Five-Year Outcomes of the Bioresorbable Peripheral Remedy Stent in the Treatment of Iliac Artery Disease.

PURPOSE: To evaluate the 5-year performance of a bioresorbable vascular scaffold, the Remedy stent, for the treatment of iliac artery atherosclerotic disease. MATERIALS AND METHODS: This prospective, multicenter, single-arm clinical study evaluated 97 patients (97 lesions) with symptomatic TransAtlantic Inter-Society Consensus II A/B iliac artery lesions for 5 years after stent placement. The primary efficacy end point was 12-month primary patency compared with the prespecified standard derived from historical data with metallic stents, and the primary safety end point was the occurrence of major adverse clinical events within 5 years. All angiographic and computed tomography angiographic findings were evaluated by an independent core laboratory for quantitative vessel analysis. RESULTS: The 12-month primary patency rate was 88.6% (95% CI, 80.1%-94.4%), which was lower than the prespecified standard. No significant difference was noted between the diameter stenosis at 9 and 12 months. There were no device- or procedure-related deaths, major amputation, or distal embolization during the follow-up period. The ankle-brachial index maintained significant improvement through the 5-year period compared with that at baseline. The Kaplan-Meier estimates of freedom from target lesion revascularization (TLR), major adverse cardiovascular events, and major adverse cardiovascular and limb events were 95.8%, 91.7%, and 87.5% at 12 months and 85.4%, 72.1%, and 62.5% at 5 years, respectively. CONCLUSIONS: The 5-year follow-up outcomes, including freedom from TLR, of the Remedy stent in iliac artery lesions were satisfactory, with a good safety profile. Nevertheless, the 12-month primary patency did not meet the expected standard compared with that of contemporary metallic stents.

Fatal arterial hemorrhage after pancreaticoduodenectomy: How do we simultaneously accomplish complete hemostasis and hepatic arterial flow?

BACKGROUND: Although arterial hemorrhage after pancreaticoduodenectomy (PD) is not frequent, it is fatal. Arterial hemorrhage is caused by pseudoaneurysm rupture, and the gastroduodenal artery stump and hepatic artery (HA) are frequent culprit vessels. Diagnostic procedures and imaging modalities are associated with certain difficulties. Simultaneous accomplishment of complete hemostasis and HA flow preservation is difficult after PD. Although complete hemostasis may be obtained by endovascular treatment (EVT) or surgery, liver infarction caused by hepatic ischemia and/or liver abscesses caused by biliary ischemia may occur. We herein discuss therapeutic options for fatal arterial hemorrhage after PD. AIM: To present our data here along with a discussion of therapeutic strategies for fatal arterial hemorrhage after PD. METHODS: We retrospectively investigated 16 patients who developed arterial hemorrhage after PD. The patients' clinical characteristics, diagnostic procedures, actual treatments [transcatheter arterial embolization (TAE), stent-graft placement, or surgery], clinical courses, and outcomes were evaluated. RESULTS: The frequency of arterial hemorrhage after PD was 5.5%. Pancreatic leakage was observed in 12 patients. The onset of hemorrhage occurred at a median of 18 d after PD. Sentinel bleeding was observed in five patients. The initial EVT procedures were stent-graft placement in seven patients, TAE in six patients, and combined therapy in two patients. The rate of technical success of the initial EVT was 75.0%, and additional EVTs were performed in four patients. Surgical approaches including arterioportal shunting were performed in eight patients. Liver infarction was observed in two patients after TAE. Two patients showed a poor outcome even after successful EVT. These four patients with poor clinical courses and outcomes had a poor clinical condition before EVT. Fourteen patients were successfully treated. CONCLUSION: Transcatheter placement of a covered stent may be useful for simultaneous accomplishment of complete hemostasis and HA flow preservation.

Impact of the Antithrombotic Effects of Prasugrel on Mid-Term Vascular Healing in Acute Coronary Syndrome vs. Stable Coronary Artery Disease.

BACKGROUND: The impact of antiplatelet drug effects on mid-term local arterial responses following percutaneous coronary intervention (PCI) remains uncertain. We evaluated the impact of the platelet reactivity of prasugrel on mid-term vascular healing between acute coronary syndrome (ACS) and stable coronary artery disease (CAD).Methods and Results:We conducted a prospective, 12-center study in 125 patients with ACS and 126 patients with stable CAD who underwent PCI with an everolimus-eluting stent (EES) and received dual antiplatelet therapy (DAPT) with prasugrel and aspirin. Serial optical coherence tomography (OCT) was performed immediately after PCI and at the 9-month follow-up to assess the association of P2Y12reaction units (PRU) with the frequency of malapposed or uncovered struts and intrastent thrombi (IST). The incidence of abnormal mid-term OCT findings did not different between the ACS and CAD arms, regardless of clinical presentation, except that uncovered struts were more frequent in the ACS than CAD arm. PRU at PCI was significantly associated with the frequency of IST at follow-up, but not with uncovered and malapposed struts. PRU at PCI was the only independent predictor of IST detected at follow-up (odds ratio 1.009). CONCLUSIONS: In patients undergoing EES implantation and receiving prasugrel, achieving an adequate antiplatelet effect at the time of stent implantation may regulate thrombus formation throughout the follow-up period.

Impact of dual antiplatelet therapy with adjusted-dose prasugrel on mid-term vascular response in patients undergoing elective percutaneous coronary intervention with everolimus-eluting stents.

The impact of dual antiplatelet therapy (DAPT) with adjusted-dose (3.75 mg/day) prasugrel for Japanese patients has not been fully investigated in terms of local arterial healing following the elective percutaneous coronary intervention (PCI). The ROUTE-01 elective study was a prospective, 12-center and single-arm registry that enrolled 123 patients who underwent elective PCI with everolimus-eluting stents (EESs) under DAPT with a combination of adjusted-dose prasugrel and aspirin. Serial optical coherence tomography (OCT) was performed at the index PCI and 9-month follow-up to assess the relationship between in-stent thorombus (IST) and residual platelet reactivity measuring platelet reactivity unit (PRU). The patients were classified as extensive, intermediate, and poor metabolizers by cytochrome P450 2C19 (CYP2C19) loss-of-function polymorphisms. The prevalence of IST was 9.0% by 9-month OCT, with no difference amongst the three groups (p = 0.886). The incidences of malapposed and uncovered struts were not different among the groups. PRU was not statistically different among the groups. In multivariate logistic regression analysis, the independent predictor for IST on 9-month OCT was irregular protrusion (odds ratio = 8.952, p = 0.037) on post-PCI OCT, not CYP2C19 loss-of-function polymorphisms. An adequate anti-thrombotic effect with an acceptable incidence of IST was observed irrespective of CYP2C19 loss-of-function polymorphisms. Our data suggests that adjusted-dose prasugrel and aspirin is a feasible treatment option in Japanese patients treated with EESs in elective PCI.

Mercury behaviour in flue gas from sewage sludge incinerators and melting furnace.

Thermal conversion of sewage sludge can be a clean source of renewable energy if the emission of air pollutants from the source is controlled. In 2013, the Minamata Convention on Mercury was adopted, placing greater emphasis on the control of mercury emissions, including mercury emissions from sewage sludge incinerators. To characterise the behaviour of mercury in flue gas, particulate and gaseous mercury concentrations in two incinerators and a melting furnace were measured by manual sampling. In a third facility, continuous emission monitoring was used to characterise temporal trends in gaseous mercury concentrations. Wet scrubbers were determined to be effective air pollution control devices suitable for mercury removal. Stack mercury concentrations were found to be <10 µg/Nm3, which meets the mercury emission standard for existing plants (50 µg/Nm3).

Long-Term (>10 Years) clinical outcomes of first-in-human biodegradable poly-l-lactic acid coronary stents: Igaki-Tamai stents.

BACKGROUND: The purpose of this study was to evaluate the long-term safety of the Igaki-Tamai stent, the first-in-human fully biodegradable coronary stent made of poly-l-lactic acid. METHODS AND RESULTS: Between September 1998 and April 2000, 50 patients with 63 lesions were treated electively with 84 Igaki-Tamai stents. Overall clinical follow-up (>10 years) of major adverse cardiac events and rates of scaffold thrombosis was analyzed together with the results of angiography and intravascular ultrasound. Major adverse cardiac events included all-cause death, nonfatal myocardial infarction, and target lesion revascularization/target vessel revascularization. During the overall clinical follow-up period (121 ± 17 months), 2 patients were lost to follow-up. There were 1 cardiac death, 6 noncardiac deaths, and 4 myocardial infarctions. Survival rates free of all-cause death, cardiac death, and major adverse cardiac events at 10 years were 87%, 98%, and 50%, respectively. The cumulative rates of target lesion revascularization (target vessel revascularization) were 16% (16%) at 1 year, 18% (22%) at 5 years, and 28% (38%) at 10 years. Two definite scaffold thromboses (1 subacute, 1 very late) were recorded. The latter case was related to a sirolimus-eluting stent, which was implanted for a lesion proximal to an Igaki-Tamai stent. From the analysis of intravascular ultrasound data, the stent struts mostly disappeared within 3 years. The external elastic membrane area and stent area did not change. CONCLUSION: Acceptable major adverse cardiac events and scaffold thrombosis rates without stent recoil and vessel remodeling suggested the long-term safety of the Igaki-Tamai stent.

Bare metal stent implantation in large-sized unprotected left main coronary artery stenosis in the drug-eluting stent era.

Recently, drug-eluting stent (DES) has been recommended as the first choice in those patients who need stent implantation in unprotected left main coronary artery (ULMCA) stenosis. However, the long-term safety and efficacy of this procedure is still controversial. The objective of this study was to evaluate the safety and efficacy of bare metal stent (BMS) implantation in ULMCA stenting in the DES era. We implanted BMS (mainly 4 mm-diameter) in large-sized ULMCA after December 2004 when DES became available. The results of BMS implantation (n = 19) were compared with those of DES implantation (n = 39). There was no significant difference between the 2 groups regarding age, gender and coronary risk factors. Emergency procedures were more frequently performed in the BMS group than in the DES group (53% vs. 26%, p = 0.08). The initial mortality was 10.5% (n = 2) in the BMS group and 2.6% (n = 1) in the DES group (p = 0.25). There was no stent thrombosis, Q-wave myocardial infarction or emergent bypass surgery in either group during their hospital stay. The restenosis rate was 0% (n = 45) in both groups, and the target vessel revascularization rate was 5.9% in the BMS group (1/17) and 2.6% (1/38) in the DES group (p = 0.53). Therefore, there were no statistically significant differences in outcomes between the two study groups. These results indicate that BMS implantation in a large-sized ULMCA may be a safe and effective treatment even in the DES era.

Histopathological findings of new in-stent lesions developed beyond five years.

We analyzed 14 cases of new lesions inside implanted bare-metal stents. In every case, there was no angiographic restenosis within 3 years, but a new lesion was observed inside a stented segment at long-term follow-up (>5 years). Fourteen cases were evaluated: 9 with Wiktor stents, 2 with Palmaz-Schatz stents, and 3 with ACS Multilink stents. The interval from stent implantation to follow-up angiography was 63-147 months (89 +/- 23). Thirteen lesions were treated by percutaneous coronary intervention (PCI) and stenotic tissue was obtained by directional coronary atherectomy (DCA) in 10 cases. All retrieved samples were composed of newly developed atherosclerosis facing the healed neointimal layer, and four samples showed histopathological findings of acute coronary syndrome. Stent struts were retrieved in four cases and no inflammation was observed surrounding them. Qualitative and quantitative analysis of stent struts was performed in two cases that showed no metal corrosion. These findings suggest that new atherosclerotic progression occurred inside the implanted stent without peristrut inflammation.

Serial angioscopic findings after successful intracoronary brachytherapy for in-stent restenosis.

The intracoronary changes that occur after brachytherapy for in-stent restenosis (ISR) have yet to be fully established. The purpose of this study in patients who had ISR was to examine the serial angioscopic changes in intracoronary lesions that occurred after brachytherapy. Forty-four patients who had ISR (49 lesions) underwent balloon angioplasty (n = 34) or directional atherectomy (n = 15), followed by intracoronary brachytherapy using a beta-emitting phosphorus-32 source wire. Angioscopic investigations were performed 3 and 9 months after brachytherapy. Uncovered stents were detected in 63.3% of lesions at 3 months. A significant decrease (p = 0.028) in this prevalence occurred over the next 6 months, with 36% of lesions having uncovered stents at 9 months. At 3 months, 33% of the lesions had visible erosion or ulceration and superficial thrombus. The prevalence of these characteristics was decreased at 9 months, although 17% of the lesions were still ulcerated or eroded at that time. Protruding thrombus was not observed in any lesion at 3 and 9 months. In conclusion, uncovered stents and intimal erosions or ulcerations were still present 9 months after brachytherapy in 36% and 17% of lesions, respectively. These results suggest that the healing process was not completed 9 months after brachytherapy in approximately 33% of lesions.

Mast cell tryptase in mast cell granules enhances MCP-1 and interleukin-8 production in human endothelial cells.

OBJECTIVE: Recent studies have highlighted the pathogenetic importance of chronic inflammation in cardiovascular disorders such as congestive heart failure and atherosclerosis. Mast cells release a wide variety of immune mediators that may initiate inflammatory responses, whereas endothelial cells (ECs) play a prominent role in the pathogenesis of cardiovascular diseases by secreting cytokines. The purpose of this study was to clarify the role of mast cells as an activator of ECs. METHODS AND RESULTS: ECs harvested from human umbilical cord veins were stimulated with mast cell granules (MCGs) prepared from sonicated human leukemic mast cells. The supernatants and total RNA from cells were collected. Levels of interleukin (IL)-1beta, tumor necrosis factor-alpha, and granulocyte colony-stimulating factor remained unchanged up to 24 hours. In contrast, levels of monocyte chemoattractant protein-1 (MCP-1) and IL-8 increased significantly within 6 hours. Northern blot analysis revealed an increase in MCP-1 and IL-8 mRNA expression in MCG-treated ECs. Induction of these chemokines was attenuated by antitryptase neutralizing antibody. Furthermore, MCP-1 and IL-8 were induced in ECs by incubation with human mast cell tryptase, but not with chymase. CONCLUSIONS: These results indicate that the production of MCP-1 and IL-8 in ECs was induced by MCG and amplified by tryptase.

Predictors of improvement in left ventricular function after initially successful angioplasty of unprotected left main coronary artery stenoses.

BACKGROUND: Percutaneous coronary intervention (PCI) has been increasingly applied to unprotected left main coronary artery (LMCA) lesions, with varied procedural success and clinical outcomes. However, the effect of PCI on left ventricular performance is still unclear, and there are no clinical studies assessing factors that influence left ventricular ejection fraction (LVEF) in these cases. METHODS: Between April 1986 and August 2002, de novo PCI was performed for unprotected LMCA stenoses in 199 patients. Close clinical and angiographic follow-up were conducted after the procedure. RESULTS: One hundred eighty patients survived over six months and analysis of paired left ventriculography was possible in 175 patients. Improvement in LVEF was observed in the entire population (52.9 +/- 15.7% to 56.1 +/- 14.3%, p = 0.048). The LVEF change was 6.7 +/- 9.5% (p < 0.01) in group with baseline LVEF < or = 50% and 0.7 +/- 6.7 % (p = NS) in group with LVEF > 50%. There was significant intergroup difference (p < 0.001). Patients with baseline diameter stenosis > or = 60% had an improvement of 5.3 +/- 8.3% (p < 0.05) whereas those with stenosis < 60% had no improvement (2.0 +/- 8.4%, p = NS). CK-MB elevation > or = 3 times normal after PCI had a significant inverse association with improvement in LVEF (p < 0.05). Multivariate analysis revealed baseline LVEF < or = 50% was the only independent predictor of improvement in LVEF (standard estimate = 3.509, 95% CI: 2.164-4.854, p < 0.001). CONCLUSIONS: Successful PCI procedure is associated with significant improvement in LVEF, especially in patients with depressed left ventricular function.

Intravascular ultrasound-guided directional coronary atherectomy for unprotected left main coronary stenoses with distal bifurcation involvement.

Stent implantation in unprotected left main coronary artery (LMCA) bifurcation lesions may improve procedural and late clinical outcomes. However, concerns regarding stent-related complications, such as stent jail, subacute thrombosis, and in-stent restenosis remain. Optimal debulking by directional coronary atherectomy (DCA) with intravascular ultrasound (IVUS) guidance may be effective in this complex lesion subset, but this strategy has not yet been established. Our objective was to evaluate the safety and efficacy of IVUS-guided DCA for unprotected LMCA stenoses with distal bifurcation involvement. A total of 67 consecutive patients were included in this study and procedural success was achieved in all cases. Two cardiac deaths (2.9%) were noted and 3 patients (4.5%) underwent repeat angioplasty during hospitalization. There was no Q-wave myocardial infarction or emergency bypass surgery. Non-Q-wave myocardial infarction (creatine kinase-MB >3 times normal) occurred in 13.4% of patients. Stent implantation was necessary in 17 cases (25.4%) to achieve an optimal result. IVUS showed an improved lumen cross-sectional area and a low plaque burden in the LMCA after intervention. All-cause mortality, angiographic restenosis, and the target lesion revascularization rates at 6 months were 7.4%, 23.8%, and 20.0%, respectively. With IVUS guidance, aggressive DCA can be performed safely in unprotected LMCA bifurcation lesions, and optimal angiographic and IVUS results can be achieved with low residual plaque burden, which leads to a low restenosis rate. Optimal lesion debulking by DCA does not necessarily need adjunctive stenting in this specific anatomic subset.

Lesion regression after percutaneous coronary intervention for unprotected left main trunk disease.

BACKGROUND: Although some studies have documented the six-month angiographic outcomes of percutaneous coronary intervention (PCI) with new devices for unprotected left main trunk disease (ULMTD), a long-term angiographic analysis is mandatory to evaluate the safety and effectiveness of this procedure. This study aims to assess a long-term (one year or more) angiographic analysis after PCI for this lesion. METHODS: PCI was performed for 225 ULMTD with de novo or restenotic lesions. There were 19 deaths and 12 repeat PCIs during the hospital stay. The remaining 194 lesions were followed, and 126 lesions showed no angiographic restenosis or target lesion revascularization within six months. Finally, long-term quantitative angiographic follow-up was completed in 78 lesions (mean 2.4 years, maximum 7.5 years after PCI). RESULTS: Minimal lumen diameter increased significantly from 2.46 +/- 0.59 mm to 2.72 +/- 0.65 mm (p < 0.0001) and percent diameter stenosis decreased significantly from 26 +/- 14% to 19 +/- 14% (p < 0.0001) between the six-month and the long-term follow-ups. No additional restenosis or new lesions were found at long-term follow-up, and significant lesion regression was ascertained in each procedure (directional coronary atherectomy, p < 0.005; ballooning, p < 0.005; stenting, p < 0.05). CONCLUSIONS: These findings support the safety and effectiveness of PCI for ULMTD during the long-term period.

New technique for superior guiding catheter support during advancement of a balloon in coronary angioplasty: the anchor technique.

To get superior guiding catheter support, we tried a new method called the anchor technique. By inflating a balloon in a nontarget vessel and holding its shaft with backward force while advancing another balloon, the anchor effect for the guiding catheter could be obtained and it appeared to be helpful for a balloon or a stent to cross the target lesion.

Circulating hepatocyte growth factor as a diagnostic marker of thrombus formation in patients with cerebral infarction.

Circulating levels of hepatocyte growth factor (HGF) are increased in the early stage of an acute myocardial infarction because of arterial thrombosis. The purpose of this study was to use a new sensitive enzyme-linked immunosorbent assay to investigate whether circulating HGF is increased in patients with cerebral infarction. Circulating HGF was measured in 32 patients with cerebral infarction on admission to hospital and on days 2, 3, 7 and 14 after the onset of symptoms. Serum HGF levels exceeded the mean value +2SD (329pg/ml) measured in controls in 10 of 20 patients (50%) within 6 h after onset and in 15 of 32 patients (47%) within 24 h. Plasma D-dimer was increased in more than half of the patients with elevated HGF values. HGF levels in 16 patients who were measured serially were persistently increased throughout the study period. The results suggests that circulating HGF is a reliable early marker of cerebral infarction, and that this new sensitive HGF assay may be useful for diagnosing cerebral thrombosis.

Comparison of the self-expanding Radius stent and the balloon-expandable Multilink stent for elective treatment of coronary stenoses: a serial analysis by intravascular ultrasound.

We compared the outcome of the self-expanding Radius stent and the balloon-expandable Multilink stent serially by angiography and intravascular ultrasound. Successful stent deployment was achieved in 66 lesions of 56 stable angina patients (34 lesions with Radius stents and 32 lesions with Multilink stents). At follow-up, there were no significant differences in minimal lumen diameter or percent diameter stenosis between the groups, nor in restenosis rates, although the Radius stent group rate was slightly lower (23.5% vs. 31.3%). In the Radius stent group, stent cross-sectional area (CSA) increased gradually after implantation until the 6-month follow-up (8.37 +/- 1.83 to 10.16 +/- 2.59 mm(2); n = 15), giving a larger CSA (P = 0.03) than the Multilink stent group, which decreased (9.00 +/- 2.05 to 8.27 +/- 2.15 mm(2); n = 17). The lumen CSA was also slightly larger (6.82 +/- 3.06 vs. 5.84 +/- 1.85 mm(2); P = 0.29) in the Radius stent group. These findings indicated that the Radius stent enlarged progressively after implantation, which might be useful for prevention of restenosis.

Evidence for a role of mast cells in the evolution to congestive heart failure.

Mast cells are believed to be involved in the pathophysiology of heart failure, but their precise role in the process is unknown. This study examined the role of mast cells in the progression of heart failure, using mast cell-deficient (WBB6F1-W/W(v)) mice and their congenic controls (wild-type [WT] mice). Systolic pressure overload was produced by banding of the abdominal aorta, and cardiac function was monitored over 15 wk. At 4 wk after aortic constriction, cardiac hypertrophy with preserved left ventricular performance (compensated hypertrophy) was observed in both W/W(v) and WT mice. Thereafter, left ventricular performance gradually decreased in WT mice, and pulmonary congestion became apparent at 15 wk (decompensated hypertrophy). In contrast, decompensation of cardiac function did not occur in W/W(v) mice; left ventricular performance was preserved throughout, and pulmonary congestion was not observed. Perivascular fibrosis and upregulation of mast cell chymase were all less apparent in W/W(v) mice. Treatment with tranilast, a mast cell-stabilizing agent, also prevented the evolution from compensated hypertrophy to heart failure. These observations suggest that mast cells play a critical role in the progression of heart failure. Stabilization of mast cells may represent a new approach in the management of heart failure.