Targeting transradial approach.

Radial access for percutaneous coronary interventions (PCI) emerged as a valid alternative to the standard femoral access with the aim of reduce the incidence of access-site bleeding and consequently improve clinical outcomes. Access-site bleeding is still one of the most common complications after PCI and is associated with increased short- and long-term morbidity and mortality. Benefits in access-site bleeding have been consistently observed in high-risk patients undergoing PCI and in particular in STEMI patients where the antithrombotic regimen is more aggressive. Moreover, other advantages with TR access have been reported including better cost-effectiveness, patient preference, reduced in-hospital length-of-stay, earlier patient ambulation, increased safety in patients on oral anticoagulant and the potential for same-day hospital discharge. The benefits of transradial access in PCI led the interventional community to expand its use to endovascular interventions and more recently, to cardiac structural interventions such as transcatheter aortic valve implantation. The aim of this review is to try to give to the reader a wide view of the state-of-the-art of transradial access in PCI and its current use in endovascular and structural interventions.

Defining a new standard for IVUS optimized drug eluting stent implantation: the PRAVIO study.

OBJECTIVES: Preliminary Investigation to the Angiographic Versus IVUS Optimization Trial is a single center prospective observational intravascular ultrasound (IVUS) guided stent implantation study assessing new criteria for optimal drug eluting stent (DES) deployment. BACKGROUND: IVUS assessment of DES often reveals underexpansion and malapposition. Optimal stent deployment is currently poorly defined and previous criteria may not be suitable in long and complex lesions. METHODS: Optimization was defined as achieving >/or 70% of the cross-sectional area (CSA) of the postdilation balloon. This criterion was applied in 113 complex lesions. The size of this balloon was calculated according to vessel media-to-media diameters at various sites inside the stented segment. The IVUS guided treated lesions were matched according to diabetes, vessel type, reference vessel diameter, minimum lumen diameter (MLD), and lesion length with a group of angiographic treated lesions to compare final MLD achieved. RESULTS: Mean minimum stent CSA according to the postdilation balloon utilized was 4.62 mm(2), 6.26 mm(2), 7.87 mm(2), and 9.87 mm(2) for 2.5 mm, 3.0 mm, 3.5 mm, and 4 mm balloons, respectively. Final MLD (mm) was significantly larger in the IVUS compared to the angiographic-guided group (3.09 +/- 0.50 vs. 2.67 +/- 0.54; P < 0.0001). There were no procedural complications related to IVUS use. CONCLUSIONS: We propose new IVUS criteria based on vessel remodeling that results in an increment in the final MLD, compared to angiographic guidance, which is much larger than any previously published study. This criterion seems to be safely achievable. A proposed randomized study (angiographic vs. IVUS optimization trial) has been launched to test these concepts.

Impact of drug-eluting stent selection on long-term clinical outcomes in patients treated for unprotected left main coronary artery disease: the sirolimus vs paclitaxel drug-eluting stent for left main registry (SP-DELFT).

AIM: To compare the long-term relative efficacy and safety of SES and PES in patients undergoing percutaneous coronary intervention (PCI) for unprotected left main coronary artery (ULMCA) disease and to evaluate the role of lesion location and stenting technique in determining outcomes. METHODS AND RESULTS: From April 2002 to April 2004, 288 consecutive patients who underwent elective PCI with DES implantation for de novo lesions on ULMCA have been retrospectively selected and analyzed in seven European and US tertiary care centers. All patients had a minimum follow-up of 3 years. SES was used in 152 patients while 136 received PES. Isolated ostial-shaft disease was present in 27% of patients. Distal LM disease (73%) was treated with single and double stent approach in 29.5% and 43.4% of patients respectively. After 3 years, rates of survival free from any of the events investigated, were independent from lesion location and stenting approach and did not differ significantly between SES and PES groups. Freedom from MACE (SES vs. PES) was 76.3% vs. 83.1% in the ostial/shaft group, 80.3% vs. 72.8% in the distal-single stent group and 67.1% vs. 66.2% in the distal-double stent group. Definite stent thrombosis occurred only in 1(0.3%) patient at 439 days. CONCLUSIONS: In elective patients who underwent PCI for de novo lesions in the ostium, shaft or distal ULMCA, long-term clinical outcomes with SES and PES use were similar independently of lesion location and stenting technique.

Bioabsorbable and biocompatible stents. Is a new revolution coming?

With the introduction of drug-eluting stents (DES) the problem of restenosis after percutaneous stent implantation was partially resolved. In the first generation of DES a stainless steel platform was coated with a durable polymer eluting and controlling the release of an active restenotic drug. The impairment of re-endothelization after DES implantation, one of the causes of late stent thrombosis, was to some extent attributed to the properties of the durable polymer and/or drug that it eluted. The introduction of biodegradable platforms and biocompatible polymers may potentially address this issue. Modern technologies are being applied to improve the characteristics of biodegradable stents and find new active pharmacological agents or combinations of standard antirestenotic and antithrombotic drugs that can be eluted from the stents, in order to improve their safety profile and clinical utility.

Revascularization of unprotected left main coronary artery disease with percutaneous coronary intervention: the role of drug-eluting stents.

The percutaneous revascularization of left main coronary artery stenosis has until recently been reserved for patients at prohibitive surgical risk or for selected emergent cases. This adopted practice of coronary artery bypass grafting, as the standard of care for left main coronary artery stenosis, has largely occurred secondary to disappointing results with bare metal stents implanted in the left main coronary artery. However, in the current era of drug-eluting stents (DES) which significantly reduce restenosis compared to bare metal stents, there has been a renewed interest in examining the role of percutaneous coronary intervention as a means of revascularization of left main disease. This article discusses recent and ongoing studies investigating the role of percutaneous intervention of left main disease, with an emphasis on the use of DES for this purpose.

Treatment of bifurcation lesions with two stents: one year angiographic and clinical follow up of crush versus T stenting.

OBJECTIVES: To compare long term outcomes of the crush versus the T technique in bifurcation lesions. DESIGN: 182 consecutive patients were identified who underwent percutaneous coronary interventions for bifurcation lesions with drug eluting stents between April 2002 and January 2004. Two techniques were used according to the operator's discretion: crush (group C, n = 121) or T (group T, n = 61). RESULTS: In-hospital outcome differed significantly between the two groups. Angiographic follow up was available for 142 (78%) patients. Groups C and T did not differ significantly regarding late loss (0.42 (0.39) mm v 0.34 (0.35) mm, p = 0.52) and rate of restenosis (16.2% v 13.0%, p = 0.80) in both the main and the side branch without final kissing balloon post-dilatation. However, when final kissing balloon post-dilatation was performed, group C had significantly lower late lumen loss (0.23 (0.21) mm v 0.37 (0.33) mm, p = 0.02) and restenosis rate (8.6% v 26.5%, p = 0.04) in the side branch. At one year's clinical follow up, group C compared with group T had lower rates of target lesion revascularisation (14.0% v 31.1%, p = 0.01) and target vessel revascularisation (16.5% v 32.8%, p = 0.02). CONCLUSIONS: In non-selected bifurcation lesions treated with drug eluting stents, the restenosis rate remains relatively high in the side branch. Compared with the T stenting technique, crush stenting with kissing balloon post-dilatation is associated with a reduced rate of restenosis in the side branch.

Applying intravascular ultrasound to optimize the placement of coronary drug-eluting stents.

Intravascular ultrasound (IVUS) has provided in the last 2 decades major insights into the pathophysiology of coronary artery disease, and the mechanisms of action of percutaneous revascularization devices, helping the widespread adoption of coronary stents. The introduction of drug-eluting stents (DES) has recently lead to a revolution in the field of interventional cardiology, by virtually eliminating restenosis in selected low-risk lesions and significantly reducing both restenosis and repeat revascularizations in higher risk lesions. At the moment, the role of IVUS in the DES era is not well defined. Clinical studies utilizing IVUS in DES implantation used this technology mainly to evaluate the endpoint of intimal hyperplasia and to study the problem of incomplete apposition. On a theoretical basis, a method able to better evaluate optimal placement of a local drug delivery system should have a high rationale. Despite this sound preamble, no specific investigation has been conducted to evaluate the clinical need and possible advantage of routine IVUS for DES implantation and uncertainty is still present. A major hindrance lays in the low incidence of restenosis in most randomized trials enrolling few selected lesions per patient, as this fact enlarges the number of patients who need to be treated to demonstrate a benefit and casts doubts on the cost effectiveness of a more expensive and time consuming approach. The situation is bound to change when more complex patients and lesions are being treated, a setting associated with a higher event rate even when DES are used. While waiting for a prospective study addressing such issue, we can only rely on indirect evidence to justify and support the usage of IVUS in complex clinical settings with implantation of DES.

The use of drug eluting stents in single and multivessel disease: results from a single centre experience.

OBJECTIVE: Drug eluting stents have been shown to reduce the rate of in-stent restenosis in cases where single lesions are treated. The performance of these stents, in patients with multivessel disease and complex lesions, however, remains unknown. Our experience with sirolimus eluting stents in such patients is presented. DESIGN AND PATIENTS: This study includes all consecutive patients treated at San Raffaele Hospital and EMO Centro Cuore Columbus, Milan, Italy treated with sirolimus eluting stents. RESULTS: Between April 2002 and March 2003, 486 patients with 1027 lesions were treated (437 males, 49 females) with a mean (SD) age of 62.2 (10.5) years. Of all patients studied, 19.1% had single vessel disease, 33.8% had two vessel disease, and 47.1% had three vessel disease. Of the whole study group, 20.3% of patients had diabetes mellitus. A mean (SD) of 2.3 (0.4) stents per patient and 1.1 (0.2) stents per lesion were implanted. The baseline mean reference diameter was 2.7 (0.6) mm with a mean minimal luminal diameter of 0.9 (0.5) mm. Post-stenting, the acute gain was 1.8 (0.6) mm. During hospital stay one patient died (0.2%) and 13 (2.7%) patients had in-hospital myocardial infarction (MI). One patient required urgent repeat percutaneous coronary intervention. Six months clinical follow up was performed in all 347 eligible patients. Six months mortality was 2.0% (n = 7) and acute MI occurred in 0.3% (n = 1). Target lesion revascularisation occurred in 9.5% (n = 33) of the patients and target vessel revascularisation (TVR) in 11.5% (n = 40) of the patients. Major adverse cardiac event rate was 13.8% (n = 48). TVR was 4.5% for single vessel disease and 13.2% for multivessel disease. Diabetes mellitus was the only significant predictor for TVR. CONCLUSION: The use of drug eluting stents in single and multivessel coronary disease produces good short and medium term results with a low rate of revascularisation. Longer term follow-up is required to confirm these observations.

Clinical and angiographic outcome of directional atherectomy followed by stent implantation in de novo lesions located at the ostium of the left anterior descending coronary artery.

BACKGROUND: Lesions located at the ostium of the left anterior descending coronary artery (LAD) are considered an ideal target for directional atherectomy (DCA), but few data are available about the value of using this strategy before stenting in comparison with stenting alone. OBJECTIVES: To investigate the immediate and mid term clinical and angiographic results of DCA followed by stent implantation for ostial LAD lesions. DESIGN: Retrospective comparison of the immediate and mid term angiographic and clinical results of a series of 117 consecutive patients with de novo lesions located at the ostium of the LAD. Of these, 46 underwent DCA before stenting and 71 were treated with stenting alone. RESULTS: Technical success in the two groups was similar at around 98%. DCA plus stenting provided a larger minimum lumen diameter at the end of the procedure than stenting alone (3.57 (0.59) mm v 3.33 (0.49) mm, p = 0.022). There were no differences for in-hospital major adverse events (MACE) (7.5% for atherectomy plus stenting, and 5.3% for stenting alone; p = 0.41). All patients had clinical follow up at a mean of 7.9 (2.7) months. Angiographic follow up was done in 89 patients (76%) at a mean of 5.9 (2.2) months. The atherectomy plus stenting group had a larger minimum lumen diameter than the stenting group (2.79 (0.64) mm v 2.26 (0.85) mm, p = 0.004) and a lower binary restenosis rate (13.8% v 33.3%, p = 0.031). Six month MACE were reduced in the atherectomy plus stenting group (8.7% v 23.9%, p = 0.048). CONCLUSIONS: Debulking before stenting in de novo lesions located at the ostium of the LAD is safe and is associated with a high rate of technical success. Follow up data show that DCA plus stenting results in a significantly larger minimum lumen diameter and a lower incidence of restenosis than stenting alone.

Drug-eluting stents.

Drug-eluting stents represent the third revolution in the field of Interventional Cardiology following balloon angioplasty (PTCA) and the implantation of metal stents. The main limitation of percutaneous coronary intervention (PCI) is restenosis. The introduction of drug eluting stents able to release antiproliferative compounds led to the evaluation of several antiproliferative drugs in order to reduce restenosis. Rapamycin (Sirolimus) has been demonstrated to inhibit smooth muscle cell (SMC) proliferation and migration in vitro and to reduce in vivo neointima formation with blockage of the cell cycle progression at the G1-S transition. In a pilot study, recently confirmed by a randomized trial, rapamycin drug-eluting stents have been reported to eliminate restenosis after stent implantation. Promising data also come from the use of paclitaxel drug-eluting stents. Paclitaxel (Taxol) is a microtubule-stabilizing agent with potent antiproliferative activity. Even if drug-eluting stents represent one of the most promising fields in Interventional Cardiology today before being sure of their real potential it is necessary to wait for results from several ongoing clinical studies, their usage in real-world lesions and extended follow-up to 5 years.

Carotid artery stenting in the first 100 consecutive patients: results and follow up.

BACKGROUND: Carotid artery stenting is now used as an alternative to surgical endarterectomy. The availability of cerebral protection systems has expanded the area of application of this procedure. OBJECTIVE: To assess the feasibility, safety, and immediate and late clinical outcome in patients undergoing percutaneous carotid interventions. METHODS: Between January 1999 and December 2000, 100 consecutive patients with 102 carotid artery stenoses were treated (71 men, 29 women, mean (SD) age 67 (8) years): 49 had coronary artery disease, 28 had previous stroke or transient ischaemic attack (TIA). On the basis of the Mayo Clinic carotid endarterectomy risk scale, 73 patients were grade III-IV and 13 grade VI. RESULTS: Baseline diameter stenosis was 78.8 (10)%, with a mean lesion length of 12.6 (5.8) mm. Angiographic success was obtained in 99 lesions (97.0%) with a final diameter stenosis of 2.4 (3.5)%. Procedural success was obtained in 96 patients (96%). Selective cannulation of three carotid arteries was impossible owing to severe vessel tortuosity. Carotid stenting was performed in 97 of the treated lesions, and protection devices were used in 67 lesions. In-hospital complications occurred in seven patients (six TIA, one (category 1) minor stroke). No major stroke or death occurred. All patients were discharged from the hospital after an average of 2.5 days. At 12 (6.2) months of follow up restenosis occurred in three patients (3.4%) (one patient with carotid occlusion had TIA). Six patients had died: two from cerebrovascular events (5 and 11 months after the procedure) and four from cardiovascular causes. CONCLUSIONS: Carotid stenting appears feasible and safe, with few major complications. Long term follow up is affected by a high incidence of cardiovascular mortality.

Effects of balloon injury on neointimal hyperplasia in streptozotocin-induced diabetes and in hyperinsulinemic nondiabetic pancreatic islet-transplanted rats.

BACKGROUND: The mechanisms of increased neointimal hyperplasia after coronary interventions in diabetic patients are still unknown. METHODS AND RESULTS: Glucose and insulin effects on in vitro vascular smooth muscle cell (VSMC) proliferation and migration were assessed. The effect of balloon injury on neointimal hyperplasia was studied in streptozotocin-induced diabetic rats with or without adjunct insulin therapy. To study the effect of balloon injury in nondiabetic rats with hyperinsulinemia, pancreatic islets were transplanted under the kidney capsule in normal rats. Glucose did not increase VSMC proliferation and migration in vitro. In contrast, insulin induced a significant increase in VSMC proliferation and migration in cell cultures. Furthermore, in VSMC culture, insulin increased MAPK activation. A reduction in neointimal hyperplasia was consistently documented after vascular injury in hyperglycemic streptozotocin-induced diabetic rats. Insulin therapy significantly increased neointimal hyperplasia in these rats. This effect of hyperinsulinemia was totally abolished by transfection on the arterial wall of the N17H-ras-negative mutant gene. Finally, after experimental balloon angioplasty in hyperinsulinemic nondiabetic islet-transplanted rats, a significant increase in neointimal hyperplasia was observed. CONCLUSIONS: In rats with streptozotocin-induced diabetes, balloon injury was not associated with an increase in neointimal formation. Exogenous insulin administration in diabetic rats and islet transplantation in nondiabetic rats increased both blood insulin levels and neointimal hyperplasia after balloon injury. Hyperinsulinemia through activation of the ras/MAPK pathway, rather than hyperglycemia per se, seems to be of crucial importance in determining the exaggerated neointimal hyperplasia after balloon angioplasty in diabetic animals.

Effects of hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin on smooth muscle cell proliferation in vitro and neointimal formation in vivo after vascular injury.

OBJECTIVES: We sought to evaluate the effects of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on vascular smooth muscle cell (VSMC) proliferation in vitro and neointimal formation in vivo after vascular injury. BACKGROUND: Neointimal hyperplasia after vascular injury is responsible for restenosis after arterial stenting, whereas arterial remodeling and neointimal formation are the causes of restenosis after percutaneous transluminal coronary angioplasty. METHODS: We assessed the effect of simvastatin on in vitro VSMC proliferation. To study the effects of simvastatin in vivo, balloon injury and stent deployment were performed in the common carotid artery of rats. Neointimal area was measured two weeks later in the balloon injury model and three weeks after stent deployment. RESULTS: Simvastatin markedly inhibits VSMC proliferation in vitro. In vivo, simvastatin reduced, in a dose-dependent manner, the neointimal area and the neointima-media ratio after balloon injury from 0.266 +/- 0.015 mm2 to 0.080 +/- 0.026 mm2 and from 1.271 +/- 0.074 to 0.436 +/- 0.158 (p < 0.001 vs. control rats) at the highest dose. Simvastatin also significantly reduced the neointimal formation and the neointima-media ratio after stenting from 0.508 +/- 0.035 mm2 to 0.362 +/- 0.047 mm2 (p < 0.05 vs. control rats) and from 2.000 +/- 0.136 to 1.374 +/- 0.180 (p < 0.05 vs. control rats). The vessel thrombosis rate after stent deployment was 30% in the control group and 11.1% in the treated group (p = NS). Moreover, the systemic administration of simvastatin did not affect hepatic and renal functions, blood pressure or heart rate. CONCLUSIONS: Simvastatin potently inhibits VSMC proliferation in vitro and reduces neointimal formation in a rat model of vascular injury.

In vivo gene transfer: prevention of neointima formation by inhibition of mitogen-activated protein kinase kinase.

BACKGROUND: The mitogen-activated protein kinase kinase (MAPKK) is a protein downstream ras which is rapidly activated in cells stimulated with various extracellular signals. These proteins are believed to play a pivotal role in integrating and transmitting transmembrane signals required for cell growth. METHODS AND RESULTS: To study the effect of inhibition of MAPKK on smooth muscle cell (SMC) proliferation in vivo after vascular injury, we performed experimental balloon angioplasty using the standard Clowes technique in male Wistar rats 14-weeks old. The animals did not receive any treatment after vascular injury (N = 6) or were randomly assigned to receive, after balloon injury, a 30% (w/v) pluronic gel solution applied to the injured carotid artery, containing respectively: 1) no plasmid DNA (n = 10); 2) RSV-lacZ (encoding the beta-galactosidase gene) as control gene without effects on SMC proliferation (n = 10); 3) Tg-CAT (encoding cloramphenicol acetyl-transferase gene under the control of thyreoglobulin promoter) as an additional control gene without effects on SMC proliferation (n = 7): 4) a negative mutant of Mitogen-Activated Protein Kinase Kinase (MAPKK-) (n = 13). Fourteen days after vascular injury, carotid arteries were removed and cross sections were cut and stained with hematoxylin/eosin. Morphometric analysis demonstrated, in the MAPKK- treated rats, a significant reduction of both neointima (0.096+/-.018 mm2 vs. 0.184+/-0.019 mm2, p < 0.01) and neointima/media ratio (0.603+/-0.103 vs. 1.471+/-0.161, p < 0.01) compared to control DNA. CONCLUSIONS: The inhibition of MAPKK, by a dominant inhibitor mutant gene, prevents the SMC proliferation after vascular injury in vivo.

Efficacy of topical tuaminoheptane combined with N-acetyl-cysteine in reducing nasal resistance. A double-blind rhinomanometric study versus xylometazoline and placebo.

The aim of this study was to functionally evaluate the decongestant effect of a topical intranasal drug (Rhinofluimucil consisting of tuaminoheptane sulphate (CAS 6411-75-2, THS), a vasoconstrictor, combined with N-acetyl-cysteine (CAS 616-91-1, NAC). This was a double-blind randomized study, versus both xylometazoline and placebo. 18 subjects (8M and 10F, aged 20-47 years), unaffected by any rhinitic pathology, underwent anterior rhinomanometry. Following the basal evaluation (T0), subjects were randomly divided into three groups and subjected, in a double-blind manner, to nasal instillations (2 puffs per nostril) of THS/NAC (R), xylometazoline (O) and saline solution (P), respectively. Rhinomanometry was repeated after 5, 10 and 20 min (T5, T10, T20). Resistance and flow were measured in both nostrils at a pressure gradient of 150 Pa. After R and O nasal resistance significantly decreased from 0.30 Pa to 0.19 Pa and from 0.31 Pa to 0.17 Pa, respectively, and flow significantly increased; no effects were observed with placebo. In this study, THS/NAC showed rapid decongestant properties, with a significant decrease of resistance and increase of inspiratory flow. The same finding was observed with xylometazoline, but not with the placebo. The decongestant effect was rapid: it could already be observed at T5, and remained constant up to T20 without any rebound effect.