Scaffold-based tissue engineering: Supercritical carbon dioxide as an alternative method for decellularization and sterilization of dense materials.

Development of ready-to-use biomaterials and scaffolds is vital for further advancement of scaffold-based tissue engineering in clinical practice. Scaffolds need to mimic 3D ultrastructure, have adequate mechanical strength, are biocompatible, non-immunogenic and need to promote tissue regeneration in vivo. Although decellularization of native tissues seems promising to deliver scaffolds that meet these criteria, adequate decellularization of hard, poorly penetrable and poorly diffusible tissues remains challenging whilst being a very time-consuming process. In this study, a method to decellularize hard, dense tissues using supercritical carbon-dioxide preceded by a freeze/thaw cycle and followed by several washing steps is presented, demonstrating decellularisation efficiency and substantially reduced production/handling time. Additionally, supercritical carbon-dioxide treatment was used as sterilization method, further reducing the time required to produce the final scaffold. Histological evaluation showed that, after fine-tuning of the process, a partially acellular scaffold was obtained, with preservation of glycosaminoglycans and collagen fibers, albeit that the amount of residual dsDNA was still higher then chemically decellularized tissue. Biomechanical properties of the scaffold were similar to the native, non-decellularized tissue. After sterilization with supercritical carbon-dioxide the simulated functional outcome was more similar to native trachea, when compared to sterilization using gamma irradiation. Thus, decellularization and sterilization using supercritical carbon-dioxide with washing steps is an effective method for dense cartilaginous materials, and tuneable to meet different demands in other applications, but further optimization may be required. STATEMENT OF SIGNIFICANCE: Further advancement of the use of tissue engineered tracheal constructs is restricted by the lack of the ideal scaffold. Decellularized trachea is considered a promising scaffold, but the hard, poorly diffusible tissue remains challenging while forming a very time consumable process. Decellularization using supercritical carbon dioxide (scCO2) seems promising, resulting in efficient removal of cellular material while reducing production and handling time. Addition of scCO2 as a sterilization method resulted in further time reduction while improving functional outcome in comparison with traditional sterilization methods. This study presents an promising alternative method for decellularization and sterilization of dense materials, which can be tuned to meet different demands in other applications.

Drug-eluting stents: trading restenosis for thrombosis?

Within the last 6 years, it has been demonstrated that drug-eluting stents (DES) reduce significantly angiographic and clinical restenosis after percutaneous coronary interventions. These results are consistent across several clinical randomized controlled trials comparing these new devices with bare metallic stents (BMS), which themselves have already markedly improved the results obtained with balloon angioplasty in the early days of this method of myocardial revascularization. Nevertheless, some concerns have been raised regarding a delayed endothelialization of the coated prostheses leading to late stent thrombosis occurring mainly when antiplatelet therapy is discontinued in the follow-up. The most recent data show that, in comparison with BMS, there is a small excess of late (> 1 year) stent thrombosis but this is not associated with an increased risk of death or myocardial infarction or all cause mortality. These concerns do not outweigh the strong benefits of DES in preventing restenosis but require a number of measures concerning a longer dual antiplatelet treatment (than initially expected), to control patient treatment compliance and to provide a complete education of patients and physicians. Future devices dealing with the two issues (antiproliferative properties with rapid controlled endothelialization preventing thrombosis) would be the next major advance in this rapidly evolving field.

Predictive value of hippocampal MR imaging-based high-dimensional mapping in mesial temporal epilepsy: preliminary findings.

BACKGROUND AND PURPOSE: We objectively assessed surface structural changes of the hippocampus in mesial temporal sclerosis (MTS) and assessed the ability of large-deformation high-dimensional mapping (HDM-LD) to demonstrate hippocampal surface symmetry and predict group classification of MTS in right and left MTS groups compared with control subjects. METHODS: Using eigenvector field analysis of HDM-LD segmentations of the hippocampus, we compared the symmetry of changes in the right and left MTS groups with a group of 15 matched controls. To assess the ability of HDM-LD to predict group classification, eigenvectors were selected by a logistic regression procedure when comparing the MTS group with control subjects. RESULTS: Multivariate analysis of variance on the coefficients from the first 9 eigenvectors accounted for 75% of the total variance between groups. The first 3 eigenvectors showed the largest differences between the control group and each of the MTS groups, but with eigenvector 2 showing the greatest difference in the MTS groups. Reconstruction of the hippocampal deformation vector fields due solely to eigenvector 2 shows symmetrical patterns in the right and left MTS groups. A "leave-one-out" (jackknife) procedure correctly predicted group classification in 14 of 15 (93.3%) left MTS subjects and all 15 right MTS subjects. CONCLUSION: Analysis of principal dimensions of hippocampal shape change suggests that MTS, after accounting for normal right-left asymmetries, affects the right and left hippocampal surface structure very symmetrically. Preliminary analysis using HDM-LD shows it can predict group classification of MTS and control hippocampi in this well-defined population of patients with MTS and mesial temporal lobe epilepsy (MTLE).

Management and outcome of patients with established coronary artery disease: the Euro Heart Survey on coronary revascularization.

AIMS: The purpose of the Euro Heart Survey Programme of the European Society of Cardiology is to evaluate to which extent clinical practice endorses existing guidelines as well as to identify differences in population profiles, patient management, and outcome across Europe. The current survey focuses on the invasive diagnosis and treatment of patients with established coronary artery disease (CAD). METHODS AND RESULTS: Between November 2001 and March 2002, 7769 consecutive patients undergoing invasive evaluation at 130 hospitals (31 countries) were screened for the presence of one or more coronary stenosis >50% in diameter. Patient demographics and comorbidity, clinical presentation, invasive parameters, treatment options, and procedural techniques were prospectively entered in an electronic database (550 variables+29 per diseased coronary segment). Major adverse cardiac events (MACE) were evaluated at 30 days and 1 year. Out of 5619 patients with angiographically proven coronary stenosis (72% of screened population), 53% presented with stable angina while ST elevation myocardial infarction (STEMI) was the indication for coronary angiography in 16% and non-ST segment elevation myocardial infarction or unstable angina in 30%. Only medical therapy was continued in 21%, whereas mechanical revascularization was performed in the remainder [percutaneous coronary intervention (PCI) in 58% and coronary artery bypass grafting (CABG) in 21%]. Patients referred for PCI were younger, were more active, had a lower risk profile, and had less comorbid conditions. CABG was performed mostly in patients with left main lesions (21%), two- (25%), or three-vessel disease (67%) with 4.1 diseased segments, on average. Single-vessel PCI was performed in 82% of patients with either single- (45%), two- (33%), or three-vessel disease (21%). Stents were used in 75% of attempted lesions, with a large variation between sites. Direct PCI for STEMI was performed in 410 cases, representing 7% of the entire workload in the participating catheterization laboratories. Time delay was within 90 min in 76% of direct PCI cases. In keeping with the recommendations of practice guidelines, the survey identified under-use of adjunctive medication (GP IIb/IIIa receptor blockers, statins, and angiotensin-converting enzyme-inhibitors). Mortality rates at 30 days and 1 year were low in all subgroups. MACE primarily consisted of repeat PCI (12%). CONCLUSION: The current Euro Heart Survey on coronary revascularization was performed in the era of bare metal stenting and provides a global European picture of the invasive approach to patients with CAD. These data will serve as a benchmark for the future evaluation of the impact of drug-eluting stents on the practice of interventional cardiology and bypass surgery.

Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study.

BACKGROUND: Despite the use of aspirin, there is still a risk of ischaemic events after percutaneous coronary intervention (PCI). We aimed to find out whether, in addition to aspirin, pretreatment with clopidogrel followed by long-term therapy after PCI is superior to a strategy of no pretreatment and short-term therapy for only 4 weeks after PCI. METHODS: 2658 patients with non-ST-elevation acute coronary syndrome undergoing PCI in the CURE study had been randomly assigned double-blind treatment with clopidogrel (n=1313) or placebo (n=1345). Patients were pretreated with aspirin and study drug for a median of 6 days before PCI during the initial hospital admission, and for a median of 10 days overall. After PCI, most patients (>80%) in both groups received open-label thienopyridine for about 4 weeks, after which study drug was restarted for a mean of 8 months. The primary endpoint was a composite of cardiovascular death, myocardial infarction, or urgent target-vessel revascularisation within 30 days of PCI. The main analysis was by intention to treat. FINDINGS: There were no drop-outs. 59 (4.5%) patients in the clopidogrel group had the primary endpoint, compared with 86 (6.4%) in the placebo group (relative risk 0.70 [95% CI 0.50-0.97], p=0.03). Long-term administration of clopidogrel after PCI was associated with a lower rate of cardiovascular death, myocardial infarction, or any revascularisation (p=0.03), and of cardiovascular death or myocardial infarction (p=0.047). Overall (including events before and after PCI) there was a 31% reduction cardiovascular death or myocardial infarction (p=0.002). There was less use of glycoprotein IIb/IIIa inhibitor in the clopidogrel group (p=0.001). At follow-up, there was no significant difference in major bleeding between the groups (p=0.64). INTERPRETATION: In patients with acute coronary syndrome receiving aspirin, a strategy of clopidogrel pretreatment followed by long-term therapy is beneficial in reducing major cardiovascular events, compared with placebo.

Effect of ACE inhibitors on angiographic restenosis after coronary stenting (PARIS): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The DD genotype for the angiotensin-I converting enzyme (ACE I) deletion allele (D) polymorphism is a possible genetic risk factor for restenosis after coronary stent implantation. We aimed to establish whether or not blockade of ACE with high doses of ACE inhibitors could reduce this risk of angiographic restenosis. METHODS: We characterised the ACE I/D polymorphism in 345 consecutive patients who were undergoing coronary stenting. 115 had the DD genotype. We assigned 91 of these 115 patients to quinapril 40 mg daily (n=46) or placebo (n=45). Treatment was started within 48 h after stent implantation and continued for 6 months. 79 patients complied with the protocol and underwent follow-up angiography after 6 months. FINDINGS: Our primary endpoint of late loss in minimum lumen diameter (a quantitative index of restenosis) was significantly higher in the quinapril group than in the controls (mean 1.11 mm [SD 0.70] vs 0.76 mm [0.60]; p=0.018). Secondary endpoints also showed consistent trends towards increased angiographic restenosis in the treatment group. INTERPRETATION: Contrary to our expectations, ACE inhibitor treatment did not reduce restenosis after coronary stent implantation in patients with DD genotype, but was associated with an exaggerated restenotic process when compared with administration of placebo.

Patency of percutaneous transluminal coronary angioplasty sites at 6-month angiographic follow-up: A key determinant of survival in diabetics after coronary balloon angioplasty.

BACKGROUND: Several reports have demonstrated a high mortality rate in diabetic patients treated by standard coronary balloon angioplasty. No clear explanation has been provided for this finding. METHODS AND RESULTS: Consecutive diabetic patients successfully treated by standard coronary balloon angioplasty (n=604) were enrolled in a follow-up program including repeated angiography at 6 months and long-term clinical follow-up. Clinical follow-up was available in 603 patients (99.8%). Twelve patients died, 2 underwent bypass surgery before scheduled repeated angiography, and 76 declined angiography. Determinants of long-term mortality were analyzed in the 513 patients with angiography at 6 months and long-term clinical follow-up (mean follow-up, 6.5+/-2.4 years). On the basis of the results of repeated angiography, 3 groups of patients were defined: group 1, 162 patients without restenosis (32%); group 2, 257 patients with nonocclusive restenosis (50%); and group 3, 94 patients with coronary occlusion (18%). Overall actuarial 10-year mortality rate was 36%. Actuarial 10-year mortality was 24% in group 1, 35% in group 2, and 59% in group 3 (P:<0.0001). Multivariate analysis demonstrated that coronary occlusion was a strong and independent correlate of long-term total mortality (hazard ratio, 2.16; 95% CI, 1.43 to 3.26; P:=0.0003) and cardiac mortality (hazard ratio, 2.38; 95% CI, 1.48 to 3.85; P:=0.0004). CONCLUSIONS: This study demonstrates that restenosis, especially in its occlusive form, is a major determinant of long-term mortality in diabetic patients after coronary balloon angioplasty.

Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting : the clopidogrel aspirin stent international cooperative study (CLASSICS).

BACKGROUND: Combination therapy with the ADP receptor antagonist ticlopidine plus aspirin has emerged as standard care after coronary stenting. Clopidogrel, a new ADP receptor antagonist, has greater molar potency than ticlopidine and better safety/tolerability. METHODS AND RESULTS: Patients (n=1020) were randomized after successful stent placement and initiated on a 28-day regimen of either (1) 300-mg clopidogrel loading dose and 325 mg/d aspirin on day 1, followed by 75 mg/d clopidogrel and 325 mg/d aspirin; (2) 75 mg/d clopidogrel and 325 mg/d aspirin; or (3) 250 mg BID ticlopidine and 325 mg/d aspirin. The primary end point consisted of major peripheral or bleeding complications, neutropenia, thrombocytopenia, or early discontinuation of study drug as the result of a noncardiac adverse event during the study-drug treatment period. The primary end point occurred in 9.1% of patients (n=31) in the ticlopidine group and 4.6% of patients (n=31) in the combined clopidogrel group (relative risk 0.50; 95% CI 0.31 to 0.81; P=0.005). Overall rates of major adverse cardiac events (cardiac death, myocardial infarction, target lesion revascularization) were low and comparable between treatment groups (0.9% with ticlopidine, 1.5% with 75 mg/d clopidogrel, 1.2% with the clopidogrel loading dose; P=NS for all comparisons). CONCLUSIONS: The safety/tolerability of clopidogrel (plus aspirin) is superior to that of ticlopidine (plus aspirin) (P=0.005). The 300-mg loading dose was well tolerated, notably with no increased risk of bleeding. Secondary end point data are consistent with the hypothesis that clopidogrel and ticlopidine have comparable efficacy with regard to cardiac events after successful stenting.

Total percentage body weight changes during add-on therapy with tiagabine, carbamazepine and phenytoin.

Changes in body weight were evaluated in 349 patients from a study comparing efficacy of add-on therapy with tiagabine (TGB), carbamazepine (CBZ) or phenytoin (PHT). TGB add-on therapy showed no significant weight changes when added to either PHT or CBZ. CBZ add-on therapy showed a significant percentage weight gain of a mean body increase of 1.5% (P = 0.002). Adjunctive TGB therapy had no significant effect on total body weight, while adjunctive CBZ therapy was associated with weight gain.

Heparin-coated Wiktor stents in human coronary arteries (MENTOR trial). MENTOR Trial Investigators.

The purpose of this study was to determine the feasibility, safety, and efficacy of elective stenting with heparin-coated Wiktor stents in patients with coronary artery disease. In experimental studies, heparin coating has been shown to prevent subacute thrombosis and restenosis. Recently, a new method of heparin coating was developed, resulting in a more stable and predictable heparin layer on stent devices. This trial constitutes the first in-human use of this coating procedure, applied on the well-known Wiktor stent device. Heparin-coated Wiktor stent implantation was performed in 132 consecutive patients (132 lesions) in a multicenter international trial from September 1996 to February 1997. Forty-three percent of patients had unstable angina, 33% had previous myocardial infarction, and 10% had diabetes mellitus. Patients were followed for 12 months for occurrence of major adverse cardiovascular events, and 96% of the eligible patients underwent quantitative angiographic control at 6 months. Stent deployment was successful in 95.5% of lesions. Minimal lumen diameter increased by 1.67 +/- 0.48 mm (from 1.02 +/- 0.38 mm before to 2.69 +/- 0.37 mm after the stent implantation). Mean percent diameter stenosis decreased from 67.4 +/- 11.3% before to 18.9 +/- 7.7% after the intervention. A successful intervention (<50% diameter stenosis and no major adverse cardiac events within 30 days) occurred in 97% of the patients. The subacute thrombosis rate was 0.8%, which compares favorably with historical controls of this stent, and a low incidence of postprocedural increase in creatine kinase-MB was noted. At 6 months, event-free survival was 85% and angiographic restenosis rate was 22% with late loss of 0.78 +/- 0.69 mm and a loss index of 0.48 +/- 0.44. Heparin-coated Wiktor stents appeared to be an efficacious device to treat Benestent-like lesions, yielding angiographic and clinical results comparable to a heparin-coated Palmaz-Schatz stent. Despite its use in more complex lesions, the incidence of subacute thrombosis appeared to be lower than historical controls with a similar noncoated stent.

Diltiazem in acute myocardial infarction treated with thrombolytic agents: a randomised placebo-controlled trial. Incomplete Infarction Trial of European Research Collaborators Evaluating Prognosis post-Thrombolysis (INTERCEPT)

BACKGROUND: Diltiazem reduces non-fatal reinfarction and refractory ischaemia after non-Q-wave myocardial infarction, an acute coronary syndrome similar to the incomplete infarction that occurs after successful reperfusion. We postulated that this agent would reduce cardiac events in patients after acute myocardial infarction treated initially with thrombolytic agents-a clinical application previously unexplored with heart-rate-lowering calcium antagonists. METHODS: A prospective, randomised, double-blind, sequential trial was done in 874 patients with acute myocardial infarction, but without congestive heart failure, who first received thrombolytic agents. Patients received either 300 mg oral diltiazem once daily, or placebo, initiated within 36-96 h of infarct onset, and given for up to 6 months. The trial primary endpoint was the cumulative first event rate of cardiac death, non-fatal reinfarction, or refractory ischaemia. Additional prespecified endpoints included several composites of non-fatal cardiac events (non-fatal reinfarction combined with refractory ischaemia, all recurrent ischaemia, or the need for myocardial revascularisation). The diagnosis of ischaemia, whether refractory or recurrent, and the need for myocardial revascularisation, was always based on objective electrocardiographical evidence of ischaemia, either at rest or on exertion. RESULTS: For the trial primary endpoint, 131 events occurred in the 444 placebo patients and 97 events in the 430 diltiazem patients (hazard ratio 0.79; 95% CI, 0.61-1.02; p=0.07). For non-fatal cardiac events, diltiazem treatment was associated with a relative decrease (0.76; 0.58-1.00) in the combined event rate of non-fatal reinfarction and refractory ischaemia. There was a similar decrease in the composite non-fatal endpoints of non-fatal reinfarction combined with all recurrent ischaemia (0.80; 0.64-1.00) and non-fatal reinfarction combined with the need for myocardial revascularisation (0.67; 0.46-0.96). The need for myocardial revascularisation alone was significantly reduced by 42% (0.61; 0.39-0.96). No major safety issues were encountered. CONCLUSIONS: Diltiazem did not reduce the cumulative occurrence of cardiac death, non-fatal reinfarction, or refractory ischaemia during a 6-month follow-up, but did reduce all composite endpoints of non-fatal cardiac events, especially the need for myocardial revascularisation.

Paraoxonase polymorphism (Gln192Arg) as a determinant of the response of human coronary arteries to serotonin.

Background-Oxidation of LDL plays a role in endothelial dysfunction. Paraoxonase, an enzyme present on HDL, protects LDL against oxidation. Paraoxonase activity is genetically determined in part, and 3 genotypes have been described with variable enzymatic activity. We hypothesized that the paraoxonase polymorphism might influence endothelial function. Methods and Results-Twenty-seven patients with clinical manifestations of coronary artery disease underwent provocative testing by intracoronary administration of serotonin. None of the coronary arteries studied had significant (>50%) stenosis. Ten patients had the QQ genotype and 17 had the QR genotype. At proximal segments, the mean percentage reduction in lumen diameter in response to serotonin was greater in QQ patients than in QR patients (10(-5) mol/L: P<0.05; 10(-4) mol/L: P<0.006). Similarly, at distal segments, constriction in response to serotonin was greater in QQ patients than in QR patients (10(-6) mol/L: P<0. 03; 10(-5) mol/L: P<0.07). Conclusions-These results suggest a higher synthesis or release of endothelium-derived relaxing factors to counteract the vasoconstrictor effect of serotonin in patients with the R allele. These findings provide evidence that the paraoxonase polymorphism may play a role in the regulation of coronary vasomotor tone.

Influence of a nonionic, iso-osmolar contrast medium (iodixanol) versus an ionic, low-osmolar contrast medium (ioxaglate) on major adverse cardiac events in patients undergoing percutaneous transluminal coronary angioplasty: A multicenter, randomized, double-blind study. Visipaque in Percutaneous Transluminal Coronary Angioplasty [VIP] Trial Investigators.

BACKGROUND: The potential merits and disadvantages of the use of ionic or nonionic contrast media in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) have been the subjects of controversy. The present study was designed to evaluate the possible influence of both types of contrast media on major adverse cardiac events (MACE) in patients undergoing PTCA. METHODS AND RESULTS: In a randomized, parallel-group, double-blind study, 1411 patients received either iodixanol (a nonionic, iso-osmolar contrast medium) or ioxaglate (an ionic, low-osmolar contrast medium) during PTCA. A standardized anticoagulation regimen was followed. Patients were monitored in the hospital for 2 days and followed-up at 1 month. The primary end point, a composite of MACE (death, stroke, myocardial infarction, coronary artery bypass grafting, and re-PTCA) after 2 days, occurred in 4.3% of the total population, with no statistically significant difference between groups (iodixanol, 4.7%; ioxaglate, 3.9%; P=0.45). Further, between 2-day and 1-month follow-ups, no significant difference (P=0.27) existed between the groups in the rates of MACE. Hypersensitivity reactions (P=0.007) and adverse drug reactions (P=0.002) were significantly less frequent in the iodixanol group. The only significant predicting factors for the occurrence of MACE were dissection/abrupt closure and country. CONCLUSIONS: No significant differences were observed between the iodixanol and ioxaglate groups with regard to MACE, although hypersensitivity and adverse drug reactions were significantly less frequent in patients who received iodixanol.

[Restenosis after angioplasty]. / La resténose après angioplastie.

Restenosis remains the main limitation of endocoronary methods of revascularisation. It is observed in 20 to over 50% of cases, depending on the prevailing risk factors and techniques used. The mechanism of post balloon angioplasty restenosis consists of neointimal hyperplasia, vascular remodelling and thrombosis. Intra-stent thrombosis is mainly caused by the neointimal hyperplasia. The strategies developed to prevent restenosis may be grouped in two categories: mechanical and pharmacological strategies. Stenting is the only mechanical method to have been shown to be effective. With respect to pharmacological methods, the general impression is rather negative even if some positive results have been reported recently. Of the new strategies which may provide a solution in the coming years, gene therapy and endocoronary irradiation justify a special mention.

[Coronary angioplasty in diabetic patients. Analysis of the problems to improve results]. / Angioplastie coronaire chez le patient diabétique. Analyser ses points faibles pour améliorer ses performances.

The object of this review is to update our knowledge of the results of revascularisation by angioplasty in diabetics. The authors discuss: 1. the clinical results in diabetic patients compared with non-diabetics and the results of coronary bypass surgery; 2. the factors influencing the prognosis of these patients after balloon angioplasty, especially with respect to restenosis; 3. the possibilities of improving the results by the use of modern techniques of revascularisation and prevention and 4. the strategies of revascularisation which may be proposed, based on available data.

ACE gene polymorphism and coronary restenosis.

In humans, circulating levels of angiotensin-converting enzyme (ACE) are linked with an insertion (I)/deletion (D) polymorphism in the ACE gene: DD genotype bearers have higher levels of ACE than either ID or II genotype bearers. Recent studies have suggested that the ACE DD genotype might be associated with a higher risk of coronary artery disease. The aim of this paper is to review studies on the influence of the I/D polymorphism on coronary restenosis. The renin-angiotensin system has been implicated in the pathogenesis of neointimal hyperplasia in experimental models. In humans, the I/D polymorphism is not associated with restenosis after balloon angioplasty, but is strongly associated with restenosis after coronary stent implantation. This may be explained by the fact that the contribution of neointimal hyperplasia to restenosis is much more important after coronary stent implantation than after balloon angioplasty.

Management strategies in unstable coronary artery disease--current problems and future directions. The UCAD Council.

Unstable coronary artery disease continues to pose a major challenge to clinicians. The advent of new therapies, such as percutaneous transluminal coronary angioplasty, low-molecular-weight heparins, and glycoprotein IIb/IIIa inhibitors, provides new management options for this indication but also raises new questions with regard to optimal management. Prospective randomized trials with well-defined, long-term outcome measures and a means of identifying which patients will derive most benefit from each treatment, together with a means of rapid and clear dissemination of study results and implications, are required in order to advance the management of unstable coronary artery disease.

Restenosis, late vessel occlusion and left ventricular function six months after balloon angioplasty in diabetic patients.

OBJECTIVES: We studied angiographic outcome and its predictors after traditional coronary balloon angioplasty in diabetics. We further examined whether changes in ejection fraction were influenced by the status of the dilated site(s) at follow-up. BACKGROUND: Recent studies have suggested that diabetics have a particularly poor outcome after balloon angioplasty. The reasons for this observation are not known. METHODS: We investigated procedural and six-month angiographic outcome, analyzed by quantitative coronary angiography, and left ventricular function in 485 consecutive diabetics (627 lesions) treated by balloon angioplasty without stent implantation. RESULTS: The procedure was successful in 455 (94%) patients; angiographic follow-up was available in 377 patients (83%). At follow-up, the rates of restenosis and total occlusion were 62% and 13%, respectively. Five independent predictors of restenosis were identified: the presence of organ damage, a saphenous vein graft (SVG) angioplasty, a bifurcation lesion, a Thrombolysis in Myocardial Infarction (TIMI) flow <3 preprocedure and the degree of residual stenosis. Four independent predictors of vessel occlusion were identified: treatment with insulin, a SVG angioplasty, a TIMI flow <3 preprocedure and the degree of residual stenosis after angioplasty. Late vessel occlusion at angioplasty site(s) was observed in 15% of patients, ranging from 11% for a one-site procedure to 37% for a three-site procedure. This complication was associated with a decrease in ejection fraction at follow-up (-6.2 +/- 9.9%, p = 0.0001), whereas no significant change was observed in patients without occlusion. CONCLUSIONS: This study shows that late vessel occlusion is a frequent mode of restenosis in diabetic patients and is associated with a significant decrease in ejection fraction. This could partly explain the poor long-term clinical outcome reported in such patients after traditional balloon angioplasty.