Ivan De Scheerder

Inhibition of restenosis with a paclitaxel-eluting, polymer-free coronary stent: the European evaLUation of pacliTaxel Eluting Stent (ELUTES) trial.

Background—The use of a stent to deliver a drug may reduce in-stent restenosis. Paclitaxel interrupts the smooth muscle cell cycle by stabilizing microtubules, thereby arresting mitosis. Methods and Results—On the basis of prior animal studies, the European evaLUation of the pacliTaxel Eluting Stent (ELUTES) pilot clinical trial (n=190) investigated the safety and efficacy of V-Flex Plus coronary stents (Cook Inc) coated with escalating doses of paclitaxel (0.2, 0.7, 1.4, and 2.7 &mgr;g/mm2 stent surface area) applied directly to the abluminal surface of the stent in de novo lesions compared with bare stent alone. The primary efficacy end point was angiographic percent diameter stenosis at 6 months. At angiographic follow-up, percent diameter stenosis was 33.9±26.7% in controls (n=34) and 14.2±16.6% in the 2.7-&mgr;g/mm2 group (n=31; P =0.006). Late loss decreased from 0.73±0.73 to 0.11±0.50 mm (P =0.002). Binary restenosis (≥50% at follow-up) decreased from 20.6% to 3.2% (P =0.056), with no significant benefit from intermediate paclitaxel doses. Freedom from major adverse cardiac events in the highest (effective) dose group was 92%, 89%, and 86% at 1, 6, and 12 months, respectively (P =NS versus control). No late stent thromboses were seen in any treated group despite clopidogrel treatment for 3 months only. Conclusions—Paclitaxel applied directly to the abluminal surface of a bare metal coronary stent, at a dose density of 2.7 &mgr;g/mm2, reduced angiographic indicators of in-stent restenosis without short- or medium-term side effects.

Defining the Transmurality of a Chronic Myocardial Infarction by Ultrasonic Strain-Rate Imaging Implications for Identifying Intramural Viability: An Experimental Study

Background—In a correlative functional/histopathologic study, we investigated the regional deformation characteristics of both chronic nontransmural and transmural infarctions before and after a dobutamine challenge. Methods and Results—After stenosing copper-coated stent implantation to produce circumflex artery endothelial proliferation, 18 pigs were followed up for 5 weeks. Posteuthanasia histology showed 10 to have a nontransmural and 8 a transmural infarction. Eight nonstented animals served as controls. Regional radial function was monitored by measuring ultrasound-derived peak systolic strain rates (SRSYS) and systolic strains (&egr;SYS) (1) before stent implantation and (2) at 5 weeks, at baseline (bs) and during an incremental dobutamine infusion. In controls, dobutamine induced a linear increase in SRSYS (dobutamine: bs, 4.8±0.4 s−1; 20 &mgr;g · kg−1 · min−1, 9.9±0.7 s−1;P <0.0001) and an initial increase of &egr;SYS at low dose (bs, 58±5%; at 5 &mgr;g · kg−1 · min−1, 78±6%;P <0.05) but a subsequent decrease during higher infusion rates. In the nontransmural group, bs SRSYS and &egr;SYS were significantly lower than prestent values (SRSYS, 2.9±0.5 s−1 and &egr;SYS, 32±6%, P <0.05 versus prestent). During dobutamine infusion, SRSYS increased slightly at 5 &mgr;g · kg−1 · min−1 (4.7±0.6 s−1, P <0.05) but fell during higher infusion rates, whereas &egr;SYS showed no change. For nontransmural infarctions, transmural scar extension correlated closely with &egr;SYS at bs (r =0.88). For transmural infarctions, SRSYS at bs was significantly reduced and &egr;SYS was almost not measurable (SRSYS, 1.8±0.3 s−1; &egr;SYS, 3±4%). Both deformation parameters showed no further change during the incremental dobutamine infusion. Conclusions—Ultrasonic deformation values could clearly differentiate chronic nontransmural from transmural myocardial infarction. The transmural extension of the scar could be defined by the regional deformation response.

Experimental Study of Thrombogenicity and Foreign Body Reaction Induced by Heparin-Coated Coronary Stents

BACKGROUND Results of recent randomized clinical trials have revealed a significant reduction in angiographic restenosis rate when adjunctive stenting was performed after conventional coronary balloon angioplasty. The thrombogenicity of metal stents, however, remains a concern. In the present study, we compare the thrombogenicity of heparin-coated coronary stents with that of bare metallic coronary stents. METHODS AND RESULTS Thrombogenicity of metallic coronary stents (four heparin-coated and eight bare stents) was studied in a rat arteriovenous shunt model with the use of 125I-labeled fibrinogen and 51Cr-labeled platelets. Total clot weight after 30-minute follow-up was significantly lower in the heparin-coated stents compared with the bare stents (8.1 +/- 3.7 versus 25.8 +/- 4.6 mg; P < .001). Relative 125I and 51Cr activities in the stents were significantly higher in the bare stents than in the heparin-coated stents (125I, 1.03 +/- 0.43 versus 0.18 +/- 0.04, P = .003; 51Cr, 17.5 +/- 6.8 versus 4.4 +/- 1.0, P = .004). Subsequently, heparin-coated and bare stents were randomly implanted in the right coronary artery of 20 domestic pigs. Angiographic parameters were similar between both groups at baseline and after 6-week follow-up. Morphometry also did not show a significant difference in lumen area (bare, 1.03 +/- 0.83 mm2; heparin-coated, 1.12 +/- 0.73 mm2; P = NS) or neointimal hyperplasia (bare, 1.01 +/- 0.81 mm2; heparin-coated, 1.21 +/- 0.57 mm2; P = NS). CONCLUSIONS Heparin coating of metallic coronary stents decreases their thrombogenicity but does not improve late vessel patency and neointimal hyperplasia at follow-up in a porcine coronary model.

Study of antirestenosis with the BiodivYsio dexamethasone-eluting stent (STRIDE): A first-in-human multicenter pilot trial

The aim of this multicenter pilot study was to evaluate the acute safety and efficacy of the dexamethasone‐eluting stent (0.5 μg/mm2 of stent) implanted in patients with de novo single‐vessel disease. This study included 71 patients, 42% of whom had unstable angina pectoris. An appropriately sized BiodivYsio Matrix Lo stent loaded with a total dexamethasone dose of 0.5 μg/mm2 of stent was used. Technical device success rate was 95%. Six‐month MACE occurred in two patients (3.3%). Binary restenosis rate was 13.3%. Late loss was 0.45. Late loss and percent diameter stenosis were lower in the unstable angina pectoris patients compared to the stable patients (0.32 ± 0.39 vs. 0.60 ± 0.55 mm, P < 0.07, and 26.86 ± 14 vs. 38.40 ± 16%, P < 0.02). This study demonstrated the feasibility and safety of the implantation of a dexamethasone‐eluting stent and its effect on in‐stent neointimal hyperplasia. Catheter Cardiovasc Interv 2003;60:172–178.

Abnormal Postsystolic Thickening in Acutely Ischemic Myocardium During Coronary Angioplasty: A Velocity, Strain, and Strain Rate Doppler Myocardial Imaging Study

We report a case in which the combination of gray scale imaging of wall thickness changes allied to color DMI regional velocity, strain, and strain rate data identified the development and regression of diastolic thickening in the acute ischemic segment during a right coronary artery percutaneous transluminal coronary angioplasty (PTCA). We also discuss the possible mechanisms and potential clinical implications of this finding.

In-vivo biocompatibility evaluation of stents coated with a new biodegradable elastomeric and functional polymer

BackgroundIn-stent restenosis may be prevented by impregnating an antiproliferative agent in a polymer from a stent platform. This approach requires both an antiproliferative agent effective in small doses and a biocompatible polymer. MethodsA series of new biodegradable elastomeric poly(ester-amide)(co-PEA) polymers having functional carboxyl groups for drug conjugation were synthesized from non-toxic building blocks. The in-vivo biocompatibility was tested in porcine coronary arteries, by comparing the polymer-coated stents with bare metal stents in 10 pigs. ResultsAll animals survived until sacrifice 28 days later and follow-up angiography prior to sacrifice revealed identical diameter stenosis (21 ± 23%) in both groups. Histology confirmed similar injury scores (0.34 ± 0.34 compared with 0.34 ± 0.32), inflammatory reaction (1.18 ± 0.38 compared with 1.11 ± 0.32) and area stenosis (26 ± 17% compared with 28 ± 22%). ConclusionsThis study suggests that the newly developed copoly(ester-amide) elastomers may be suitable for stent-based local drug delivery.

Stenting of venous bypass grafts: A new treatment modality for patients who are poor candidates for reintervention

Abstract During a 2-year period, 136 self-expanding Wall-stents were implanted in saphenous vein bypass grafts in 69 patients with end-stage coronary artery disease. All patients had severe symptoms and the majority were poor candidates for either repeat surgery or conventional bypass coronary angioplasty because of unfavorable native anatomy, impaired left ventricular function, or a high-risk bypass lesion anatomy for coronary angioplasty. All procedures were technically successful without major complications and a need for emergency bypass surgery. However, during the hospital stay acute thrombotic complications occurred in seven patients (10%) resulting in one death and acute myocardial infarction in five patients and necessitating emergency repeat PTCA in two patients and repeat CABG in four. Twenty-three patients had serious hemorrhagic complications directly related to the rigorous anticoagulation schedule. Two patients died of fatal cerebral bleeding. During follow-up, another five patients died accounting for a total mortality rate of 12%. At late angiographic follow-up (4.9 ± 3.4 months, n = 53), 25 patients (47%) had a restenosis (≥50% DS) within or immediately adjacent to the stent, necessitating reintervention in 19 patients (PTCA, n = 12; repeat CABG, n = 7). In the group without stent-related restenosis (n = 28), 15 patients had progression of disease in either the native or bypass vessels leading to recurrence of major anginal symptoms within 1 to 24 months. Ten of these patients required further intervention (stent, n = 6; PTCA, n = 3; repeat CABG, n = 1). Stenting in saphenous coronary bypass grafts can be performed safely with excellent immediate angiographic and clinical results. Early occlusion, late restenosis, and bleeding complications associated with the aggressive anticoagulant treatment remain significant limitations. Reintervention as a result of restenosis or progression of disease in other lesions is common. Stenting of diseased bypass grafts in symptomatic patients with end-stage coronary artery disease (who are at high risk for conventional angioplasty or surgical reintervention) may be useful as palliative therapy.

Post-Cardiac Injury Syndrome and an Increased Humoral Immune Response Against the Major Contractile Proteins (Actin and Myosin

To better understand the pathogenesis of the post-cardiac injury syndrome (PCIS) 2 models of cardiac injury were studied. One hundred twenty-nine patients who underwent cardiac surgery and 80 patients with acute myocardial infarction (AMI) were prospectively followed and the levels of anti-heart antibodies (AHA), anti-actin antibodies (AAA) and anti-myosin antibodies (AMA) were determined. In the surgical group, PCIS developed in 27 patients (21%) and incomplete PCIS in 36 (28%). In the AMI group, PCIS did not develop in any patient, but incomplete PCIS developed in 11 patients (14%) (p less than 0.001). The surgical group showed a significantly higher humoral immune response than the AMI group when analyzed for AHA and anti-contractile protein antibodies. After cardiac surgery, AHA developed in 59 patients (46%), AAA developed in 33 (26%) and AMA developed in 49 (38%); in the AMI group, significant levels of AHA, AAA and AMA developed in 16 (20%), 7 (9%) and 13 patients (16%), respectively. These studies show a significant correlation between the PCIS clinical classification and auto-antibodies raised against heart contractile proteins.

Electrochemical polishing of 316L stainless steel slotted tube coronary stents

Surface smoothness is one of the properties determining the performance of stents. Therefore, surface polishing shows its importance in the exploitation and production of stents. The present study explores electrochemical polishing of 316L stainless steel slotted tube coronary stents produced by laser cutting. Acid pickling was also studied as a pre-treatment of electrochemical polishing of the stents to remove the slag (oxides) formed in the production of the stents. Meanwhile, removal of the material was measured as well, caused by both acid pickling and electrochemical polishing processes. It is found that the slag formed on the surface of stents due to the laser cutting production process could be removed by means of acid pickling. Electrochemical polishing results in a smooth stent surface. Meanwhile, both acid pickling and electrochemical polishing applied in the present study have a proper removal of the stent material.

Cellular Mechanisms of Contractile Dysfunction in Hibernating Myocardium

Abstract— Ischemic heart disease is a leading cause of chronic heart failure. Hibernation (ie, a chronic reduction of myocardial contractility distal to a severe coronary stenosis and reversible on revascularization) is an important contributing factor. The underlying cellular mechanisms remain however poorly understood. In young pigs (n=13, ISCH), an acquired coronary stenosis >90% (4 to 6 weeks) resulted in the development of hibernating myocardium. Single cardiac myocytes from the ISCH area were compared with cells from the same area obtained from matched normal pigs (n=12, CTRL). Myocytes from ISCH were larger than from CTRL. In field stimulation, unloaded cell shortening was reduced and slower in ISCH; relaxation was not significantly different. The amplitude of the [Ca2+]i transient was not significantly reduced, but reducing [Ca2+]o for CTRL cells could mimic the properties of ISCH, inducing a significant reduction of contraction, but not of [Ca2+]i. Action potentials were longer in ISCH. With square voltage-clamp pulses of equal duration in ISCH and CTRL, the amplitude of the [Ca2+]i transient was significantly smaller in ISCH, as was the Ca2+ current. Near-maximal activation of the myofilaments resulted in smaller contractions of ISCH than of CTRL cells. There was no evidence for increased degradation of Troponin I. In conclusion, cellular remodeling is a major factor in the contractile dysfunction of the hibernating myocardium. Myocytes are hypertrophied, action potentials are prolonged, and L-type Ca2+ currents and Ca2+ release are decreased. The steep [Ca2+]i dependence of contraction and possibly a reduction of maximal myofilament responsiveness further enhance the contractile deficit.