnosis Procedure Combination database. The primary outcome was in-hospital mortality. The secondary outcomes were myocardial infarction, ischemic stroke, bleeding stroke, gastrointestinal bleeding, and blood transfusion. RESULTS: Overall, 5,777 patients were eligible in this analysis. The patients were divided into 4 subgroups according to the type of P2Y12 inhibitor and OAC: clopidogrel/DOAC (n = 1,628), clopidogrel/VKA (n = 1,334), prasugrel/DOAC (n = 1,607), and prasugrel/VKA (n = 1,208). There was no significant difference in the incidence of death and gastrointestinal bleeding among the 4 subgroups. The prasugrel/DOAC group had significantly lower incidence of MI (OR 0.566, 95% CI 0.348-0.921). The incidence of ischemic stroke was significantly lower in the prasugrel/DOAC group (OR 0.701, 95% CI 0.502-0.979), and significantly higher in the clopidogrel/VKA group (OR 1.680, 95% CI 1.273-2.216). Need for blood transfusion was less frequent in the prasugrel/DOAC group (OR 0.729, 95% CI 0.598-0.890), and more frequent in both the clopidogrel/VKA group (OR 1.424, 95% CI 1.187-1.708) and the prasugrel/VKA group (OR 1.633, 95% CI 1.367-1.950). CONCLUSIONS: Combination of low-dose prasugrel and DOAC was associated with lower incidence of MI, ischemic stroke, and blood transfusion. Low-dose prasugrel may be feasible as part of triple therapy in patients undergoing PCI.

AIMS: The Academic Research Consortium (ARC) has proposed international criteria to standardize the definition of high bleeding risk (HBR) in patients undergoing percutaneous coronary intervention (PCI). In this context, Japan has also established its own guidelines, that is, the Japanese version of HBR (J-HBR) criteria. However, the J-HBR criteria have not been fully validated, especially in patients with acute myocardial infarction (MI). METHODS: This bi-center registry included 1079 patients with acute MI undergoing primary PCI in a contemporary setting. Patient bleeding risks were evaluated using the ARC-HBR and J-HBR criteria. The primary endpoint was rates of major bleeding events (Bleeding Academic Research Consortium type 3 or 5) at 1 year. RESULTS: Of the 1079 patients, 505 (46.8%) and 563 (52.2%) met the ARC-HBR and J-HBR criteria, respectively. Patients who met the J-HBR criteria were found to have a higher rate of major bleeding events at 1 year than those who did not (12.8% vs. 3.3%, p＜0.001). When patients were scored and stratified using the J-HBR major and minor criteria, risks of major bleedings were progressively increased with the increase in the number of J-HBR criteria. In the receiver operating characteristic curve analysis, the ARC-HBR and J-HBR significantly predicted subsequent major bleedings after PCI, with ARC-HBR having greater predictive ability than J-HBR. CONCLUSIONS: More than half of the patients with acute MI undergoing primary PCI in Japan met the J-HBR criteria. Although the J-HBR criteria successfully identified patients who were likely to develop major bleeding events after primary PCI, the superiority of J-HBR to ARC-HBR in predicting bleeding outcomes warrants further investigation.

Mucopolysaccharidosis type II, known as Hunter syndrome, is a rare inherited metabolic disorder with glycosaminoglycan accumulation leading to progressive multisystem involvement, such as heart, respiratory, and central nervous systems. In particular, concurrence of major heart and respiratory problems in this syndrome often causes difficulty in performing curative and invasive treatments. Transcatheter aortic valve implantation (TAVI) has been an established therapy for severe aortic stenosis (AS). In patients who cannot undergo surgical aortic valve replacement because of high risk for general anesthesia, TAVI with local anesthesia has become an alternative therapy for severe AS. We report herein a case of 50-year-old man with Hunter syndrome accompanied by severe airway obstruction who underwent TAVI with local anesthesia for severe AS. <Learning objective: Mucopolysaccharidosis is characterized by glycosaminoglycan accumulation leading to progressive multisystem involvement. Heart disease and respiratory problems are often concomitant in patients with mucopolysaccharidosis. When surgical treatment is required, consideration about treatment strategy and perioperative management are important because of its high surgical risk or inoperable status. We describe a case with mucopolysaccharidosis accompanied by severe airway obstruction who underwent transcatheter aortic valve implantation with local anesthesia for severe aortic stenosis.>.

BACKGROUND: It has been reported that Achilles tendon xanthoma (ATX), being one of the important diagnostic criteria for familial hypercholesterolemia, is independently associated with the severity of coronary artery disease (CAD). The aim of this study was to investigate plaque vulnerability in CAD patients with ATX. METHODS: Patients with CAD who underwent percutaneous coronary intervention (PCI) with near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) guidance were enrolled. Soft X-ray radiography of the Achilles tendon was performed, and a maximum thickness of 9 mm or more was regarded as ATX. Using NIRS-IVUS, the degree of lipid core plaque (LCP) was evaluated by calculating the maximum value of lipid core burden index (LCBI) for any of the 4-mm segments (maxLCBI4mm) in the target lesion and non-target vessel. RESULTS: In a total of 156 patients, 14 patients (9.0%) had ATX. MaxLCBI4mm in the ATX group was significantly greater in the target lesion (p<0.001) and in the non-target vessel (p=0.032) compared to the non-ATX group. When patients were divided into tertiles according to Achilles tendon thickness, maxLCBI4mm was progressively increased in favor of thickness, although there was only a tendency in the target lesion (p=0.062), and no statistical significance in the non-target vessel (p=0.189). Multiple linear regression analysis determined ATX as an independent predictor for maxLCBI4mm in the target lesion and non-target vessel. CONCLUSIONS: ATX was associated with the degree of LCP in CAD patients requiring PCI. High-risk patients with lipid-rich vulnerable plaque can possibly be detected by evaluating Achilles tendon thickness.

Introduction: The present study aimed to compare the accuracy of quantitative measurements by contemporary intravascular imaging systems including optical frequency domain imaging (OFDI), frequency domain optical coherence tomography (FD-OCT), and 6 intravascular ultrasound (IVUS) systems. Methods: We imaged five cylindrical phantom models made from an acrylic resin with known lumen diameters (1.51, 2.03, 3.04, 4.04, and 5.04 mm, respectively) using OFDI (FastView and LUNAWAVE, Terumo), FD-OCT (Dragonfly JP and ILUMIEN OPTIS, Abbott Vascular), and 6 mechanically rotating IVUS systems including a system, two 40-MHz, one 45-MHz, two 60-Mhz and one broad-band frequency IVUS systems. The OFDI, FD-OCT, and IVUS images were obtained using automated motorized pullback in a tank filled with 37-degree Celsius saline and, in cases of OFDI and FD-OCT, contrast-saline mixture (1:1 ratio) and contrast under the system setting of the refractive index for the corresponding flush medium. Results: All the imaging systems showed good accuracy and excellent precision of lumen measurement with the relative differences between the measured diameter and actual phantom diameter being ranging from -2.9% to 8.0% and minimum standard deviations of the measured diameters (≤0.02 mm). Conclusion: The present study demonstrated that contemporary intravascular imaging systems including OFDI, FD-OCT, and IVUS provided clinically acceptable accuracy and excellent precision of quantitative lumen measurement in phantom models in vitro across a wide range of dimensions. Future research to confirm these findings in vivo are warranted.

Previous studies indicated that serum uric acid (SUA) level is a marker of endothelial function in subsets of ischemic heart disease (IHD). In the present study, we aimed to evaluate the relation between the SUA level and endothelial function in patients with a broad spectrum of IHD, including obstructive coronary artery disease (CAD) and ischemia with no obstructive CAD (INOCA). Three prospective studies and one retrospective study were pooled, in which the SUA level was measured, and systemic endothelial function was assessed using the reactive hyperemia index (RHI). The primary endpoint of the present study was a correlation of the SUA level with RHI. A total of 181 patients with a broad spectrum of IHD were included, among whom, 46 (25%) had acute coronary syndrome presentation and 15 (8%) had INOCA. Overall, the SUA level was negatively correlated with the RHI (r = -0.22, p = 0.003). Multivariable analysis identified the SUA level and INOCA as significant factors associated with RHI values. In conclusion, in patients with a broad spectrum of IHD, including obstructive epicardial CAD (chronic and acute coronary syndromes) and INOCA, the SUA level was significantly and negatively correlated with systemic endothelial function assessed with the RHI. INOCA, rather than obstructive CAD, was more associated with endothelial dysfunction.

BACKGROUND: The PARIS and CREDO-Kyoto risk scores were developed to identify patients at risks of thrombotic and bleeding events individually after percutaneous coronary intervention (PCI). However, these scores have not been well validated in different cohorts.Methods and Results:This 2-center registry enrolled 905 patients with acute myocardial infarction (MI) undergoing primary PCI. Patients were divided into 3 groups according to the PARIS and CREDO-Kyoto thrombotic and bleeding risk scores. The study endpoints included ischemic (cardiovascular death, recurrent MI, and ischemic stroke) and major bleeding events. Of 905 patients, 230 (25%) and 219 (24%) had high thrombotic and bleeding risks, respectively, with the PARIS scores, compared with 78 (9%) and 50 (6%) patients, respectively, with the CREDO-Kyoto scores. According to the 2 scores, >50% of patients with high bleeding risk had concomitant high thrombotic risk. During the mean follow-up period of 714 days, 163 (18.0%) and 95 (10.5%) patients experienced ischemic and bleeding events, respectively. Both PARIS and CREDO-Kyoto scores were significantly associated with ischemic and bleeding events after primary PCI. For ischemic events, the CREDO-Kyoto rather than PARIS thrombotic risk score had better diagnostic ability. CONCLUSIONS: In the present Japanese cohort of acute MI patients undergoing contemporary primary PCI, the PARIS and CREDO-Kyoto thrombotic and bleeding risk scores were discriminative for predicting ischemic and bleeding events.

Patients with cancer have an increased risk of cardiovascular events including myocardial infarction (MI) and vice versa, and are at high risks of ischemic and bleeding events after MI. However, short- and long-term clinical outcomes in patients with acute MI based on cancer status are not fully understood. This bi-center registry included 903 patients with acute MI undergoing primary percutaneous coronary intervention in a contemporary setting. Patients were divided into active cancer, a history of cancer, and no cancer according to the status of malignancy. Major adverse cardiovascular events (MACE), a composite of all-cause death, recurrent MI, and stroke, and major bleedings were evaluated. Of 903 patients, 49 (5.4%) and 65 (7.2%) had active cancer and a history of cancer, and 87 (9.6%) patients died during the hospitalization. In-hospital MACE was not significantly different among the 3 groups (16.3% vs 10.8% vs 10.9%, p = 0.48), whereas the rate of major bleeding events during the index hospitalization was significantly higher in patients with active cancer than their counterpart (20.4% vs 6.2% vs 5.8%, p = 0.002). After discharge, patients with active cancer had an increased risk of MACE and major bleedings compared with those with a history of cancer and no cancer during the mean follow-up period of 853 days. In conclusions, active cancer rather than a history of cancer and no cancer had significant impact on in-hospital bleeding events, and MACE and major bleedings after discharge in patients with acute MI undergoing primary percutaneous coronary intervention.

BACKGROUND: The long-term prognostic impact of IVUS findings following Absorb BVS implantation remains uncertain. This study aimed to identify the IVUS predictors of long-term clinical outcomes following ABSORB bioresorbable vascular scaffold (BVS) implantation from the pooled IVUS substudy cohorts of the ABSORB III and Japan trials. METHODS: A total of 298 lesions in 286 patients were enrolled with 2:1 randomization to ABSORB BVS vs. cobalt-chromium everolimus-eluting stents. This sub-analysis included 168 lesions of 160 patients in the Absorb arm whose post-procedural quantitative IVUS were available. The primary endpoint of this analysis was device-oriented composite endpoint (DOCE) of target lesion failure, including cardiac death, target vessel-related myocardial infarction, or ischemia-driven target lesion revascularization. The median follow-up duration was 4.9 [3.1-5.0] years. RESULTS: During follow-up, DOCE occurred in 10.1% of lesions treated with Absorb BVS. Among several post-procedural IVUS indices associated with DOCE, non-uniform device expansion (defined as uniformity index = minimum / maximum device area) (hazard ratio 0.47 per 0.1 increase [95%CI 0.28 to 0.77]; p = 0.003) and residual reference plaque burden (hazard ratio 4.01 per 10% increase [95%CI 1.50 to 10.77]; p = 0.006) were identified as independent predictors of DOCE by Cox multivariable analysis. CONCLUSIONS: Nonuniform device expansion and substantial untreated residual plaque in reference segments were associated with long-term adverse events following BVS implantation. Baseline imaging to identify the appropriate device landing zone and procedural imaging to achieve uniform device expansion if possible (e.g. through post-dilatation) may improve clinical outcomes of BVS implantation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01751906 (ABSORB III); NCT01844284 (ABSORB Japan).

BACKGROUND: Recent guidelines recommend risk stratification using objective scoring systems in patients with acute coronary syndrome. In this context, the CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) and GRACE (Global Registry of Acute Coronary Events) risk scores were both originally established to predict short-term mortality. However, their impact on short- and long-term clinical outcomes in a contemporary cohort of patients with acute myocardial infarction (MI) is unclear. METHODS: This bi-center registry included 809 patients with acute MI undergoing primary percutaneous coronary intervention. Patients were divided into three groups according to the pre-defined thresholds and tertiles of the CADILLAC and GRACE scores. The study endpoints included all-cause death and major adverse cardiovascular events (MACE) during the index hospitalization and after discharge. RESULTS: Of 809 patients, 323 (39.9%) and 255 (31.5%) had high CADILLAC and GRACE risk scores. During the index hospitalization, 61 (7.5%) patients died and 262 (32.4%) had MACE. Both CADILLAC and GRACE risk scores were associated with in-hospital mortality and MACE rates. After discharge, out of 683 patients with available follow-up information who survived to discharge, 42 (6.1%) died and 123 (18.0%) had MACE during the median follow-up period of 632 days. Significantly higher incidence of MACE in higher CADILLAC and GRACE risk scores was observed in a stepwise manner. CONCLUSION: Both CADILLAC and GRACE risk scores were predictive for short- and long-term mortality and MACE rates in a contemporary cohort of acute MI patients undergoing primary percutaneous coronary intervention.

Background Previous studies have reported that glucose variability leads to endothelial dysfunction and progression of coronary atherosclerosis. However, few studies have directly evaluated the relation between glucose variability and coronary endothelial function in patients with coronary artery disease (CAD). Methods A total of 38 patients with chronic CAD and a history of coronary drug-eluting stent implantation were enroled. Coronary endothelial function was evaluated by measuring the coronary vasoreactivity using quantitative coronary angiography in the segment distal to implanted stent in response to intracoronary acetylcholine (ACh) infusion (10-7 mol/l). Peripheral endothelial function was also assessed with reactive hyperemia index (RHI). The mean amplitude of glycemic excursion (MAGE) was calculated as a primary metric of glucose variability using a flash glucose monitoring system. Results Of 38 patients, 17 (45%) had diabetes mellitus. The mean levels of glycated hemoglobin, MAGE, and RHI were 6.3 ± 0.8%, 71.4 ± 29.8 mg/dl, and 1.85 ± 0.63. In the distal segment to coronary stent, lumen diameter was constricted by 0.6 ± 7.3% in response to intracoronary ACh infusion compared to that at baseline. While peripheral endothelial function assessed with RHI was not significantly associated with MAGE (r = -0.16, p = 0.35), coronary endothelial function was correlated with MAGE (r = -0.38, p = 0.02). Conclusion Greater glucose variability was significantly associated with coronary rather than peripheral endothelial dysfunction in patients with CAD, suggesting an impact of glucose variability on coronary atherosclerosis. Endothelial function; Coronary artery disease; Acetylcholine; Glucose variability.

OBJECTIVES: The aim of this study was to investigate whether lipid core plaque (LCP) in the entire stented segment detected by near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) could predict procedural myocardial infarction (PMI) in patients undergoing percutaneous coronary artery intervention (PCI). BACKGROUND: NIRS-IVUS can identify LCP, described as high lipid core burden index (LCBI). Previously, the highest LCBI contained only in the 4-mm segment (maxLCBI4mm ) was reported to predict PMI. METHODS: Patients who underwent NIRS-IVUS examination during PCI for coronary artery disease at Chiba University Hospital were included. The extent of LCP in the stented segment derived from NIRS-IVUS analysis was presented as LCBI, maxLCBI4mm , and LCP area index (LAI), reflecting the total amount of LCP in the entire stented segment calculated as LCBI×lesion length. PMI was defined as an elevation of creatine kinase MB > 3 times upper reference level (URL), and periprocedural myocardial injury (PMInj) was defined as an elevation of troponin I>5 times URL within 12 to 24 h after PCI. RESULTS: Out of 141 enrolled patients, PMI occurred in 20 (14.2%) and PMInj occurred in 62 (44.0%) patients. Receiver-operating characteristic curve analysis revealed LAI was the strongest predictor for both PMI and PMInj (area under curve 0.771, p < 0.001, and 0.717, p < 0.001, respectively). Multiple logistic regression analysis determined high LAI value as the independent predictor of both PMI and PMInj. CONCLUSIONS: Greater extent of LCP in the entire stented segment detected by NIRS-IVUS was significantly associated with PMI as well as PMInj in patients undergoing PCI.

Various types of blood pressure (BP) variability have been recognized as risk factors for future cardiovascular events. However, the prognostic impact of in-hospital BP variability in patients with symptomatic peripheral arterial disease (PAD) has not yet been thoroughly investigated. A total of 386 patients with PAD who underwent endovascular therapy in two hospitals were retrospectively included. BP variability was assessed by the coefficient of variation (CV) of systolic BP measured during hospitalization by trained nurses. The primary endpoint was a composite of major adverse cardiovascular events (cardiovascular death, acute coronary syndrome, stroke, and hospitalization for heart failure) and major adverse limb events (major amputation, acute limb ischemia, and surgical limb revascularization). The mean systolic BP and the CV of systolic BP during hospitalization were 130.8 ± 15.7 mmHg and 11.2 ± 4.1%, respectively. During the median follow-up period of 22 months, 80 patients (21%) reached the primary endpoint. Receiver operating characteristic curve analysis showed that the CV of systolic BP significantly predicted major adverse cardiovascular and limb events (area under the curve 0.60, best cutoff value 9.8, P = 0.01). Using the best cutoff value, patients with high BP variability (n = 242) had a higher risk of clinical events than those with low BP variability (n = 144) (26% vs. 12%, P < 0.001). Multivariable analysis indicated that the CV of systolic BP, age, hemodialysis, and atrial fibrillation were associated with the primary endpoint. In conclusion, greater in-hospital systolic BP variability was associated with major adverse cardiovascular and limb events in patients with symptomatic PAD undergoing endovascular therapy.

INTRODUCTION: Patients with cancer have an increased risk of cardiovascular disease including ischemic heart disease and vice versa. Anticancer drugs and radiotherapy are known to contribute to endothelial injury and vasospasm. However, the relations between vasospastic angina (VSA) and cancer or its treatment are poorly investigated. METHODS: A total of 786 patients underwent intracoronary acetylcholine (ACh) provocation tests to diagnose VSA. The positive ACh provocation test was defined as angiographic coronary artery spasm accompanied by chest pain and/or ischemic electrocardiographic changes. Patients were divided into active cancer, a history of cancer, and no cancer according to the status of malignancy. The impact of types of cancer, anticancer drugs, and radiotherapy on VSA was evaluated. RESULTS: Of 786 patients, 38 (4.8%) and 84 (10.7%) had active cancer and a history of cancer, respectively, and 401 (51.0%) were diagnosed as VSA. There was no significant difference in rates of positive ACh test among patients with active cancer, a history of cancer, and no cancer (39.5% vs. 57.1% vs. 50.9%, p = 0.20). Types of cancer and cancer treatment also had no impact on positive ACh provocation test. CONCLUSIONS: In this cross-sectional observational study, we did not find an association of active and a history of cancer with the diagnosis of VSA. Anticancer treatment including chemotherapy and radiotherapy was not significantly associated with positive ACh provocation test.

AIM: High platelet reactivity (HPR) is associated with increased risks of thrombotic events in patients with coronary artery disease. The recently developed ABCD-GENE score identified five clinical and genetic factors (age, body mass index, chronic kidney disease, diabetes, and the CYP2C19 loss-of-function allele) for HPR, although the significance of various stages of each factor is unclear. METHODS: Four prospective studies were pooled, in which platelet reactivity was measured using the VerifyNow assay with clopidogrel and prasugrel; genotyping of CYP2C19 was also performed. Each component of the ABCD-GENE score was divided into three subcategories. VerifyNow P2Y12 reactivity units ＞208 were defined as HPR. RESULTS: A total of 184 patients were included, of which 111 (60%) and 51 (28%) had HPR with clopidogrel and prasugrel. Chronic kidney disease had an impact on HPR on both clopidogrel and prasugrel, whereas the impact of diabetes was more evident in patients treated with prasugrel. Although the number of CYP2C19 loss-of-function alleles was clearly associated with a likelihood of HPR with clopidogrel, P2Y12 reactivity units with prasugrel treatment were also significantly and progressively higher in patients with more CYP2C19 loss-of-function alleles. CONCLUSIONS: Clinical and genetic factors had a differential effect on a P2Y12 inhibitor reactivity with clopidogrel and prasugrel in patients with coronary artery disease. The severity of the factors also had a different impact on HPR.

AIMS: Little is known regarding factors that predict the occurrence of lethal ventricular arrhythmias (VAs) occurring after acute myocardial infarction (AMI). This observational cohort study aimed to identify factors that predicted lethal VAs during the late phase after AMI in patients with reduced left ventricular ejection fraction (LVEF). METHODS AND RESULTS: Data were collected from our AMI database regarding consecutive patients with an LVEF of ≤40% after AMI (January 2012 to July 2018). The 'late phase' was defined as ≥7 days after AMI onset, and the primary endpoint was defined as lethal VAs in the late phase. The study included 136 patients (82% men; mean age: 66 ± 13 years). The average LVEF at admission was 32.7 ± 8.2%. During a mean follow-up period of 20.7 months, 14 patients (10%) experienced lethal VAs, including ventricular fibrillation (n = 8) and sustained ventricular tachycardia (n = 10). Univariate analyses revealed that lethal VAs were predicted by age and LVEF at admission. Receiver operating characteristic curve analysis indicated that the optimal cut-off value was 23% for using the LVEF at admission to predict the primary endpoint (area under the curve: 0.77, P < 0.0001). Multivariable analysis also demonstrated that LVEF at admission was an independent predictor of the primary endpoint (risk ratio = 7.12, P = 0.001). CONCLUSIONS: Lethal VAs in the late phase are common in patients with AMI, and reduced LVEF and cardiac function at admission play a significant role in the risk stratification for future lethal VAs in this population.

BACKGROUND: Accurate segmentation of the coronary arteries with intravascular ultrasound (IVUS) is important to optimize coronary stent implantation. Recently, deep learning (DL) methods have been proposed to develop automatic IVUS segmentation. However, most of those have been limited to segmenting the lumen and vessel (i.e. lumen-intima and media-adventitia borders), not applied to segmenting stent dimension. Hence, this study aimed to develop a DL method for automatic IVUS segmentation of stent area in addition to lumen and vessel area. METHODS: This study included a total of 45,449 images from 1576 IVUS pullback runs. The datasets were randomly split into training, validation, and test datasets (0.7:0.15:0.15). After developing the DL-based system to segment IVUS images using the training and validation datasets, we evaluated the performance through the independent test dataset. RESULTS: The DL-based segmentation correlated well with the expert-analyzed segmentation with a mean intersection over union (± standard deviation) of 0.80 ± 0.20, correlation coefficient of 0.98 (95% confidence intervals: 0.98 to 0.98), 0.96 (0.95 to 0.96), and 0.96 (0.96 to 0.96) for lumen, vessel, and stent area, and the mean difference (± standard deviation) of 0.02 ± 0.57, -0.44 ± 1.56 and - 0.17 ± 0.74 mm2 for lumen, vessel and stent area, respectively. CONCLUSION: This automated DL-based IVUS segmentation of lumen, vessel and stent area showed an excellent agreement with manual segmentation by experts, supporting the feasibility of artificial intelligence-assisted IVUS assessment in patients undergoing coronary stent implantation.

Elevated serum uric acid level was reportedly associated with greater coronary lipid plaque. Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine metabolism and believed to play an important role in coronary atherosclerosis. However, the relation of XOR to coronary lipid plaque and its mechanism are unclear. Patients with stable coronary artery disease undergoing elective percutaneous coronary intervention under near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) guidance were prospectively enrolled. They were divided into three groups according to serum XOR activities: low, normal, and high. Coronary lipid core plaques in non-target vessels were evaluated by NIRS-IVUS with lipid core burden index (LCBI) and a maximum LCBI in 4 mm (maxLCBI4mm). Systemic endothelial function and inflammation were assessed with reactive hyperemia index (RHI) and high-sensitivity C-reactive protein, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio. Of 68 patients, 26, 31, and 11 were classified as low, normal, and high XOR activity groups. LCBI (474.4 ± 171.6 vs. 347.4 ± 181.6 vs. 294.0 ± 155.9, p = 0.04) and maxLCBI4mm (102.1 ± 56.5 vs. 65.6 ± 48.5 vs. 55.6 ± 37.8, p = 0.04) were significantly higher in high XOR group than in normal and low XOR groups. Although RHI was significantly correlated with body mass index, diabetes, current smoking, and high-density lipoprotein cholesterol, no relation was found between XOR activity and RHI. There were also no relations between XOR activity and C-reactive protein, neutrophil-to-lymphocyte ratio, or platelet-to-lymphocyte ratio. In conclusion, elevated XOR activity was associated with greater coronary lipid core plaque in patients with stable coronary artery disease, without significant relations to systemic endothelial function and inflammation.

Objective Glycemic variability is being increasingly recognized as an early indicator of glucose metabolic disorder and may contribute to the development of diabetic vascular complications, such as coronary microvascular dysfunction. The present study sought to investigate the relationship between coronary microvascular function assessed by intracoronary thermodilution method and glycemic variability on a continuous glucose monitoring system (CGMS). Methods We prospectively enrolled 40 patients with or without known diabetes mellitus who had epicardial coronary artery disease referred for coronary angiography and were not treated with diabetic medications. Of these, two had a significant stenosis in the left main coronary artery and were therefore excluded from the analyses. In the end, 38 patients were equipped with a CGMS and underwent intracoronary physiological assessments in the unobstructed left anterior descending artery. The mean amplitude of glycemic excursion (MAGE) and standard deviation were calculated from the obtained CGMS data as indicators of glucose variability. Results Coronary flow reserve (CFR) was negatively correlated with MAGE (r=-0.328, p=0.044) and standard deviation (r=-0.339, p=0.037) on CGMS, while the index of microcirculatory resistance showed no such correlation. Multivariable linear regression analyses showed that MAGE on CGMS was significantly associated with CFR after adjusting for age, sex, fractional flow reserve and hemoglobin A1c. Conclusion Higher MAGE on CGMS was associated with reduced CFR in stable patients with coronary artery disease, suggesting a potential effect of glycemic variability on coronary microvascular flow regulation. A further study with a larger sample size needs to be conducted to confirm our findings.

Near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) studies have demonstrated that lipid core plaque (LCP) is frequently observed in the culprit segment of myocardial infarction (MI). However, little is known about the impact of clinical presentations such as chronic coronary syndrome (CCS) and acute coronary syndrome (ACS) including unstable angina (UA), non ST-segment elevation MI (NSTEMI), and ST-segment elevation MI (STEMI) on LCP. The present prospective single-center registry included a total of 178 patients who underwent percutaneous coronary intervention under NIRS-IVUS guidance. Patients were divided into CCS and ACS groups, and ACS patients were further sub-divided into the 3 groups according to the clinical presentation. The primary endpoint was coronary LCP in the target lesion assessed by NIRS-IVUS with maximal lipid core burden index over any 4 mm segment (maxLCBI4mm). The study population included 124 and 54 patients with CCS and ACS. MaxLCBI4mm in the target lesion was significantly higher in the ACS group than in the CCS group (503 [284-672] vs. 406 [250-557], p = 0.046). Among ACS patients, MaxLCBI4mm in the target lesion was also significantly different in those with UA (n = 18), NSTEMI (n = 21), and STEMI (n = 15) (288 [162-524] vs. 518 [358-745] vs. 646 [394-848], p = 0.021). In conclusion, LCP assessed by NIRS-IVUS, a surrogate of coronary plaque vulnerability, was significantly different according to the clinical presentations such as CCS, UA, NSTEMI, and STEMI.

The ISCHEMIA was eagerly awaited study in the field of ischemic heart disease. Following the presentation and publication of ISCHEMIA, multiple opinions and viewpoints get complicated. The ongoing debates have been including the relevance of coronary revascularization, non-invasive diagnostic methods, and invasive ischemic testing in patients with stable ischemic heart disease (SIHD). Prior to ISCHEMIA, observational studies indicated the potential of coronary revascularization for improving clinical outcomes, while the randomized COURAGE trial did not support the plausible concept. Although the FAME 2 trial implied the superiority of percutaneous coronary intervention over medical therapy alone, the clinical relevance of coronary revascularization to improve outcomes and quality of life has been questioned. As a consequence, the ISCHEMIA trial did not demonstrate clear benefits in reducing clinical events but showed antianginal effects of revascularization. This landmark trial also suggested the difficulties of non-invasive ischemia testing rather than computed tomography angiography. Despite the complex results, the ISCHEMIA trial may simplify the clinical indications of coronary revascularization in patients with SIHD. Future publications from the ISCHEMIA trial and debates on the results will sharpen our thinking and understanding.

BACKGROUND: High platelet reactivity (HPR) is associated with subsequent thrombotic events in patients undergoing percutaneous coronary intervention (PCI). Recently, the ABCD-GENE score was developed to identify patients at risk for HPR, incorporating both clinical and genetic factors. However, this score was derived and validated in mostly Caucasian subjects and it has not been validated in an East Asian population. METHOD: Individual patient data from 4 prospective studies were pooled, in which platelet reactivity was measured using the VerifyNow assay on clopidogrel and genotyping of CYP2C19 was performed after PCI. Study populations included patients with general stable coronary artery disease, hemodialysis, age ≥75 and/or body weight <50 kg, and acute coronary syndrome. VerifyNow P2Y12 reactivity units >208 was defined as HPR. RESULTS: Of 184 patients, 111 (60%) had HPR on clopidogrel. In the receiver operating characteristics curve analyses, the ABCD-GENE score significantly predicted HPR on clopidogrel (AUC 0.78, best cut-off value 9, p < 0.001). Across the 4 studies and their combinations, the diagnostic ability and cut-off values of ABCD-GENE score for HPR on clopidogrel were consistent. CONCLUSIONS: The ABCD-GENE score had significant and moderate diagnostic ability for HPR on clopidogrel in Japanese patients undergoing PCI. The predictivity was consistent across a broad spectrum of patient populations, suggesting the applicability of this novel scoring system in clinical practice worldwide.

BACKGROUND: Vasospastic angina (VSA) reportedly accounts for one form of sudden cardiac arrest (SCA). Intracoronary acetylcholine (ACh) testing is useful for diagnosing VSA although invasive provocation testing after SCA is a clinical challenge. In addition, even if the ACh test is positive, any causal relationship between VSA and SCA is often unclear because patients with VSA may have other underlying cardiac disorders. METHODS: A total of 20 patients without overt structural heart disease who had been fully resuscitated from SCA were included. All patients underwent the ACh provocation test and scrutiny such as cardiac computed tomography or magnetic resonance imaging. Patients were followed up for all-cause death or recurrent SCA including appropriate implantable cardioverter defibrillator therapy. RESULTS: An ACh provocation test was performed 20 ± 17 days after cardiac arrest. Fifteen out of 20 (75.0%) patients had a positive ACh test and 2 (10.0%) had adverse events such as ventricular tachycardia and transient cardiogenic shock during the test. In patients with a positive ACh test, 6 of 15 (40.0%) patients had other overlapping cardiac disorders such as long QT syndrome, Brugada syndrome, cardiac sarcoidosis, myocarditis, or cardiomyopathy. Long-term prognosis was not different regardless of a positive ACh test or the presence of other cardiac disorders overlapping with VSA. CONCLUSIONS: Three-quarters of the patients who had been resuscitated from SCA had a positive ACh test. Further examinations revealed other overlapping cardiac disorders in addition to VSA in 40% of patients with a positive ACh test.

AIMS: High platelet reactivity (HPR) has been associated with an increased risk of thrombotic events in patients undergoing percutaneous coronary intervention. HPR has been well examined in patients treated with clopidogrel; however, HPR on prasugrel is poorly investigated. METHODS: Four prospective studies were pooled, in which platelet reactivity on prasugrel was measured using VerifyNow assay; genotyping of CYP2C19 was also performed. Factors associated with HPR on prasugrel were identified using multivariable analysis to develop a risk prediction model. RESULTS: In total, 180 patients were examined in this study, of whom 51 (28%) had HPR on prasugrel. The multivariable analysis indicated that hypertension, diabetes, hemodialysis, and the number of CYP2C19 loss-of-function (LOF) alleles are significant factors for HPR on prasugrel. These four factors were then incorporated to develop the HHD-GENE score. The receiver operating characteristic curve analysis showed that the HHD-GENE score predicted HPR on prasugrel (area under the curve (AUC) 0.74, best cutoff value 5, p＜0.001). With the best cutoff value, patients with the HHD-GENE score ≥ 5 had a significantly increased risk of HPR on prasugrel than their counterpart (50% vs. 18%, p＜0.001). CONCLUSIONS: The HHD-GENE score consisting of hypertension, diabetes, hemodialysis, and CYP2C19 LOF alleles may be useful in identifying patients on prasugrel who are at high risk for HPR. External validation is needed to define the clinical utility of this novel scoring system.

Background: Device underexpansion is associated with late adverse outcomes after bioresorbable vascular scaffold (BVS) implantation. This study, representing official IVUS results of the ABSORB Japan trial, aimed to characterize IVUS findings, focusing specifically on acute device expansion, and to investigate its impact on late lumen loss (LLL) with Absorb-BVS compared with cobalt-chromium everolimus-eluting stents (CoCr-EES). Methods: ABSORB Japan enrolled 148 patients (2:1 randomization) in the IVUS cohort. Serial IVUS was prescheduled at post-procedure and 3 years. Acute device expansion was evaluated with respect to the degree and uniformity of the implanted device. Results: Overall, Absorb-BVS showed smaller and more nonuniform device expansion at post-procedure, compared with CoCr-EES, which was particularly prominent in small-vessel lesions. In serial analysis, Absorb-BVS showed unique associations of smaller device expansion (r = 0.40, p = 0.001) and more nonuniformity (r = 0.29, p = 0.007) at post-procedure with greater LLL at 3 years, primarily attributable to greater negative remodeling (r = 0.39, p = 0.006). In contrast, acute device expansion showed no relation with subsequent lumen change in CoCr-EES. In Absorb-BVS, ischemic-driven target lesion or vessel revascularization (ID-TLR or ID-TVR) at 3 years occurred more frequently in small- versus large-vessel lesions (12.5% vs. 0%, p = 0.04 for ID-TLR and 15.6% vs. 2.3%, p = 0.08 for ID-TVR). Conversely, Absorb BVS had no target lesion nor vessel failure, even in small-vessel lesions, when adequate device expansion was achieved at post-procedure. Conclusions: Unlike CoCr-EES, underexpansion was associated with greater negative remodeling and LLL in Absorb-BVS. This may in part account for the poorer outcomes of Absorb-BVS than CoCr-EES when under-expanded.

BACKGROUND: Previous studies showed the relation of mental distress such as anxiety and depression to coronary vasoconstriction and myocardial ischemia. However, the mental health status of patients suspected to have vasospastic angina is unclear. METHODS: A total of 99 patients underwent intracoronary acetylcholine (ACh) provocation tests for the diagnosis of vasospastic angina and mental health assessment using the 12-item General Health Questionnaire (GHQ-12) and State-Trait Anxiety Inventory Form Y (STAI Y-2). Patients with binary GHQ-12 ≥ 4 were defined as having poor mental health. RESULTS: Median GHQ-12 and STAI Y-2 were 3 [1, 6] and 44 [36, 50]. Forty-one (41%) patients had binary GHQ-12 ≥ 4, and 48 (48%) had positive ACh provocation tests. The number of provoked vasospasms and rate of electrocardiographic change and chest pain during ACh tests were not significantly different between patients with and without GHQ-12 ≥ 4. The incidence of positive ACh provocation test was similar between the two groups (49% vs. 48%, p = 1.00). The multivariable analysis indicated that younger age, no history of percutaneous coronary intervention and no diabetes mellitus were factors associated with higher GHQ-12 and/or STAI Y-2 scores. CONCLUSIONS: More than 40% of patients who underwent ACh provocation tests had poor mental condition. No impact of mental distress on positive ACh tests was found in this study.

BACKGROUND: Tendon xanthoma, represented as Achilles tendon xanthoma (ATX), is one of the important diagnostic criteria for familial hypercholesterolemia (FH). However, there are some cases with ATX who do not meet these criteria. This study aimed to investigate the severity of coronary artery disease (CAD) in patients with ATX. METHODS: A total of 394 patients with CAD undergoing percutaneous coronary intervention (PCI) at Chiba University Hospital between June 2016 and February 2018 were enrolled. Soft X-ray radiography of Achilles tendon was performed, and a maximum thickness of 9 mm or more was regarded as ATX. Heterozygous FH was diagnosed according to the diagnostic criteria proposed by the Japan Atherosclerosis Society in 2017. CAD severity was assessed by SYNTAX score before the first PCI during the study period. RESULTS: There were 43 (10.9%) patients with ATX, and 16 (4.1%) were diagnosed as FH (15 with ATX and 1 without ATX). The ATX group showed greater body mass index, lower high-density lipoprotein cholesterol level, and the higher prevalence of FH, diabetes, prior myocardial infarction, acute coronary syndrome, multivessel disease, hemodialysis, and prior statin administration. SYNTAX score and the rate of SYNTAX score ≥23 were significantly higher in the ATX group compared with the non-ATX group (p < 0.001 for each). When patients were divided into quartiles according to Achilles tendon thickness, SYNTAX score and the prevalence of SYNTAX score ≥23 were progressively increased in favor of greater Achilles tendon thickness (p < 0.001 for each). Multivariate analysis determined male, diabetes, and ATX as independent predictors for higher SYNTAX score. CONCLUSIONS: In CAD patients undergoing PCI, ATX was independently associated with severity of CAD. Detecting ATX may be useful not only for diagnosing FH, but also for identifying patients with advanced CAD.

BACKGROUND: Ticagrelor and prasugrel are novel and potent P2Y12 inhibitors. Ticagrelor 90mg or 60mg twice daily is known to reduce ischemic events but be associated with an increased risk of bleeding in patients with prior myocardial infarction in Western countries. Although ticagrelor 90mg twice daily was tested in a randomized clinical trial in East Asia, the clinical significance of ticagrelor 60mg twice daily is unclear. This study aimed to evaluate platelet inhibition of low-dose ticagrelor compared to prasugrel in Japanese patients. METHODS: A total of 33 patients with prior myocardial infarction (>3 months) who received aspirin and prasugrel 3.75mg once daily were enrolled. Prasugrel was switched to ticagrelor 60mg twice daily. Platelet inhibition was assessed by VerifyNow assay (Accumetrics, San Diego, CA, USA) at baseline and 14 days after switching to ticagrelor. P2Y12 reaction unit (PRU) ≤95 was defined as low on-treatment platelet reactivity (LPR) and PRU≥262 as high on-treatment platelet reactivity. RESULTS: Ticagrelor treatment resulted in significantly lower PRU [10 (7-39) vs. 143 (102-201), p<0.001] and a higher rate of LPR (94% vs. 24%, p<0.001), compared to prasugrel treatment. Neither patients treated with ticagrelor nor prasugrel had high on-treatment platelet reactivity. During 2-week follow-up on ticagrelor therapy, no major bleeding occurred in both groups, while four minor bleeding events were observed. CONCLUSION: In Japanese patients with prior myocardial infarction, significantly lower PRU and a higher rate of LPR were observed on ticagrelor 60mg twice daily compared to prasugrel 3.75mg once daily.

Previous studies reported that elevated serum uric acid level was associated with greater coronary lipid plaque. Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine metabolism and is believed to play important roles in coronary atherosclerosis. However, the relation between XOR and coronary lipid plaque is unclear. Patients with stable coronary artery disease who underwent elective percutaneous coronary intervention under near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) guidance were prospectively included. They were divided into 3 groups according to plasma XOR activities based on a previous report: low, normal, and high. Quantitative coronary angiography and gray-scale IVUS were analyzed. The primary end point was coronary lipid plaques in a nontarget vessel assessed by NIRS-IVUS with lipid core burden index (LCBI) and maximum LCBI in 4 mm (maxLCBI4mm). Out of 68 patients, 26, 31, and 11 patients were classified as low, normal, and high XOR activity groups. Quantitative coronary angiography demonstrated that the high XOR activity group had longer lesion length, smaller minimum lumen diameter, and higher percentage of diameter stenosis in a nontarget vessel among the 3 groups. Gray-scale IVUS analysis also showed smaller lumen area in the high XOR activity group than the others. LCBI (102.1 ± 56.5 vs 65.6 ± 48.5 vs 55.6 ± 37.8, p = 0.04) and maxLCBI4mm (474.4 ± 171.6 vs 347.4 ± 181.6, 294.0 ± 155.9, p = 0.04) in a nontarget vessel were significantly higher in the high XOR group than in the normal and low groups. In conclusion, elevated XOR activity was associated with coronary lipid-rich plaque in a nontarget vessel in patients with stable coronary artery disease.

BACKGROUND: Autonomic nerve system and endothelial function play important roles in vasospastic angina. Elevated heart rate (HR), blood pressure (BP), and double product (DP) can increase endothelial-dependent coronary artery dilation and blood flow. However, the impact of HR, BP, and DP on occurrence and severity of VSA in the clinical setting is unclear. METHOD: A total of 170 patients undergoing intracoronary acetylcholine (ACh) provocation test during hospitalisation was included. Resting HR, BP, and DP were measured at least four times, and their variabilities were evaluated by standard deviations (SD) and coefficient of variations (CVs). Angiographic coronary artery vasospasm was defined as total or subtotal occlusion induced by ACh provocation. RESULTS: Mean±SD HR (65.7±9.1 vs 69.6±7.9 beats per minute; p=0.003), systolic BP (122.3±13.4 vs 127.7±14.6 mmHg; p=0.01), and DP (8,001±1,229 vs 8,903±1,495; p<0.001) were significantly lower in patients with a positive ACh test than the counterpart, whereas SD and CV of both HR and systolic BP were not significantly different between the two groups. Mean HR, BP, and DP progressively decreased with increase in the number of vessels with angiographic vasospasm. Multivariate analysis showed current smoking and lower DP as independent predictors of the greater number of vessels with provoked angiographic vasospasm. CONCLUSIONS: Resting HR, BP, and DP were lower in patients with vasospastic angina, especially in those with severe vasospasm.

BACKGROUND: Little is known about the prognostic impact of heart failure (HF) duration in patients with advanced HF. METHODS: A total of 109 consecutive patients with advanced HF referred to the institutional heart transplant program between July 2014 and December 2017 were prospectively enrolled. The patients were divided into two groups according to the HF duration using a pre-specified cutoff (> 18 months, n = 38; ≤ 18 months, n = 71). The Cox proportional hazards model was generated to investigate the association between the HF duration and a 1-year composite endpoint (all-cause mortality, left ventricular assist device implantation, and hospitalization due to HF). RESULTS: Patients with a longer HF duration were older and had significantly lower blood pressure, and greater left ventricular volume compared with those with a shorter HF duration. The 1-year event-free survival rate was significantly lower in patients with a longer HF duration (49.1% vs. 80.0%, log-rank p < 0.001). After adjustment, a longer HF duration was independently associated with an increased risk for the composite endpoint (hazard ratio, 2.44; 95% confidence interval, 1.03-5.76; p = 0.04). Additionally, longer HF duration was independently associated with an increased wall motion score index and a decreased heart-to-mediastinum ratio of 123I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy (all associations, p < 0.05). CONCLUSIONS: A longer HF duration is associated with an increased risk of adverse outcomes as well as more severe myocardial damage among patients with advanced HF.

OBJECTIVES: The aim of this study was to investigate the vascular responses and fates of the scaffold after bioresorbable vascular scaffold (BVS) implantation using multimodality imaging. BACKGROUND: Serial comprehensive image assessments after BVS implantation in the context of a randomized trial have not yet been reported. METHODS: In the ABSORB Japan trial, 400 patients were randomized to a BVS (n = 266) or a cobalt-chromium everolimus-eluting stent (n = 134). Through 3 years, patients underwent serial angiography and intravascular ultrasound or optical coherence tomography (OCT). RESULTS: Luminal dimension at 3 years was consistently smaller with the BVS than with the cobalt-chromium everolimus-eluting stent (mean angiographic minimal luminal diameter 2.04 ± 0.63 mm vs. 2.40 ± 0.56 mm, mean difference -0.37 mm [95% confidence interval: -0.50 to -0.24 mm]; p < 0.001), mainly because of smaller device area (6.13 ± 2.03 mm2 vs. 7.15 ± 2.16 mm2, mean difference -1.04 mm2 [95% confidence interval: -1.66 to -0.42 mm2]; p < 0.001), and larger neointimal area (2.10 ± 0.61 mm2 vs. 1.86 ± 0.64 mm2, mean difference 0.24 mm2 [95% confidence interval: 0.06 to 0.43 mm2]; p = 0.01) by OCT. BVS-treated vessels did not show previously reported favorable vessel responses, such as positive vessel remodeling, late luminal enlargement, and restoration of vasomotion, although the OCT-based healing score was on average zero (interquartile range: 0.00 to 0.00). At 3 years, intraluminal scaffold dismantling (ISD) was observed in 14% of BVS. On serial OCT, ISD was observed in 6 lesions at 2 years, where the struts had been fully apposed at post-procedure, while ISD was observed in 12 lesions at 3 years, where 8 lesions were free from ISD on 2-year OCT. In 5 cases of very late scaffold thrombosis, strut discontinuities were detected in all 4 cases with available OCT immediately before reintervention. CONCLUSIONS: In this multimodality serial imaging study, luminal dimension at 3 years was smaller with the BVS than with the cobalt-chromium everolimus-eluting stent. ISD, suspected to be one of the mechanisms of very late BVS thrombosis, was observed in a substantial proportion of cases at 3 years, which developed between post-procedure and 2 years and even beyond 2 years. (AVJ-301 Clinical Trial: A Clinical Evaluation of AVJ-301 [Absorb™ BVS] in Japanese Population [ABSORB JAPAN]; NCT01844284).

INTRODUCTION: Several measures of blood pressure (BP) variability have been associated with kidney disease and cardiovascular events. Although BP is routinely measured during hospitalization in daily practice, the prognostic impact of in-hospital BP and its variability are uncertain. METHODS: A total of 226 participants who underwent elective percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) were included. BP was measured by trained nurses during the 4-day hospitalization for PCI. BP variability was assessed by standard deviation (SD) and coefficient variation of systolic BP. Estimated glomerular filtration rate (eGFR) was calculated at baseline and follow-up (≥6 months). The cardiovascular end point was defined as a composite of cardiovascular death, acute coronary syndrome, stroke, heart failure hospitalization, and any coronary revascularization. RESULTS: In-hospital BP was measured 9.5 ± 0.8 times. During a median follow-up period of 1.7 years, mean eGFR change was -1.7 mL/min/1.73 m2 per year, and 35 (15.5%) participants met the cardiovascular end point. Mean systolic BP and SD were negatively correlated with eGFR change. In the receiver operating characteristic curve analysis, SD of systolic BP predicted the cardiovascular end point (AUC 0.63, best cutoff value 14.2 mm Hg, p = 0.003). Kaplan-Meier analysis demonstrated a significantly higher incidence of the cardiovascular end point in patients with SD of systolic BP ≥14.2 mm Hg compared to their counterpart (p = 0.003). A multivariable analysis showed SD of systolic BP as an independent predictor for the cardiovascular end point. When assessed with coefficient variation, BP variability was similarly related to eGFR change and clinical outcomes. CONCLUSION: Greater in-hospital BP variability was associated with renal function decline and cardiovascular events in patients with stable CAD.

BACKGROUND: Although current guidelines recommend admission to the intensive/coronary care unit (ICU/CCU) for patients with ST-segment elevation myocardial infarction (MI), routine use of the CCU in uncomplicated patients with acute MI remains controversial. We aimed to evaluate the safety of management in the general ward (GW) of hemodynamically stable patients with acute MI after primary percutaneous coronary intervention (PCI). METHODS: Using a large nationwide administrative database, a cohort of 19426 patients diagnosed with acute MI in 52 hospitals where a CCU was available were retrospectively analyzed. Patients with mechanical cardiac support and Killip classification 4, and those without primary PCI on admission were excluded. A total of 5736 patients were included and divided into the CCU (n = 3488) and GW (n = 2248) groups according to the type of hospitalization room after primary PCI. Propensity score matching was performed, and 1644 pairs were matched. The primary endpoint was in-hospital mortality at 30 days. RESULTS: The CCU group had a higher rate of Killip classification 3 and ambulance use than the GW group. There was no significant difference in the incidence of in-hospital mortality within 30 days among the matched subjects. Multivariable Cox proportional hazard model analysis among unmatched patients supported the findings (hazard ratio 1.12, 95% confidence interval 0.66-1.91, p = 0.67). CONCLUSIONS: The use of the GW was not associated with higher in-hospital mortality in hemodynamically stable patients with acute MI after primary PCI. It may be feasible for the selected patients to be directly admitted to the GW after primary PCI.

Trans-catheter aortic valve implantation (TAVI) has been recognized as a useful treatment for patients with severe aortic valve stenosis, particularly those with moderate to high risks of open heart surgery. A thorough evaluation of the aortic valve complex, including the size or presence of calcifications of the leaflets and annulus, is important for the selection of appropriate candidates, artificial valve types and approach. Echocardiography is useful for the precise evaluation of aortic valve stenosis severity and aortic valve complex morphology, but it is not useful to evaluate three-dimensional aortic valve anatomy and pathway for the catheter of aortic valve implantation. Electrocardiography (ECG)-gating computed tomography (CT) has recently been recognized as a useful modality for evaluating significant coronary artery stenosis because of its higher spatial and temporal resolution and diagnostic accuracy based on recent studies. ECG-gating CT is also useful for evaluating aortic valve complex morphology, including calcifications and whole aorta and iliac arteries, as the access route of catheter in TAVI. TAVI candidates, who are at high risk of open surgery, tend to be old and require anti-platelet after TAVI; therefore CT, is also useful for screening for non-cardiac diseases including malignant tumors just before TAVI. Therefore, here we introduce the utility of cardiac and whole body CT in cases of severe aortic valve stenosis before and after TAVI.

Although it has been reported that prasugrel achieves stronger antiplatelet effect and fewer cardiovascular events compared to clopidogrel in Japanese patients, there are limited data comparing the safety between the 2 dose regimens. Data from 1031 consecutive patients with coronary artery disease undergoing PCI at 5 institutions from May 2014 to April 2016, who received aspirin plus either clopidogrel (619 patients) or prasugrel (412 patients), were retrospectively analyzed. The choice of clopidogrel or prasugrel was left to the operator's discretion. Adverse events were defined as a composite of bleeding, hepatopathy, leukopenia, thrombopenia, exanthema, and major adverse cardiovascular events (MACE). MACE was defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal ischemic stroke. The average follow-up period was 143 days in the prasugrel group and 263 days in the clopidogrel group. Adverse events occurred in 34.5% of patients in the prasugrel group and in 28.6% in the clopidogrel group. Although the Kaplan-Meier curves showed lower survival rates from MACE, all-bleeding, major bleeding, minor bleeding, and adverse events, in the prasugrel group compared to the clopidogrel group (log rank test p = 0.009, p = 0.001, p = 0.012, p = 0.018, and p < 0.001, respectively), multivariate Cox-regression analyses determined prasugrel as a significant risk factor for all-bleeding, minor bleeding, and adverse events, but not for MACE and major bleeding events. Dual antiplatelet therapy with prasugrel was independently associated with minor bleeding events, but not with MACE and major bleeding events, compared to clopidogrel, after PCI in common clinical settings.

Familial hypercholesterolemia (FH) is reportedly associated with the development of coronary artery disease (CAD), especially acute coronary syndrome (ACS). However, the prevalence of FH in patients with stable CAD is still unclear. The aim of this study was to investigate the prevalence of Achilles tendon xanthoma (ATX) and heterozygous FH in patients with stable CAD and ACS undergoing percutaneous coronary intervention (PCI). A total of 423 patients with CAD (273 stable CAD and 150 ACS) undergoing PCI at Chiba University Hospital between June 2016 and February 2018 were enrolled in this study. Soft X-ray radiography of the Achilles tendon was performed in all patients, and a maximum thickness of 9 mm or more is regarded as ATX. Heterozygous FH was diagnosed according to the Japan Atherosclerosis Society Guidelines. In comparisons between stable CAD and ACS patients, ATX was observed in 9.2% vs. 15.3% (p = 0.055), and heterozygous FH was diagnosed in 3.7% vs. 5.3% (p = 0.416), respectively. Among ACS patients, those with ST elevation myocardial infarction (STEMI) showed the highest prevalence of ATX (19.5%) and FH (7.3%). Whereas ATX and heterozygous FH were considerably observed in patients with ACS, a certain number of ATX and heterozygous FH were also detected in stable CAD patients.

The SYNERGY coronary stent is new-generation drug-eluting stents, which has a thin-strut platinum-chromium platform with everolimus in a biodegradable polymer applied to the abluminal surface. It would be speculated that favorable arterial healing with early strut coverage could be achieved. The present study investigated the degree of strut coverage using optical coherence tomography (OCT) 2 weeks after SYNERGY implantation and clinical factors contributing to strut coverage. A total of 29 patients who underwent staged percutaneous coronary intervention (PCI) to residual lesions 2 weeks after the index PCI with SYNERGY stent implantation were enrolled. At the time of staged PCI, OCT examinations of the SYNERGY stent were performed for conventional OCT analysis on both cross-sectional and strut level. SYNERGY stent showed a high level of strut coverage and apposition, and the percentage was 82.4 ± 12.4% and 96.2 ± 5.0%, respectively. The lesion complexity was significantly related to greater strut coverage on univariate analysis; however, it was found to be insignificant in multivariate analysis. Our findings suggest early arterial healing after SYNERGY stent implantation.

OBJECTIVES: Coronary endothelial and circulatory dysfunction plays important roles in the pathogenesis of vasospastic angina (VSA). However, a complete understanding of the entire coronary circulation including microvasculature in patients with VSA is lacking. PATIENTS AND METHODS: A total of 32 patients without obstructive coronary artery disease in the left descending coronary artery, who underwent an intracoronary acetylcholine (ACh) provocation test for diagnosis of VSA, were enrolled prospectively. A positive diagnosis of the ACh test was defined as total/subtotal coronary artery narrowing accompanied by chest pain and/or ischemic ECG changes. Angina frequency and severity at baseline, and 1 and 3 months were recorded. Coronary circulation was evaluated invasively using a thermodilution method by obtaining the mean transit time (Tmn) at rest and hyperemia, coronary flow reserve, and index of microcirculatory resistance. Systemic endothelial function was assessed by the reactive hyperemia index. RESULTS: There were 14 (44%) and 18 (56%) patients with and without a positive ACh provocation test. The baseline characteristics did not differ significantly between the two groups. Patients with VSA had a significantly lower reactive hyperemia index compared with those without VSA (1.70±0.33 vs. 2.12±0.53, P=0.02). Coronary flow reserve, index of microcirculatory resistance, and hyperemic Tmn were not different between the two groups, whereas resting Tmn was significantly longer in patients with VSA (1.20±0.44 vs. 0.71±0.37, P=0.002). Although the frequency and severity of angina improved from baseline to 1 and 3 months in patients with both positive and negative ACh tests, there was no difference between the two groups. CONCLUSION: Patients with VSA had decreased resting coronary flow and impaired endothelial function.