Plasma MMP-9 and TIMP-1 levels on ICU admission are associated with 30-day survival.

BACKGROUND: Matrix metalloproteinases (MMPs) are involved in systemic inflammatory responses and organ failure. The aim of this study was to evaluate early circulating plasma levels of MMP­2, MMP­9 and their inhibitors TIMP­1 and TIMP­2 and their prognostic significance in critically ill patients on admission to the intensive care unit (ICU). METHODS: In a single center prospective study 120 consecutive patients (72.5% male, mean age 66.8 ± 13.3 years, mean simplified acute physiology score [SAPS II] score 52.9 ± 21.9) were enrolled on transfer to the ICU of a cardiology department. The most common underlying conditions were cardiac diseases (n = 42.5%), respiratory failure (n = 10.8%) and sepsis (n = 6.7%). Blood samples were taken within 12 h of ICU admission. The MMP­2, MMP­9, TIMP­1 and TIMP­2 levels in plasma were evaluated in terms of 30-day survival, underlying condition and clinical score. RESULTS: On ICU admission 30-day survivors had significantly lower plasma MMP­9 (odds ratio, OR 1.67 per 1 SD; 95% confidence interval, CI 1.10-2.53; p = 0.016) and TIMP­1 (OR 2.15 per 1 SD; 95% CI 1.27-3.64; p = 0.004) levels than non-survivors; furthermore, MMP­9 and TIMP­1 correlated well with SAPS II (both p < 0.01). In patients with underlying cardiac diseases, MMP­9 (p = 0.002) and TIMP­1 (p = 0.01) were independent predictors of survival (Cox regression). No significant correlation was found between MMP­2 and TIMP­2 levels, MMP/TIMP ratios and 30-day mortality. CONCLUSION: The MMP­9 and TIMP­1 levels are significantly elevated in acute critical care settings with increased short-term mortality risk, especially in patients with underlying heart disease. These findings support the value of MMPs and TIMPs as prognostic markers and potential therapeutic targets in conditions leading to systemic inflammation and acute organ failure.

Olive phenolics increase glutathione levels in healthy volunteers.

Several in vitro and in vivo studies have shown that olive phenols exert potent biological activities including, but not limited to, antioxidant actions. These activities are shared by phenols found in olives, olive oil, and olive mill wastewater (OMWW). The aim of this study was to investigate whether a commercially available OMWW preparation could influence some parameters of oxidative status in healthy human volunteers. Ninety-eight healthy subjects with normal body weight were recruited, and 5 mL of blood was drawn from their antecubital vein after an overnight fast of at least 12 h. After this, subjects were asked to ingest 2 mL of a commercially available OMWW preparation. Another 5 mL of blood was drawn 1 h after ingestion of the preparation. Plasma antioxidant capacity and total and reduced glutathione were measured. No difference in plasma antioxidant capacity was observed between baseline and 1 h after the ingestion of the extract. Conversely, a significant increase in total plasma glutathione concentration was measured. This increase involved both the reduced and oxidized forms of glutathione; hence, their ratio was unaffected by the treatment. The observed effects of OMWW on glutathione levels might be governed by the antioxidant response element (ARE)-mediated increase in phase II enzyme expression, including that of gamma-glutamylcysteine ligase and glutathione synthetase. Future studies on groups of individuals who may benefit from an increase in their glutathione levels, for example, the elderly, will further elucidate the biological activities of this formulation.

Impact of low high-density lipoproteins on in-hospital events and one-year clinical outcomes in patients with non-ST-elevation myocardial infarction acute coronary syndrome treated with drug-eluting stent implantation.

High-density lipoprotein (HDL) cholesterol has protective cardiovascular effects. We investigated the effect of baseline HDL cholesterol on the outcomes of patients who underwent drug-eluting stent implantation for acute coronary syndrome. Since March 2003, 1,032 consecutive patients were, according to their baseline HDL cholesterol level, included in a low HDL cholesterol group (n = 550, <40 mg/dl in men, <45 mg/dl in women, mean 32 +/- 7) or a high HDL cholesterol group (n = 482, >40 mg/dl in men, >45 mg/dl in women, mean 55 +/- 19). End points were death, Q-wave myocardial infarction, target lesion revascularization, and a composite of major adverse cardiac events at 30 days and 1 year. We assessed the relation between HDL cholesterol and end points. Patients with low HDL cholesterol more often had diabetes, a higher body mass index, higher triglyceride levels, and lower total cholesterol levels. Low-density lipoprotein cholesterol and statin treatment (98% in the 2 groups) were comparable. Incidences of mortality and major adverse cardiac events at 30 days were higher in the low than in the high HDL cholesterol group (p <0.001 and p = 0.002, respectively; chi-square analysis). At 1 year, more deaths occurred in the low HDL cholesterol group (p <0.001; chi-square analysis), as did major adverse cardiac events (p <0.001; chi-square analysis). Multivariate analysis showed low HDL cholesterol at baseline (hazard ratio 2.61, 95% confidence interval 1.33 to 5.12) to be a key predictor of major adverse cardiac events and death (hazard ratio 3.33, 95% confidence interval 1.15 to 10.0) at 1 year. In conclusion, regardless of baseline low-density lipoprotein cholesterol levels and statin therapy, additional strategies to increase HDL cholesterol should be evaluated in patients with acute coronary syndrome.

Switching from Enoxaparin to Bivalirudin in Patients with Acute Coronary Syndromes without ST-segment Elevation who Undergo Percutaneous Coronary Intervention. Results from SWITCH--a multicenter clinical trial.

BACKGROUND: Enoxaparin is an established therapy for the treatment of patients with acute coronary syndrome (ACS), and bivalirudin is commonly used as the antithrombotic agent during percutaneous coronary intervention (PCI). This study was designed to examine the safety of switching from enoxaparin to bivalirudin in these patients. METHODS: The Switching from Enoxaparin to Bivalirudin in Patients with Acute Coronary Syndromes without ST-segment Elevation Undergoing Percutaneous Coronary Intervention (SWITCH) trial was a prospective, open-label, multicenter study including 91 patients who presented with an ACS without ST-segment elevation, and who had received greater than or equal to 1 dose of enoxaparin (1 mg/kg SC) within the 12 hours prior to PCI. Patients were enrolled into 3 time categories: Group 1: 0-4; Group 2: 4-8; and Group 3: 8-12 hours from last enoxaparin dose to PCI. The primary endpoint of the study was major bleeding complications. RESULTS: Baseline characteristics and average number of enoxaparin injections prior to PCI were similar in all 91 patients and among the groups. There was no occurrence of death, Q-wave myocardial infarction (MI), or acute revascularization in any group and no incidence of intracranial or retroperitoneal bleeding. The overall rate of major bleeding (7.7%) was comparable among groups (p = 0.39), as was the incidence of periprocedural non-Q-wave MI (overall 12%; p = 0.58), irrespective of the time interval between enoxaparin and bivalirudin administration. CONCLUSIONS: Switching from enoxaparin to bivalirudin for patients with ACS undergoing PCI appears to be clinically safe without increased risk of major bleeding complications, regardless of the time of enoxaparin administration, and is safe enough to warrant testing it in larger numbers.

Endovascular brachytherapy for prophylaxis of restenosis after femoropopliteal angioplasty: five-year follow-up--prospective randomized study.

PURPOSE: To report the 5-year results from the prospective randomized Vienna-2 trial, which was designed to evaluate the safety and effectiveness of adjunctive endovascular brachytherapy (EBT) compared with no further treatment after successful revascularization in patients with long-segment femoropopliteal lesions. MATERIALS AND METHODS: Each patient gave written informed consent to participate in the study, which was approved by the hospital's ethics committee. One hundred two patients (men, 53.9%; mean age, 72.1 years +/- 8.7 [standard deviation]; lesion length, 8.1 cm +/- 4.9) underwent percutaneous transluminal angioplasty (PTA) without further stent implantation. Patients were then assigned to either receive EBT (n = 51) by using an iridium 192 source, with a prescribed dose of 12 Gy at 3 mm from the source axis, or no further treatment (n = 51). Radiation was delivered without a centering catheter. Data were analyzed by using a Student t test for continuous values and a chi(2) test to compare categorical values. A Cox proportional hazards regression analysis was performed to evaluate predictors of recurrence at follow-up. RESULTS: After 6 months, the restenosis rate for the 102 patients with completed 5-year follow-up was significantly reduced for the PTA plus EBT group versus the PTA alone group (29.4% vs 56.9%, P < .05). During follow-up we observed a late catch-up phenomenon, and after 5 years the recurrence rate was comparable in both groups (72.5% vs 72.5%, P > .99). Time to recurrence, however, was significantly delayed in the PTA plus EBT group (17.5 months +/- 14.7 vs 7.4 months +/- 6.8 for the PTA alone group, P < .05). CONCLUSION: At 5-year follow-up, PTA followed by gamma radiation EBT with a dose of 12 Gy resulted in a delay but not an inhibition of restenosis when compared with that of PTA alone.

Role of prophylactic intra-aortic balloon pump in high-risk patients undergoing percutaneous coronary intervention.

Intra-aortic balloon pump (IABP) has been shown to support patients who are at high risk for percutaneous coronary interventions (PCIs) or becoming hemodynamically unstable during PCI, but the longer term outcomes of these strategies are unknown. This study investigated the outcomes of high-risk patients who received a prophylactic IABP (P-IABP) versus patients who required rescue IABP (R-IABP) because of intraprocedural complications. Clinical outcomes of 68 consecutive patients (69 procedures) who underwent high-risk PCI with P-IABP support were compared with those of 46 patients who required R-IABP. Patients who presented with cardiogenic shock or acute ST-segment elevation myocardial infarction, and those who were on mechanical ventilators were excluded. Clinical baseline characteristics were similar between groups except for more diabetics and patients with hypercholesterolemia in the P-IABP group. The procedural success was higher in the P-IABP group, with lower in-hospital mortality and major complications, than in the R-IABP group. At 6 months, the mortality and major adverse cardiac event rates were lower in the P-IABP group (8% vs 29%, p < 0.01, and 12% vs 32%, p = 0.02, respectively). Multivariate analysis showed that prophylactic insertion of an IABP is the only independent predictor of survival at 6 months. The incidence of vascular complications was low and comparable except for more major bleeding (15% vs 3%, p = 0.03) in the R-IABP group. In conclusion, patients who undergo high-risk PCI and then receive P-IABP support have favorable outcomes compared with those who require R-IABP for intraprocedural complications. Therefore, in high-risk patients undergoing PCI, liberal use of a P-IABP should be considered.

Procedural results and outcomes after extensive stent coverage with drug-eluting stent implantation in single coronary lesions.

Longer stent length has remained associated with the incidence of major adverse cardiac events (MACEs) in the drug-eluting stent (DES) era; therefore, we aimed to determine clinical outcomes after extensive stent coverage with DES implantations in single coronary lesions. We evaluated the data from 99 consecutive patients treated with extensive DES coverage, defined as > or = 50 mm (mean 63.3 +/- 13.2, range 50 to 115), and a concurrent series of 466 patients with < or = 24-mm DES length (mean 18.4 +/- 3.8, range 8 to 24). The periprocedural, 1-, and 6-month outcomes were compared between the 2 groups. The baseline characteristics were mostly comparable between the 2 groups, and procedural and in-hospital outcomes were similar. Although the incidence of death and myocardial infarction at follow-up were comparable, the combined end points of target lesion revascularization plus MACEs at 6 months occurred more often with extensive stent coverage. Multivariate analysis revealed stent length to be the only independent predictor of target lesion revascularization plus MACEs. Patients treated with extensive DES coverage had similar procedural success, major in-hospital complications, and death and myocardial infarction at follow-up, but had more combined adverse events because of an overall higher target lesion revascularization rate.

Sirolimus-eluting stents versus Paclitaxel-eluting stents in the treatment of coronary artery disease in patients with diabetes mellitus.

This study was performed to compare the safety and efficacy of sirolimus-eluting stents (SESs) and paclitaxel-eluting stents (PESs) on the outcomes of diabetic patients. Recent data with drug-eluting stents have shown improved clinical outcomes in diabetic patients. This study compared outcomes between the 2 available drug-eluting stents, SESs and PESs. From the prospective drug-eluting stent registries at the investigators' institution, 1,320 consecutive diabetic patients treated with SESs (n=873, 1,293 lesions) and PESs (n=447, 733 lesions) were identified and their in-hospital and 1- and 6-month clinical outcomes compared. Baseline characteristics showed more men, more patients with previous coronary bypass surgery, and smaller ejection fractions in the PES group and more obese patients in the SES group. Procedural characteristics were similar except for more left anterior descending artery and proximal lesions and the greater use of glycoprotein IIb/IIIa inhibitors in the SES group and more type C lesions, direct stenting, and stents per patient in the PES group. In-hospital complications were similar. Clinical follow-up at 1 month was also similar between the 2 groups, including subacute stent thrombosis. At 6 months, the 2 groups had similar mortality (7% vs 7%), myocardial infarctions (18% vs 21%), target lesion revascularization, target vessel revascularization, major adverse cardiac events (11% vs 12%), and late thrombosis (0.3% vs 0%). Subanalysis of insulin-treated diabetic patients showed no significant differences in outcomes in the 2 groups. No significant differences were found between SESs and PESs on Cox regression analysis for hazard ratios. In conclusion, SESs and PESs are associated with similar efficacy and safety with regard to repeat revascularization rates, major adverse cardiac events, and stent thrombosis up to 6 months for the treatment of coronary artery disease in patients with diabetes mellitus regardless of insulin therapy.

Percutaneous coronary intervention with drug-eluting stents in octogenarians: characteristics, clinical presentation, and outcomes.

OBJECTIVES: We aimed to compare clinical outcomes of octogenarians > or =80 years of age after coronary drug-eluting stent (DES) implantation. BACKGROUND: Although octogenarians constitute a fast-growing portion of cardiovascular patients, they are not adequately represented in current clinical revascularization trials. METHODS: We analyzed the data of 3,166 consecutive patients who underwent percutaneous coronary intervention (PCI) and DES implantation since March 2003. Periprocedural events, 1- and 6-month clinical outcomes were compared between octogenarians (n = 339) and patients <80 years of age (n = 2,827). RESULTS: Baseline characteristics revealed a higher prevalence of females (P < 0.001), Caucasians (P = 0.004), chronic renal failure (P < 0.001), heart failure (P < 0.001), number of diseased vessels (P = 0.009), and lower ejection fraction (P = 0.03) in octogenarians. Patients <80 years showed more positive family history (P < 0.001), hyperlipidemia (P = 0.006), smoking (P < 0.001), and obesity (P < 0.001). Clinical presentation and procedural success were similar in both groups as were death, myocardial infarction (MI), and repeat revascularization in-hospital. At 6 months, restenosis rates were low and comparable. In the subgroup of octogenarians who presented with acute coronary syndrome, mortality (15% vs. 3%, P < 0.001) and Q-wave MI occurred more often. Multivariate analysis revealed age >80 (P = 0.008), cardiogenic shock (P < 0.001), Q-wave MI at presentation (P = 0.003), and length of hospital stay (P = 0.003) to be independent predictors of mortality. CONCLUSIONS: PCI with DES in octogenarians results in a similar reduction of restenosis rates when compared to patients <80 years. Yet in octogenarians who presented with acute coronary syndrome, incidence of mortality and Q-wave MI at 6 months was higher as compared to younger patients.

Clinical outcomes after percutaneous coronary intervention with drug-eluting stents in dialysis patients.

OBJECTIVES: We aimed to compare the clinical outcomes of dialysis versus nondialysis patients after coronary drug-eluting stent (DES) implantation. BACKGROUND: The revascularization of ischemic heart disease in dialysis patients has remained controversial due to consistent exclusion of this population from major trials, especially in the context of percutaneous coronary interventions (PCI) with DES. METHODS: We analyzed the data on 3,442 consecutive patients who underwent PCI and DES implantation since March 2003. Periprocedural events, 1- and 6-month clinical outcomes were then compared between dialysis (n = 72) and nondialysis patients (n = 3,370). RESULTS: Baseline characteristics revealed a higher prevalence of female gender (p = 0.03), African Americans (p < 0.001), hypertension (p < 0.001), diabetes mellitus (p < 0.001), number of diseased vessels (p = 0.04), lower ejection fraction (p < 0.001), and a higher prevalence of acute myocardial infarction (MI) (p = 0.04) in dialysis patients. Nondialysis patients showed more history of smoking (p < 0.001) and obesity (p = 0.02). Procedural success was higher (p = 0.05), while there was a trend toward a lower mortality rate, in the nondialysis group during hospitalization. At 6 months, the restenosis rate was low and comparable, but mortality occurred more often (16% vs. 3.8%; p < 0.001) in dialysis patients. Multivariate analysis revealed cardiogenic shock (p = 0.04) to be an independent predictor of mortality. CONCLUSIONS: PCI with DES in dialysis patients is safe and feasible, with a similar reduction of repeat revascularization when compared with nondialysis patients. There was, however, a higher incidence of mortality in dialysis patients at 6 months, mostly influenced by contributing comorbidities and more severe conditions at presentation.

Comparison of effectiveness and safety of drug-eluting stents versus vascular brachytherapy for saphenous vein graft in-stent restenosis.

We investigated the safety and efficacy of drug-eluting stents (DESs) for the treatment of patients who presented with in-stent restenosis (ISR) of saphenous vein grafts (SVGs) and compared the in-hospital and 6-month clinical outcomes of DESs with those of intravascular brachytherapy and balloon angioplasty alone. Records of 187 patients who presented with ISR of SVGs were analyzed. Of these, 34 consecutive patients were treated with DES implantation, 93 were treated with intravascular brachytherapy (n = 60 with gamma-radiation, n = 33 with beta-radiation), and 60 patients underwent conventional treatment with balloon angioplasty alone. Clinical and angiographic characteristics at baseline were comparable between groups. The DES group had less non-Q-wave myocardial infarction than did the intravascular brachytherapy and balloon angioplasty groups (0%, 20%, and 26%, p = 0.003 and <0.001, respectively). At 6 months, death occurred in 0% of the DES group, 2% of the intravascular brachytherapy group, and 5% of the balloon angioplasty group (p = 0.36 and <0.18, respectively). Target lesion revascularization/major adverse cardiac events were similar in the intravascular brachytherapy and DES groups (12% and 3%, p = 0.13) and significantly decreased compared with patients who were treated with balloon angioplasty alone (55%, p <0.001 for the 2 comparisons). The results of this retrospective analysis suggest that DES implantation is at least as effective and safe as intravascular brachytherapy for the treatment of SVG ISR and that these treatment modalities are superior to balloon angioplasty alone.

Clopidogrel loading dose (300 versus 600 mg) strategies for patients with stable angina pectoris subjected to percutaneous coronary intervention.

We evaluated the effect of high versus low loading doses of clopidogrel in patients with stable angina pectoris who underwent percutaneous coronary intervention (PCI) on periprocedural events, in-hospital complications, and 30-day outcomes. The recommended loading dose of clopidogrel for patients with PCI is currently 300 mg. Recent studies have suggested that 600 mg may decrease periprocedural complications in patients with unstable angina. However, whether this holds for patients with stable angina pectoris is unknown. We reviewed records of 445 patients with stable angina pectoris who underwent PCI and were loaded with 300 mg (n = 126) or 600 mg (n = 319) of clopidogrel immediately before the procedure. Study end points were periprocedural ischemic events, bleeding complications, and a composite of major adverse cardiac events at 30 days. Baseline characteristics and procedural indexes were similar between groups. Major in-hospital complications were recorded in 2 patients in the 600-mg group and in no patient in the 300-mg group (p = 1.00). Postprocedural increase of cardiac enzymes (troponin I, p = 0.91; creatinine kinase-MB, p = 0.395) and major bleeding (0.6% vs 0%, p = 1.00) were comparable, as was 30-day major adverse cardiac events (1.2% vs 0%, p = 0.56). Multivariate analysis did not identify any risk decrease for periprocedural myocardial infarction with 600 mg of clopidogrel (odds ratio 2.68, 95% confidence interval 0.74 to 9.78, p = 0.135). In conclusion, in patients with stable angina pectoris, a 300-mg clopidogrel loading dose, when given immediately before PCI, is sufficient. Although 600 mg was clinically safe, it was not associated with fewer periprocedural events and improved 30-day outcomes compared with 300 mg.

Salivary isoprostanes indicate increased oxidation injury in periodontitis with additional tobacco abuse.

Isoprostanes (IPs) are indicators of in-vivo oxidative stress, and have been successfully used as markers for chronic inflammatory processes. The presence of chronic periodontal disease and cigarette smoking has been individually linked to the development of atherosclerosis, yet data regarding oxidative stress in this context are not available yet. The aim of this study was to evaluate levels of the salivary prostaglandins (PGs) 8-epi-PGF(2alpha), 6-oxo-PGF(1alpha), thromboxane B(2) (TXB(2)) and PGF(2alpha) in association with periodontal disease status with and without additional cigarette smoking. We analyzed saliva samples from 121 adults, (aged 21-73 years, 90 non-smokers, 31 smokers) for levels of 8-epi-PGF(2alpha), 6-oxo-PGF(1alpha), TXB(2) and PGF(2alpha). On the basis of periodontal disease indices the periodontal status of each subject was assessed and outcomes were then correlated with smoking status and laboratory findings. Salivary 8-epi-PGF(2alpha) levels increased with deteriorating plaque index, and were significantly higher (115.5 +/- 23.5 pg/ml) in smoking individuals, when compared to non-smokers (70.2 +/- 20.4 pg/ml, p<0.0001). In addition, smokers showed higher TXB(2) and PGF(2alphas) and lower 6-oxo-PGF(1alpha) levels p<0.0001). Oxidative stress, as reflected by elevated salivary 8-epi-PGF(2alpha) levels, is associated with the extent of periodontal disease and is significantly aggravated by concomitant tobacco abuse. Chronic inflammation and smoking have been individually associated with the development of atherosclerosis. The results of this study indicate that: 1) salivary IPs can reliably assess the degree of oxidative stress, and: 2) smoking and periodontal disease are two modifiable cardiovascular risk factors, able to potentiate each other.

Bivalirudin compared with IIb/IIIa inhibitors in patients with in-stent restenosis undergoing intracoronary brachytherapy.

BACKGROUND: Bivalirudin is replacing heparin in percutaneous coronary interventions (PCIs), including vascular brachytherapy (VBT). The aim of the study was to compare bivalirudin with eptifibatide in patients with in-stent restenosis (ISR) undergoing PCI and VBT. METHODS: One hundred forty-four patients treated with bivalirudin as a single antithrombotic agent were compared with 150 patients treated with eptifibatide. Bivalirudin as a bolus of 0.75 mg/kg followed by 1.75 mg/kg/h infusion until the end of the procedure, and eptifibatide as a double bolus of 180 microg/kg followed by 2 microg/kg/min infusion for 18 h after the procedure were used. The main outcome measures were in-hospital events and 30-day clinical outcomes. RESULTS: Baseline clinical characteristics were similar except that patients in the eptifibatide group were younger (P=.02) and had more saphenous vein graft lesions (P<.001). Patients in the bivalirudin group had a higher number of lesions in the right coronary artery (P<.001) and a higher number of vessels treated (P<.001). Postprocedure creatinine phosphokinase (CPK)-MB levels were significantly lower in the bivalirudin group (P<.03). In-hospital events showed significantly less minor bleeding (P=.01) and a trend toward lower major bleeding and major adverse cardiac events (MACE) in the bivalirudin group (P=.06). Thirty-day outcomes showed a significantly lower incidence of non-Q-wave myocardial infarction (MI) in the bivalirudin group (P=.004). CONCLUSION: Bivalirudin, as a single antithrombotic agent during PCI and VBT, is associated with significantly lower postprocedural CPK-MB elevation, minor bleeding complications, 30-day non-Q-wave MI rates, and a trend toward lower major bleeding and in-hospital MACE when compared with eptifibatide.

Brachytherapy and bivalirudin evaluation study.

BACKGROUND: Bivalirudin is shown to be a competent substitute for heparin in percutaneous coronary intervention (PCI). The safety and efficacy of bivalirudin in patients undergoing PCI and vascular brachytherapy (VBT) are not known. This study aimed to assess the safety and efficacy of bivalirudin as a single antithrombotic agent in patients undergoing PCI and VBT. METHODS: A total of 152 patients enrolled in the Brachytherapy and Bivalirudin Evaluation Study underwent PCI and VBT with either gamma (n = 8) or beta radiation (n = 144). The main outcome measures were in-hospital events and 30-day clinical outcomes. All patients were treated with bivalirudin (0.75 mg/kg bolus and 1.75 mg/kg per hour infusion for beta radiation, 1 mg/kg bolus and 2.5 mg/kg per hour infusion for gamma radiation) as a single antithrombotic agent during the entire procedure. RESULTS: Baseline clinical and angiographic characteristics were similar between the 2 groups. More than 90% of the patients received beta radiation. In-hospital events showed a higher prevalence of acute procedural intracoronary thrombosis in patients treated with gamma- vs beta radiation (25% vs. 0.7%, P < .001). Thirty-day outcomes including death, Q-wave, and non-Q-wave myocardial infarctions, subacute stent thromboses, and repeat revascularizations were similar in both groups. CONCLUSION: Bivalirudin, as a single antithrombotic agent during PCI and VBT with beta emitters, may be used safely, but its use in the setting of PCI and gamma radiation may not be acceptable due to an increased incidence of acute procedural intracoronary thrombosis.

Vascular brachytherapy with 192Ir after femoropopliteal stent implantation in high-risk patients: twelve-month follow-up results from the Vienna-5 trial.

PURPOSE: To prospectively evaluate the effectiveness of endovascular brachytherapy in the prevention of restenosis after femoropopliteal stent implantation in high-risk patients. MATERIALS AND METHODS: Patients provided written informed consent to participate in this study, which was approved by the ethics committee. A total of 88 patients (mean age, 67.7 years +/- 10.1; 57 men [65%], 31 women [35%]) with femoropopliteal lesions (mean treatment length, 16.8 cm +/- 7.3) were included. Patients underwent percutaneous transluminal angioplasty (PTA) and stent implantation and were randomized in a double-blind fashion to undergo either gamma brachytherapy with an iridium 192 source or treatment with nonradioactive seeds. A 14-Gy dose of iridium 192 was prescribed at 2 mm into the arterial wall (target depth equals vessel radius plus 2 mm). The primary end point of the study was angiographic binary restenosis of more than 50% at 6-month follow-up. Secondary end point was either percutaneous or surgical target lesion revascularization after 6 months. Continuous data are presented as mean +/- standard deviation. Categorical data are expressed as percentages. Student t test was used to compare continuous data; chi(2) test was used to compare categorical values. Survival function was calculated with the Kaplan-Meier method. Multivariate Cox proportional hazard regression analysis was performed to enable evaluation of multivariate predictors of recurrence at 6- and 12-month follow-up. Variables included brachytherapy, clinical stage, lesion length, de novo and recurrent lesion, vessel run off, prior stenosis or occlusion, diabetes mellitus, and stent model. RESULTS: Revascularization and brachytherapy were accomplished successfully in all patients. The overall 6-month recurrence rate was 35% in patients who underwent only stent implantation and 33% in patients who underwent both stent implantation and brachytherapy (P = .89). Nine (10%) patients developed early reocclusion in the segment treated with a stent (two patients [4%] in the stent group and seven [17%] in the stent and brachytherapy group); of these patients, three in the stent and brachytherapy group experienced reocclusion within 24 hours of the intervention. Late (>30 days after intervention) thrombotic occlusion was observed in three patients (7%) in the stent and brachytherapy group. CONCLUSION: Brachytherapy does not improve 6-month patency after femoropopliteal stent implantation in high-risk patients because of a high incidence of early and late thrombotic occlusion.

Endovascular brachytherapy: restenosis in de novo versus recurrent lesions of femoropopliteal artery--the Vienna experience.

PURPOSE: To determine the effectiveness of endovascular brachytherapy in the prevention of restenosis in recurrent versus de novo femoropopliteal lesions. MATERIALS AND METHODS: Ethics committee approval and patient informed consent were obtained. After they had undergone femoropopliteal angioplasty, 199 patients (mean age, 71.9 years +/- 9.6; 115 men, 84 women) were treated with either percutaneous transluminal angioplasty (PTA) and brachytherapy (n = 100) or PTA alone (n = 99). The patients were part of prospective randomized trials, the Vienna 2 and 3 trials, and were evaluated according to the stratification criterion of de novo or recurrent disease. Sixty-six of 134 patients with a de novo lesion and 34 of 65 patients with a recurrent lesion were randomly assigned to the PTA and brachytherapy arm; the remaining patients were treated with PTA alone. Outcomes were compared between the groups. The Student t test or one-way analysis of variance was used to compare continuous variables, and the chi2 test or Fisher exact test was used to assess dichotomous variables. Kaplan-Meier curves were calculated, and the log-rank test was performed to determine freedom from recurrence at 12 months in both groups. A multivariate Cox proportional hazard regression analysis was performed to evaluate the multivariate predictors of recurrence at 12-month follow-up. RESULTS: For patients with de novo lesions, the frequency of recurrence at 12 months was not significantly different between those who underwent brachytherapy and PTA and those who underwent PTA alone (24 [36%] of 66 patients vs 30 [44%] of 68 patients, P = .32). For patients with recurrent lesions, however, the 12-month recurrence rate was significantly lower in those who received brachytherapy than in those who did not (nine [26%] of 34 patients vs 22 [71%] of 31 patients, P = .004). CONCLUSION: Endovascular brachytherapy with gamma radiation significantly reduces the restenosis rate after femoropopliteal angioplasty of recurrent but not de novo lesions.

Novel site-specific systemic delivery of Rapamycin with perfluorobutane gas microbubble carrier reduced neointimal formation in a porcine coronary restenosis model.

Earlier studies demonstrated that perfluorobutane gas microbubble carrier (PGMC) adheres to injured arteries and enhances the drug uptake specifically into the cells of the denuded vessel segment. The purpose of this study was to investigate the effect of PGMC-based systemic delivery of Rapamycin on expression of p27 in vascular tissue and restenosis in porcine coronary arteries after stent implantation. Eight pigs underwent coronary stent implantation (three stents per animal). Five pigs were treated with i.v. injection of PGMC with 2 mg of Rapamycin and three animals served as control. Four hours postprocedure, three pigs were sacrificed and stented segments were analyzed by high-performance liquid chromatography (HPLC) and Western blot. In chronic experiments, five pigs (15 stent sites) were sacrificed at 28 days following intervention and vessels were perfusion-fixed. HPLC of the treated arteries demonstrated high drug concentration in the vessel tissue, and Western blot analysis showed elevated expression of p27 at 4 hr postprocedure. Histomorphometry revealed significantly reduced (by 40%) neointimal formation in the PGMC/Rapamycin group compared with controls (1.84 +/- 0.84 vs. 4.77 +/- 1.71 mm2, respectively; P < 0.001). In the porcine coronary model, site-specific systemic delivery of Rapamycin utilizing PGMC resulted in overexpression of p27 and a significant reduction of neointimal formation within the stented segments.

Endovascular brachytherapy prevents restenosis after femoropopliteal angioplasty: results of the Vienna-3 randomised multicenter study.

BACKGROUND AND PURPOSE: The aim of the trial was to investigate the effect of Iridium-192 gamma endovascular brachytherapy on reduction of restenosis after femoropopliteal angioplasty. PATIENTS AND METHODS: Between Oct, 1998 and Jul, 2001 a total of 134 patients have been randomized after successful angioplasty to brachytherapy or sham irradiation in a prospective, randomized, multicenter, double blind controlled trial. Patients with de novo lesion of at least 5 cm or recurrent lesion of any length after prior angioplasty have been enrolled. Brachytherapy was performed with 7F centering catheter. Mean lesion length was 9.1cm (1.5-25 cm) and mean intervention length 13.6 cm (4-27.5 cm) in brachytherapy cohort. RESULTS: In placebo cohort mean lesion length was 10.3 cm (2-25 cm) and mean intervention length 14.1 cm (2-29 cm). A dose of 18 Gy was prescribed 2 mm from the surface of centering balloons. Analyzed (based on angiography) on intention to treat basis the binary restenosis rate at 12 months was 41.7% (28/67) in brachytherapy cohort and 67.1% (45/67) in placebo cohort (chi2 test, P<0.05). Corresponding data for as treated analysis (A total of 38 patients was excluded from analysis due to lack of follow-up, early recurrence within 30 days and >30% residual stenosis after angioplasty) have been 23.4% in the brachytherapy and 53.3% in the placebo group (P<0.05), respectively. The cumulative patency rates after 24 months on intention to treat analysis were 54% in the brachytherapy and 27% in the placebo group (P<0.005). Corresponding data for as treated analysis were 77% in the brachytherapy and 39% in the placebo group (P<0.001). Late thrombosis was not seen. CONCLUSIONS: Significant reduction of restenosis rate was obtained with endovascular gamma brachytherapy after femoropopliteal angioplasty.