A case of spontaneous coronary artery dissection that later turned out to be Takayasu arteritis.

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome (ACS), which typically occurs in women at low risk of atherosclerosis. We herein report a case of SCAD in a 57-year-old man who later developed Takayasu arteritis. The patient presented to our hospital complaining of chest pain and was diagnosed with unstable angina. Emergent coronary angiography was performed, and optical coherence tomography revealed that ACS was caused by SCAD. The patient was treated medically without further ballooning or stenting. Because there was a bilateral difference in blood pressure, the systemic artery was screened by contrast-enhanced computed tomography, which showed left subclavian artery occlusion, proximal stenosis of the superior mesenteric artery, right common iliac artery dissection, and left external iliac artery dissection. Based on these results and 18F-fluorodeoxyglucose positron emission tomography findings, we diagnosed Takayasu arteritis. Prednisolone and tocilizumab were selected for medical treatment, and the patient was in a good condition at one year after the diagnosis. Takayasu arteritis can cause dissection of various arteries and should be suspected when atypical SCAD or multiple dissections are present. Early initiation of immunosuppressive therapy can control disease activity. Learning objective: Spontaneous coronary artery dissection (SCAD) is an important cause of acute coronary syndrome. In this case, we experienced a case of SCAD which turned out to be the first symptom of Takayasu arteritis. Immunosuppressive therapy was effective for both coronary lesion and systemic vasculitis. Not only fibromuscular dysplasia, but also various types of vasculitis should therefore be considered in the differential diagnosis when encountering atypical SCAD cases.

Mechanisms of Very Late Stent Thrombosis in Japanese Patients as Assessed by Optical Coherence Tomography.

BACKGROUND: Although very late stent thrombosis (VLST) remains an important concern, the underlying etiology and clinical characteristics are not fully elucidated in Japanese patients who undergo intravascular imaging-guided percutaneous coronary intervention (PCI) regularly. METHODS: We identified 50 VLST lesions (bare-metal stent [BMS] [n = 16], first-generation drug-eluting stent [DES] [n = 14] and newer-generation DES [n = 20]) in patients managed in our institutes. The underlying mechanism of VLST was assessed by optical coherence tomography (OCT), and the major etiology of each lesion was determined. The aim of this study was to explore the mechanisms of VLST of BMSs and DESs in Japanese patients. RESULTS: The median duration since stent implantation was 10 years (range: 1-20). The most frequent etiology of VLST was neoatherosclerotic rupture (44%), followed by neointimal erosion (24%). Edge disease (10%) and evagination (10%) were similarly observed. Malapposition (8%) was deemed to be acquired late by looking at intravascular imaging from the index procedure. Uncovered struts (2%) and in-stent calcified nodule (2%) were the least frequent etiologies. Regardless of etiology, signs of neoatherosclerosis were present in most lesions (82%). Most patients received single (68%) or dual (8%) antiplatelet therapy or oral anticoagulation alone (4%), whereas a considerable proportion of patients discontinued medication (20%). Regarding the treatment strategy, drug-coated balloon was the most frequent strategy (56%), followed by implantation of newer DESs (34%). CONCLUSIONS: Various mechanisms have been identified in Japanese patients with VLST. In these patients, biological responses seemed to be more relevant than the index procedure-related factors.

Assessment of Residual Vasospasm in Patients with Plaque Rupture or Plaque Erosion using Optical Coherence Tomography.

AIMS: Coronary vasospasm is associated with acute coronary syndrome (ACS) and may persist during primary percutaneous coronary intervention (PCI). We aimed to elucidate the incidence, morphological characteristics, and prognostic impact of residual vasospasm in plaque rupture (PR) and plaque erosion (PE) lesions using optical coherence tomography (OCT). METHODS: We enrolled 142 patients with ACS who underwent OCT-guided primary PCI. All patients received intracoronary vasodilators before OCT examination. Residual vasospasm was identified as intimal gathering and categorised as polygonal- or wavy- patterned depending on the luminal shape. A wavy pattern was defined as a curved intimal surface line. A polygonal pattern was defined as a lumen with multiple angles. The incidence of major cardiovascular events, defined as death, non-fatal myocardial infarction, stroke, and any revascularization, within 1-year of PCI was identified. RESULTS: The prevalence of residual vasospasm in PR and PE was 15.1% (13 of 86) and 21.4% (12 of 56), respectively. Wavy pattern was the major shape of the residual vasospasm. Polygonal-patterned lumen was more frequently observed in PR than in PE (38.5 vs. 8.3 %). The polygonal-patterned lumens had significantly larger lipid arcs (257.9 vs. 78.0 °; P＜0.01), and significantly smaller areas (1.27 vs. 1.88 mm2; P=0.05) than wavy patterned lumens. Residual vasospasm had a prognostic impact on PR but not PE at 1-year of successful primary PCI. CONCLUSION: Considerable proportion of ACS including both PR and PE had residual vasospasm with variable morphological feature and different prognostic impact.

Diagnosis and Prognostic Value of the Underlying Cause of Acute Coronary Syndrome in Optical Coherence Tomography-Guided Emergency Percutaneous Coronary Intervention.

Background The prognostic impact of optical coherence tomography-diagnosed culprit lesion morphology in acute coronary syndrome (ACS) has not been systematically examined in real-world settings. Methods and Results This investigator-initiated, prospective, multicenter, observational study was conducted at 22 Japanese hospitals to identify the prevalence of underlying ACS causes (plaque rupture [PR], plaque erosion [PE], and calcified nodules [CN]) and their impact on clinical outcomes. Patients with ACS diagnosed within 24 hours of symptom onset undergoing emergency percutaneous coronary intervention were enrolled. Optical coherence tomography-guided percutaneous coronary intervention recipients were assessed for underlying ACS causes and followed up for major adverse cardiac events (cardiovascular death, myocardial infarction, heart failure, or ischemia-driven revascularization) at 1 year. Of 1702 patients with ACS, 702 (40.7%) underwent optical coherence tomography-guided percutaneous coronary intervention for analysis. PR, PE, and CN prevalence was 59.1%, 25.6%, and 4.0%, respectively. One-year major adverse cardiac events occurred most frequently in patients with CN (32.1%), followed by PR (12.4%) and PE (6.2%) (log-rank P<0.0001), primarily driven by increased cardiovascular death (CN, 25.0%; PR, 0.7%; PE, 1.1%; log-rank P<0.0001) and heart failure trend (CN, 7.1%; PR, 6.8%; PE, 2.2%; log-rank P<0.075). On multivariate Cox regression analysis, the underlying ACS cause was associated with 1-year major adverse cardiac events (CN [hazard ratio (HR), 4.49 [95% CI, 1.35-14.89], P=0.014]; PR (HR, 2.18 [95% CI, 1.05-4.53], P=0.036]; PE as reference). Conclusions Despite being the least common, CN was a clinically significant underlying ACS cause, associated with the highest future major adverse cardiac events risk, followed by PR and PE. Future studies should evaluate the possibility of ACS underlying cause-based optical coherence tomography-guided optimization.

Neointimal characteristic changes following drug-coated balloons in lesions with repeated revascularization.

BACKGROUND: Since their emergence, drug-coated balloons (DCBs) have been used widely to treat in-stent lesions with coronary artery disease (CAD). However, despite their superior efficacy to balloon angioplasty, how DCBs affect neointimal characteristics is poorly understood. OBJECTIVES: We aimed to assess the neointimal characteristic changes following DCB treatment. METHODS: Using optical frequency domain imaging (OFDI), we serially observed the in-stent lesion site just after and 1 year after DCB angioplasty in 12 lesions of 11 patients with repeated revascularization. Neoatherosclerosis was defined as lipid-laden neointima with or without calcification in the stented lesion. Progression or regression of neoatherosclerosis, newly formed neointimal calcification, newly formed uncovered strut and newly formed evagination were assessed. Tiny tissue protrusion was also recorded as mushroom-like protrusion. RESULTS: Underlying stents were first-generation (n = 5) or newer (n = 7) drug-eluting stents (DESs) with implantation durations ranging from 1 to 15 years (median 8 years). Surprisingly, two-thirds of the lesions (67%, 8 of 12) showed progression of neoatherosclerosis, while a quarter of lesions (25%, 3 of 12) showed regression of neoatherosclerosis. The maximal lipid arc increased from 122° to 174°. Newly formed neointimal calcification was observed in 2 of 12 lesions (16%). Newly formed uncovered struts (33%; 4 of 12) and newly formed evaginations (33%; 4 of 12) were not rare. Mushroom-like protrusion was found in a quarter of lesions (25%; 3 of 12). CONCLUSION: Our study demonstrated that a considerable number of lesions showed varied neointimal characteristic changes in a small number of patients. Further studies in a larger population are needed to understand the clinical impact of these findings.

Percutaneous coronary intervention for a healed erosion with excimer laser coronary angioplasty and drug-coated balloon angioplasty: a case report.

Background: Healed plaque, characterized by distinct layers of organizing thrombus and collagen, is the hallmark of tissue self-repair. However, the efficacy of excimer laser coronary angioplasty (ELCA) followed by drug-coated balloon (DCB) angioplasty in patients with healed plaques is not fully understood. Case summary: A 42-year-old woman with a history of anxiety disorder was admitted to our institution with worsening chest pain and subsequently diagnosed with anterior non-ST-elevation myocardial infarction. Coronary angiography revealed severe stenosis in the proximal left anterior descending artery (LAD) despite Thrombolysis in Myocardial Infarction (TIMI) grade 3. Optical coherence tomography (OCT) showed healed plaques with partial macrophage accumulation and no fresh thrombus. Plaque disruption and thin-cap fibrous atheroma were not identified in the culprit lesions. Intravascular ultrasound (IVUS) confirmed high-intensity marginal irregular masses at the culprit site, suggesting that the thrombus was formed by plaque erosion rather than lipid plaque or necrotic tissue. With lesion modification using ELCA prior to DCB angioplasty, OCT examination of the LAD after ELCA showed a significant reduction in plaque burden and preserved lumen size. Post-percutaneous coronary intervention angiography revealed no stenosis with TIMI grade 3. A follow-up coronary computed tomography scan showed no angiographic restenosis, and the patient remained symptom-free. Conclusions: Here we describe a case in which OCT and IVUS evaluation suggested organizing thrombus due to erosion healing, and a favorable outcome was achieved with the combination of ELCA and DCB. The combination use of ELCA and DCB might be a potential strategy for acute coronary syndrome patients with organizing thrombus.

Optical Coherence Tomography-Guided Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: Rationale and Design of the ATLAS-OCT Study.

Even after successful revascularization with primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI), subsequent adverse events still occur. Previous studies have suggested potential benefits of intravascular imaging, including optical coherence tomography (OCT). However, the feasibility of OCT-guided primary PCI has not been systematically examined in these patients. The ATLAS-OCT (ST-elevation Acute myocardial infarcTion and cLinicAl outcomeS treated by Optical Coherence Tomography-guided percutaneous coronary intervention) trial was designed to investigate the feasibility of OCT guidance during primary PCI for STEMI in experienced centers with expertise on OCT-guided PCI as a prospective, multicenter registry of consecutive patients with STEMI who underwent a primary PCI. The sites' inclusion criteria are as follows: (1) acute care hospitals providing 24/7 emergency care for STEMI, and (2) institutions where OCT-guided PCI is the first choice for primary PCI in STEMI. All patients with STEMI who underwent primary PCI at participating sites will be consecutively enrolled, irrespective of OCT use during PCI. The primary end point will be the rate of successful OCT imaging during the primary PCI. As an ancillary imaging modality to angiography, OCT provides morphologic information during PCI for the assessment of plaque phenotypes, vessel sizing, and PCI optimization. Major adverse cardiac events, defined as a composite of all-cause death, myocardial infarction, and target vessel revascularization at 1 year, will also be recorded. The ATLAS-OCT study will clarify the feasibility of OCT-guided primary PCI for patients with STEMI and further identify a suitable patient group for OCT-guided primary PCI.

Association between Eicosapentaenoic Acid to Arachidonic Acid Ratio and Characteristics of Plaque Rupture.

AIMS: Eicosapentaenoic acid (EPA) has shown beneficial effects on coronary plaque stabilization. Based on our previous study, we speculated that EPA might be associated with the development of healed plaques and might limit thrombus size. This study aimed to elucidate the association between EPA and arachidonic acid (AA) ratios and various plaque characteristics in patients with plaque rupture. METHODS: A total of 95 patients with acute coronary syndrome (ACS) caused by plaque rupture who did not take lipid-lowering drugs and underwent percutaneous coronary intervention using optical coherence tomography (OCT) were included. Clinical characteristics, lipid profiles, and OCT findings were compared between patients with lower and higher EPA/AA ratios (0.41) according to the levels in the Japanese general population. RESULTS: In the high EPA/AA (n=29, 30.5%) and low EPA/AA (n=66, 69.5 %) groups, the high EPA/AA group was significantly older (76.1 vs. 66.1 years, P＜0.01) and had lower peak creatine kinase (556 vs. 1651 U/L, P=0.03) than those with low EPA/AA. Similarly, patients with high EPA/AA had higher prevalence of layered and calcified plaque (75.9 vs. 39.4 %, P＜0.01; 79.3 vs. 50.0 %, P＜0.01, respectively) than low EPA/AA group. Multivariate logistic regression analysis demonstrated that a high EPA/AA ratio was an independent factor in determining the development of layered and calcified plaques. CONCLUSION: A high EPA/AA ratio may be associated with the development of layered and calcified plaques in patients with plaque rupture.

Impact of triglyceride-rich lipoproteins on early in-stent neoatherosclerosis formation in patients undergoing statin treatment.

BACKGROUND: Neoatherosclerosis (NA), which refers to neointimal atherosclerosis within a stent, is considered one of the underlying causes of late-phase stent failure following a newer generation drug-eluting stent (DES) placement procedure. Even contemporary guideline-directed medical therapy may be insufficient to prevent NA. OBJECTIVE: This study aimed to investigate how intricately lipid markers are associated with NA formation in the early phase of treatment with well-maintained low-density lipoprotein cholesterol (LDL-C) levels. METHODS: We enrolled 114 consecutive patients undergoing statin treatment and percutaneous coronary intervention (PCI) with current-generation DES for coronary artery disease. At a median 12 months after PCI, optical coherence tomography (OCT) was performed. Various lipid markers, including LDL-C, triglyceride (TG), triglyceride-rich lipoprotein cholesterol (TRL-C), non-high-density lipoprotein cholesterol (non-HDL-C), malondialdehyde-modified LDL (MDA-LDL), and several apolipoproteins, were also evaluated. RESULTS: NA was observed in 17 (14.9%) patients. The LDL-C level was equivalent in patients with or without NA (77.2 vs. 69.8 mg/dL; p=0.15). However, the levels of TG, apolipoprotein C3 (apoC3), TRL-C, non-HDL-C, and apolipoprotein B (apoB), and MDA-LDL were significantly higher in the patients with NA. Furthermore, multivariate logistic regression adjusting for HbA1c and stent duration revealed apoC3, TRL-C, non-HDL-C, apoB, and MDA-LDL levels as risk factors for NA. However, when apoB was included as a covariate, other factors became nonsignificant. CONCLUSIONS: Abnormal triglyceride-rich lipoprotein metabolism and high atherogenic apoB-containing lipoprotein particle numbers are associated with the formation of NA in patients undergoing statin treatment at a median 12 months post-PCI.

Clopidogrel Monotherapy After 1-Month Dual Antiplatelet Therapy in Patients With Diabetes Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Diabetes was reported to be associated with an impaired response to clopidogrel. OBJECTIVES: The aim of this study was to evaluate the safety and efficacy of clopidogrel monotherapy after very short dual antiplatelet therapy (DAPT) in patients with diabetes undergoing percutaneous coronary intervention (PCI). METHODS: A subgroup analysis was conducted on the basis of diabetes in the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2) Total Cohort (N = 5,997) (STOPDAPT-2, n = 3,009; STOPDAPT-2 ACS [Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 for the Patients With ACS], n = 2,988), which randomly compared 1-month DAPT followed by clopidogrel monotherapy with 12-month DAPT with aspirin and clopidogrel after cobalt-chromium everolimus-eluting stent implantation. The primary endpoint was a composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) or bleeding (TIMI [Thrombolysis In Myocardial Infarction] major or minor) endpoints at 1 year. RESULTS: There were 2,030 patients with diabetes (33.8%) and 3967 patients without diabetes (66.2%). Regardless of diabetes, the risk of 1-month DAPT relative to 12-month DAPT was not significant for the primary endpoint (diabetes, 3.58% vs 4.12% [HR: 0.87; 95% CI: 0.56-1.37; P = 0.55]; nondiabetes, 2.46% vs 2.49% [HR: 0.99; 95% CI: 0.67-1.48; P = 0.97]; Pinteraction = 0.67) and for the cardiovascular endpoint (diabetes, 3.28% vs 3.05% [HR: 1.10; 95% CI: 0.67-1.81; P = 0.70]; nondiabetes, 1.95% vs 1.43% [HR: 1.38; 95% CI: 0.85-2.25; P = 0.20]; Pinteraction = 0.52), while it was lower for the bleeding endpoint (diabetes, 0.30% vs 1.50% [HR: 0.20; 95% CI: 0.06-0.68; P = 0.01]; nondiabetes, 0.61% vs 1.21% [HR: 0.51; 95% CI: 0.25-1.01; P = 0.054]; Pinteraction = 0.19). CONCLUSIONS: Clopidogrel monotherapy after 1-month DAPT compared with 12-month DAPT reduced major bleeding events without an increase in cardiovascular events regardless of diabetes, although the findings should be considered as hypothesis generating, especially in patients with acute coronary syndrome, because of the inconclusive result in the STOPDAPT-2 ACS trial. (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 [STOPDAPT-2], NCT02619760; Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 for the Patients With ACS [STOPDAPT-2 ACS], NCT03462498).

Prevalence and Effects of High-Intensity Statins for Japanese Patients Presenting With Acute Coronary Syndrome　- A Post Hoc Secondary Analysis of STOPDAPT-2 ACS.

BACKGROUND: The REAL-CAD trial, reported in 2017, demonstrated a significant reduction in cardiovascular events with high-intensity statins in patients with chronic coronary syndrome. However, data are scarce on the use of high-intensity statins in Japanese patients with acute coronary syndrome (ACS).Methods and Results: In STOPDAPT-2 ACS, which exclusively enrolled ACS patients between March 2018 and June 2020, 1,321 (44.2%) patients received high-intensity statins at discharge, whereas of the remaining 1,667 patients, 96.0% were treated with low-dose statins. High-intensity statins were defined as the maximum approved doses of strong statins in Japan. The incidence of the cardiovascular composite endpoint (cardiovascular death, myocardial infarction, definite stent thrombosis, stroke) was significantly lower in patients with than without high-intensity statins (1.44% vs. 2.69% [log-rank P=0.025]; adjusted hazard ratio [aHR] 0.48, 95% confidence interval [CI] 0.24-0.94, P=0.03) and the effect was evident beyond 60 days after the index percutaneous coronary intervention (log-rank P=0.01; aHR 0.38, 95% CI 0.17-0.86, P=0.02). As for the bleeding endpoint, there was no significant difference between the 2 groups (0.99% vs. 0.73% [log-rank P=0.43]; aHR 0.96, 95% CI 0.35-2.60, P=0.93). CONCLUSIONS: The prevalence of high-intensity statins has increased substantially in Japan. The use of the higher doses of statins in ACS patients recommended in the guidelines was associated with a significantly lower risk of the primary cardiovascular composite endpoint compared with lower-dose statins.

Radial versus femoral access in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction: A propensity-matched analysis from real-world data of the K-ACTIVE registry.

BACKGROUND: The access site for primary percutaneous coronary intervention (PCI) for patients with ST-elevation myocardial infarction (STEMI) recently shifted from femoral to radial. However, few real-world data on Japanese patients exist. METHODS: To elucidate the clinical selection and impact of the access site in STEMI patients, we analyzed a Japanese observational prospective multicenter registry of acute myocardial infarction (K-ACTIVE: Kanagawa ACuTe cardIoVascular rEgistry) in 2015 to 2021. Data were analyzed in the entire population and a propensity score-matched population adjusted for confounding factors. Major adverse cardiac event (MACE) was defined as cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Bleeding Academic Research Consortium (BARC) type 3 or 5 was used to assess bleeding events. MACE plus BARC type 3 or 5 bleeding were considered composite events. Clinical outcomes were followed for 30 days. RESULTS: The 6802 STEMI patients included 4786 patients with radial access (70.3 %) and 2016 with femoral access (29.7 %). Femoral access tended to be selected for more severe conditions than radial access. The median door-to-device time in the radial access group was significantly shorter than the femoral access group in the entire population (75 min versus 79 min, p < 0.01). After propensity score matching (each group, n = 1208), the incidence of MACE tended to be lower in the radial access group [risk ratio (RR) 0.83, 95 % confidence interval (CI) 0.63-1.09, p = 0.17]. The incidence of BARC 3 or 5 bleeding was significantly less in the radial access group (RR 0.47, 95%CI 0.23-0.97, p = 0.04). The incidence of composite events was significantly less in the radial access group (RR 0.74, 95%CI 0.57-0.96, p = 0.02). CONCLUSION: In STEMI patients undergoing primary PCI, in comparison to femoral access, radial access reduced composite events in the entire population and the matched population, through a reduction in MACE and BARC 3 or 5 bleeding.

Angioscopic Findings of Stenosis Versus Occlusion in Femoropopliteal Artery Disease.

BACKGROUND: Despite the increase in the number of patients with peripheral artery disease (PAD), the pathophysiology is not fully elucidated. Recently, angioscopy with a 0.48-megapixel equivalent resolution camera became available for patients with PAD. We aimed to compare the plaque component between native stenosis and occlusion in the femoropopliteal artery using this modality. MATERIALS AND METHODS: Thirty-two consecutive patients who underwent endovascular treatment for native femoropopliteal artery disease with angioscopy were studied. The major angioscopic classifications of each lesion were defined as follows: atheromatous plaque (AP) was defined as luminal narrowing without any protrusion, calcified nodule (CN) was defined as a protruding bump with surface irregularity, a mainly reddish thrombus was defined as organizing thrombus (OG), and organized thrombus (OD) was defined by more than half of the thrombus showing a whitish intima-like appearance. RESULTS: A total of 34 lesions (stenosis, n=18; occlusion, n=16) from 32 patients were included. All stenotic lesions showed AP or CN (n=8 [44%], n=10 [56%], respectively), whereas all occluded lesions showed OG or OD (n=5 [31%], n=11 [69%], respectively), which amounted to a statistically significant difference (p<0.001). In occluded lesions, stiff wires (>3 g) were required to cross all lesions classified as OD, whereas this was not always necessary for lesions classified as OG (11 [100%] of 11, 1 [25%] of 5, respectively; p=0.04). Yellow color plaques were observed to a similar degree in all angioscopic classifications. Major adverse limb events, defined as amputation and any reintervention at 12 months, were highly variable, depending on the angioscopic findings, and tended to be more frequently observed in CN and OD (13% in AP, 40% in CN, 0% in OT, and 36% in OD, p=0.25). CONCLUSION: Angioscopy revealed varying components in stenosis and occlusion with different degrees of clinical impact. This may provide new information on the pathophysiology of PAD.

Regnase-1 Prevents Pulmonary Arterial Hypertension Through mRNA Degradation of Interleukin-6 and Platelet-Derived Growth Factor in Alveolar Macrophages.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a type of pulmonary hypertension (PH) characterized by obliterative pulmonary vascular remodeling, resulting in right-sided heart failure. Although the pathogenesis of PAH is not fully understood, inflammatory responses and cytokines have been shown to be associated with PAH, in particular, with connective tissue disease-PAH. In this sense, Regnase-1, an RNase that regulates mRNAs encoding genes related to immune reactions, was investigated in relation to the pathogenesis of PH. METHODS: We first examined the expression levels of ZC3H12A (encoding Regnase-1) in peripheral blood mononuclear cells from patients with PH classified under various types of PH, searching for an association between the ZC3H12A expression and clinical features. We then generated mice lacking Regnase-1 in myeloid cells, including alveolar macrophages, and examined right ventricular systolic pressures and histological changes in the lung. We further performed a comprehensive analysis of the transcriptome of alveolar macrophages and pulmonary arteries to identify genes regulated by Regnase-1 in alveolar macrophages. RESULTS: ZC3H12A expression in peripheral blood mononuclear cells was inversely correlated with the prognosis and severity of disease in patients with PH, in particular, in connective tissue disease-PAH. The critical role of Regnase-1 in controlling PAH was also reinforced by the analysis of mice lacking Regnase-1 in alveolar macrophages. These mice spontaneously developed severe PAH, characterized by the elevated right ventricular systolic pressures and irreversible pulmonary vascular remodeling, which recapitulated the pathology of patients with PAH. Transcriptomic analysis of alveolar macrophages and pulmonary arteries of these PAH mice revealed that Il6, Il1b, and Pdgfa/b are potential targets of Regnase-1 in alveolar macrophages in the regulation of PAH. The inhibition of IL-6 (interleukin-6) by an anti-IL-6 receptor antibody or platelet-derived growth factor by imatinib but not IL-1ß (interleukin-1ß) by anakinra, ameliorated the pathogenesis of PAH. CONCLUSIONS: Regnase-1 maintains lung innate immune homeostasis through the control of IL-6 and platelet-derived growth factor in alveolar macrophages, thereby suppressing the development of PAH in mice. Furthermore, the decreased expression of Regnase-1 in various types of PH implies its involvement in PH pathogenesis and may serve as a disease biomarker, and a therapeutic target for PH as well.

Impact of small dense low-density lipoprotein cholesterol and triglyceride-rich lipoproteins on plaque rupture with ST-segment elevation myocardial infarction.

BACKGROUND: Plaque rupture (PR), characterized by a disruption of the fibrous cap of lipid-rich plaques, is the major etiology of ST-segment elevation myocardial infarction (STEMI). Dyslipidemia is a well-known risk factor for PR. Nonetheless, the impact of detailed atherogenic lipid profiles, including small dense low-density lipoprotein cholesterol (sd-LDL-C) and triglyceride-rich lipoproteins (TRLs), on PR has not yet been investigated. OBJECTIVE: To elucidate the impact of sd-LDL-C and TRL levels on PR in patients with STEMI using optical coherence tomography (OCT). METHODS: A total of 106 consecutive statin-naive patients with STEMI were enrolled. The PR in culprit lesions was assessed on pre-intervention OCT images, and serum samples were collected immediately before coronary angiography. Sd-LDL-C was directly measured using a homogeneous assay. TRL-cholesterol (TRL-C) was estimated by subtracting the LDL-C level from the non-high-density lipoprotein cholesterol level. Clinical characteristics and lipid profiles were compared between the PR and intact fibrous cap (IFC). RESULTS: No difference in LDL-C levels was observed between the PR (n=64) and IFC (n=42) groups (120.0 mg/dL vs. 129.5 mg/dL, p=0.97); however, sd-LDL-C levels were significantly higher in the PR group (38.9 mg/dL vs. 32.4 mg/dL, p=0.04). Similarly, the PR group had higher TRL-C (24.0 mg/dL vs. 18.0 mg/dL, p=0.01) and triglyceride (130.0 mg/dL vs. 100.3 mg/dL, p=0.03) levels than the IFC group. Multivariate logistic regression analysis showed that sd-LDL-C was an independent factor determining PR (odds ratio, 1.53 per 10 mg/dL; p=0.04). CONCLUSION: Only sd-LDL-C levels were significantly associated with PR in culprit lesions in patients with STEMI.

Clinical features and lipid profiles of plaque erosion over lipid-rich plaque versus fibrous plaque in patients with acute coronary syndrome.

BACKGROUND AND AIMS: Pathological reports have shown that plaque erosion (PE), a common cause of acute coronary syndrome (ACS), can form in both fibrous plaque and lipid-rich plaque (LRP). In plaque rupture (PR), which is the main cause of ACS, the underlying plaque is LRP with a thin fibrous cap. In this study, we aimed to investigate the clinical features and lipid profiles of PE with or without LRP in comparison with those of PR. METHODS: A total of 166 patients with ACS, who underwent percutaneous coronary intervention using optical coherence tomography (OCT) and met the criteria for PR or PE, were included. LRP was defined as plaque with a maximal lipid arc (>180°). Culprit lesions were categorized into PR and PE with/without LRP [PE(Lipid) or PE(Fibrous)]. RESULTS: The prevalence of PR, PE(Lipid), and PE(Fibrous) was 104 (62.7%), 43 (25.9%), and 19(11.4%), respectively. The patients with PR and PE(Lipid) had a significantly higher peak creatine kinase level (1338 and 1584U/L, respectively, p < 0.01) and prevalence of ST-elevation myocardial infarction (71.2% and 79.1%, respectively, p < 0.01) than those with PE(Fibrous) (214U/L and 21.1%, respectively). The various lipid profiles were mostly comparable between the patients with PE(Lipid) and PR, but different in those with PE(Fibrous). The levels of small dense low-density lipoprotein cholesterol were significantly higher in the patients with PR and PE(Lipid) than in those with PE(Fibrous) (39.0, 35.3, and 25.7 mg/dL, respectively, p = 0.02). CONCLUSIONS: The clinical features and lipid profiles are substantially different between PE(Lipid) and PE(Fibrous), but are somewhat similar between PE(Lipid) and PR.

Rationale and design of the TACTICS registry: Optical coherence tomography guided primary percutaneous coronary intervention for patients with acute coronary syndrome.

BACKGROUND: Recent retrospective investigations have suggested that optical coherence tomography (OCT) enables the diagnosis of underlying acute coronary syndrome (ACS) causes such as plaque rupture, plaque erosion, and calcified nodule. The relationships of these etiologies with clinical outcomes, and the clinical utility of OCT-guided primary percutaneous coronary intervention (PCI) are not systematically studied in real-world ACS treatment settings. METHODS: The TACTICS registry is an investigator-initiated, prospective, multicenter, observational study to be conducted at 21 hospitals in Japan. A total of 700 patients with ACS (symptom onset within 24 h) undergoing OCT-guided primary PCI will be enrolled. The primary endpoint of the study is to identify the underlying causes of ACS using OCT-defined morphological assessment of the culprit lesion. The key secondary clinical endpoints are hazard ratios of the composite of cardiovascular death, non-fatal myocardial infarction, heart failure, or ischemia-driven revascularization in patients with underlying etiologies at the 12- and 24-month follow-ups. The feasibility of OCT-guided primary PCI for ACS will be assessed by the achievement rates of optimal post-procedural results and safety endpoints. CONCLUSION: The TACTICS registry will provide an overview of the underlying causes of ACS using OCT, and will reveal any difference in clinical outcomes depending on the underlying causes. The registry will also inform on the feasibility of OCT-guided primary PCI for patients with ACS.

Impact of small dense low-density lipoprotein cholesterol on cholesterol crystals in patients with acute coronary syndrome: An optical coherence tomography study.

BACKGROUND: The presence of cholesterol crystals (CCs) is recognized as a component of vulnerable atherosclerotic plaques at risk of rupture. The phagocytosis of atherogenic lipid factors by macrophages precedes and promotes the formation of vulnerable plaques, but it is not clear how these factors affect the formation of CC. OBJECTIVE: This study aimed to evaluate the relationship between lipid biomarkers such as small dense low-density lipoprotein cholesterol (sd-LDL-c) and CC detected by optical coherence tomography (OCT) in patients with acute coronary syndrome (ACS). METHODS: Serum samples were collected immediately before coronary angiography in consecutive 174 patients with ACS who did not take statins and underwent OCT imaging of the culprit lesion. The sd-LDL-c levels were measured using a direct homogenous assay. CC was defined as a thin linear structure with high reflectivity and low signal attenuation on the OCT images. RESULTS: CC was identified in 85 patients (48.9%). The prevalence of CC was significantly higher in lesions with ruptured plaques and greater macrophage grade. The sd-LDL-c levels were significantly higher in the patients with CC (41.6 vs. 31.2 mg/dL, p = 0.01) although there were no significant differences in the levels of LDL-c and apolipoprotein B. The CC group also had higher levels of apolipoprotein C3 and HbA1c levels. In multiple logistic regression analysis, sd-LDL-c was an independent risk factor of CC (odds ratio, 1.19 per 10 mg/dL; p = 0.03). CONCLUSIONS: sd-LDL may play an important role in the presence of CC in patients with ACS.