Variation in the histopathological features of patients with ascending aortic aneurysms: a study of 111 surgically excised cases.

BACKGROUND: Ascending aortic aneurysms (AA) are a common, though poorly understood medical condition. AIMS: To document the histological changes in a large series of human ascending AA, and to correlate these changes with clinical variables. METHODS: 111 ascending AA were excised at surgery over a 3 year period. Each aneurysm was received as a continuous ring of tissue. Sections were taken from the anterior, posterior, greater and lesser curvature of the aorta and graded in a semi-quantitative fashion for the degree of elastin fragmentation, elastin loss, smooth muscle cell (SMC) loss, intimal changes and inflammation. RESULTS: Mean patient age at surgery was 58.7 (15.6) years; there were 70 men and 41 women. 12 patients had Marfan syndrome, 34 (30.6%) had a bicuspid aortic valve (BAV), while 71 (64.0%) had a tricuspid aortic valve (TAV). Inflammatory cells were present in 28 cases (25.2%) and were confined to the adventitia. No particular region of the aortic circumference was more severely affected, however a BAV was associated with significantly less intimal change, and less fragmentation and loss of elastic tissue compared with patients with a TAV. Advanced age (>65 years), female gender and Marfan syndrome were all associated with more severe elastin degeneration and smooth muscle cell loss (p<0.05 for all). CONCLUSION: Results indicate a wide variation in the histological appearance in ascending AA, depending on patient characteristics. They suggest that the underlying aneurysm pathogenesis may also be highly variable; this warrants further investigation.

Implications of a congenitally abnormal valve: a study of 1025 consecutively excised aortic valves.

BACKGROUND: An increasing proportion of patients with congenitally abnormal aortic valves (AV) present for AV replacement. AIMS: To review morphological changes in a large contemporary patient population undergoing AV replacement. METHODS: A detailed review was conducted for all 1025 patients who underwent AV replacement from 2002 to 2005, including the clinical indication for surgery, the type of native AV disease, the pathological changes observed in each valve and the need for related surgery. RESULTS: Tricuspid (TAV), bicuspid (BAV) and unicuspid (UAV) aortic valves were observed in 64.5%, 31.9% and 3.0% of all patients respectively. A decreased number of cusps was associated with increasing predilection for male gender (83.9%, 73.4%, 59.2% for UAV, BAV, TAV respectively), a younger patient age at surgery (41.6 (14.3), 61.3 (12.8), 67.5 (12.9) years), and an increased occurrence of pathological changes in the cusps, including calcification of both the cusp and the base, ossification and ulceration. UAV and BAV were also associated with increasing replacement of the ascending aorta due to dilatation and aneurysm formation (54.8, 38.8%, 16.6%). The incidence of infective endocarditis and rheumatic heart disease was 3.8% and 11.2% of all excised valves respectively. CONCLUSION: UAV and BAV were increasingly likely to affect men, fail at an earlier age, and show an increasing incidence of pathological changes in the cusps and ascending aorta than TAV. These results suggest that TAV, BAV and UAV may represent a phenotypic continuum of a similar disease process.

Matrix metalloproteinases: a therapeutic target in cardiovascular disease.

Cardiovascular disease is the leading cause of death in Western society. Extracellular matrix turnover is important in many cardiovascular pathologies, such as arterial remodeling, plaque rupture, restenosis, aneurysm formation and heart failure. Matrix metalloproteinases (MMPs) belong to a group of zinc and calcium dependent proteases and cause breakdown of the extracellular matrix. MMP inhibitors have been developed and tested for their effect on the outcome of oncological disease [1]. Recent preclinical research revealed that these MMP inhibitors could also have great potential in the field of cardiovascular disease. This preclinical research has encouraged investigators to design and start the first clinical studies with cardiovascular endpoints. In the present paper, the various aspects of MMP participation in cardiovascular disease will be summarized. Preclinical animal studies that demonstrated the effect and potential of applicable MMP inhibitors on different cardiovascular disease entities will be discussed. We will specifically focus on the role of MMPs and the potential of their inhibitors in de novo atherosclerotic plaque destabilization, arterial remodeling, restenosis after ballon angioplasty and stenting, aneurysm formation and heart failure. We conclude that MMP inhibitors are likely to be useful in the development of pharmacological approaches to reduce cardiovascular death, considering the positive outcomes after usage of MMP inhibitors in restenosis and arterial remodeling.

Administration of exogenous endothelin-1 following vascular balloon injury: early and late effects on intimal hyperplasia.

Administration of exogenous endothelin-1 (ET-1) has been shown to stimulate neointimal hyperplasia following arterial balloon angioplasty (BA). However, the specific effects of ET-1 on the cellular and extracellular matrix response of the vessel wall after balloon injury and the persistence of these ET-1 effects have not been studied. The objectives of this study were to determine the acute (1 week) and long term (10 weeks) effects of administering exogenous ET-1 after arterial BA on neointimal hyperplasia, collagen synthesis and content, cellular proliferation, and ET(A) and ET(B) receptor expression. Thirty-one rabbits were randomized to receive subcutaneous ET-1 (500 pmol/kg/day for 1 week) or placebo time-release pellets and sacrificed at either 1 or 10 weeks after BA. At 1 week, there was a significant two-fold increase in intimal cross-sectional area (CSA) in ET-1 treated animals compared with placebo. ET-1 treated animals showed significant increases in collagen synthesis (ten-fold) and collagen content (three-fold) compared to placebo treated animals. ET-1 treated animals also had a significant increase (two-fold) in proliferation rates. In addition, ET(A) and ET(B) receptor expression were significantly upregulated in ET-1 treated animals. By 10 weeks these stimulatory effects on intimal CSA and collagen content were no longer evident with a 'catch up' phenomenon observed in the placebo treated animals. Similarly, ET(A) and ET(B) mRNA levels had declined significantly in both groups. Therefore, exogenous ET-1 acutely stimulates extracellular and cellular processes including increased expression of ET(A) and ET(B) receptors contributing to intimal hyperplasia. However, these effects are transient and not maintained long term after withdrawal of exogenous ET-1 stimulation.

Arterial elastase activity after balloon angioplasty and effects of elafin, an elastase inhibitor.

Increased proteolytic activity may be a factor in intimal hyperplasia after balloon angioplasty (BA). The objectives of this study were to assess elastase activity after BA in a rabbit arterial double-injury model and the effects of elastase inhibition. Elastase activity increased immediately after BA, reached an 8-fold peak at 1 week, and declined to baseline levels by 4 weeks. Elastin zymography showed that the elastase activity was associated predominantly with a molecular mass of 25 kDa. Elastase activity was significantly inhibited in vitro by elafin and phenylmethylsulfonyl fluoride, selective inhibitors of serine elastases. A second group of animals was transfected after BA with a plasmid containing the cDNA for either elafin or a control (chloramphenicol acetyltransferase, CAT) construct by using a hemagglutinating virus of Japan-liposome transfection technique. Arterial segments were obtained at 48 hours, 1 week, and 4 weeks to assess transgene expression, arterial wall elastase activity, and intimal cross-sectional area, respectively. Elafin transgene expression was evident at 48 hours and resulted in a significant (80%) inhibition of elastase activity compared with chloramphenicol acetyltransferase-transfected arteries. There was a 43% reduction in intimal cross-sectional area in elafin-transfected arteries (0.28+/-0.22 versus 0.16+/-0.07 mm(2) for CAT-transfected versus elafin-transfected arteries, respectively; P<0.05). These data suggest that an early increase in serine elastase activity after BA contributes to intimal hyperplasia. Serine elastase inhibition may be a potential therapeutic approach to inhibit intimal hyperplasia.

Bleeding risks with abciximab after full-dose thrombolysis in rescue or urgent angioplasty for acute myocardial infarction.

BACKGROUND: The bleeding risk associated with platelet glycoprotein IIb/IIIa inhibition in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) after full-dose thrombolysis for acute myocardial infarction (AMI) is unclear. We examined the risk and predictors of bleeding complications in patients with AMI who received abciximab during rescue or urgent PTCA after full-dose thrombolytic therapy. METHODS: A multicenter retrospective cohort of 147 consecutive patients who underwent PTCA within 48 hours after full-dose thrombolysis for AMI was studied. Bleeding events (major, minor, nuisance) from the onset of AMI to discharge were compared between those who received abciximab (n = 57) and those who did not (n = 90). RESULTS: Baseline clinical characteristics were similar between the two groups. Despite lower doses of procedural heparin, the incidence of non-coronary artery bypass graft-related major and minor bleeding was higher in the abciximab group than in controls (63% vs 39%, P =.004). Although the risk of major bleeding was 4-fold with abciximab (12% vs 3%, P =.04), only one intracranial and one fatal bleeding event occurred. Multivariable regression identified abciximab therapy as the most powerful independent predictor of combined major and minor bleeding, with a hazard risk ratio of 1.9 (P =.04). CONCLUSIONS: In the setting of rescue or urgent PTCA within 48 hours after full-dose thrombolytic therapy after AMI, major and particularly minor bleeding were frequently encountered. The adjunctive use of abciximab increased these bleeding risks by approximately 2-fold.

Pharmacological treatment for prevention of restenosis.

Coronary artery disease (CAD) is the leading cause of mortality and morbidity among adults in the Western world. Coronary artery bypass grafting and percutaneous coronary interventions (PCI) have gained widespread acceptance for the treatment of symptomatic CAD. There has been an explosive growth worldwide in the utilisation of PCI, such as balloon angioplasty and stenting, which now accounts for over 50% of coronary revascularisation. Despite the popularity of PCI, the problem of recurrent narrowing of the dilated artery (restenosis) continues to vex investigators. In recent years, significant advances have occurred in the understanding of restenosis. Two processes seem to contribute to restenosis: remodelling (vessel size changes) and intimal hyperplasia (vascular smooth muscle cell [VSMC] proliferation and extracellular matrix [ECM] deposition). Despite considerable efforts, pharmacological approaches to decrease restenosis have been largely unsuccessful and the only currently applied modality to reduce the restenosis rate is stenting. However, stenting only prevents remodelling and does not inhibit intimal hyperplasia. Several potential targets for inhibiting restenosis are currently under investigation including platelet activation, the coagulation cascade, VSMC proliferation and migration, and ECM synthesis. In addition, new approaches for local drug therapy, such as drug eluting stents, are currently being evaluated in preclinical and clinical studies. In this article, we critically review the current status of drugs that are being evaluated for restenosis at various stages of development (in vitro, preclinical animal models and human trials).

Evaluation of the role of abciximab (Reopro) as a rescue agent during percutaneous coronary interventions: in-hospital and six-month outcomes.

Abciximab is effective for the prevention of complications when administered prior to percutaneous coronary intervention (PCI). The efficacy and safety of abciximab as an unplanned or rescue agent for complications of PCI is unknown. Rescue versus planned use was compared in 186 consecutive patients. Primary or rescue PCI for acute myocardial infarction (MI) and shock were excluded. Rescue abciximab use was undertaken in 101 patients (54.3%) and planned abciximab was used in 85 (45.7%). The rescue abciximab patients had a lower incidence of previous MI, preprocedural thrombus, multivessel, and vein graft intervention. In-hospital endpoints in the rescue versus planned abciximab patients were death (1.0% vs. 1. 2%, P = 1.0), Q-wave MI (2.0% vs. 2.4%, P = 1.0), any MI (14.9% vs. 9.4%, P = 0.3), target vessel revascularization (TVR; 0% vs. 1.2%, P = 1.0), and composite (15.8% vs. 10.6%, P = 0.3). At 6 months, events were death (4.0% vs. 2.3%, P = 0.69), MI (14.9% vs. 9.4%, P = 0.26), TVR (20.8% vs. 4.7%, P = 0.001), and composite (30.7% vs. 15. 3%, P = 0.01). In-hospital complications between the rescue and planned abciximab patients of major bleed (1.0% vs. 1.8%, P = NS), stroke (0% vs. 1.8%, P = NS), and thrombocytopenia (3.0% vs. 1.8%, P = NS) were similar. There was a significantly higher procedural time (99.6 min vs. 86.1 min, P = 0.02), contrast volume (278.8 ml vs. 223. 5 ml, P = 0.04), and heparin use (8984 u vs. 6003 u, P = 0.0006) in the rescue group. In this nonrandomized comparison, rescue abciximab allowed for the safe discharge from hospital in the majority of patients. However, during a 6-month follow-up, more patients treated with rescue abciximab required TVR with either repeat PCI or CABG. Further studies are warranted to evaluate the overall strategy of rescue abciximab use in PCI.

Homocysteine, lipoprotein(a), and restenosis after percutaneous transluminal coronary angioplasty: a prospective study.

BACKGROUND: Restenosis complicates 30% to 40% of angioplasty procedures and may be unrelated to traditional coronary risk factors. Homocysteine, lipoprotein(a), and methylenetetrahydrofolate reductase (MTHFR 677T) (a genetic determinant of plasma homocysteine concentrations) are novel risk factors for coronary artery disease. Their roles in restenosis are unclear, and the potential synergism between homocysteine and lipoprotein(a) has not previously been studied. The objective of this study was to determine the relations among homocysteine, lipoprotein (a), MTHFR 677T, and restenosis after percutaneous transluminal coronary angioplasty. METHODS: This prospective study enrolled patients with successful elective percutaneous transluminal coronary angioplasty or stenting of a single, de novo, native coronary lesion. Fasting blood was drawn the morning of the procedure for homocysteine, lipoprotein(a), and MTHFR 677T. Follow-up angiography was performed 6 months after the procedure or earlier if clinically indicated. All cineangiograms were analyzed quantitatively. RESULTS: A total of 144 (92%) of 156 eligible patients underwent follow-up coronary angiography. The overall angiographic restenosis rate (residual stenosis >50%) was 31%. Mean homocysteine concentration was 10.1 +/- 3.7 micromol/L. Plasma homocysteine concentrations were not significantly different in patients with or without angiographic restenosis (9.6 +/- 3.3 vs 10.3 +/- 3.8 micromol/L; P =.31). Mean lipoprotein(a) concentration was 21.2 +/- 20.1 mg/dL. Plasma lipoprotein(a) concentrations were not significantly different in patients with or without restenosis (21.9 +/- 21.8 vs 20.9 +/- 19.5 mg/dL). Homozygosity for MTHFR 677T was present in 6.5% and was not associated with increased restenosis. No interaction between homocysteine and lipoprotein(a) was detected. CONCLUSIONS: Homocysteine, lipoprotein(a), and MTHFR 677T are not associated with restenosis after percutaneous transluminal coronary angioplasty.

Plasma urokinase antigen and plasminogen activator inhibitor-1 antigen levels predict angiographic coronary restenosis.

BACKGROUND: The fibrinolytic system is intimately involved in several processes that contribute to restenosis, including clot dissolution, cell migration, and tissue remodeling. However, the role of the individual activators (urokinase [uPA] and tissue plasminogen [tPA] activators) and inhibitors (plasminogen activator inhibitor [PAI-1]) of the fibrinolytic system in maintaining patency after coronary artery angioplasty and stenting is unclear. METHODS AND RESULTS: We prospectively studied 159 patients with stable angina who underwent successful elective angioplasty (n=110) or stenting (n=49) of de novo native coronary artery lesions. Plasma samples were drawn at baseline (before angioplasty) and serially after angioplasty (immediately afterward and 6 hours, 24 hours, 3 days, 7 days, 1 month, 3 months, and 6 months afterward). Antigen and activity assays were performed for uPA, tPA, and PAI-1. Follow-up quantitative coronary angiography was performed in 92% of eligible patients. The overall angiographic restenosis rate (diameter stenosis >50%) was 31% (37% in PTCA patients, 17% in stented patients). At all time periods, including baseline, uPA antigen levels were significantly higher and PAI-1 antigen levels were significantly lower in patients with restenosis. Restenosis rates for patients in the upper tertile of baseline uPA antigen levels were 2-fold higher than for those in the lower 2 tertiles (46% versus 24% and 22%, respectively; P<0.004). In a stepwise regression multivariate analysis, obstruction diameter after the procedure and uPA antigen were significant predictors of follow-up diameter stenosis. CONCLUSIONS: Plasma uPA antigen levels and PAI-1 antigen levels identify patients at increased risk for restenosis after percutaneous coronary revascularization.

Inhibitory mechanisms by which suramin may attenuate neointimal formation after balloon angioplasty.

Restenotic neointimal lesions, a major limitation to coronary angioplasty, develop in response to diverse signals and depend on three properties of activated arterial smooth muscle cells (SMCs): proliferation, migration, and abnormal production of extracellular matrix. Most of the pharmacologic approaches targeting specific pathogenic factors facilitating development of restenosis have failed in clinical trials. Our results indicate that the polysulfonated naphthylurea suramin, a "non-specific drug" that interferes with multiple cellular proteins, inhibits neointimal formation in rabbit iliac arteries after balloon-catheter injury administered throughout the critical period of several weeks after the procedure. In vitro studies aimed at dissecting the mechanism(s) underlying the suramin-dependent effect demonstrated that, in addition to an inhibitory effect on SMC proliferation, suramin inhibited fibronectin and elastin deposition and the migration of SMCs through elastin membranes and into scratch gaps of monolayer cultures. We also demonstrated that suramin causes cell-surface accumulation of the elastin binding protein, a receptor that not only anchors SMCs to the extracellular matrix, but also inhibits SMC response to interleukin-1beta (IL-1beta). We conclude that suramin acts as a multitarget inhibitor of SMC activation and has a therapeutic potential as an agent that may attenuate arterial restenosis after angioplasty.

Combined use of Orgaran and Reopro during coronary angioplasty in patients unable to receive heparin.

Orgaran, a heparinoid, has been used successfully in patients with heparin-induced thrombocytopenia. We report three cases in which Orgaran was combined with the glycoprotein IIbIIa receptor antagonist Reopro during coronary angioplasty. Orgaran was given as a single intravenous bolus of 1500 anti-factor Xa units. No ischemic or hemorrhagic complications occurred during or following the procedure.

Failed coronary stent deployment.

BACKGROUND: Coronary stent deployment failure may be more common in clinical practice than generally appreciated. The incidence of failed deployment in routine clinical practice and the clinical sequelae have not been described. This study sought to determine the incidence and consequences of failed coronary stent deployment and to identify clinical and angiographic characteristics associated with deployment failure. METHODS AND RESULTS: A series of 1303 consecutive procedures involving attempted coronary stenting were reviewed retrospectively. Failed stent deployment was defined as failure of the stent to be either delivered to or adequately deployed at the target lesion site. Clinical records and angiograms were reviewed and qualitative coronary angiography was performed for all cases of failed deployment. Deployment was unsuccessful in 108 (8.3%) cases involving 134 stents. Stenting was attempted as a primary procedure in 40%, as bailout in 18%, and for suboptimal angioplasty in 43% of cases. In 87% of cases, attempts were made to withdraw the stent from the coronary artery. Stent retrieval was successful in 45%, peripheral embolization occurred in 38% of patients, and in 4% the stent dislodged in the left main artery. In 35% of cases, additional stent(s) were successfully deployed. Deployment failure was associated with an overall in-hospital adverse outcome in 19% of patients, including 16% urgent coronary artery bypass grafting, 5% nonfatal myocardial infarction, and 3 in-hospital deaths. At 6-month follow-up, 39% of patients had had at least 1 adverse clinical outcome of death, myocardial infarction, or repeat target lesion revascularization. CONCLUSIONS: Failure to deploy stents is a serious and relatively common problem that is associated with significant morbidity and mortality rates. Improved deployment strategies, including new stent designs, are required to improve procedural outcomes.

The extracellular matrix in balloon arterial injury: a novel target for restenosis prevention.

The role of the extracellular matrix (ECM) in the pathobiology of restenosis has not been fully appreciated. Recent discoveries have shown the ECM to be a complex, heterogeneous structure whose components are dynamically altered in response to vascular injury. This report reviews the structure and function of vascular ECM and the importance of the matrix in modulating the vascular response to arterial injury such as balloon angioplasty and atherosclerosis.

In vivo collagen turnover following experimental balloon angioplasty injury and the role of matrix metalloproteinases.

Extracellular matrix formation is the major component of the restenosis lesion that develops after balloon angioplasty. Although ex vivo studies have shown that the synthesis of collagen is stimulated early after balloon angioplasty, there is a delay in accumulation in the vessel wall. The objectives of this study were to assess collagen turnover and its possible regulation by matrix metalloproteinases (MMPs) in a double-injury iliac artery rabbit model of restenosis. Rabbits were killed at four time points (immediately and at 1, 4, and 12 weeks) after balloon angioplasty. In vivo collagen synthesis and collagen degradation were measured after a 24-hour incubation with [14C]proline. Arterial extracts were also run on gelatin zymograms to determine MMP (gelatinase) activity. Collagen turnover studies were repeated in a group of 1-week postangioplasty rabbits that were treated with daily subcutaneous injections of either a nonspecific MMP inhibitor, GM6001 (100 mg/kg per day), or placebo. Collagen synthesis and degradation showed similar temporal profiles, with significant increases in the balloon-injured iliac arteries compared with control nondilated contralateral iliac arteries immediately after angioplasty and at 1 and 4 weeks. Peak collagen synthesis and degradation occurred at 1 week and were increased (approximately four and three times control values, respectively). Gelatin zymography was consistent with the biochemical data by showing an increase of a 72-kD gelatinase (MMP-2) in the balloon-injured side immediately after the second injury, peaking at 1 week, and still detectable at 4 and 12 weeks (although at lower levels). In balloon-injured arteries, the MMP inhibitor reduced both collagen synthesis and degradation. Overall, at 1 week after balloon angioplasty, GM6001 resulted in a 33% reduction in collagen content in balloon-injured arteries compared with placebo (750 +/- 143 to 500 +/- 78 micrograms hydroxyproline per segment, P < .004), which was associated with a nonsignificant 25% reduction in intimal area. Our data suggest that degradation of newly synthesized collagen is an important mechanism regulating collagen accumulation and that MMPs have an integral role in collagen turnover after balloon angioplasty.

Absence of increased in-hospital complications with reused balloon catheters.

A reanalysis of data from a prospective Canadian study suggests that catheter reuse is not associated with an increased rate of in-hospital complications. However, these results should be replicated in clinical trials before catheter reuse becomes routinely established.

Excimer laser angioplasty vs. balloon angioplasty in saphenous vein bypass grafts: quantitative angiographic comparison of matched lesions.

Technologies which ablate or debulk tissue may result in better angiographic outcomes by altering the elastic properties of the vessel wall. Accordingly, the procedural outcomes of 88 vein graft lesions treated by either excimer laser angioplasty with adjunct balloon angioplasty (PELCA + PTCA, n = 44) (Spectranetics CVX-300, 1.4-, 1.7-, or 2.0-MM catheters) or balloon angioplasty alone (PTCA, n = 44) were analyzed by quantitative angiography (Cardiac Measurement System). Lesions were individually matched for vessel position, reference diameter (RD), and minimal luminal diameter (MLD). Matching was deemed adequate as the preprocedure MLD (PELCA + PTCA, 1.14 +/- 0.48 mm; PTCA, 1.20 +/- 0.47 mm) and RD (PELCA + PTCA, 3.23 +/- 0.56 mm; PTCA, 3.25 +/- 0.57 mm) were not significantly different. There were also no significant differences between PELCA + PTCA- and PTCA-treated lesions with respect to patient age, graft age, lesion length, symmetry, and plaque area. Balloon diameter at maximal inflation was 2.77 +/- 0.55 mm (PELCA + PTCA group) and 2.84 +/- 0.59 mm (PTCA group), P = NS. Final MLD postprocedure was 2.17 +/- 0.54 mm and 2.19 +/- 0.55 mm for PELCA + PTCA- and PTCA-treated lesions (P = NS), respectively. Vessel stretch [(balloon diameter - MLD pre)/RD], elastic recoil [(balloon diameter - MLD post)/RD], and acute gain [(MLD post - MLD pre)/RD] were calculated and normalized for vessel size (RD). Vessel stretch (PELCA + PTCA, 0.60 +/- 0.22; PTCA, 0.59 +/- 0.24; P = NS), elastic recoil (PELCA + PTCA, 0.28 +/- 0.18; PTCA, 0.26 +/- 0.16), and acute gain (PELCA + PTCA, 0.34 +/- 0.24; PTCA, 0.31 +/- 0.23; P = NS) were not significantly different between the two treatment groups. In a matched population of successfully treated vein graft lesions, PELCA + PTCA did not reduce elastic recoil or improve immediate angiographic outcome, as compared with PTCA alone.

Effect of intracoronary saline infusion on dissection during excimer laser coronary angioplasty: a randomized trial. The Percutaneous Excimer Laser Coronary Angioplasty (PELCA) Investigators.

OBJECTIVES: We sought to evaluate whether intracoronary saline infusion during excimer laser coronary angioplasty decreases the incidence of significant laser-induced coronary artery dissections. BACKGROUND: Despite procedural success rates > 90%, coronary artery dissections occur in 17% to 27% of excimer laser coronary angioplasty procedures. Excimer laser irradiation of blood results in vapor bubble formation and acoustomechanical trauma to the vessel wall. Saline infusion into a coronary artery may minimize blood irradiation and consequent arterial wall damage. METHODS: In this prospective, randomized, controlled study, consecutive patients undergoing excimer laser coronary angioplasty were randomly assigned to conventional laser irradiation in a blood medium or to laser irradiation with blood displacement by intracoronary saline infusion. In the patients randomized to intracoronary saline infusion, prewarmed normal saline was injected through the coronary artery guide catheter at a rate of 1 to 2 ml/s using a power injector. The incidence and severity of dissection after excimer laser ablation were evaluated in a core laboratory by angiographers with no knowledge of treatment assignment. The severity of coronary artery dissection was rated on an ordinal scale of 1 to 5. Dissections of grade 2 or higher were considered significant. RESULTS: The mean (+/- SE) dissection grade after laser angioplasty in patients treated with intracoronary saline infusion was 0.43 +/- 0.13 compared with 0.91 +/- 0.26 in patients undergoing laser angioplasty in a blood medium. The incidence of significant dissection was 7% in saline-treated patients compared with 24% in conventionally treated patients (p < 0.05). No significant complications were associated with saline infusion. CONCLUSIONS: Intracoronary saline infusion should be incorporated into all excimer laser coronary angioplasty procedures.

Early and late quantitative angiographic results of vein graft lesions treated by excimer laser with adjunctive balloon angioplasty.

BACKGROUND: Percutaneous excimer laser coronary angioplasty (PELCA) has been approved for treatment of diseased saphenous vein bypass grafts. However, detailed and complete quantitative angiographic analysis of immediate procedural and late follow-up results has not been performed. METHODS AND RESULTS: PELCA using the CVX-300 excimer laser system was performed in 125 bypass lesions (mean graft age, 96 +/- 53 months; range, 2 to 240 months) in 106 consecutive patients at eight centers. Quantitative analyses of the procedural and follow-up angiograms were done with the Cardiac Measurement System. Stand-alone PELCA was done in 21 lesions (17%). Lesions were located at the ostium (20%), body (67%), or distal anastomosis (13%). The graft reference diameter was 3.26 +/- 0.79 mm (mean +/- SD). Minimal lumen diameter increased from 1.09 +/- 0.52 mm before treatment to 1.61 +/- 0.69 mm after laser and 2.18 +/- 0.63 mm after adjunctive balloon dilation (P < .001) but had declined at follow-up to 1.40 +/- 1.17 mm. Dissections were evident in 45% of lesions after laser treatment (types A and B, 27%; types C through F, 18%), including 7% occlusions. Angiographic success (< or = 50% diameter stenosis [% DS]) was 54% after laser and 91% after adjunctive PTCA, with an overall clinical success rate of 89%. In-hospital complications were death, 0.9%; myocardial infarction (Q-wave and non-Q-wave), 4.5%; and bypass surgery, 0.9%. Independent predictors of % DS after laser were reference diameter, lesion length, and minimal lumen diameter before laser. At angiographic follow-up in 83% of eligible patients, the restenosis rate per lesion (DS > 50%) was 52%, including 23 occlusions (24%). The only independent predictor of increased % DS at follow-up was lesion symmetry. Logistic regression indicated that smaller reference diameter was an independent predictor of late occlusion. Overall 1-year mortality was 8.6%. Actuarial event-free survival (freedom from death, myocardial infarction, bypass surgery, or target vessel percutaneous transluminal coronary angioplasty) was 48.2% at 1 year. CONCLUSIONS: Excimer laser angioplasty with adjunctive balloon angioplasty can be safely and successfully performed in diseased, old saphenous vein bypass graft lesions considered at high risk for reintervention. The extent of laser ablation remains limited by the diameter and effectiveness of the catheters. Late restenosis and, in particular, total occlusion mitigate the early benefits of the procedure. Other approaches such as the routine use of additional anticoagulation (eg, warfarin) should be considered to reduce the risk of late occlusions and restenosis after laser angioplasty of bypass grafts.