Adrenomedullin expression in coronary circulation after stent implantation as a prognostic factor for restenosis

The authors determined the changes in adrenomedullin (AM) expression in the coronary circulation of patients with ischemic heart disease who underwent coronary stent implantation. Blood samples were drawn from the coronary sinus before, immediately after and four hours after coronary stent implantation, and plasma levels of AM were measured. AM levels in the coronary sinus blood were significantly increased four hours after stent implantation. On the other hand, in the femoral arterial blood, no significant changes in AM levels were observed. A significant positive correlation was found between AM level in the coronary sinus blood four hours after stent implantation and late loss index six months after the procedure. These results suggest that inflammation after coronary stent implantation induces AM expression, which might play an important role in restenosis after stenting.     

No influence of hemochromatosis-related gene mutations on restenosis rate in a retrospective study of 137 patients after coronary stent implantation

BACKGROUND: Recent publications have shown an increased risk of coronary artery disease and myocardial infarction in patients with alteration of the hemochromatosis-related gene (HFE gene). The HFE gene mutation is associated with elevated iron uptake and serum iron overloading. Iron plays an important role in promoting the oxidation of LDL cholesterol. The iron deposition in the endothelium and in the media is closely associated with the progression of atherosclerosis. However, it is unclear whether the mutation of the HFE gene also influences the rate of restenosis after coronary stent implantation. METHODS: In a retrospective analysis, 137 patients (pts.) who underwent elective coronary stent implantation were angiographically reevaluated after six months. All patients were part of the OPTICUS-study population which investigated optimized stent implantation guided by intravascular ultrasound. Computerized quantitative analysis was performed in all procedures in a double-blinded fashion. At six-month follow-up, DNA fragments containing the substitution of tyrosine for cytosine at codon 282 were amplified by PCR. The results were analyzed by polyacrylamide gel electrophoresis. Statistical analysis was performed by multivariate linear regression. RESULTS: According to the HFE gene polymorphism we formed two subgroups: 129 pts. (94%) did not show changes in HFE gene (NH), 8 pts. (6%) were heterozygous for HFE Cys282Tyr (H). The groups did not differ in age, gender, extent of coronary artery disease, initial degree and length of stenosis and all patients underwent re-angiography. At six-month follow-up the average luminal narrowing in the stented vessel was 36.2 +/- 20.3% in the NH group compared with 27.8 +/- 20.0% in the H group which was statistically not significant (n. s.). The minimal luminal diameter was 1.9 +/- 0.71 mm in the NH group and 2.2 +/- 0.66 mm in the H group respectively (n. s.). 33 pts (26%) in the NH group versus 2 pts (25%) in the H group had >/= 50% diameter narrowing at follow-up (n. s.). The odds ratio of stent restenosis in H patients was 0.932. CONCLUSIONS: The authors did not find any association between restenosis rate and HFE gene alteration and therefore, we conclude that the polymorphism of the HFE gene is not a risk factor for restenosis after coronary stent implantation.     

Bridging therapy for early surgery in patients on dual antiplatelet therapy after drug-eluting stent implantation

Objectives

To evaluate stent-related adverse cardiac events and bleeding complications within 30 days after surgical procedures in patients with recent drug-eluting stent (DES) implantation, in whom a bridging protocol was used.

Methods

In our centre a bridging protocol is used in patients scheduled for cardiac or non-cardiac surgery within 6 months after PCI with DES implantation. Clopidogrel and in some cases also acetylsalicylic acid is discontinued 5 days prior to the planned intervention and patients are admitted 2 to 3 days before the intervention for tirofiban infusion. This is discontinued 4 h before intervention. Close postoperative monitoring is performed and double antiplatelet therapy is restarted as soon as possible. Thirty-six consecutive patients were included in the protocol, 15 receiving coronary artery bypass graft and 21 non-cardiac interventions. Thrombotic and bleeding complications were studied for up to 30 days after the bridged procedure.

Results

No incidences of stent thrombosis or other adverse cardiac events (mortality, myocardial infarction) were seen in up to 30 days of follow-up. However, 6 bleeding events were reported of which 5 required a blood transfusion.

Conclusion

Our bridging protocol in patients requiring surgery after recent PCI with DES seems adequate to prevent stent thrombosis in this high-risk group. The bleeding risk is not insignificant but in our patient group controllable without major late sequelae. Larger studies should be performed to establish safety and efficacy in order to develop guidelines for these patients.     

Inadvertent intracoronary stent extraction 10 months after implantation complicating cutting balloon angioplasty for in-stent restenosis

We report the case of an unusual complication for Cutting Balloon Angioplasty (CBA) during treatment for instent restenosis (ISR), which resulted in inadvertent intracoronary stent extraction 10 months after implantation. In this case report, CBA was utilized to treat an ISR lesion in the distal right coronary artery (RCA). Due to difficulty in withdrawing the cutting balloon into the guide after treatment of the lesion, the entire system (guide, cutting balloon, and guidewire) was removed as a unit from the body. Upon examination of the system, the previously placed stent in the distal RCA was attached to the microtomes of the cutting balloon. Although the precise mechanisms for stent extraction in this case remain speculative, the initial stent used in the distal RCA may have been undersized, and this may have played a major role in this complication. Although there is limited data regarding the optimal strategy to treat the site of the inadvertent stent extraction, we opted to re-stent the area with a properly-sized coronary stent. Following the intervention, there was no residual stenosis with TIMI 3 flow through the vessel. The patient remained asymptomatic and a serum troponin drawn 18 hours after the procedure was normal, and he was discharged the next day. The interventionist must be vigilant about this rare but serious complication when applying CBA in the treatment of ISR, particularly when an undersized or underdeployed stent is suspected.     

Inflammation and in-stent restenosis: the role of serum markers and stent characteristics in carotid artery stenting

Background

Carotid angioplasty and stenting (CAS) may currently be recommended especially in younger patients with a high-grade carotid artery stenosis. However, evidence is accumulating that in-stent restenosis (ISR) could be an important factor endangering the long-term efficacy of CAS. The aim of this study was to investigate the influence of inflammatory serum markers and procedure-related factors on ISR as diagnosed with duplex sonography.

Methods

We analyzed 210 CAS procedures in 194 patients which were done at a single university hospital between May 2003 and June 2010. Periprocedural C-reactive protein (CRP) and leukocyte count as well as stent design and geometry, and other periprocedural factors were analyzed with respect to the occurrence of an ISR as diagnosed with serial carotid duplex ultrasound investigations during clinical long-term follow-up.

Results

Over a median of 33.4 months follow-up (IQR: 14.9–53.7) of 210 procedures (mean age of 67.9±9.7 years, 71.9% male, 71.0% symptomatic) an ISR of ≥70% was detected in 5.7% after a median of 8.6 months (IQR: 3.4–17.3). After multiple regression analysis, leukocyte count after CAS-intervention (odds ratio (OR): 1.31, 95% confidence interval (CI): 1.02–1.69; p = 0.036), as well as stent length and width were associated with the development of an ISR during follow-up (OR: 1.25, 95% CI: 1.05–1.65, p = 0.022 and OR: 0.28, 95% CI: 0.09–0.84, p = 0.010).

Conclusions

The majority of ISR during long-term follow-up after CAS occur within the first year. ISR is associated with periinterventional inflammation markers and influenced by certain stent characteristics such as stent length and width. Our findings support the assumption that stent geometry leading to vessel injury as well as periprocedural inflammation during CAS plays a pivotal role in the development of carotid artery ISR.     

Influence of vessel curvature and plaque composition on drug transport in the arterial wall following drug-eluting stent implantation

Biomechanics and Modeling in Mechanobiology - In the last decade, many computational models have been developed to describe the transport of drug eluted from stents and the subsequent uptake into...     

Study design and rationale of 'Influence of Cilostazol-based triple anti-platelet therapy on ischemic complication after drug-eluting stent implantation (CILON-T)' study: A multicenter randomized trial evaluating the efficacy of Cilostazol on ischemic vascular complications after drug-eluting stent implantation for coronary heart disease

Background

Performance of primary school students in India lags far below government expectations, and major disparity exists between rural and urban areas. The Naandi Foundation has designed and implemented a programme using community members to deliver after-school academic support for children in over 1,100 schools in five Indian states. Assessments to date suggest that it might have a substantial effect. This trial aims to evaluate the impact of this programme in villages of rural Andhra Pradesh and will compare test scores for children in three arms: a control and two intervention arms. In both intervention arms additional after-school instruction and learning materials will be offered to all eligible children and in one arm girls will also receive an additional 'kit' with a uniform and clothes.

Methods/Design

The trial is a cluster-randomised controlled trial conducted in conjunction with the CHAMPION trial. In the CHAMPION trial 464 villages were randomised so that half receive health interventions aiming to reduce neonatal mortality. STRIPES will be introduced in those CHAMPION villages which have a public primary school attended by at least 15 students at the time of a baseline test in 2008. 214 villages of the 464 were found to fulfil above criteria, 107 belonging to the control and 107 to the intervention arm of the CHAMPION trial. These latter 107 villages will serve as control villages in the STRIPES trial. A further randomisation will be carried out within the 107 STRIPES intervention villages allocating half to receive an additional kit for girls on the top of the instruction and learning materials. The primary outcome of the trial is a composite maths and language test score.

Discussion

The study is designed to measure (i) whether the educational intervention affects the exam score of children compared to the control arm, (ii) if the exam scores of girls who receive the additional kit are different from those of girls living in the other STRIPES intervention arm. One of the goals of the STRIPES trial is to provide benefit to the controls of the CHAMPION trial. We will also conduct a cost-benefit analysis in which we calculate the programme cost for 0.1 standard deviation improvement for both intervention arms.

Trial Registration

Current controlled trials ISRCTN69951502     

Cyclic strain amplitude dictates the growth response of vascular smooth muscle cells in vitro: role in in-stent restenosis and inhibition with a sirolimus drug-eluting stent

The putative effects of changes in mean strain and cyclic strain amplitude on vascular smooth muscle cell (vSMC) growth (proliferation and apoptosis) were examined. Subsequently, a quantitative measure of vSMC growth was obtained to determine the prolonged effect of changes in mechanical burden following bare-metal stent (BMS) and sirolimus drug-eluting stent (DES) deployment in vitro. Bovine aortic vSMCs were exposed to prolonged cyclic strain using a Flexercell^TM Tension system and a novel Sylgard^TM phantom vessel following stent implantation before the level of vSMC proliferation and apoptosis was assessed by FACS analysis, cell counting, and immunocytochemistry. Physiological cyclic strain (5%) decreased vSMC proliferation and increased apoptosis in a temporal manner. There was no significant difference in cell growth following exposure to varying mean strains with similar amplitude. In contrast, exposure to varying strain amplitudes with similar mean strains resulted in significant differences in cell proliferation and apoptosis. In parallel studies, the level of vSMC proliferation and cell survival was significantly increased within low amplitude, high mean strain regions of a phantom vessel following BMS implantation when compared to regions of higher strain amplitude upstream and downstream of the stent, respectively. Moreover, the level of vSMC growth within the stented region was significantly attenuated following implantation of a sirolimus-coated DES independent of significant changes in cell survival. Cyclic strain amplitude is an important regulator of vSMC growth capacity within a stent and is a target for inhibition using a sirolimus-coated DES.     

Release of TNF-alpha during stent implantation into saphenous vein aortocoronary bypass grafts and its relation to plaque extrusion and restenosis

The reduction in plaque volume during stent implantation is associated with the release of particulate debris and plaque-derived soluble substances. We studied the potential release of the proinflammatory cytokine TNF-alpha into the coronary circulation and whether such release is related to the reduction in plaque volume and, possibly, a predictor for restenosis. In 18 male patients (n = 24 stents) with severe stenosis in a saphenous vein aortocoronary bypass graft (SVG), we used a distal balloon occlusion-aspiration device during stent implantation. The aspirate TNF-alpha levels were determined before and after stent implantation and related to the angiographic and intravascular ultrasound-assessed severity of stenosis and restenosis. We found that TNF-alpha is, indeed, released into the aspirate of stented SVG (9 +/- 1 and 28 +/- 3 pg/ml before and after stent implantation, respectively, P < 0.0001) and that such release is related to the reduction in plaque volume (r = 0.88, P < 0.0001) and associated with restenosis after 5 mo (r = 0.71, P = 0.001). The periprocedural release of plaque-derived TNF-alpha possibly represents the amount and activity of the atherosclerotic process and might be a predictor for restenosis.     

Stent implantation in acute myocardial infarction using a heparin-coated stent: a pilot study as a preamble to a randomized trial comparing balloon angioplasty and stenting

Preliminary experience with primary stenting in myocardial infarction has suggested a greater benefit in clinical outcome than has been obtained with direct balloon angioplasty. However, subacute thrombosis (SAT) remains a limitation for this new mode of therapy. In the BENESTENT II Pilot and main trials, the incidence of SAT with the heparin-coated Palmaz-Schatz stent was only 0.15%. Therefore, as a preamble to a large randomized trial, the feasibility and safety of the use of the Heparin-Coated Palmaz-Schatz trade mark Stent in Acute Myocardial Infarction (AMI) was tested in 101 patients enrolled between April and September 1996 in 18 clinical centres. In 101 stent-eligible AMI patients, as dictated by protocol, a heparin-coated stent was implanted. The primary objectives were to determine the in-hospital incidence of major adverse cardiac events (MACE: death, MI, target lesion revascularization) and bleeding complications, while the secondary objectives were the procedural success rate and the MACE, the restenosis and reocclusion rates at 6.5 months. Stent implantation (n 3 129 stents) was successful in 97 patients of the 101 who were included in this trial. During their hospital stay, two patients died and no patient experienced re-infarction, ischaemia prompting re-PTCA or CABG. Four patients suffered a bleeding complication, three major and one minor, of whom three required surgical repair. At 210 days follow-up, 81% of the patients were event free. At 6.5 months restenosis was documented in 18% of the 88 patients who underwent follow-up angiography, including three total occlusions. The results, both with respect to QCA and the occurrence of MACE, compare favourably with studies using elective stenting in both stable and unstable angina patients. As a result of this pilot study, a large randomized trial comparing direct balloon angioplasty with direct stenting in 900 patients with AMI was initiated in December 1996.     

Immediate and long-term outcomes of coronary stenting in relation to stent implantation pressure in patients with coronary heart disease

The paper evaluates the pressure impact of implantation of intracoronary stents of different designs on the immediate and long-term outcomes of stenting. A retrospective study included 192 patients. Matrix and wire stents were implanted in 97 (50.5%) and 95 (49.5%) patients, respectively. In one part of the patients, the coronary stent was implanted under nominal pressure, in the other, the stent after implantation was extended with a balloon by using high pressure. Good immediate angiographic and clinical results were obtained in all 192 patients. Thirty three (17.2%) patients were found to have coronary spasm at the site of a stent. There was no significant difference in the development of coronary spasm, which was associated with the type of an implanted (matrix or wire) stent and with the pattern of its implantation (under high or nominal pressure). Dissection along the stent edges developed in 17 of the 192 patients, which amounted to 8.8%. It significantly more frequently developed in patients from Subgroup IA than in those from Subgroup IB. There was no significant difference in the development of restenosis in patients after implantation of matrix or wire stents and in the relation to the stent implantation pressure.     

Immediate and long-term results of coronary stent implantation without predilatation (direct stenting) in patients with coronary heart disease

The paper assesses the immediate and long-term results of direct stenting (without the stage of predilation) and compares with the outcomes of conventional stent implantation. A prospective study included 183 patients. All the patients were divided into two groups according to the procedure of stent implantation. In 85 (46.7%) patients, the stent was implanted without preliminary predilation of stenosis (direct stenting). These patients formed Group 1. Group 2 comprised 97 (53.3%) patients in whom the stent was placed by using the routine procedure. All the patients enrolled into the study had types A, B1, and B2 stenoses according to the ACC/AHA classification and received the conventional antiaggregatory and anticoagulant therapy. The technical success of direct stenting was 97.7%. There were no cases of stent dislocation and loss during direct stenting or expansion of a balloon and stent. Analyzing the immediate results in all the patients of the both groups showed a positive angiographic success. Thus, a primary angiographic and clinical success of direct stenting was achieved in all (100%) patients. Recurrent angina pectoris with restenosis was observed in 8 (9.4%) patients in Group 1 and in 21 (21.6%) in Group 2 (p < 0.05). Direct stenting significantly differs from the routine stent implantation in all procedure parameters. Thus, direct stenting in patients with uncomplicated stenoses is a safe and feasible procedure.     

Comparative study of Newtonian and non-Newtonian simulations of drug transport in a model drug-eluting stent

To elucidate the difference between Newtonian and shear thinning non-Newtonian assumptions of blood in the analysis of DES drug delivery, we numerically simulated the local flow pattern and the concentration distribution of the drug at the lumen-tissue interface for a structurally simplified DES deployed in a curved segment of an artery under pulsatile blood flow conditions. The numerical results showed that when compared with the Newtonian model, the Carreau (shear thinning) model could lead to some differences in the luminal surface drug concentration in certain areas along the outer wall of the curved vessel. In most areas of the vessel, however, there were no significant differences between the 2 models. Particularly, no significant difference between the two models was found in terms of the area-averaged luminal surface drug concentration. Therefore, we believe that the shear thinning property of blood may play little roles in DES drug delivery. Nevertheless, before we draw the conclusion that Newtonian assumption of blood can be used to replace its non-Newtonian one for the numerical simulation of drug transport in the DES implanted coronary artery, other more complex mechanical properties of blood such as its thixotropic behavior should be tested.     

RAD sequencing yields a high success rate for westslope cutthroat and rainbow trout species-diagnostic SNP assays

Hybridization with introduced rainbow trout threatens most native westslope cutthroat trout populations. Understanding the genetic effects of hybridization and introgression requires a large set of high-throughput, diagnostic genetic markers to inform conservation and management. Recently, we identified several thousand candidate single-nucleotide polymorphism (SNP) markers based on RAD sequencing of 11 westslope cutthroat trout and 13 rainbow trout individuals. Here, we used flanking sequence for 56 of these candidate SNP markers to design high-throughput genotyping assays. We validated the assays on a total of 92 individuals from 22 populations and seven hatchery strains. Forty-six assays (82%) amplified consistently and allowed easy identification of westslope cutthroat and rainbow trout alleles as well as heterozygote controls. The 46 SNPs will provide high power for early detection of population admixture and improved identification of hybrid and nonhybridized individuals. This technique shows promise as a very low-cost, reliable and relatively rapid method for developing and testing SNP markers for nonmodel organisms with limited genomic resources.     

A rapid banding technique for routine use in human and comparative cytogenetics

Summary A simple combined enzyme-stain technique is described which gives within 20 min clear banding patterns in mammalian chromosomes.

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Zusammenfassung Es wird eine einfache kombinierte Enzym-Farbe-Technik beschrieben, die innerhalb von 20 min klare Bandenmuster bei Säugerchromosomen ergibt.