A randomized, double-blind, placebo-controlled trial investigating the effect of ticagrelor on saphenous vein graft patency in patients undergoing coronary artery bypass grafting surgery-Rationale and design of the POPular CABG trial.

RATIONALE: An estimated 15% of saphenous vein grafts (SVGs) occlude in the first year after coronary artery bypass grafting (CABG) despite aspirin therapy. Graft occlusion can result in symptoms, myocardial infarction, and death. SVG occlusion is primarily caused by atherothrombosis, in which platelet activation plays a pivotal role. Evidence regarding the effect of stronger platelet inhibition on SVG patency after CABG is limited. The main objective of the POPular CABG trial is to determine whether dual antiplatelet therapy with aspirin plus ticagrelor improves SVG patency when compared to aspirin alone. STUDY: The POPular CABG is a randomized, double-blind, placebo-controlled, multicenter trial investigating the effect of adding ticagrelor to standard aspirin therapy on the rate of SVG occlusion. A total of 500 patients undergoing CABG with ≥ 1 SVG are randomized to ticagrelor or placebo. The primary end point is SVG occlusion rate, assessed with coronary computed tomography angiography at 1 year. Secondary end points are stenoses and occlusions in both SVGs and arterial grafts and SVG failure at 1 year, defined as a composite of SVG occlusion on coronary computed tomography angiography or coronary angiography, SVG revascularization, myocardial infarction in the territory supplied by an SVG, or sudden death. Safety end points are bleeding events at 30 days and 1 year. CONCLUSION: The POPular CABG trial investigates whether adding ticagrelor to standard aspirin after CABG reduces the rate of SVG occlusion at 1 year.

Contact Activation Inhibitor and Factor XI Antibody, AB023, Produces Safe, Dose-Dependent Anticoagulation in a Phase 1 First-In-Human Trial.

Objective- Factor XI (FXI) contributes to thrombotic disease while playing a limited role in normal hemostasis. We generated a unique, humanized anti-FXI antibody, AB023, which blocks factor XIIa-mediated FXI activation without inhibiting FXI activation by thrombin or the procoagulant function of FXIa. We sought to confirm the antithrombotic activity of AB023 in a baboon thrombosis model and to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy adult subjects. Approach and Results- In a primate model of acute vascular graft thrombosis, AB023 reduced platelet and fibrin accumulation within the grafts by >75%. To evaluate the safety of AB023, we performed a first-in-human study in healthy adult volunteers without any serious adverse events. Overall, 10 of 21 (48%) subjects experienced 20 treatment-emergent adverse events, with 7 of 16 (44%) subjects following active treatment and 3 of 5 (60%) subjects following placebo. AB023 did not increase bleeding or prothrombin times. Anticoagulation was verified by a saturable ≈2-fold prolongation of the partial thromboplastin time for over 1 month after the highest dose. Conclusions- AB023, which inhibits contact activation-initiated blood coagulation in vitro and experimental thrombus formation in primates, produced a dose-dependent duration of limited anticoagulation without drug-related adverse effects in a phase 1 trial. When put in context with earlier observations suggesting that FXI contributes to venous thromboembolism and cardiovascular disease, although contributing minimally to hemostasis, our data further justify clinical evaluation of AB023 in conditions where contact-initiated FXI activation is suspected to have a pathogenic role. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT03097341.

Mid-Term Outcomes of Thrombolysis for Acute Lower Extremity Ischemia at a Tertiary Care Center.

BACKGROUND: Acute limb ischemia (ALI) is challenging to treat because of high morbidity and mortality. Endovascular-first options beginning with thrombolysis are technically feasible with similar results to open surgery. We examined our experience with thrombolysis to identify patients and target conduits that are predictive of improved outcomes. METHODS: We performed a retrospective review of our institutional database of thrombolysis cases for arterial lower extremity disease. Thrombolysis was the index procedure, and any subsequent treatment was a reintervention. Conversion to open surgery perioperatively such as thromboembolectomy or bypass was considered a technical failure. Primary outcomes included primary patency, secondary patency, amputation-free survival (AFS), and survival. Secondary outcomes included conversion to open, reintervention <30 days, and amputation <30 days. Descriptive statistics and analysis of variance were performed for preoperative and intraoperative risk factors. Kaplan-Meier estimation and Cox proportional hazard models were used for primary and secondary outcomes. RESULTS: Ninety-nine patients with ALI were treated with thrombolysis from 2007 to 2017. Thrombolysis was attempted on native artery (40%), vein bypass (7%), prosthetic bypass (33%), and stent (19%). Rutherford class distribution was 50% class 1, 41% class 2a, 5% class 2b, and 3% class 3. Technical success was 70%, characterized by an all-endovascular approach, patency at 30 days, and AFS for 30 days. Primary patency at 1- and 2-years was 31% and 22%, respectively. Secondary patency at 1- and 2-years was 39% and 27%, respectively. Overall, 30% required conversion to open surgery at the time of the index procedure, 7% reintervention <30 days, 5% mortality <30 days, and 5% major amputation <30 days. Prosthetic grafts and vein bypasses had the worst primary and secondary patency (P < 0.05). Five out of 7 vein bypasses required open conversion. Thrombolysis of native arteries was most successful maintaining primary patency (P < 0.05), secondary patency (P < 0.05), and AFS (P < 0.05). Patients who had adjunctive procedures at the time of thrombolysis had a significantly greater primary patency (P < 0.05) and secondary patency (P < 0.05) but not greater AFS. CONCLUSION: Outcomes in thrombolysis for ALI have not significantly improved 20 years after the STILE trial. Technical success and mid-term patency rates are modest at best. Thrombolysis of vein bypasses and prosthetic grafts have poor technical success and primary patency compared with native arteries. However, aggressive adjunctive interventions during thrombolysis appear to improve primary and secondary patency.

Reactive Oxygen Species: Modulators of Phenotypic Switch of Vascular Smooth Muscle Cells.

Reactive oxygen species (ROS) are natural byproducts of oxygen metabolism in the cell. At physiological levels, they play a vital role in cell signaling. However, high ROS levels cause oxidative stress, which is implicated in cardiovascular diseases (CVD) such as atherosclerosis, hypertension, and restenosis after angioplasty. Despite the great amount of research conducted to identify the role of ROS in CVD, the image is still far from being complete. A common event in CVD pathophysiology is the switch of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic phenotype. Interestingly, oxidative stress is a major contributor to this phenotypic switch. In this review, we focus on the effect of ROS on the hallmarks of VSMC phenotypic switch, particularly proliferation and migration. In addition, we speculate on the underlying molecular mechanisms of these cellular events. Along these lines, the impact of ROS on the expression of contractile markers of VSMCs is discussed in depth. We conclude by commenting on the efficiency of antioxidants as CVD therapies.

A comprehensive report of long-term outcomes after catheter-directed thrombolysis for occluded infrainguinal bypass grafts.

OBJECTIVE: The objective of this study was to assess the technical and short- and long-term clinical outcomes of catheter-directed thrombolysis (CDT) with urokinase for occluded infrainguinal bypass grafts. In addition, factors associated with technical success and amputation-free survival were assessed. METHODS: A retrospective analysis of a cohort of patients treated with catheter-directed urokinase-based thrombolysis for occluded infrainguinal bypass grafts was conducted between January 2000 and December 2015. Demographics, procedural data, and short- and long-term outcome data, including patency rates of the bypasses, limb salvage, and overall survival, were collected. Statistical models for clustered data were applied to assess predictive factors. RESULTS: In 177 patients, 251 CDTs were performed on 204 bypasses. In 209 procedures (83.3%), the occluded bypass was reopened; clinical disappearance of ischemic symptoms occurred after 157 procedures (62.6%). Premature cessation of thrombolysis occurred in 33 procedures (13.2%), and periprocedural and postprocedural complications were noted in 91 patients (36.3%). Factors associated with long-term limb salvage are fewer vascular interventions before CDT (P = .0003), higher number of patent outflow vessels before start of CDT (P < .0001), and higher number of patent outflow vessels after CDT (P < .0001). The 1- and 5-year patency rates of bypasses after successful CDT were 64.6% and 48.9%; amputation-free survival after 1 year, 5 years, and 7 years was 81.5%, 71.3%, and 70.5%, respectively. CONCLUSIONS: Clinical success after CDT was observed in 62% of procedures with an associated complication rate of 36%. Patent outflow vessels before and after CDT are factors associated with long-term limb salvage. Amputation-free survival after 5 years is 71.3%.

What Is the Secondary Patency of Thrombosed Bypasses of the Lower Limbs Cleared by Fibrinolysis In Situ?

BACKGROUND: In case of acute thrombosis, lower limb bypasses can, in certain cases, be cleared by local intra-arterial fibrinolysis (LIF). The aim of this study is to evaluate the secondary patency of thrombosed bypasses after fibrinolysis. METHODS: This retrospective study includes all patients hospitalized for thrombosed bypasses of the lower limbs that were treated with in situ fibrinolysis using urokinase, between 2004 and 2013, in 2 French university hospital centers. Fibrinolysis was indicated in case of recent thrombosis (<3 weeks) provoking acute limb ischemia without sensory-motor deficit and in the absence of general contraindications. The secondary patency of the grafts was defined as the time after fibrinolysis without a new thrombotic event. RESULTS: There were 207 patients, hospitalized for recent thrombosis of 244 bypasses. The LIF was efficient in 74% of the cases (n = 180). Secondary patency of these bypasses was 54.2% and 32.4% overall, 68.3% and 50.3% for the suprainguinal bypasses, and 48.3% and 21.5% for the infrainguinal bypasses at 1 and 5 years, respectively. There is a significant difference (P = 0.002) regarding the permeability of the suprainguinal and infrainguinal bypasses. The survival rate was 75% (±6.4%) at 5 years and the limb salvage rate was 89% (±3.3%), 78.2% (±5.1%), and 75% (±5.8%) at 1, 3, and 5 years, respectively. The only independent factor influencing the secondary patency of infrainguinal bypasses that was significant in a multivariate analysis was the infragenicular localization of the distal anastomosis (P = 0.023). CONCLUSIONS: LIF is an effective approach that often allows the identification of the underlying cause, permitting elective adjunctive treatment of the underlying cause. Although LIF is at least as effective as its therapeutic alternatives described in the literature, the secondary patency of the bypasses remains modest and encourages close monitoring, particularly in patients with an infragenicular bypass.

Lower on-treatment platelet reactivity during everolimus-eluting stent implantation contributes to the resolution of post-procedural intra-stent thrombus: serial OCT observation in the PRASFIT-Elective study.

Intra-stent thrombus (IS-Th) formed immediately after percutaneous coronary intervention (PCI) is associated with subsequent adverse coronary events. However, the impact of on-treatment platelet reactivity on IS-Th is unknown. PRASFIT-Elective is a multicenter study of PCI patients receiving prasugrel (20/3.75 mg, loading/maintenance dose) or clopidogrel (300/75 mg), with aspirin (100 mg). Among the 742 study patients, 111 were pre-specified for the OCT sub-study. Of these, 82 underwent OCT immediately after PCI to assess IS-Th and at an 8-month follow-up to evaluate the fate of the IS-Th. Lesions were considered resolved when IS-Th were detected after PCI but not on the follow-up or persistent when IS-Th were observed on both scans. The P2Y12 Reactive Unit (PRU) value was determined at the initial PCI and 4 and 48 weeks post-PCI. In 76 patients (86 lesions), we detected 230 IS-Th initially, and 196 IS-Th (85.2%) were resolved at the 8-month OCT. At PCI, but not 4 or 48 weeks after, the resolved IS-Th group had a lower PRU than the persistent IS-Th group (199 ± 101 vs. 266 ± 102, p = 0.008). Multivariate logistic regression analyses revealed that lower PRU at PCI and less calcified lesions were independent predictive factors for the resolution of IS-Th. Local lesion-related factors and lower on-treatment platelet reactivity at the time of PCI may contribute to the resolution of IS-Th after EES implantation, potentially improving clinical outcome.

Paclitaxel-Coated Balloons for the Treatment of Symptomatic Central Venous Stenosis in Dialysis Access: Results from a Randomized Controlled Trial.

PURPOSE: To compare the clinically-assessed intervention-free period (IFP) of paclitaxel-coated balloon (PCB) vs conventional balloon angioplasty (CBA) for the treatment of symptomatic central venous stenosis (CVS) in dialysis access. MATERIALS AND METHODS: Within 20 months, 40 dialysis patients (19/40 arteriovenous fistulae [AVFs] and 21/40 arteriovenous grafts [AVGs]) were randomized to undergo angioplasty either with a PCB (PCB group, n = 20; 14/20 male; age: 56.7) or CBA (CBA group, n = 20; 15/20 male; age: 57). There were 15/20 restenotic lesions in PCB group and 12/20 in CBA group. In 25/40 cases, patients had an ipslateral catheter insertion in the past. Primary endpoint was clinically-assessed intervention-free period (IFP) of the treated segment at 6 months, while secondary endpoints included complication rates during follow-up period and identification of factors influencing IFP. RESULTS: Median IFP was significantly better in PCB group (PCB group: 179 days, vs CBA group: 124.5 days, P = .026). Mean follow-up period was 180 days (range, 5-479). There was no significant difference between AVGs and AVFs (P = .17), treatment of de novo vs restenotic lesions (P = .33), or prior presence of catheter insertion (P = .21). No complications were observed. In restenotic lesions in PCB group, longitudinal comparison between treatments also showed a significant difference in favor of PCB treatment (median IFP in PCB* group 177 vs 91 days in CBA* group; P = .01). CONCLUSIONS: In this prospective study, PCB had significantly better results compared with CBA for the treatment of symptomatic central venous stenosis in dialysis access. Retrospective longitudinal comparison of treatments in the same patients also showed a significant difference in favor of PCBs.

Long-term Outcome after Thrombolysis for Acute Lower Limb Ischaemia.

OBJECTIVES: The purpose was to study long-term outcome after thrombolysis for acute arterial lower limb ischaemia, and to evaluate the results depending on the underlying aetiology of arterial occlusion. METHODS: This was a retrospective study of patients entered into a prospective database. Patients were identified in prospective databases from two vascular centres, including a large number of variables. Case records were analysed retrospectively. Through cross linkage with the Population Registry 100% accurate survival data were obtained. Between January 2001 and December 2013, 689 procedures were included. The aetiology of ischaemia was graft/stent/stent graft occlusion in 39.8%, arterial thrombosis in 27.7%, embolus in 25.1% and popliteal aneurysm in 7.4%. RESULTS: The mean follow-up was 59.4 months (95% CI, 56.1-62.7), during which 32.9% needed further re-interventions, 16.4% underwent amputation without re-intervention, and 50.7% had no re-intervention. The need for re-intervention during follow-up was 48.0% in the graft/stent occlusions group, 34.0% of the popliteal aneurysm group, 25.4% in the thrombosis group, and 16.3% in the embolus group (p < .001). The overall primary patency rates were 69.1% and 55.9% at 1 and 5 years, respectively. Primary patency at 5 years was higher for the embolus group (83.3%, p = .002) and lower for the occluded graft/stent group (43.3%, p < .001). Secondary patency rates were 80.1% and 75.2% at 1 and 5 years, respectively, without difference between the subgroups. The amputation rate was lower in the embolic group at 1 and 5 years (8.1% and 11.1%, respectively, p = .001). Survival was higher in the group with occluded popliteal aneurysms at 5 years (83.3%, p = 0.004). Amputation free survival was 72.1% and 45.2% at 1 and 5 years; lower in the occluded graft/stent group at five years (37.9%, p = .007). CONCLUSION: Intra-arterial thrombolytic therapy achieves good medium and long-term clinical outcome, reducing the need of open surgical treatment in most patients.

Impact of proton pump inhibitors on clinical outcomes in patients treated with a 6- or 24-month dual-antiplatelet therapy duration: Insights from the PROlonging Dual-antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY trial.

BACKGROUND: Proton pump inhibitors (PPIs) are frequently prescribed in combination with clopidogrel, but conflicting data exist as to whether PPIs diminish the efficacy of clopidogrel. We assessed the association between PPI use and clinical outcomes for patients treated with percutaneous coronary intervention (PCI) and dual-antiplatelet therapy (DAPT) with clopidogrel plus aspirin. METHODS AND RESULTS: In the PRODIGY trial, 1,970 patients were randomized to 6- or 24-month DAPT at 30 days from index procedure. Among them, 738 patients (37.5%) received PPI (mainly lansoprazole; 90.1%) at the time of randomization. Proton pump inhibitor users were older, were most likely to be woman, had a lower creatinine clearance, presented more frequently with acute coronary syndrome, and had a higher CRUSADE bleeding score. After adjustment, the primary efficacy end point (composite of all-cause death, myocardial infarction, and cerebrovascular accident) was similar between no PPI and PPI users (9.2% vs 11.5%, adjusted hazard ratio [HR] 1.051, 95% CI 0.788-1.400, P = .736). Bleeding rates did not differ between the 2 groups (Bleeding Academic Research Consortium type 2, 3, or 5: adjusted HR 0.996, 95% CI 0.672-1.474, P = .980). Net clinical adverse events were also similar in no PPI and PPI patients (12.9% vs 14.9%, adjusted HR 0.99, 95% CI 0.772-1.268, P = .93). Results remained consistent at sensitivity analysis when focusing on the 548 patients who remained on PPI for the whole study duration. CONCLUSIONS: The current findings suggest that the concomitant use of PPIs, when clinically indicated, in patients receiving clopidogrel is not associated with adverse clinical outcome.

Is It Worthwhile Treating Occluded Cold Stored Venous Allografts by Thrombolysis?

OBJECTIVES: Thrombolysis has been reported to be suboptimal in occluded vein grafts and cryopreserved allografts, and there are no data on the efficacy of thrombolysis in occluded cold stored venous allografts. The aim was to evaluate early outcomes, secondary patency and limb salvage rates of thrombolysed cold stored venous allograft bypasses and to compare the outcomes with thrombolysis of autologous bypasses. METHODS: This was a single center study of consecutive patients with acute and non-acute limb ischemia between September 1, 2000, and January 1, 2014, with occlusion of cold stored venous allografts, and between January 1, 2012, and January 1, 2014, with occlusion of autologous bypass who received intra-arterial thrombolytic therapy. RESULTS: Sixty-one patients with occlusion of an infrainguinal bypass using a cold stored venous allograft (n = 35) or an autologous bypass (n = 26) underwent percutaneous intra-arterial thrombolytic therapy. The median duration of thrombolysis was 20 h (IQR 18-24) with no difference between the groups (p = .14). The median follow up was 18.5 months (IQR 11.0-52.0). Secondary patency rates of thrombolysed bypass at 6 and 12 months were 44 ± 9% and 32 ± 9% in patients with a venous allograft bypass and 46 ± 10% and 22 ± 8% with an autologous bypass, with no difference between groups (p = .40). Limb salvage rates at 1, 6, and 12 months after thrombolysis in the venous allograft group were 83 ± 7%, 72 ± 8% and 63 ± 9%, and in the autologous group 91 ± 6%, 76 ± 9%, and 65 ± 13%, with no difference between groups (p = .69). CONCLUSIONS: Long-term results of thrombolysis of venous allograft bypasses are similar to those of autologous bypasses. Occluded cold stored venous allograft can be successfully re-opened in most cases with a favorable effect on limb salvage.

Low-Dose Alteplase Infusion for the Treatment of Mechanical Aortic Valve Thrombosis: A Spotlight on the Importance of Medication Adherence.

A rare, yet serious, complication of mechanical heart valves is symptomatic obstructive prosthetic valve thrombosis. The risk of valve thrombosis is magnified in patients who are nonadherent to prescribed anticoagulation. In this case report, we describe a 48-year-old male patient with a history of mechanical aortic valve replacement surgery, who stopped taking prescribed warfarin therapy 2 years before presentation and subsequently developed acute decompensated heart failure secondary to valvular dysfunction. Low-dose alteplase therapy was administered successfully with no bleeding complications and a complete return of valvular function.

Saphenous vein graft failure after coronary artery bypass surgery: insights from PREVENT IV.

BACKGROUND: Coronary artery bypass grafting success is limited by vein graft failure (VGF). Understanding the factors associated with VGF may improve patient outcomes. METHODS AND RESULTS: We examined 1828 participants in the Project of Ex Vivo Vein Graft Engineering via Transfection IV (PREVENT IV) trial undergoing protocol-mandated follow-up angiography 12 to 18 months post-coronary artery bypass grafting or earlier clinically driven angiography. Outcomes included patient- and graft-level angiographic VGF (≥75% stenosis or occlusion). Variables were selected by using Fast False Selection Rate methodology. We examined relationships between variables and VGF in patient- and graft-level models by using logistic regression without and with generalized estimating equations. At 12 to 18 months post-coronary artery bypass grafting, 782 of 1828 (42.8%) patients had VGF, and 1096 of 4343 (25.2%) vein grafts had failed. Demographic and clinical characteristics were similar between patients with and without VGF, although VGF patients had longer surgical times, worse target artery quality, longer graft length, and they more frequently underwent endoscopic vein harvesting. After multivariable adjustment, longer surgical duration (odds ratio per 10-minute increase, 1.05; 95% confidence interval, 1.03-1.07), endoscopic vein harvesting (odds ratio, 1.41; 95% confidence interval, 1.16-1.71), poor target artery quality (odds ratio, 1.43; 95% confidence interval, 1.11-1.84), and postoperative use of clopidogrel or ticlopidine (odds ratio, 1.35; 95% confidence interval, 1.07-1.69) were associated with patient-level VGF. The predicted likelihood of VGF in the graft-level model ranged from 12.1% to 63.6%. CONCLUSIONS: VGF is common and associated with patient and surgical factors. These findings may help identify patients with risk factors for VGF and inform the development of interventions to reduce VGF. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00042081.

Occluded Tunneled Venous Catheter in Hemodialysis Patients: Risk Factors and Efficacy of Alteplase.

Thrombosis of tunneled central venous catheters (CVC) in hemodialysis (HD) patients is common and it can lead to the elimination of vascular sites. This study aimed to evaluate the incidence of thrombotic obstruction of tunneled CVC in HD patients and the efficacy of occlusion treatment with alteplase use, and identify factors associated with thrombotic occlusion. It was a prospective cohort study performed in two centers which evaluated the diagnosis and treatment of thrombotic occlusion of CVC in HD patients for 24 consecutive months. The catheter occlusion was defined as the difficulty infusing or withdrawing fluid from their paths. Alteplase dose was infused to fill the lumen of the occluded catheter and remained for 50 min. As there was no obstruction of the catheter, the procedure was repeated. Three hundred and thirty-nine CVC in 247 patients were evaluated and followed, totalling 67,244 CVC-days. One hundred fifty-seven patients had only one CVC, 88 patients had two CVC during the study, and two patients had three CVC. The median age was 58 (47-66) years, patients were predominantly men (54%), with diabetic nephropathy as the main cause of chronic kidney disease (44%), the internal jugular vein as the main site of implantation (82%), and duration of dialysis before CVC implantation of 119 (41.5 to 585.5) days. Eight hundred and fifteen occlusion episodes were diagnosed (12 episodes/1000 CVC-days), with primary success with alteplase in 596 episodes (77%) and secondary in 81 cases (10%). In 99 episodes (13%), success was not achieved after the second dose of alteplase. Two hundred and thirty CVC were removed during the study and the removal causes were arteriovenous fistula use in 88 patients (38.3%), infectious and mechanical complications in 89 (38.7%) and 21 (9.1%), respectively, and others (transplantation, transfer, or death) in 32 patients (13.9%). Adverse effects were also not observed. In the multivariate analysis, we identified the greatest number of days with CVC (OR = 1.02, CI = 1.01-1.04, P = 0.004), the presence of diabetes (OR = 1.560, CI = 1.351-1.894, P = 0.015), and exit site infection (ESI) (OR = 1.567 CI = 1347-1926, P = 0.023) as factors associated with obstruction. Thrombotic occlusion showed frequent mechanical complication in CVC of HD patients. We observed 12 episodes of obstruction per 1000 CVC-days, with a high success rate after alteplase use (87%). In the multivariate analysis, the time with CVC, the presence of diabetes, and ESI were identified as variables associated with thrombotic obstruction.

Correlates of saphenous vein graft hyperplasia and occlusion 1 year after coronary artery bypass grafting: analysis from the CASCADE randomized trial.

BACKGROUND: Intimal hyperplasia of saphenous vein grafts (SVGs) can lead to subsequent graft atherosclerosis and occlusion after coronary artery bypass grafting (CABG). This study examined whether patient characteristics, anatomic factors, and medications are associated with SVG intimal hyperplasia and occlusion after CABG. METHODS AND RESULTS: We performed a post hoc analysis of the Clopidogrel After Surgery for Coronary Artery Disease (CASCADE) trial, where 322 grafts were assessed by angiography and 90 grafts were examined by intravascular ultrasound at 1 year after CABG. We assessed the following correlates for intimal hyperplasia and occlusion: patient characteristics, discharge medications, target vessel characteristics, and SVG diameter. At 1 year, the SVG mean intimal area was 4.3 ± 2.1 mm(2), and the occlusion rate was 6.2% (13/209). Independent correlates of hyperplasia were larger SVG diameter (1.9 ± 0.2 mm(2)/mm; P<0.001), hypertension (0.7 ± 0.3 mm(2); P=0.03), and grafting to the right coronary territory (0.6 ± 0.3 mm(2); P=0.03), whereas statin (-0.8 ± 0.3 mm(2); P=0.01) and ß-blocker use (-1.0 ± 0.4 mm(2); P=0.03) were associated with less hyperplasia. Low target vessel quality was an independent correlate of SVG occlusion (odds ratio, 5.2 ± 3.1; P<0.01). CONCLUSIONS: Hypertension, SVG diameter, grafting to the right coronary artery, and low quality of the target vessel correlate with the development of SVG hyperplasia or occlusion by 1 year after CABG, whereas ß-blockers and statins are associated with less SVG disease. These new findings further our understanding of SVG remodeling after bypass surgery and may guide future research to help prevent post-CABG SVG disease. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00228423.

Transient right internal thoracic arterial graft kink related to respiratory movements: documentation of its existence, relevance and proposed management.

In this case report, we provide the first detailed description of an intermittent mechanical kink of a right internal thoracic artery (ITA) graft to the left anterior descending coronary artery secondary to respiratory movements, and its assessment by pressure wire derived fractional flow reserve (FFR). The patient presented with recurrent unstable angina and documented anterior/anterolateral ischemia. Persistent symptoms were attributed to the ITA kink and stenting was planned on clinical grounds. However, the lesion proved not physiologically significant when FFR was assessed after intermittency related to respiratory movements was documented. Complex stenting was therefore avoided and medical therapy was prescribed for distal diagonal disease. We therefore propose that intermittency should be actively investigated when a kink is documented in a coronary bypass graft by conventional angiography (using dedicated angiographic evaluation in maximal inspiration and expiration). Furthermore, when this type of lesion is encountered, we suggest that it should be assessed physiologically using pressure wire derived FFR before potentially complex interventions are considered.

Independent factors predicting early lower limb intra-arterial thrombolysis failure.

BACKGROUND: Risk factors for early catheter-directed intra-arterial thrombolysis failure in acute lower limb ischemia remain unclear. METHODS: One hundred forty-nine limbs with acute artery or bypass graft thrombosis underwent catheter-directed thrombolysis (maximum of 48 hours). A retrospective data analysis was carried out to assess possible risk factors for early, 30-day treatment failure. RESULTS: Seventy-nine men (53%) and 70 women (47%) with a median age of 70 (range 32-93) years were treated. Treatment outcomes were determined as success (N = 115, 77%) or failure (N = 34, 23%). The failure criteria comprised rapid progression of ischemia (N = 4, 2.7%) and major bleeding complications (N = 2, 1.3%), both requiring thrombolysis termination and surgery. Inability to reopen native arteries/grafts (N = 10, 6.7%), run-off vessels (N = 10, 6.7%), in-hospital death (N = 4, 2.7%), the need for major amputation (N = 13, 8.7%), and reocclusions (N = 5, 3.4%) within the 30-day follow-up period were also considered as failures. Multivariate analysis of the risk factors' impact on the success of thrombolysis revealed such independent parameters as hypercholesterolemia (OR 0.16, 95% CI 0.06-0.42, P < 0.0001), previous bypass grafting of the ipsilateral limb (OR 0.18, 95% CI 0.06-0.53, P = 0.002), and duration of ischemia prior to the initiation of thrombolysis (OR 0.95, 95% CI 0.91-0.99, P = 0.009, per day). CONCLUSION: According to our results, factors independently predicting early failure include hypercholesterolemia, previous bypass grafting, and a delay in treatment initiation. Moreover, catheter-directed intra-arterial thrombolysis can be considered safe and effective in the treatment of acute lower limb ischemia.

Inhibitory effects of roscovitine on proliferation and migration of vascular smooth muscle cells in vitro.

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are the major cause of in-stent restenosis (ISR). Intervention proliferation and migration of VSMCs is an important strategy for antirestenotic therapy. Roscovitine, a second-generation cyclin-dependent kinase inhibitor, can inhibit cell cycle of multiple cell types. We studied the effects of roscovitine on cell cycle distribution, proliferation and migration of VSMCs in vitro by flow cytometry, BrdU incorporation and wound healing assay, respectively. Our results showed that roscovitine increased the proportion of G0/G1 phase cells after 12 h (69.57±3.65 vs. 92.50±1.68, P=0.000), 24 h (80.87±2.24 vs. 90.25±0.79, P=0.000) and 48 h (88.08±3.86 vs. 88.87±2.43, P=0.427) as compared with control group. Roscovitine inhibited proliferation and migration of VSMCs in a concentration-dependent way. With the increase of concentration, roscovitine showed increased capacity for growth and migration inhibition. Roscovitine (30 µmol/L) led to an almost complete VSMCs growth and migration arrest. Combined with its low toxicity and selective inhibition to ISR-VSMCs, roscovitine may be a potential drug in the treatment of vascular stenosis diseases and particularly useful in the prevention and treatment of ISR.