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Background This study evaluated the mechanism of decline in coronary pressure from the proximal to the distal part of the coronary arteries in the left anterior descending (LAD) versus the right coronary artery (RCA) from the insight of coronary hemodynamics using wave intensity analysis (WIA). Methods Twelve patients with angiographically normal LAD and RCA were prospectively enrolled. Distal coronary pressure, mean aortic pressure, and average peak velocity were measured at 4 different positions: 9, 6, 3, and 0 cm distal from each coronary ostium. Results The distal-to-proximal coronary pressure ratio during maximum hyperemia gradually decreased in proportion to the distance from the ostium (0.92±0.03 and 0.98±0.03 at 9 cm distal to the LAD and RCA ostium). WIA showed the dominant forward-traveling compression wave gradually decreased and the backward-traveling suction wave gradually decreased in proportion to the decrease in coronary pressure through the length of the non-diseased LAD but not the RCA. Conclusions The pushing wave and suction wave intensities on WIA were diminished in proportion to the distance from the ostium of the LAD despite the wave intensity not changing across the length of the RCA, which may lead to gradual intracoronary pressure drop in the angiographically normal LAD.

Purpose: To identify intravascular ultrasound (IVUS) findings that predict midterm stent patency in femoropopliteal (FP) lesions. Materials and Methods: A retrospective analysis was undertaken of 335 de novo FP lesions in 274 consecutive patients (mean age 72.4±8.2 years; 210 men) who had IVUS assessment before and after successful stent implantation. The mean lesion length was 13.2±9.8 cm. The primary outcome was primary patency at 24 months, defined as freedom from major adverse limb event (MALE) and in-stent restenosis (ISR). MALE was defined as major amputation or any target lesion revascularization (TLR). ISR was defined by a peak systolic velocity ratio >2.4 by duplex ultrasonography. Logistic regression analyses were performed to identify independent predictors of stent patency at 24 months; the results are presented as the odds ratio (OR) and 95% confidence interval (CI). Receiver operator characteristic (ROC) curve analysis was performed to determine the optimal threshold for prediction of stent patency at 24 months. Results: Over the 24-month follow-up, 18 (7%) patients died and 43 (15%) of 286 lesions were responsible for MALE (42 TLRs and 1 major amputation). Primary patency was estimated at 82.5% (95% CI 78.1% to 86.9%) at 12 months and 73.2% (95% CI 67.9% to 78.5%) at 24 months. Multivariable analysis revealed that longer lesion length (OR 0.89, 95% CI 0.82 to 0.97, p2 as the optimal cut-point for prediction of 24-month stent patency (area under the ROC curve 0.764). Kaplan-Meier estimates of 24-month primary patency were 83.7% (95% CI 78.3% to 89.2%) in lesions with a distal EEM area >29.0 mm2 vs 53.1% (95% CI 42.9% to 63.3%) in those with a distal EEM area ≤29.0 mm2 (p

Objective: Copper (Cu) is essential micronutrient, and its dysregulation is implicated in aortic aneurysm (AA) development. The Cu exporter ATP7A (copper-transporting P-type ATPase/Menkes ATPase) delivers Cu via the Cu chaperone Atox1 (antioxidant 1) to secretory Cu enzymes, such as lysyl oxidase, and excludes excess Cu. Lysyl oxidase is shown to protect against AA formation. However, the role and mechanism of ATP7A in AA pathogenesis remain unknown. Approach and Results: Here, we show that Cu chelator markedly inhibited Ang II (angiotensin II)–induced abdominal AA (AAA) in which ATP7A expression was markedly downregulated. Transgenic ATP7A overexpression prevented Ang II–induced AAA formation. Conversely, Cu transport dysfunctional ATP7A mut/+ /ApoE −/− mice exhibited robust AAA formation and dissection, excess aortic Cu accumulation as assessed by X-ray fluorescence microscopy, and reduced lysyl oxidase activity. In contrast, AAA formation was not observed in Atox1 −/− /ApoE −/− mice, suggesting that decreased lysyl oxidase activity, which depends on both ATP7A and Atox1, was not sufficient to develop AAA. Bone marrow transplantation suggested importance of ATP7A in vascular cells, not bone marrow cells, in AAA development. MicroRNA (miR) array identified miR-125b as a highly upregulated miR in AAA from ATP7A mut/+ /ApoE −/− mice. Furthermore, miR-125b target genes (histone methyltransferase Suv39h1 and the NF-κB negative regulator TNFAIP3 [tumor necrosis factor alpha induced protein 3]) were downregulated, which resulted in increased proinflammatory cytokine expression, aortic macrophage recruitment, MMP (matrix metalloproteinase)-2/9 activity, elastin fragmentation, and vascular smooth muscle cell loss in ATP7A mut/+ /ApoE −/− mice and reversed by locked nucleic acid-anti-miR-125b infusion. Conclusions: ATP7A downregulation/dysfunction promotes AAA formation via upregulating miR-125b, which augments proinflammatory signaling in a Cu-dependent manner. Thus, ATP7A is a potential therapeutic target for inflammatory vascular disease.

Our group has previously reported that lack of adipose tissue (lipodystrophy) leads to glucose intolerance and impaired endothelial-dependent vasorelaxation (EDR) via reduced signaling of the adipokine, leptin in the endothelium. However, the identity of the adipose depot responsible for endothelial leptin signaling activation and the underlying mechanism remains ill-defined. Our new data indicate that the perivascular adipose tissue (PVAT) is an important source of leptin. Thus, we hypothesized that leptin specifically derived from PVAT restores EDR and glucose tolerance in a mouse model with global deficiency in adipose tissue (lipodystrophic, BSCL2 -/- ). Restoration of PVAT in BSCL2 -/- mice corrected systemic glycemic status (GTT AUC, BSCL2 -/- + PVAT 635.3 ± 31.28 vs sham 741.6 ± 45.87, p-/- + PVAT 224.9 ± 23.97 vs 109 ± 19, P-/- + PVAT 143.8 ± 22.29 vs sham 131.3 ± 11.54, P-/- mice showed a trend towards an increase in PFKFB3 mRNA expression compared to WT mice. Moreover, we found that overexpression of PFKFB3 in aortic rings and endothelial cells impaired EDR and increased the ROS generating enzyme, Nox1 expression, respectively. Collectively, our results showed the critical role of PVAT-driven leptin and endothelial leptin receptor signaling in regulating systemic glucose disposal as well as endothelial function via a mechanism that potentially regulates endothelial glycolysis and oxidative stress-mediated via PFKFB3/NOX1.

Introduction: Abdominal aortic aneurysms (AAA) are characterized by inflammation and matrix metalloproteinase (MMP)-mediated degradation of extra cellular matrix proteins leading to aortic dilation and potentially rupture. Inflammatory chemokines that promote AAA are modulated by binding to the Duffy antigen receptor for chemokines (DARC), a non-signaling receptor expressed primarily on erythrocytes. Interestingly, African Americans exhibit reduced frequency of AAA, and the majority of African descendent individuals do not express DARC on their erythrocytes. Here, we tested the hypothesis that DARC gene deletion protects against the development of AAA. Methods: The induction of AAA was performed using both angiotensin II (AngII) infusion and calcium chloride (CaCl 2 ) application models. Eight week old LDLR knockout (KO, control) and LDLR KO/DARC KO mice were infused with AngII via osmotic mini-pumps for four weeks. For the CaCl 2 application model, twelve week old DARC KO and WT control mice underwent laparotomy and 0.5 mol/L CaCl 2 was applied to the infrarenal aorta. Aortic dilation and AAA formation was assessed using ultrasound, mice were then euthanized and tissues were harvested for analysis. Results: The aortic diameter of LDLR KO/DARC KO mice was significantly lower relative to control mice after AngII infusion (P=0.02). There was no difference in the pressor response to AngII between groups. Furthermore, IL-6 levels were significantly reduced in the aortas of LDLR KO/DARC KO mice compared to control mice (P=0.001). Expression of MCP-1, which has strong affinity for DARC, tended to be higher in aortas from LDLR KO/DARC KO mice compared to control (P=0.063). In contrast, plasma IL-6 levels were similar in both LDLR KO/DARC KO and control mice, while MCP-1 tended to be lower in the plasma of LDLR KO/DARC KO (P=0.07). DARC KO mice likewise exhibited a trend toward reduced aortic dilation in the CaCl 2 application model compared to controls (P=0.09). Conclusions: DARC KO mice are protected against AAA formation, perhaps through differential regulation of aortic chemokine trafficking. Understanding the mechanisms by which loss of DARC confers protection from AAA formation may be relevant to ethnic differences in susceptibility to AAA.

BACKGROUND Coronary angioscopy (CAS) is used to comprehensively evaluate vascular responses after drug-eluting stent (DES) implantation. This study sought to evaluate the capability of CAS for evaluating DES strut coverage grade and color grade of the intima compared with histological images in coronary autopsy specimens. Methods and Results: A total of 23 DES extracted from 11 autopsy hearts were imaged by CAS. All stent segments were graded as white or yellow according to the luminal surface color, and thrombus was evaluated according to a previous report. Neointimal coverage over the DES was graded as 0 (stent struts fully visible) to grade 3 (stent struts fully embedded and invisible). Of 76 segments, neointimal coverage was graded as 0 in 35 (46%), 1 in 22 (29%), 2 in 8 (11%), and 3 in 11 (14%). The neointimal thickness increased significantly with increasing neointimal coverage grade on angioscopy. Neointimal color was graded as white in 40 (53%) and yellow in 36 segments (47%). Histological analysis revealed that yellow neointima contained fibroatheroma, foam cells accumulation or superficial calcium deposition. A thrombus was identified in 13 segments. Thrombi adherent around the stent strut were partly intimal erythrocyte accumulation around the strut. CONCLUSIONS In-stent yellow segment had atherosclerotic components. CAS could evaluate vascular status comprehensively after DES implantation.

This study evaluated the impact of optical coherence tomography (OCT)-derived low-backscattered tissue on mid-term coronary endothelial function after drug-eluting stent (DES) implantation. Although OCT enables detailed in vivo evaluation of neointimal tissue characterization after DES implantation, its association with physiological vascular healing response is unclear. Thirty-three stable angina pectoris patients underwent OCT examination and endothelial function testing with intracoronary infusion of incremental doses of acetylcholine 8-month after DES implantation in a single lesion of the left anterior descending artery. Neointimal tissue was classified into two patterns based on the predominant OCT light backscatter: high backscatter and low backscatter. Although the presence of uncovered or malapposed stent strut was not associated with the degree of vasoconstriction, the degree of vasoconstriction was significantly greater in the DES with low-backscattered neointima than in the DES without low-backscattered neointima (- 32.1 ± 25.7 vs. - 4.1 ± 20.1%, p = 0.003). Moreover, there was an inverse linear relationship between low backscatter tissue index and degree of vasoconstriction after acetylcholine infusion (r = 0.50 and p = 0.003). The endothelium-dependent vasomotor response after 8-month of DES was impaired in patients with low neointimal tissue backscatter on OCT imaging. OCT assessment of low-backscattered tissue may be used as surrogate markers for impairment of endothelial function after DES.

In addition to plaque rupture (PR), calcified nodule (CN) may also have the potential to develop into arterial thrombus in the peripheral arteries. This study evaluated the distribution of plaque ruptures and calcified nodules in the peripheral arteries and their impact on the outcome of endovascular therapy (EVT). Consecutive 159 patients who underwent EVT with intravascular ultrasound guidance were enrolled. The position of CNs and PRs were assigned to any of common iliac artery, external iliac artery, common femoral artery, and superficial femoral artery. Forty-six (29%) patients had calcified nodule and twenty-eight (18%) patients had plaque rupture somewhere in the lower limb arteries. Although calcified nodules were evenly distributed throughout the length of the arteries plaque ruptures were predominantly located in the proximal segment of the iliofemoral arteries. Stent expansion ratio was significantly smaller in the target arteries with calcified nodules than in those with plaque rupture. Multivariate logistic regression analysis identified hemodialysis as an independent clinical predictor of calcified nodule (odds ratio 8.15, 95% confidence interval 1.73-38.3; P = 0.008). CN definitely affects incomplete stent deployment in the peripheral artery contributing to adverse events, on the other hand, PR has more acceptable outcomes after stent implantation. In the clinical setting, it is important that we realize the features of peripheral artery disease and its patient characteristics which having CNs and PRs to make a strategy for revascularization.

The aim of this study was to elucidate the vascular responses to paclitaxel-eluting stent (Zilver PTX stent) in superficial femoral artery lesion at different elapsed times using angioscopy. Patients who received Zilver PTX stent implantation from five centers were enrolled. We performed angioscopic examinations at 2, 6, and 12 months after implantation and evaluated neointimal coverage (NIC) grade, intra-stent thrombus (IS-Th) grade, and presence of yellow plaque. NIC grade 0 was defined as stent struts exposed; grade 1, struts transparently visible although covered; grade 2, struts embedded in the neointima, but translucent; and grade 3, struts fully embedded and invisible. IS-Th was graded as follows: grade 0 (none), 1 (focal), and 2 (diffusely spread). Angioscopic follow-up evaluation was performed at 2 months (25 patients, 42 lesions), 6 months (18 patients, 23 stents), and 12 months (14 patients, 24 stents) after stent implantation. Dominant NIC grade significantly increased over time; however, 16.3% of the cases had NIC grade 1 or 2 at 12 months. IS-Th grade decreased; however IS-Th and yellow plaque were persistently observed in 62.5% and 83.3% cases, respectively, at 12 months. An ongoing healing response was observed at 12 months after implantation; however, thrombogenic findings were noted. Prolonged dual antiplatelet therapy could potentially enhance the clinical utility of Zilver PTX.

Background: Anemia and chronic kidney disease (CKD) are common in patients with heart failure with preserved left ventricular fraction (HFpEF). However, it is entirely unknown about the impact of anemia on prognosis in HFpEF patients with CKD. In this study, we investigated the impact of anemia on prognosis and the optimal hemoglobin (Hb) levels to predict prognosis in HFpEF patients with CKD. Methods and Results: We prospectively examined 523 consecutive HFpEF patients enrolled in Japanese heart failure syndrome with preserved ejection fraction registry. CKD was defined as an estimated glomerular filtration rate (eGFR) of

Background Optical coherence tomography (OCT) is one of the tools trying to distinguish neoatherosclerosis from other neointimal tissue but its role has to be still validated. This study evaluated the diagnostic accuracy of OCT for characterization of lipid-atherosclerotic neointima following drug-eluting stent (DES) implantation. Methods Twelve stented coronary arteries from the 7 autopsy hearts were imaged by OCT. These OCT images were compared with histology. By OCT, the morphological appearances of neointima were classified into three patterns: homogeneous pattern, heterogeneous pattern with visible strut, or heterogeneous pattern with invisible strut. Results Of 21 histological cross-sections, 6 were categorized as homogeneous patterns (29%), 11 as heterogeneous patterns with visible stent strut (52%), and 4 as heterogeneous patterns with invisible stent strut (19%). All homogeneous patterns were composed of smooth muscle cells with collagen fibers. The heterogeneous patterns with visible stent strut included proteoglycan-rich myxomatous matrix and calcium deposition. On the other hand, the heterogeneous patterns with invisible stent strut comprised atheromatous tissue, including a large amount of foam cell accumulation (25%) or large fibroatheroma/necrotic core (75%) inside the stent struts within neointima. The optical attenuation coefficient was highest in the heterogeneous pattern with invisible stent strut due to scattering of light by atheromatous tissue. Conclusion The heterogeneous patterns with invisible stent strut on OCT imaging identify the presence of lipid-atherosclerotic tissue within neointima after DES. This may suggest the potential capability of OCT based on visualization of stent struts for discriminating atheromatous formation within neointima from other neointimal tissue.

Objectives This study aimed to investigate the influence of analysis interval size on optical frequency domain imaging (OFDI) assessment of stent therapy for lesions of the superficial femoral artery (SFA). Background. No consensus or validating data are available with respect to the methodology of intravascular imaging analysis for the peripheral arteries. Methods. OFDI was performed for 30 SFA lesions, during endovascular therapy and at the 6-month follow-up. Initially, lumen and stent borders were traced at 1-mm axial intervals. Volumes were calculated using a PC-based software, and the volume index (VI) was defined as the volume divided by the stent length. Two additional OFDI analyses were performed using 2-mm and 5-mm intervals, thereby reducing the number of cross-sectional image frames analyzed. Results. The mean stent length was 89.7 ± 35.2 mm. The mean difference in baseline minimum lumen area (MLA) was 0.4 mm2 between MLA values from the 1-mm and 2-mm interval analyses, and 2.2 mm2 between MLA values from the 1-mm and 5-mm interval analyses. In volumetric analysis, there were excellent correlations and good agreements for stent, lumen, and neointimal VI measurements obtained on the basis of different analysis intervals. Conclusions. Using large intervals in OFDI analyses of SFA lesions resulted in few differences in measurement variability of volumetric parameters. However, planar analysis for MLA assessment can be susceptible to high variability when large intervals are applied. © 2016 Wiley Periodicals, Inc.

Perivascular adipose tissue (PVAT) surrounds the arterial adventitia and plays an important role in vascular homeostasis. PVAT expands in obesity, and inflamed PVAT can locally promote endothelial dysfunction and atherosclerosis. Here, using adipose tissue transplantation, we tested the hypothesis that expansion of PVAT can also remotely exacerbate vascular disease. Fifty milligrams of abdominal aortic PVAT was isolated from high-fat diet (HFD)-fed wild-type mice and transplanted onto the abdominal aorta of lean LDL receptor knockout mice. Subcutaneous and visceral adipose tissues were used as controls. After HFD feeding for 10 weeks, body weight, glucose/insulin sensitivity, and lipid levels were measured. Adipocytokine gene expression was assessed in the transplanted adipose tissues, and the thoracic aorta was harvested to quantify atherosclerotic lesions by Oil-Red O staining and to assess vasorelaxation by wire myography. PVAT transplantation did not influence body weight, fat composition, lipid levels, or glucose/insulin sensitivity. However, as compared with controls, transplantation of PVAT onto the abdominal aorta increased thoracic aortic atherosclerosis. Furthermore, PVAT transplantation onto the abdominal aorta inhibited endothelium-dependent relaxation in the thoracic aorta. MCP-1 and TNF-α expression was elevated, while adiponectin expression was reduced, in the transplanted PVAT tissue, suggesting augmented inflammation as a potential mechanism for the remote vascular effects of transplanted PVAT. These data suggest that PVAT expansion and inflammation in obesity can remotely induce endothelial dysfunction and augment atherosclerosis. Identifying the underlying mechanisms may lead to novel approaches for risk assessment and treatment of obesity-related vascular disease.

Postcatheterization pseudoaneurysm is one of the most common vascular complications of peripheral angiographic procedures. An 83-year-old male received endovascular treatment (EVT) for a total occlusion lesion of left superficial femoral artery (SFA) due to intermittent claudication. After the subintimal angioplasty procedure with implantation of three self-expandable nitinol stents, angiography revealed contrast staining outside the stent margins. Duplex ultrasonography immediately after the procedure confirmed a pseudoaneurysm of 12mm in diameter. There was no change in the size of pseudoaneurysm during the follow-up period. Four years after the initial procedure, he was admitted to our hospital because of swelling and pain in his left thigh. The angiography showed stent fracture at the proximal shaft of the stent. Furthermore, a fractured fragment of the stent was lying within the ruptured pseudoaneurysm, and active extravasation of contrast medium was identified. Surgical repair of the pseudoaneurysm was performed. We report a case of spontaneous pseudoaneurysm rupture of the SFA that had developed because of subintimal stent placement 4 years previously. If pseudoaneurysm is confirmed after EVT with subintimal stent placement, it should be treated by surgical or percutaneous methods, regardless of its size.

Although intravascular ultrasound (IVUS) predictors of stent patency for the coronary artery lesion have been established, little is known about IVUS predictors of stent patency for the aorto-iliac artery lesion. We analyzed 154 lesions of 122 patients who underwent stent implantation for iliac artery lesions. Quantitative and qualitative IVUS analyses were performed for pre- and post-procedural IVUS imaging in all lesions. Target lesion revascularization (TLR) was defined as clinically driven revascularization with >50 % angiographic stenosis of the target lesion. The mean follow-up period was 39 ± 16 months. TLRs were performed in 13 lesions (8.4 %). Post-procedural minimum stent area (MSA) was significantly smaller in the TLR group compared to the no-TLR group (16.0 ± 5.8 vs. 25.6 ± 8.5 mm(2), p < 0.001). Stent edge dissection was frequently observed in the TLR group compared to the no-TLR group (53.8 vs. 24.1 %, p = 0.04). Multivariate analysis revealed that post-procedural MSA (OR = 0.76, p < 0.01) and stent edge dissection (OR = 10.4, p < 0.01) were independent IVUS predictors of TLR. Receiver-operating characteristic analysis identified post-procedural MSA

Background We performed an ex vivo study to investigate optical coherence tomography (OCT) imaging for differentiating several types of neointimal tissue during the later phases after bare-metal stent (BMS) implantation as compared with histologic results. Methods and results OCT imaging was performed in 6 autopsy hearts for 10 BMS with implant duration >4 years. OCT qualitative neointimal tissue characterization was based on tissue structure and classified as homogeneous pattern, heterogeneous pattern with visible struts, or heterogeneous pattern with invisible struts. Corresponding histological analyses of each 2-mm cross-section of the entire BMS were performed. Of 81 cross-sections, histological analysis revealed that the homogeneous pattern of neointima on OCT (n=39) contained smooth muscle cells with collagen, indicating high neointimal maturity. The heterogeneous patterns with visible struts (n=35) contained different tissues, including a proteoglycan-rich myxomatous matrix or dense calcified plate deposition. The heterogeneous patterns with invisible struts (n=7) included neointimal lipid/necrotic core formation, accumulation of foam cells, or microcalcification scattering. Of the 66 cross-sections containing large microvessels within the neointima on histology, only 6 (9%) were visualized by OCT. Conclusions The present study confirmed the potential use of OCT in differentiating several types of neointima after BMS implantation. The image interpretation of OCT, based on visualization of stent struts, enables identification of several types of neointimal tissues, including in-stent fibroatheroma formation, more accurately.

Although atrial fibrillation (AF) is one of the most frequent causes of ischemic stroke, coronary artery embolism (CE) from AF is rare, and 2.9% of all myocardial infarctions are caused by CE. We present a case of an 87-year-old female patient who suffered ischemic stroke and myocardial infarction at the same time and received intracranial and coronary thrombectomy. Pathological investigation revealed that thrombi were similar and both infarctions were considered as cardioembolism.

Perivascular adipose tissue (PVAT) surrounds most large blood vessels and plays an important role in vascular homeostasis. PVAT releases various chemokines and adipocytokines, functioning in an endocrine and paracrine manner to regulate vascular signaling and inflammation. Mounting evidence suggests that PVAT plays an important role in atherosclerosis and hypertension; however, the role of PVAT in non-atherosclerotic vascular diseases, including neointimal formation, aortic aneurysm, arterial stiffness and vasculitis, has received far less attention. Increasing evidence suggests that PVAT responds to mechanical endovascular injury and regulates the subsequent formation of neointima via factors that promote smooth muscle cell growth, adventitial inflammation and neovascularization. Circumstantial evidence also links PVAT to the pathogenesis of aortic aneurysms and vasculitic syndromes, such as Takayasu's arteritis, where infiltration and migration of inflammatory cells from PVAT into the vascular wall may play a contributory role. Moreover, in obesity, PVAT has been implicated to promote stiffness of elastic arteries via the production of reactive oxygen species. This review will discuss the growing body of data and mechanisms linking PVAT to the pathogenesis of non-atherosclerotic vascular diseases in experimental animal models and in humans.

Background We have previously shown that dietary iron restriction prevents the development of renal damage in a rat model of chronic kidney disease (CKD). However, iron deficiency is associated with appetite loss. In addition, calorie restriction is reported to prevent the development of end-stage renal pathology in CKD rats. Thus, the beneficial effect of iron restriction on renal damage may depend on calorie restriction. Here, we investigate the effect of pair-feeding iron restriction on renal damage in a rat model of CKD. Methods First, to determine the amount of food intake, Sprague-Dawley (SD) rats were randomly given an ad libitum normal diet or an iron-restricted diet, and the food intake was measured. Second, CKD was induced by a 5/6 nephrectomy in SD rats, and CKD rats were given either a pair-feeding normal or iron-restricted diet. Results Food intake was reduced in the iron-restricted diet group compared to the normal diet group of SD rats for 16 weeks (mean food intake; normal diet group and iron-restricted diet group: 25 and 20 g/day, respectively). Based on the initial experiments, CKD rats received either a pair-feeding normal or iron-restricted diet (20 g/day) for 16 weeks. Importantly, pair-feeding iron restriction prevented the development of proteinuria, glomerulosclerosis, and tubulointerstitial damage in CKD rats. Interestingly, pair-feeding iron restriction attenuated renal expression of nuclear mineralocorticoid receptor in CKD rats. Conclusions Pair-feeding iron restriction affected renal damage in a rat model of CKD.

Previous studies reported that invasive physiological assessment for significance of the lesions in the patients with claudication under the condition of pharmacological hyperemia was important to identify the patients who will benefit from revascularization. However, the maximal hyperemic response in lower limb and the method to induce maximum dilatation of vascular bed in lower limb were not well established. The aim of this study was to investigate the range of maximal hyperemic response in lower limb of the normal subjects and to identify the ideal lower limb vasodilatory stimulation. Twelve limbs without stenotic lesions from 12 subjects (average age: 72 ± 6 years) were analyzed. Thermodilution-derived mean transit time (Tmn) was obtained at baseline and during pharmacological hyperemia with incremental dose of intra-arterial papaverine (10, 20, 30, and 40 mg) using a 0.014-inch pressure/temperature sensor-tipped wire in the superficial femoral artery (SFA). Percent increase in blood flow (%IBF) of lower limb was defined as the ratio between baseline Tmn and hyperemic Tmn. Mean ankle brachial index score of the subjects was 1.14 ± 0.09. The %IBF values were enhanced by papaverine in a dose-dependent manner. A dose of 30 mg of intra-arterial papaverine was sufficient to achieve maximum hyperemia (%IBF: range 219-769 %). In conclusion, the increase in blood flow of lower limb during maximal hyperemia varied between individuals and maximal hyperemia can be achieved with 30 mg of papaverine for the SFA lesion.

AIMS This study sought to investigate differences in vascular response between self-expanding bare metal nitinol stents (BMS) and paclitaxel-eluting nitinol stents (PES), in superficial femoral artery (SFA) disease, using optical frequency domain imaging (OFDI). METHODS AND RESULTS Six months after stent implantation, follow-up quantitative vascular angiography (QVA) and OFDI assessment were scheduled to evaluate vascular response. Volume index (VI) was defined as volume divided by stent length. The primary endpoint was OFDI-derived late lumen area loss, defined as lumen VI post stent implantation minus lumen VI at follow-up. A total of 28 SFA lesions were analysed, with cases randomised to receive either BMS or PES implantation. QVA-derived diameter stenosis at six-month follow-up was lower in the PES group than in the BMS group (28.5% vs. 39.7%, p=0.04). After six months, BMS VI increased by 33.8% (20.7±3.7 to 27.7±3.5 mm3/mm), whilst PES exhibited an increase of 32.1% (19.0±2.3 to 25.1±4.7 mm3/mm). Neointimal VI was smaller (7.4±2.6 mm3/mm vs. 10.5±3.2 mm3/mm, p

Background The optimal sizing of self-expanding paclitaxel-eluting stents (PES) in the treatment for superficial femoral artery (SFA) lesions is unclear. This study sought to investigate the influence of PES diameter on stent patency in SFA lesions using optical frequency domain imaging (OFDI). Methods A total of 20 de novo SFA lesions were randomized 1:1 to receive either self-expanding PES with a nominal diameter of 6 mm or 8 mm. Follow-up angiography and OFDI was scheduled six months after stent implantation, and volumetric OFDI analysis was performed to evaluate vascular response to the stents. Volume index (VI) was defined as the volume divided by the stent length. The primary end point was lumen VI at the 6-month follow-up. Secondary end point was minimum lumen diameter (MLD) by quantitative vascular angiography (QVA) at the follow-up. Results Stent length was 78.0 ± 23.9 mm in the 6-mm group and 70.0 ± 23.6 mm in the 8-mm group ( p = 0.46). Baseline QVA data were also similar between the two groups. MLD immediately after stent implantation was similar between the two groups (4.2 ± 0.5 mm in the 6-mm group and 3.9 ± 0.5 mm in the 8-mm group, p = NS). At the 6-month follow-up, MLD was greater in the 8-mm group compared to the 6-mm group (4.0 ± 1.0 mm vs. 3.2 ± 0.4 mm, p 3 /mm vs. 22.2 ± 1.2 mm 3 /mm, p = 0.01). Neointimal VI was similar between the two groups (5.8 ± 2.9 mm 3 /mm vs. 5.2 ± 2.6 mm 3 /mm, p = 0.68). Lumen VI was greater in the 8-mm group (23.2 ± 7.6 mm 3 /mm vs. 17.3 ± 2.6 mm 3 /mm, p = 0.04). Conclusions Chronic stent enlargement resulted in greater lumen area after implantation of self-expanding PES with a large diameter at the mid-term follow-up. Stent diameter might be important for stent patency in procedure with PES for SFA lesions.

Although spontaneous coronary artery dissection (SCAD) is usually diagnosed by coronary angiography, diagnosis may be missed because of various presentations and imperfections of coronary angiography. We report a case of a 41-year-old female with pregnancy-related SCAD who presented with cardiac arrest. Initial coronary angiography was normal without intimal flap. Unexpectedly, 4 days after admission, SCAD in left main trunk was revealed with recurrent myocardial infarction. Intimal flap was sealed at the time of first angiography and this is an interesting point that made us report this case. SCAD is a rare but not negligible cause of not only acute myocardial infarction but also sudden cardiac arrest even if first coronary angiography is normal. .

Purpose: To identify intravascular ultrasound (IVUS) measurements that can predict angiographic in-stent restenosis (ISR) following nitinol stent implantation in superficial femoral artery (SFA) lesions. Methods: A retrospective review was conducted of 97 patients (mean age 72.9±8.9 years; 63 men) who underwent IVUS examination during endovascular treatment of 112 de novo SFA lesions between July 2012 and December 2014. Self-expanding bare stents were implanted in 46 lesions and paclitaxel-eluting stents in 39 lesions. Six months after stenting, follow-up angiography was conducted to assess stent patency. The primary endpoint was angiographic ISR determined by quantitative vascular angiography analysis at the 6-month follow-up. Variables associated with restenosis were sought in multivariate analysis; the results are presented as the odds ratio (OR) and 95% confidence interval (CI). Results: At follow-up, 27 (31.8%) angiographic ISR lesions were recorded. The lesions treated with uncoated stents were more prevalent in the ISR group compared with the no restenosis group (74.1% vs 44.8%, p=0.02). Lesion length was longer (154.4±79.5 vs 109.0±89.3 mm, p=0.03) and postprocedure minimum stent area (MSA) measured by IVUS was smaller (13.9±2.8 vs 16.3±1.6 mm2, p2 as the optimal cutpoint below which the incidence of restenosis increased (area under the curve 0.769). Conclusion: Postprocedure MSA can predict ISR in SFA lesions, which suggests that adequate stent enlargement during angioplasty might be required for superior patency.

Background: Although statins vary in their effectiveness in lowering low-density lipoprotein cholesterol (LDL-C) and increasing high-density lipoprotein cholesterol (HDL-C) levels, there is little evidence that the degree of these changes can explain cardiac risk reduction in Japan. Our objective was to compare the efficacy of statins on serum lipid levels and to explore the association between those changes and cardiac events in patients after percutaneous coronary intervention (PCI). Methods and Results: The 743 consecutive patients who underwent PCI from 2001 to 2008 were retrospectively investigated. Treatment with either atorvastatin or pitavastatin significantly reduced LDL-C compared with pravastatin or no statin. In contrast, only pitavastatin treatment significantly increased HDL-C (13.4±22.9%, P=0.01 vs. no statin). Each statin significantly prevented major adverse cardiac events (MACE) compared with no statin, and pitavastatin was the most effective of all. Multivariate-adjusted analysis revealed that percent changes of both LDL-C and HDL-C independently predicted the incidence of MACE (hazard ratio [HR]: 1.015; 95% confidence interval [CI]: 1.010-1.020, HR: 0.988; 95%CI: 0.981-0.996, respectively). This relationship was preserved in patients with a baseline HDL-C level ≤45mg/dl, but not HDL-C level >45mg/ml. Conclusions: The extent of changes in LDL-C and HDL-C with statin treatment would independently alter the risk of cardiac events in Japanese patients for secondary prevention. Statins with varying lipid-modifying ability might provide differing prognosis in patients after PCI. (Circ J 2011; 75: 1951-1959)

We recently reported the coronary thermodilution curve can be evaluated by analyzing the thermodilution curve obtained from a pressure sensor/thermistor-tipped guidewire, and presence of a bimodal-shaped thermodilution curve following primary percutaneous coronary intervention (pPCI) in ST-segment elevation myocardial infarction (STEMI) patients was associated with worse outcomes. This study evaluated whether the bimodal-shaped thermodilution curve predicts left ventricular (LV) remodeling after STEMI. The coronary thermodilution curve patterns were evaluated for 75 patients treated by pPCI for their first STEMI using a pressure sensor/thermistor-tipped guidewire, and classified into the three groups according to the thermodilution curve shape: narrow unimodal (n = 39), wide unimodal (n = 26), and bimodal pattern (n = 10). Echocardiography was performed at baseline and 6 months after STEMI. LV remodeling was defined as a >20 % increase in LV end-diastolic volumes (LVEDV). LVEDV at 6-month follow-up was greater in the bimodal group than in the other groups (p

The mechanical properties of the self-expanding nitinol stents (SENS) and chronic biological stimulation on the wall from the SENS have not been fully investigated. This study evaluated the mechanical vascular response to SENS implantation in superficial femoral artery (SFA) lesions using serial volumetric intravascular ultrasound (IVUS). Twenty-five symptomatic patients due to de novo SFA lesions scheduled for SENS placement were prospectively enrolled. Serial IVUS studies were performed immediately after crossing with a guidewire, immediately after the procedure, and at a 8-month follow-up. Serial IVUS volumetric analysis was conducted after stent deployment and at follow-up. Mean stent, lumen and neointimal areas were calculated as the volume divided by the stent length, and the calcium arc was measured. At follow-up, SENS had increased 40.6 % in overall volume. The chronic stent expansion tended to be larger, and the mean neointimal area at the 8-month follow-up was significantly larger in less calcified lesions compared to heavily calcified lesions. As a result, the mean late lumen area loss was significantly larger in lesions with calcium arcs of 0° and in the first and second quadrants than in those with calcium arcs in the third and fourth quadrants (2.8 ± 7.2, 1.3 ± 5.6, 0.6 ± 5.9, 1.2 ± 5.4, -0.8 ± 5.2 mm(2), respectively; p

Background— The purpose of this study was to verify whether the concept of coronary blood flow reserve can be applied to patients with critical limb ischemia who are undergoing endovascular treatment (EVT) for isolated infrapopliteal lesions. Methods and Results— Forty patients diagnosed with critical limb ischemia (Rutherford category 5) who were undergoing EVT for isolated infrapopliteal lesions were prospectively enrolled. All lesions were treated with conventional balloon angioplasty without stent placement. After successful EVT, a pressure/temperature sensor–tipped guidewire was positioned in the proximal popliteal artery. Using the thermodilution technique, the mean transit time (Tmn) was determined after bolus injections of 3-mL saline at baseline and at the onset of intra-arterial papaverine induced maximum hyperemia. Vascular flow reserve (VFR) was calculated as resting Tmn divided by hyperemic Tmn. Complete epithelialization of the reference wound (wound healing) was completely closed by either surgical or secondary intervention within 3 months after EVT. Wound healing was achieved in 22 patients after EVT (healing group) but was not achieved in 18 patients (nonhealing group). Postprocedural VFR was significantly lower in the nonhealing group than in the healing group (2.40; interquartile range, 2.00–3.08 versus 4.05; interquartile range, 3.60–4.60; P 3.6 as the best threshold value for complete wound healing after EVT. Univariate analysis revealed that postprocedural VFR >3.6 was a predictor of wound healing ( P =0.0002). Conclusions— Advanced lower limb clinical setting may be caused by a poor capability of microvasculature. VFR, which is easily assessable, is useful in clinical risk stratification for patients with critical limb ischemia after EVT in the catheterization laboratory. Clinical Trial Registration— URL: http://www.umin.ac.jp/ctr . Unique identifier: UMIN000009313.

Similar to the coronary artery, late stent thrombosis (ST) due to delayed vascular healing is concerned after drug-eluting stent (DES) implantation in the superficial femoral artery (SFA). Therefore, we analyzed vascular response after DES implantation in the SFA with optical frequency domain

DVT has rarely been observed in the inferior vena cava (IVC). Pulmonary embolism (PE), which can be life-threatening, often occurred in patients with IVC thrombosis. Therefore, an IVC filter is frequently used in those patients for the prevention of PE. A case of successful endovascular treatment of an IVC thrombus in a patient with relative contraindications to implantation of an IVC filter is presented. This case report shows that aspiration of thrombi caught in the removable IVC filter may be an alternative to surgery in high-risk patients with catheter-related suprarenal inferior vena cava thrombosis.

To date, there are no prospective studies on the relationship between plaque characteristics identified by 40 MHz IVUS and future adverse events. This prospective study evaluated the relationship between plaque morphology in nonculprit nonsignificant lesions, determined by 40 MHz IVUS, and long-term clinical outcomes. Consecutively, 45 patients who underwent 3-vessel intravascular ultrasound (IVUS) examinations were prospectively enrolled. Qualitative and quantitative IVUS analyses including scoring of echogenicity for assessment of plaque characterization were performed for each nonsignificant nonculprit lesion. The number, the length, the location (superficial or deep), and maximum arc were measured for each calcium deposit within plaques. Spotty calcification was defined as calcium deposits

Durable long-term effectiveness with paclitaxel-eluting stent (Zilver PTX stent) in superficial femoral artery (SFA) lesion over standard endovascular therapy has been demonstrated. However, delayed vascular healing which may lead to rare but serious adverse event of late stent thrombosis remains a

Aims This study evaluated whether optical frequency domain imaging (OFDI) could identify various coronary calcifications and accurately measure calcification thickness in comparison with histopathology. Methods and results A total of 902 pathological cross-sections from 44 coronary artery specimens of human cadavers were examined to compare OFDI and histological images. Histological coronary calcification was classified into four different types: (i) superficial dense calcified plates, (ii) deep intimal calcification, (iii) scattered microcalcification, and (iv) calcified nodule. The thickness of calcification was measured when both the leading and trailing edges of calcification were visible on OFDI. Of the 902 histological cross-sections, 158 (18%) had calcification: 105 (66%) were classified as superficial dense calcified plates, 20 (13%) as deep intimal calcifications, 30 (19%) as scattered microcalcifications, and 3 (2%) as calcified nodules. Superficial dense calcified plates appeared as well-delineated heterogeneous signal-poor regions with sharp borders on OFDI. Deep intimal calcifications could not be identified on OFDI. Scattered microcalcification appeared as homogeneous low intensity areas with indiscriminant borders. Calcified nodule, a high-backscattering protruding mass with an irregular surface, also appeared as a low intensity area with a diffuse border. The ROC analysis identified calcium thicknesses

The histology of peri-strut low intensity areas (PLIA) identified by optical coherence tomography (OCT) is still not well assessed by human autopsy. A total of 15 stents (7 bare-metal stents; BMS, 8 drug-eluting stents; DES) implanted human coronary artery were collected from 5 cadavers. The

Patient initials or identifier number B.Y ### Relevant clinical history and physical exam A 89-years-old man, who had hypertension, presented with swelling of his left thigh after rehabilitation. Four years ago, the patient underwent primary stenting of the left SFA to treat total occlusion (

Frailty increases the risk of adverse outcomes in older people. Patients with critical limb ischemia (CLI) also had several clinical frailties. The aim of this study is to investigate between the physiological parameter in patients with CLI undergoing endovascular treatment (EVT) for isolated