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Aims: This study aimed to assess the clinical efficacy of intravascular ultrasound (IVUS)-guided intraplaque wiring for femoropopliteal (FP) chronic total occlusion (CTO). Methods: This single-center, retrospective, observational study was performed at the Japanese Red Cross Kyoto Daini Hospital. From March 2013 to June 2017, a total of 75 consecutive patients (mean age: 75.4 ± 8.5 years; 59 males), who underwent endovascular treatment (EVT), having 82 de novo FP-CTO lesions, were enrolled in this study. Eleven of the lesions that met the exclusion criteria were excluded, and the remaining 71 lesions were divided into the IVUS-guided wiring group (n = 34) and non-IVUS-guided wiring group (n = 37). Primary patency, defined as a peak systolic velocity ratio of < 2.4 on duplex ultrasonography, and freedom from clinically driven target lesion revascularization (CD-TLR) at 12 months were the primary outcomes. Results: The mean lesion length was 21.6 ± 8.9 cm. The frequencies of primary patency and freedom from CD-TLR were significantly higher in the IVUS-guided wiring group than in the non-IVUS-guided wiring group (70.0% vs. 52.2%, p = 0.045; 83.9% vs. 62.8%, p = 0.036, respectively). The complete clinically true lumen angioplasty rate was also higher in the IVUS-guided wiring group than in the non-IVUS-guided wiring group (91.1% vs. 51.3%, p < 0.001, respectively). The clinically true and false wire passage rates were respectively 97.3% and 2.7% in the IVUS-guided wiring group. Conclusion: IVUS-guided wiring improves the clinical outcomes of EVT for FP-CTO by achieving a high clinically true lumen wire passage rate.

Left ventricular mechanical dyssynchrony (LVMD) induced by exercise stress was reported to be clinically useful in detecting multivessel coronary artery diseases. The aim of this study was to compare the prognostic value of LVMD induced by pharmacological stress with that induced by exercise stress. We retrospectively examined 918 consecutive patients who underwent exercise (N = 310) or pharmacological stress (N = 608) 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) with normal myocardial perfusion. LVMD was evaluated by phase analysis as the indices of phase bandwidth and phase standard deviation (PSD). During the follow-up period (2.2 ± 1.9 years), 74 major cardiac events (MCEs) occurred (7 cases of cardiac death, 17 cases of heart failure, and 50 cases of coronary intervention). In global patients, the indices of LVMD on rest images were significantly greater in patients with MCEs (bandwidth (°): 51 ± 31 vs 37 ± 21, P = .001, PSD: 14 ± 9 vs 10 ± 6, P = .001). The exercise stress bandwidth was significantly higher in patients with MCEs (62 ± 37° vs 42 ± 21°, P = .026), as was the pharmacological stress bandwidth (57 ± 35° vs 43 ± 24°, P = .006). Multivariate analysis demonstrated the exercise stress bandwidth to be an independent predictor of MCEs (HR 1.017, CI 1.003 to 1.032, P = .019), but the pharmacological stress bandwidth had no influence on MCEs. LVMD induced by exercise stress was an independent predictor of MCEs in patients with normal perfusion SPECT, whereas that induced by pharmacological stress had no association with further events.

This study aimed to evaluate the utility and feasibility of physiological maps coregistered with angiograms using the pullback of a pressure guidewire with continuous instantaneous wave-free ratio (iFR) measurements. iFR pullback was obtained for 70 lesions from 70 patients with stable angina pectoris using SyncVision (Philips Corp.). Physiological maps were created, whereby the post-intervention iFR (post-iFR) was predicted as iFRpred. The iFR gap was defined if the difference between the iFRpred and post-iFR was ≥ 0.3. The lesion morphology changed from that during the physiological assessment to that during the angiographic assessment in 26 lesions (37.1%). In particular, 22.6% of angiographic tandem lesions changed to physiological focal lesions. The mean pre-intervention iFR, post-iFR, and iFRpred were 0.73 ± 0.17, 0.90 ± 0.06, and 0.93 ± 0.05, respectively. The mean difference between the iFRpred and post-iFR was 0.029 ± 0.099, with 95% limits of agreement of -0.070–0.128. iFR gaps occurred in 28 patients (40%). Notably, a new iFR gradient causing a ≥ 0.03 iFR drop after stenting occurred in 11 (15.7%) cases. The study patients were divided into two groups according to biases between post-iFR and iFRpred p = 0.027). Physiological maps under resting conditions may contribute to a reduction in unnecessary stent placements without missing lesions requiring treatment. However, the predictive accuracy of post-iFR performance in the present study was slightly lower than that in the previous reports.

This study investigated the correlation between vascular flow reserve (VFR) values and wound healing rate in patients with critical limb ischemia.Peripheral VFR may be useful for predicting complete wound healing after endovascular therapy (EVT). However, published reports included small numbers of patients from single centers and long-term outcomes remain unknown.This was a prospective multicenter study that consecutively enrolled 104 patients (115 limbs) who received EVT for ischemic ulcerations. All lesions were treated with conventional balloon angioplasty. After EVT, VFR was measured using a pressure/temperature guidewire. The study endpoints were correlation between VFR values and wound healing rate at 3 months and 1 year.The median VFR was 2.9. A total of 110 and 104 limbs completed the 3-month and 1-year follow-up, respectively. The 3-month and 1-year wound healing rates were 49% and 76%, respectively. VFR was significantly associated with the 3-month and 1-year wound healing (p 0.001 for both). The crude hazard ratios of VFR (per 2-fold increase) for the 3-month and 1-year wound healing were 2.6 (1.7 to 3.9) and 2.9 (2.0 to 4.2), respectively. The estimated median time to wound healing was 5.0 (3.2 to 7.2) months, 3.3 (2.8 to 4.9) months, and 2.5 (2.0 to 3.0) months, when the VFR value was 2.4, 2.9, and 3.9, respectively.Post-procedure VFR is significantly associated with wound healing. VFR, measured in the catheterization laboratory, is useful in clinical risk stratification for patients with critical limb ischemia after EVT. (Predictor of Wound Healing in Patients with Critical Limb Ischemia-Multicenter Prospective Study; UMIN000012746).

Purpose: To examine the efficacy of pedal artery angioplasty (PAA) for chronic limb-threatening ischemia (CLTI) according to the severity of inframalleolar disease. Methods: In total, 257 consecutive CLTI patients (mean age 73.2 years; 175 men) with de novo infrapopliteal and inframalleolar artery disease were enrolled from the retrospective RENDEZVOUS registry. Inframalleolar artery disease was classified as moderate (Kawarada type 2, 144 patients) or severe (Kawarada type 3, 113 patients). PAA was performed in 140 patients: 66 (45.8%) with moderate disease and 74 (65.5%) with severe disease. The remaining 117 patients (78 with moderate disease and 39 with severe disease) underwent interventions that did not include PAA. The primary outcomes were the wound healing and limb salvage rates at 12 months after the initial treatment. The outcomes of the PAA and no-PAA groups were examined to determine any correlation between treatment efficacy and baseline disease severity. Results: The success rates of PAA among the patients with moderate and severe inframalleolar disease were 89.4% and 87.8%, respectively (p=0.683). The wound healing rate at 12 months was significantly higher in the PAA group than in the no-PAA group regardless of the severity of inframalleolar disease [moderate: 58.8% vs 40.0% (p=0.049); severe: 59.6% vs 33.2% (p=0.021), respectively]. The worst limb salvage rate (76.9%) was seen among patients in the no-PAA group with severe inframalleolar disease (no-PAA/moderate: 94.8%; PAA/moderate: 90.9%; and PAA/severe: 87.8%, p=0.028). Conclusion: PAA improves the wound healing rate of patients with CLTI regardless of the severity of inframalleolar disease. This treatment modality also might improve limb salvage rates in patients with severe inframalleolar disease affecting both the anterior and posterior pedal circulations.

With technological improvements in the endovascular armamentarium, there have been tremendous advances in catheter-based femoropopliteal artery intervention during the last decade. However, standardization of the methodology for assessing outcomes has been underappreciated, and unvalidated peak systolic velocity ratios (PSVRs) of 2.0, 2.4, and 2.5 on duplex ultrasonography have been arbitrarily but routinely used for assessing restenosis. Quantitative vessel analysis (QVA) is a widely accepted method to identify restenosis in a broad spectrum of cardiovascular interventions, and PSVR needs to be validated by QVA. This multidisciplinary review is intended to disseminate the importance of QVA and a validated PSVR based on QVA for binary restenosis in contemporary femoropopliteal intervention.

Purpose: To assess calcium patterns in superficial femoral artery (SFA) disease before and after balloon angioplasty ± stent implantation using fluoroscopy, angiography, and intravascular ultrasound (IVUS) imaging and then correlate calcification severity and midterm clinical outcomes. Materials and Methods: A multicenter investigation was carried out to retrospectively review 130 symptomatic patients (mean age 73.2±8.4 years; 86 men) with de novo SFA lesions who had successfully undergone endovascular therapy (EVT) at 7 centers between January and October 2015. The primary outcome was lumen gain measured as minimum lumen area (MLA) in post-EVT IVUS images according to calcification severity. The secondary outcomes included rates of stent malapposition, restenosis, and clinically-driven target lesion revascularization (TLR). Results: A total of 102 (78.5%) cases had calcification in the lesions over a mean length of 64.3±72.8 mm. Of these, 70 cases were classified as having bilateral calcification according to fluoroscopy and angiography; 50 (49%) lesions had ≥180° calcification according to IVUS. The lumen gain in calcified lesions was significantly smaller than in the 28 noncalcified lesions (14.1±4.4 vs 17.8±5.2 mm2, p

To identify the risk factors for major adverse cardiovascular events (MACEs) in real-world practice for symptomatic peripheral artery disease in Japan.Data on Japanese patients (N = 880) from the Observational Prospective Multicenter Registry Study on Outcomes of Peripheral Arterial Disease Patients Treated by Angioplasty Therapy for Aortoiliac Artery who underwent de novo aortoiliac stent placement. The 3-year risk of incident MACEs was investigated.The median age of the patients was 72.6 years (range, 34-97 years), and 83.1% of the patients were men. The patients had the following conditions: smoking (35.6%), hypertension (94.1%), dyslipidemia (81.7%), diabetes (48.0%), renal failure on dialysis (12.6%), myocardial infarction (12.7%), stroke (15.8%), and chronic limb-threatening ischemia (7.1%). Femoropopliteal lesions were present in 38.8% of the limbs with aortoiliac lesions. The 3-year rate of freedom from MACEs was 89.1%. Baseline characteristics, such as age, renal failure on dialysis, myocardial infarction, stroke, and femoropopliteal lesions, were independently associated with the risk of incident MACEs. When the study population was stratified according to these risk factors, the rate of MACEs was highest in patients with at least 3 risk factors (32.9% at 3 years).The 3-year rate of freedom from MACEs was reported. Baseline characteristics, such as age, renal failure on dialysis, myocardial infarction, stroke, and femoropopliteal lesions, are independent risk factors for MACEs after aortoiliac stent placement.

Purpose To assess skin perfusion pressure (SPP) changes after endovascular treatment (EVT) of patients with chronic limb-threatening ischemia (CLTI) and to explore preoperative factors that affect SPP changes. Materials and Methods This prospective, multicenter study recruited 147 patients (mean age 74 years; 99 men) with ischemic wounds at 6 vascular centers in Japan between July 2017 and December 2018. Over half of the patients (92, 63%) were diabetic, and 76 (52%) required dialysis. Sixty-four patients (43%) had WIfI (wound, ischemia, foot infection) wound grades of 2 or 3; 59 (40%) had foot infections. SPP was measured before and 1, 2, 7, and 30 days after EVT to establish inline flow to the ischemic foot based on the angiosome concept when feasible. The anterior and posterior tibial arteries and the peroneal artery were revascularized in 66 (45%), 50 (34%), and 30 (21%) patients, respectively. Results Both the dorsal and plantar SPPs at 1 or 2 days post-EVT were significantly higher than those at baseline (pConclusion The SPP increased continuously up to 1 month after EVT, though the increase was smaller in patients with wound infections. The SPP on the dorsal and plantar surfaces increased, regardless of the vessel revascularized, which could justify indirect revascularization when direct revascularization is technically challenging.

The purpose of this study was to evaluated the clinical characteristics of calcified nodule-like in-stent restenosis (ISR) lesions using optical coherence tomography (OCT) in vivo. A total of 124 ISR lesions that were treated with a repeat coronary intervention under OCT guidance were included in this analysis. ISR neointimal morphology was classified as “calcified nodule-like ISR”, that appeared as a high-backscattering protruding mass with an irregular surface covered by signal-rich bands, or “non-calcified nodule-like ISR”. The maximum arc and thickness of calcium behind the stent struts was also measured. Of the 124 ISR lesions, calcified nodule-like ISR was observed in 11 lesions (9%). OCT analysis data showed that the maximum arc of calcium and the maximum calcium thickness behind the stent were significantly larger in the calcified nodule-like ISR lesions than in the non-calcified nodule-like ISR lesions (269 ± 51 vs. 179 ± 92°, p

Objectives To assess the efficacy of indigo carmine angiography for wound healing after successful below-the-knee intervention in patients with critical limb ischemia (CLI). Methods A multi-center prospective intervention study was conducted. Fifty-four limbs of 53 patients in Rutherford categories 5 and 6 underwent endovascular therapy (EVT). After successful EVT, 5 mL of indigo carmine was injected through a catheter at the distal popliteal artery and color changes in the foot were evaluated. The results of indigo carmine angiography were divided into three groups: In type I, the color change of the wound was deeper than the surrounding tissue; in type II, the change in wound color was similar to the surrounding tissue; and in type III, no discoloration of the wound was observed by the indigo carmine. Results The wound healing rates at 3 months were 78% (25/32) for type I, 70% (7/10) for type II, and 42% (5/12) for type III (P for trend = 0.025). Indigo carmine angiography-related complications were not seen. Conclusion Indigo carmine angiography was found to be a safe and useful procedure to provide visual information on foot perfusion. This dye coloring method demonstrated that after successful angioplasty, the perfused area was made visible at the microcirculation level. Indigo carmine angiography can thus be considered an important predictor for wound healing by EVT in patients with CLI.

Objectives The aim of this study was to investigate the clinical outcomes of pedal artery angioplasty (PAA) for patients with critical limb ischemia. Background Pedal artery disease is considered a predictor of delayed wound healing (DH) after endovascular therapy. Adjunctive PAA might improve the speed and extent of wound healing. Methods Consecutive patients with critical limb ischemia (n = 257) presenting with de novo infrapopliteal and pedal artery disease were retrospectively reviewed from a multicenter registry. Patients were divided into 2 groups according to whether PAA was performed (n = 140) or not (n = 117). The rate of wound healing and time to wound healing were compared between these groups. DH score was calculated using the number of independent predictors of DH. Patients were stratified into 3 groups according to DH score: low risk (DH score = 0), moderate risk (DH score = 1 or 2), and high risk (DH score = 3). Estimated efficacy was analyzed for each risk-stratified population. Results The rate of wound healing was significantly higher (57.5% vs. 37.3%, p = 0.003) and time to wound healing significantly shorter (211 days vs. 365 days; p = 0.008) in the PAA group. In a multivariate analysis, nonambulatory status, target wound depth (UT grade ≥2), and daily hemodialysis were revealed as predictors of DH. In the moderate-risk population, adjunctive PAA significantly improved the rate of wound healing (59.3% vs. 33.9%; p = 0.001). In the high-risk population, however, PAA did not affect wound healing. Conclusions Patients who underwent PAA showed a higher rate of wound healing and shorter time to wound healing, especially in the moderate-risk population. With regard to wound healing, this aggressive strategy might become a salvage procedure for patients with critical limb ischemia presenting with pedal artery disease.

The most important factor for preventing contrast-induced nephropathy (CIN) during percutaneous coronary intervention (PCI) in patients with severe renal dysfunction is to minimize the contrast volume. Herein, we report a successful case of complete revascularization after 3 separate PCI procedures using a super-low volume of contrast medium in a patient with 3-vessel disease, including two chronic total occlusions (CTOs). A 70-year-old man having exertional angina despite maximal medical therapy was referred to our hospital. He had severe renal dysfunction (estimated glomerular filtration rate 19 mL/minute/1.73 m2). Coronary angiography, in which a total volume of 15 mL (over 3 injections) of contrast medium was used after hydration with normal saline, demonstrated 2 CTOs in the proximal left circumflex artery (LCX) and the proximal right coronary artery (RCA) as well as focal stenosis in the mid left descending artery (LAD). Because the patient refused coronary artery bypass grafting, we opted for revascularization with PCI, divided into 3 procedures. We made full use of microcatheter tip injection and evaluation with intravascular ultrasound and achieved complete revascularization with a total of 31 mL of contrast medium: 9 mL for RCA, 6 mL for LAD, and 16 mL for LCX, without the occurrence of CIN. Additionally, we present tips for performing PCI using super-low contrast medium.

This study aimed to evaluate the feasibility and utility of using motorized pullback of the pressure guidewire to provide a graphic assessment and prediction of the benefits of coronary intervention. Fractional flow reserve (FFR) measurements were performed with motorized pullback imaging in 20 patients who underwent successful percutaneous coronary intervention (PCI) of the left anterior descending artery. Physiological lesion length (PLL) was calculated using frame counts to determine stent length. FFR area was calculated by integrating the FFR values recorded during pullback tracing (FFRarea). The percentage increase in FFR area (%FFRarea) was defined as the ratio of the difference between the pre- and post-intervention FFRarea to the total frame count. The average FFR values were enhanced following PCI, from 0.64 to 0.82, and the median value of the difference between pre- and post-interventional FFR values (D-FFR) and %FFRarea were 0.13 and 10.6%, respectively. The %FFRarea demonstrated a significant positive correlation with D-FFR (R 2, 0.61; p

Calcified lesions still remain a technical challenge even in the treatment of infrainguinal artery disease. The aim of this retrospective, multicenter observational study was to investigate interventional outcomes of a high-speed rotational atherectomy device (Rotablator™) and to compare clinical outcomes in patients who underwent Rotablator and those who did not even after failed balloon angioplasty because of underlying calcified lesions. This study enrolled patients who underwent Rotablator (Rota group) and those who did not (Non-rota group) between January 2010 and 2014 December at 12 hospitals. A total of 67 limbs and 68 lesions in 65 patients were included (Rota group; 54 limbs and 55 lesions in 52 patients, Non-rota group; 13 limbs and 13 lesions in 13 patients). In the Rota group, a technical success rate was 94.5% with a complication rate of 1.8%, and all lesions underwent subsequent postdilatation following the adjunctive use of Rotablator, and approximately half of above-the-knee lesions underwent stent implantation. The Rota group had a significantly lower clinically driven reintervention rate at 12 months than the Non-rota group (26.5% vs. 58.3%, respectively, p = 0.046). In addition, Rota group showed a trend toward a higher amputation-free survival compared to the Non-rota group at 1 month (Rota; 98.0% vs. Non-rota; 84.6%, respectively, p = 0.10). Rotablator was used as an adjunctive device with a high technical success and a low complication rates, and Patients who underwent Rotablator yielded a significantly lower clinically driven reintervention rate at 12 months compared to those who did not even after failed balloon angioplasty.

This study aimed to investigate the efficacy of guiding sheath delivery with the crossover approach using a newly customized inner dilator for a 0.018-in. guidewire of the Destination® guiding sheath (Terumo Corporation, Tokyo, Japan) (18-system), compared with that of the conventional-type 0.035-in. guidewires with inner dilators (35-system), and to predict failure of guiding sheath delivery. We conducted a prospective multicenter case series study of the contralateral crossover approach using Destination®, to determine whether the 18-system could be a rescue system in cases in which the conventional 35-system failed. To evaluate the efficacy of the 18-system, we created an in vitro aortoiliac bifurcation model by using a silicone vessel. We enrolled 172 cases consecutively. The initial crossover approach with the 35-system failed in 37 cases (21.5%), and a second attempt with the 18-system was successful in all failed cases. The bifurcation angles in the 35-system failure cases were significantly steeper than those in the 35-system success cases. A receiver operating characteristic curve analysis demonstrated that an aortoiliac bifurcation angle of 68° was the optimal cut-off value for predicting failure of the crossover procedure. Data from the analysis using the silicone vessel model suggested that the 18-system provided superior results, especially in aortoiliac bifurcation angles steeper than 60°, consistent with the in vivo findings. The results of the initial use of the 18-system with the crossover approach suggest that it may be superior to the conventional 35-system, especially in cases of steeper aortoiliac bifurcation angles.

Objectives This study sought to investigate the characteristics of in-stent restenosis (ISR) after drug-eluting stent (DES) implantation for femoropopliteal (FP) lesions, and to examine 1-year prognosis after repeat endovascular therapy (re-EVT) for these DES-ISR. Background The morphology of DES-ISR and its association with clinical outcomes after re-EVT have not been well examined. Methods This was a subanalysis of the ZEPHYR (Zilver PTX for the femoral artery and proximal popliteal artery) study. The current study included 210 cases with loss of patency confirmed 1 year after DES implantation. Morphology of DES-ISR was classified into the following subgroups: class I, focal lesions (≤50 mm in length), class II, diffuse lesions (>50 mm in length), and class III, totally occluded ISR. One-year prognosis after re-EVT for DES-ISR was assessed by restenosis and major adverse limb events (MALE). Results Classes I, II, and III accounted for 50%, 25%, and 25% of DES-ISR, respectively. Factors associated with the morphology of DES-ISR were the presence of chronic total occlusion and the size of the external elastic membrane area before DES implantation (p = 0.009 and 0.017). Compared with the class I restenotic lesion, the class II and III lesions had a significantly higher risk of restenosis (74% and 78% vs. 53%: p = 0.048 and 0.019, respectively) and MALE (56% and 56% versus 32%: p = 0.025 and 0.022, respectively) 1 year after re-EVT. Conclusions We evaluated the characteristics of ISR after DES implantation for FP lesions and 1-year prognosis of re-EVT for DES-ISR. The morphology of DES-ISR had a significant association with 1-year prognosis after re-EVT.

AIMS: The aim of this study was to evaluate the clinical outcomes of endovascular treatment (EVT) for chronic aortic occlusion (CAO) using multicentre registry data. METHODS AND RESULTS: From April 2003 to December 2015, data on 73 consecutive patients (55 men and 18 women; aged 70.7±12.2 years) who underwent EVT for CAO were collected retrospectively from 15 centres in Japan. The primary endpoint was the primary patency at 12 months after EVT. Secondary endpoints were procedural success and periprocedural complication rates. We analysed 67 patients who underwent complete endovascular revascularisation after 2007. Initial procedural success was achieved in 63 cases (94.0%). Complications occurred in three patients (4.5%) (stroke, n=1; distal embolism, n=1; access-site haematoma requiring blood transfusion, n=1). In patients after successful EVT (n=63), the primary and secondary patency rates at 12 months were 90.7% and 97.7%, respectively. During a mean follow-up period of 17.8 months, restenosis/re-occlusion was observed in eight patients (12.7%). CONCLUSIONS: EVT for CAO could be performed safely with a high procedural success rate. The short-term clinical outcome was acceptable despite lesion complexity.

Patient initials or identifier number Y.Kawagoe ### Relevant clinical history and physical exam A patient was 78-year-old female with past history of CREST syndrome, rheumatoid arthritis, brain infarction and hypertension was admitted to our hospital because of refractory 1st toe ulcer on the

Objectives There have been limited data regarding the prediction of cardiac benefits after renal artery stenting for patients with atherosclerotic renal artery disease (ARAD). The aim of this multicentre retrospective study was to identify clinical or echocardiographic factors associated with improvements of cardiac symptoms after renal artery stenting. Methods We enrolled 58 patients with de novo ARAD undergoing successful renal artery stenting for heart failure, angina or both between January 2000 and August 2015 at 13 hospitals. Results Improvement of cardiac symptoms was observed in 86.2% of patients during a mean follow-up of 6.0±2.7 months. Responders demonstrated significantly lower New York Heart Association functional class, higher estimated glomerular filtration rate, lower serum creatinine and lower interventricular septal wall thickness (IVS), lower left ventricular mass index, lower left atrial dimension and lower E-velocity than non-responders. Backward stepwise multivariate analysis identified IVS as an independent predictor of improvement of cardiac symptoms (OR 0.451, 95% CI 0.209 to 0.976; p=0.043). According to receiver operating characteristic curve analysis, an IVS cut-off of 11.9 mm provided the best predictive value, with sensitivity of 71.4%, specificity of 75.5% and accuracy of 73.5%. The positive predictive value was 74.5% and the negative predictive value was 72.5%. Conclusions This multicentre retrospective study shows that the echocardiographic index of IVS is an independent predictor for improvement of cardiac symptoms after renal artery stenting.

Background The involvement of cholesterol crystals (CCs) in plaque progression and destabilization of atherosclerotic plaques has been recently recognized. This study aimed to evaluate the association between the intraplaque localization of CCs and plaque vulnerability. Methods We investigated 55 acute coronary syndrome (ACS) and 80 stable angina pectoris (stable AP) lesions using optical frequency domain imaging (OFDI) prior to percutaneous coronary intervention. The distance between CCs and the luminal surface of coronary plaques was defined as CC depth. Results Although the incidence of CCs had similar frequencies in the ACS and stable AP groups (95% vs. 89%, p = 0.25), CC depth was significantly less in patients with ACS than in those with stable AP (median [25th to 75th percentile]: 68 μm [58 to 92 μm] vs. 152 μm [115 to 218 μm]; p < 0.001). The incidences of plaque rupture, thrombus, lipid-rich plaques, and thin-cap fibroatheroma were significantly greater in patients with ACS than in those with stable AP (62% vs. 18%, p < 0.001; 67% vs. 16%, p < 0.001; 84% vs. 57%, p < 0.01; and 56% vs. 19%, p < 0.001, respectively). Conclusion OFDI analysis revealed that CCs were found in the more superficial layers within the coronary atherosclerotic plaques in patients with ACS than in those with stable AP, suggesting that CC depth is associated with plaque vulnerability. CC depth, a novel OFDI-derived parameter, could be potentially used as an alternative means of evaluating plaque vulnerability in coronary arteries.

This study investigated the effect of fractional flow reserve (FFR) after stent implantation on clinical outcomes. Pressurewire measurements and follow-up data were obtained after stent implantation. Regarding the end point, target lesion revascularization (TLR) occurred in 11 patients (15.9 %). Patients with TLR had higher frequencies of multiple stenting (54.5 vs. 19.0 %, p = 0.01), lower post-interventional FFRs (0.84 vs. 0.88, p = 0.01), and longer stent lengths (42.20 vs. 27.69 mm, p = 0.01) than patients without TLR. The post-interventional FFR cutoff for TLR was 0.79, although this value had a weak discriminatory ability. However, multivariate analysis did not show any significant independent predictors of TLR (odds ratio 6.33; confidence interval 0.75–53.4, p = 0.09). Post-interventional FFR values were not significantly associated with TLR when a sub-analysis was performed in patients who underwent only drug-eluting stent (DES) implantation. It was difficult to achieve post-interventional FFRs of 0.9 or greater. DES implantation eliminated the effect of post-interventional FFR on TLR. Post-interventional FFR was not able to predict TLR in the present study.

The aim of this study was to investigate the clinical outcomes of pedal artery angioplasty (PAA) for patients with critical limb ischemia.Pedal artery disease is considered a predictor of delayed wound healing (DH) after endovascular therapy. Adjunctive PAA might improve the speed and extent of wound healing.Consecutive patients with critical limb ischemia (n = 257) presenting with de novo infrapopliteal and pedal artery disease were retrospectively reviewed from a multicenter registry. Patients were divided into 2 groups according to whether PAA was performed (n = 140) or not (n = 117). The rate of wound healing and time to wound healing were compared between these groups. DH score was calculated using the number of independent predictors of DH. Patients were stratified into 3 groups according to DH score: low risk (DH score = 0), moderate risk (DH score = 1 or 2), and high risk (DH score = 3). Estimated efficacy was analyzed for each risk-stratified population.The rate of wound healing was significantly higher (57.5% vs. 37.3%, p = 0.003) and time to wound healing significantly shorter (211 days vs. 365 days; p = 0.008) in the PAA group. In a multivariate analysis, nonambulatory status, target wound depth (UT grade ≥2), and daily hemodialysis were revealed as predictors of DH. In the moderate-risk population, adjunctive PAA significantly improved the rate of wound healing (59.3% vs. 33.9%; p = 0.001). In the high-risk population, however, PAA did not affect wound healing.Patients who underwent PAA showed a higher rate of wound healing and shorter time to wound healing, especially in the moderate-risk population. With regard to wound healing, this aggressive strategy might become a salvage procedure for patients with critical limb ischemia presenting with pedal artery disease.

Myocardial perfusion single-photon emission-computed tomography (SPECT) can predict cardiac events in patients with coronary artery disease with high accuracy; however, pseudo-negative cases sometimes occur. Heart Risk View, which is based on the prospective cohort study (J-ACCESS), is a software for evaluating cardiac event probability. We examined whether Heart Risk View was useful to evaluate the cardiac risk in patients with normal myocardial perfusion SPECT (MPS). We studied 3461 consecutive patients who underwent MPS to detect myocardial ischemia and those who had normal MPS were enrolled in this study (n = 698). We calculated cardiac event probability by Heart Risk View and followed-up for 3.8 ± 2.4 years. The cardiac events were defined as cardiac death, non-fatal myocardial infarction, and heart failure requiring hospitalization. During the follow-up period, 21 patients (3.0 %) had cardiac events. The event probability calculated by Heart Risk View was higher in the event group (5.5 ± 2.6 vs. 2.9 ± 2.6 %, p

Previous reports have suggested that right ventricular apical pacing may lead to cardiac dysfunction. Septal pacing is thought to be superior to apical pacing in the prevention of cardiac dyssynchrony, however, there have been no reports on the contribution of septal pacing to improving clinical outcome.We retrospectively evaluated factors associated with cardiac events in patients with right ventricular pacing.The study population consisted of 256 consecutive patients newly implanted with permanent pacemakers and followed-up for 29 ± 18 months. Cardiac events, consisting of cardiac death or heart failure requiring hospitalization, occurred in 22 patients. Kaplan-Meier curves revealed that patients with a high percentage of ventricular pacing (> 90%, n = 101, group H) had a higher incidence of cardiac events than patients with a low percentage of ventricular pacing (< 10%, n = 83, group L) (P = 0.002). In group H, multivariate analysis showed that age (HR: 1.174, 95%CI: 1.066-1.291, P = 0.001), ejection fraction (EF) (HR: 0.898, 95%CI: 0.836-0.964, P = 0.003), QRS duration during cardiac pacing (HR: 1.059, 95%CI: 1.017-1.103, P = 0.006), and existing basal cardiac diseases (HR: 13.080, 95%CI: 2.463-69.479, P = 0.003) were significant predictors of cardiac events, although pacing site had no significant association with prognosis (P = 0.56).Higher age, lower EF, longer QRS duration during cardiac pacing, and existing basal cardiac diseases are associated with poor prognosis in patients with a high percentage of ventricular pacing.

Angiography is not always an accurate indicator of physiologically significant stenosis. We examined the usefulness of functional evaluation of coronary stenosis severity by determining the fractional flow reserve (FFR) using a pressure wire in patients who received hemodialysis with angiographically intermediate lesions. We recruited 44 patients with intermediate lesions; of these, 22 were undergoing hemodialysis while 22 were not. Quantitative coronary angiography (QCA) was performed to measure the minimal lumen diameter (MLD) and calculate the percent diameter stenosis (%DS). The FFR was calculated as the ratio of the coronary pressure at the distal stenotic site to the mean aortic pressure during maximum hyperemia. In each group, we investigated the relationship between the FFR and %DS and FFR and MLD. The patients in the hemodialysis group were significantly younger and had more calcified and type B2/C lesions than those in the non-dialysis group. Although the FFR was correlated with both %DS (r = 0.71, p

SummaryThe patient was a 74-year-old woman with angina pectoris, who had undergone percutaneous coronary intervention with stent placement in the right coronary artery on October 2, 2007. On November 12 of the same year, she suffered from paroxysmal atrial fibrillation. She was treated with pilsicainide hydrochloride administered by intravenous injection, which was followed by a sudden sinus standstill, with marked bradycardia and a shock state. The patient was then treated with a catecholamine, however, the shock state persisted for about an hour. An electrocardiogram revealed persistent ST depression in leads V4–6 along with elevation of the serum creatinine kinase. A coronary angiography performed on the admission day revealed no abnormality. On the third hospital day, a dual-isotope myocardial SPECT using 201Tl and 99mTc-pyrophosphate demonstrated an annular accumulation of 99mTc-pyrophosphate concordant with the endocardium from apex to the mid-portion of the left ventricle, suggestive of subendocardial infarction. The case is reported here, as there are few reports of subendocardial infarction developing due to ischemia arising from a shock state.

Objectives— Bone marrow (BM)-derived endothelial progenitor cells (EPCs) and vascular smooth muscle progenitor cells (VPCs) contribute to neointima formation, whereas the angiotensin II (Ang II) type 1 receptor (AT 1 )-mediated action on BM-derived progenitors remains undefined. Methods and Results— A wire-induced vascular injury was performed in the femoral artery of BM-chimeric mice whose BM was repopulated with AT 1 -deficient (BM-Agtr1 −/− ) or wild-type (BM-Agtr1 +/+ ) cells. Neointima formation was profoundly reduced by 38% in BM-Agtr1 −/− mice. Although the number of circulating EPCs (Sca-1 + Flk-1 + ) and extent of reendothelialization did not differ between the 2 groups, the numbers of both circulating VPCs (c-Kit − Sca-1 + Lin − ) and tissue VPCs (Sca-1 + CD31 − ) incorporated into neointima were markedly decreased in BM-Agtr1 −/− mice. The accumulation of aggregated platelets and their content of stromal cell–derived factor-1α (SDF-1α) were significantly reduced in BM-Agtr1 −/− mice, accompanied by a decrease in the serum level of SDF-1α. Thrombin-induced platelets aggregation was dose-dependently inhibited (45% at 0.1 IU/mL, P −/− platelets compared with Agtr1 +/+ platelets, accompanied by the reduced expression and release of SDF-1α. Conclusions— The BM-AT 1 receptor promotes neointima formation by regulating the mobilization and homing of BM-derived VPCs in a platelet-derived SDF-1α–dependent manner without affecting EPC-mediated reendothelialization.

There are more than a few risks of hemorrhage complication in patients with amyloidosis. Although most cases with amyloidosis exhibit minor bleeding manifestations, they can be occasionally associated with life-threatening problems. To our knowledge, there are only a few cases of spontaneous pericardial hematoma associated with amyloidosis. We here report a patient who suddenly died of cardiac tamponade with massive pericardial hematoma 7 years after the diagnosis of familial amyloid polyneuropathy (FAP). A 69-year-old female with FAP with cardiogenic shock was admitted to our emergency room. Although she previously underwent permanent pacemaker implantation for atrial fibrillation with slow ventricular response, electrocardiogram showed a critical pacing failure. Emergent telemetry check revealed a sudden extreme increase of pacing capture threshold in the right ventricle. Maximum pacing voltage could not improve the critical condition, and she died 7 h after arrival. Autopsy showed a massive pericardial hematoma in the right ventricular free wall, and microscopic examination revealed typical amyloid deposition in the arterial wall of the pericardium. In this case, it is assumed that a sudden rupture of fragile pericardial vessels with amyloid deposition led to the lethal pericardial hematoma.

Background—The angiotensin II (Ang II) type 1 (AT1) receptor is expressed in bone marrow (BM) cells, whereas it remains poorly defined how Ang II regulates differentiation/proliferation of monocyte-lineage cells to exert proatherogenic actions.Methods and Results—We generated BM chimeric apoE−/−mice repopulated with AT1-deficient (Agtr1−/−) or wild-type (Agtr1+/+) BM cells. The atherosclerotic development was significantly reduced in apoE−/−/BM-Agtr1−/−mice compared with apoE−/−/BM-Agtr1+/+mice, accompanied by decreased numbers of BM granulocyte/macrophage progenitors (GMP:c-Kit+Sca-1−Lin−CD34+CD16/32+) and peripheral blood monocytes. Macrophage-colony-stimulating factor (M-CSF)–induced differentiation from hematopoietic stem cells (HSCs:c-Kit+Sca-1+Lin−) to promonocytes (CD11bhighLy-6Glow) was markedly reduced in HSCs from Agtr1−/−mice. The expression of M-CSF receptor c-Fms was decreased in HSCs/promonocytes from Agtr1−/−mice, accompanied by a marked inhibition in M-CSF–induced phosphorylation of PKC-δ and JAK2. c-Fms expression in HSCs/promonocytes was mainly regulated by TNF-α derived from BM CD45−CD34−stromal cells, and Ang II specifically regulated the TNF-α synthesis and release from BM stromal cells.Conclusions—Ang II regulates the expression of c-Fms in HSCs and monocyte-lineage cells through BM stromal cell–derived TNF-α to promote M-CSF–induced differentiation/proliferation of monocyte-lineage cells and contributes to the proatherogenic action.

Short-Term Treatment with an Angiotensin II Receptor Blocker Prevents Necrotic Core Formation by Inhibiting Oxidative Stress-Mediated Apoptosis in Macrophages Objective: To study the role of angiotensin II (Ang II) type 1 receptor (AT1R) on necrotic core formation associated with endoplasmic reticulum (ER) stress-induced macrophage apoptosis. Methods and Results: Eight-week-old ApoE-deficient mice were fed a high-cholesterol diet and administered AT1R blocker (ARB), hydralazine, or vehicle from 15 weeks of age. Histochemical analysis of brachiocephalic artery at 19 weeks of age showed a marked reduction of necrotic core area in ARB-treated mice. At 17 weeks of age, mRNA expression levels of C/EBP Homologous Protein (CHOP) and the percentage of TUNEL-positive cells were also decreased in ARB-treated mice, concomitant with the significantly lower expressions of NOX2 and NOX4 genes. Free cholesterol (FC)-loaded thioglycollate-induced peritoneal macrophages (TGPM) showed a significant increase in CHOP mRNA expression and the number of annexin V- or propidium iodide (PI)-positive cells; however, these were not affected by cotreatment with Ang II or Ang II plus ARB. In contrast, TGPM isolated from Ang II-treated mice, exhibiting higher expression levels of NOX2 and p22phox genes, showed a more robust increase in CHOP mRNA expression after FC loading. Conclusions: Our findings demonstrate that ARB treatment inhibits necrotic core formation, in part by alleviating oxidative stress-mediated amplification of ER stress-induced macrophage apoptosis.

Objective Although clinical trials demonstrated the superiority of the Zilver (Cook Medical, Bloomington, Ind) paclitaxel-eluting stent (PTX), a recently developed drug-eluting stent (DES), to conventional therapy for femoropopliteal (FP) lesions, the incidence and risk factors of the repetition of reintervention after DES implantation in clinical practice remained unrevealed. Methods This was a subanalysis of the ZEPHYR (ZilvEr PTX for tHe Femoral ArterY and Proximal Popliteal ArteRy) study, enrolling FP lesions undergoing endovascular therapy (EVT) with DES implantation. The current study analyzed the 2-year database including 583 FP lesions in 495 patients undergoing preoperative intravascular ultrasound imaging before DES implantation. The primary outcome measure was re-re-EVT, defined as undergoing additional EVT more than once during the 2-year follow-up after DES implantation. The secondary outcome measure was re-EVT, defined as undergoing at least one additional EVT during the follow-up. Results Critical limb ischemia (CLI) was present in 28% of the study population, 23% had a history of EVT, and 43% had chronic total occlusion. Mean lesion length was 16 ± 10 cm, and intravascular ultrasound imaging-evaluated external elastic membrane area was 28 ± 10 mm 2 . The cumulative incidence rate of re-re-EVT at 2 years was estimated to be 14%, whereas that of re-EVT was 31%. After multivariate analysis, CLI and smaller external elastic membrane area were independently associated with the outcome. Conclusions The incidence and risk factors of the repetition of reintervention after DES implantation for FP lesions were revealed. The current findings suggest that DES implantation might be a careful indication in CLI cases especially with a small vessel.

"Heart Risk View" is the software to evaluate the cardiac event probability, and it is based on the results of the prospective cohort study (J-ACCESS). We examined the usefulness of this software. Study population consisted of 83 patients, who were diagnosed that cardiac event probability was over 20% by "Heart Risk View." During the follow-up period (596 +/- 356 days), cardiac event occurred in 23 patients (27.7%), including 7 patients death. No significant differences were observed in the ejection fraction by Quantitative Gated SPECT, total defect score calculated from SPECT, and the percentage of stress perfusion abnormality detected by SPECT between event and non-event groups. However, the percentage of cardiac revascularization therapy based on the SPECT was significantly lower in the event group (9 vs. 38%, p = 0.03). In conclusion, cardiac event probability calculated by "Heart Risk View" was reliable in our study cohort. Cardiac event strongly depended on the cardiac ischemia, for which the therapy was difficult because of lesion complexity or combined diseases.

Recently, it is suggested that the use of nonsteroidal anti-inflammatory drugs (NSAID) may contribute to the occurrence of cardiovascular events, while the formation of atherosclerotic lesions is related to inflammation. Loxoprofen sodium, a non-selective NSAID, becomes active after metabolism in the body and inhibits the activation of cyclooxygenase. We fed apoE(-/-) mice a western diet from 8 to 16 weeks of age and administered loxoprofen sodium. We measured atherosclerotic lesions at the aortic root. We examined serum levels of cholesterol and triglycerides with HPLC, platelet aggregation, and urinary prostaglandin metabolites with enzyme immune assay. Atherosclerotic lesion formation was reduced to 63.5% and 41.5% as compared to the control in male and female apoE(-/-) mice treated with loxoprofen sodium respectively. Urinary metabolites of prostaglandin E(2), F(1α), and thromboxane B(2), and platelet aggregation were decreased in mice treated with loxoprofen sodium. Serum levels of cholesterol and triglycerides were not changed. We conclude that loxoprofen sodium reduced the formation of early to intermediate atherosclerotic lesions at the proximal aorta in mice mediated by an anti-inflammatory effect.

[BACKGROUND] The angiotensin II (Ang II) type 1 (AT 1 ) receptor is crucially involved in atherogenesis, but bone marrow (BM) AT 1 -mediated proatherogenic action remains undefined- . [METHOD AND RESULT] BM-derived mononuclear cells (BM-MNCs) more abundantly express AT 1 than VSMCs (2.2 fold) with similar affinities to Ang II. BM cells in 8-week-old apoE-deficient −/− ) or wild-type (Agtr1 + / + ) cells. Four (apoE-KO) mice were replaced with AT 1 -deficient (Agtr1 weeks after the initiation of western diet and Ang II infusion (500ng/kg/min), atherosclerotic lesion area in aortic root was examined. ApoE-KO mice reconstituted with Agtr1 −/− marrow (apoE-KO/BM-Agtr1 −/− ) showed a significant reduction in atherosclerotic lesions compared with apoE-KO/BM-Agtr1 + / + mice (55%, P −/− mice (55%, P hi monocytes (76%, P + and CX3CR1 + monocytes were also reduced in apoE-KO/BM-Agtr1 −/− mice (87±16 vs 298±66; CCR2 + monocyte, 72±12 vs 550±119 cells/μl; CX3CR1 + monocyte, respectively, P −/− compared with Agtr1 + / + mice. We next examined the effect of BM-AT 1 on the number of hematopoietic stem cells (HSCs), common myeloid progenitors (CMP), and granulocyte/macrophage progenitors (GMP) to determine at which point of the lineage pathway, BM-AT 1 is involved. The number of HSCs did not differ between the two groups (3.6±0.8 vs 2.9±0.6 × 10 3 cells/tibia, P =n.s.), whereas the numbers of CMP and GMP were much lower in apoE-KO/BM-Agtr1 −/− mice (4.7±0.7 vs 10.2±1.4 ×10 3 cells/tibia, 9.9±2.7 vs 20.2±2.8 × 10 3 cells/tibia, respectively, P [CONCLUSION] BM-MNCs expressed the abundant densities of AT1, and AT1-mediated signals on BM-MNCs exaggerated atherosclerotic lesion development. BM-AT 1 is closely implicated in the differentiation of HSCs into macrophage progenitors and the behavior of monocytes/macrophages, indicating that BM-AT 1 could be a promising therapeutic target for the prevention of cardiovascular events.

症例1は心不全症状を主訴とした69歳の女性で, 99mTc-tetrofosminおよび123I-BMIPP心筋SPECTにおいて前壁中隔および下壁に集積低下所見が認められた.症例2は前胸部痛を主訴とした65歳の女性で, 99mTc-tetrofosminおよび123I-BMIPP心筋SPECTにおいて前壁中隔および心尖部に集積低下所見が認められた.両症例ともに冠動脈造影では三枝の冠動脈拡張および造影遅延,そして左室造影ではびまん性の壁運動低下が認められた.さらに心外膜血管に狭窄病変は認められなかったため,その病態に冠微小循環障害が関与していることが示唆された.