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Biomedical subjects

Ron Waksman

Publications and source records attributed to Ron Waksman.

At least 181 records · Page 10Linked to original sources

Impact of intravascular ultrasound-guided direct stenting on clinical outcome of patients treated for native coronary disease.

BACKGROUND: Despite the fact that in animal models direct stenting (DS) reduces the vessel injury, in clinical practice this treatment strategy did not reduce late restenosis as compared to conventional strategy with balloon predilatation (PD). However, the influence of DS was not evaluated when stent expansion is optimized by intravascular ultrasound (IVUS) assessment. METHODS: We analyzed the in-hospital and 1-year outcomes of patients at Washington Hospital Center who were treated with percutaneous coronary interventions and stent implantation when percutaneous intervention was guided by IVUS. Only patients treated for single de novo lesions were included. RESULTS: In 1386 patients, 251 (18.1%) were treated with DS and 1135 (71.9%) were treated with PD. Pre- and postprocedure characteristics by angiography and IVUS were similar in both groups. Postprocedure non-Q-wave myocardial infarction (MI) occurred in 4.9% of the DS group and in 12.5% of the PD group (P = .005). At 1-year follow-up, target lesion revascularization (TLR) rate was 4.9% in the DS group and 14.8% in the PD group (P = .005). DS strategy (odds ratio = .46, confidence interval = .25-.85, P = .013) was independently correlated to lower risk for revascularization in multivariate analysis. CONCLUSION: When DS is implemented by IVUS assessment, it is associated with low in-hospital and long-term events.

Angioplasty, Balloon, Coronary↗

Peroxisome proliferator-activated receptor gamma: its role in metabolic syndrome.

Here we review PPARgamma function in relation to human adipogenesis, insulin sensitization, lipid metabolism, blood pressure regulation and prothrombotic state to perhaps provide justification for this nuclear receptor remaining a key therapeutic target for the continuing development of agents to treat human metabolic syndrome.

Adipose Tissue↗

Peroxisome proliferator-activated receptor gamma; Its role in atherosclerosis and restenosis.

Cellular proliferation and migration are fundamental processes that contribute to the injury response in major blood vessels. The resultant pathologies are atherosclerosis and restenosis. As we begin to understand the cellular changes associated with vascular injury, it is critical to determine whether the inhibition of growth and movement of cells in the vasculature could serve as a novel therapeutic strategy to prevent atherosclerosis and restenosis.

Animals↗

Effect of ionizing radiation on the stability and performance of the TAXUS Express2 paclitaxel-eluting stent.

BACKGROUND: The advent of drug-eluting stents has provided the interventional cardiologist an effective new tool in treating coronary restenosis. There remains, however, a small group of patients that still require intervention following drug-eluting stent therapy. Currently, intravascular brachytherapy (IVBT) is approved for use in the treatment of in-stent restenosis (ISR). This study investigated the effect of gamma and beta radiation doses typically used in IVBT on the performance of the TAXUS Express(2) paclitaxel-eluting stent. METHODS AND RESULTS: It was determined that there were no statistically significant changes to in vitro paclitaxel release from stent exposed to radiation compared to controls subjected to the same conditions except for the radiation exposure. The molecular weight of the Translute polymer carrier matrix and the level of paclitaxel degradants were not changed following exposure to radiation doses up to twice what is typically used in IVBT. Beta and gamma radiation doses typically used in IVBT had no significant effect on the Translute polymer carrier, paclitaxel degradation, or paclitaxel release in this in vitro model. CONCLUSION: The data are encouraging and support further evaluation of the use of IVBT in the treatment of ISR in the presence of drug-eluting stents.

Analysis of Variance↗

Addition of heparin to contrast media is associated with increased bleeding and peripheral vascular complications during percutaneous coronary intervention with bivalirudin and drug-eluting stents.

BACKGROUND: Nonionic radiographic contrast media (CM) is reported to be thrombogenic while performing diagnostic or interventional procedures. To avoid thrombosis, heparin is often added to the CM. Bivalirudin, used to replace heparin during percutaneous coronary intervention (PCI), is reported to be associated with reduced bleeding complications. We aimed to evaluate the impact of adding heparin to the CM during PCI in patients (pts) who underwent sirolimus-eluting stent (SES) implantation when bivalirudin was utilized as the sole antithrombotic agent. METHODS: A total of 664 pts with 756 lesions underwent standard PCI with SES for various coronary artery lesions. Pts were treated with either bivalirudin only (the bivalirudin group; 0.75 mg/kg bolus and 1.75 mg/kg/h infusion, n = 323 pts) or bivalirudin (same dose) plus low-dose heparin added to the CM (the heparin mix group; mean dose = 2101.8+/-882.5 U, n = 341 pts) during PCI. The periprocedural, in-hospital, and 30-day clinical outcomes were compared. RESULTS: Baseline clinical and angiographic parameters were similar between both groups. Periprocedural, in-hospital, and 1-month clinical outcomes, including thrombotic complications, were similar between the two groups. There was no difference in the periprocedural thrombosis rate between the groups. In the heparin mix group, the overall incidence of hematoma was significantly higher (3.8% vs. 8.5%, P = .01), there was a trend toward higher rates of blood transfusion (2.6% vs. 6.6%, P = .06) and overall vascular complications (0.01% vs. 5.3%, P <.001), including pseudoaneurysm (PSA; 0.0% vs. 2.6%, P = .004), and pts who required surgical repair (0.3% vs. 1.8%, P = .07). CONCLUSIONS: The routine addition of low-dose heparin to CM during contemporary PCI does not add any protection value and is associated with higher rates of bleeding and vascular complications.

Angioplasty, Balloon, Coronary↗

Transepicardial autologous bone marrow-derived mononuclear cell therapy in a porcine model of chronically infarcted myocardium.

OBJECTIVE: Cell therapy is becoming a viable strategy to improve revascularization and myocardial function after myocardial injury. We evaluated the effect of bone marrow-derived mononuclear cell (BMMNC) transplantation on collateral vessel development and myocardial function in a porcine model of chronically infarcted heart. METHODS: Myocardial infarction was produced in 13 domestic swine. At 4 weeks, animals were randomized to receive transepicardial injections of autologous BMMNCs (approximately 24x10(6) cells, n=8) or phosphate buffered saline (PBS; control, n=5) into infarcted and border regions. Collateral growth, angiogenesis, and infarct size were assessed by angiography, immunohistochemistry, and histomorphometry. RESULTS: Regional contractility was assessed by transepicardial echocardiography at baseline and 4 weeks following treatment. Angiography revealed a trend toward increased collateral growth in the BMMNC group. Wall motion score index (myocardial function) was similar in both groups at baseline (1.63+/-0.16 vs. 1.25+/-0.25, P=.21) and at 4 weeks (1.83+/-0.22 vs. 1.63+/-0.38, P=.62). alpha-Actin-positive smooth muscle cells (SMCs) and Factor VIII positive endothelial cells were significantly greater in the BMMNC-injected animals (314.8+/-37.4/0.1 vs. 167.1+/-11.9/0.1 mm(2) in controls, P=.02, and 363.3+/-28.2 cells/0.1 mm(2) vs. 254.4+/-28.1 cells/0.1 mm(2) in controls, P=.03, respectively). The number of blood vessels >50 mum in diameter was significantly increased in the BMMNC group (317.9+/-54.9 vs. 149.1+/-6.1, P<.05). The size of the infarct area was smaller in the BMMNC-transplanted group than in the controls (P=.015). CONCLUSION: BMMNC transplantation appears to improve angiogenesis and reduce infarct size yet results in no improvement in left ventricular function in a chronically infarcted heart.

Animals↗

Late thrombosis in cypher stents after the discontinuation of antiplatelet therapy.

Drug-eluting stents, since their approval in the United States, have become the treatment of choice for de novo coronary artery narrowing due to their ability to reduce restenosis and the need for repeat revascularization. We present two patients who underwent percutaneous coronary intervention for the treatment of multivessel coronary artery disease; both patients were treated with sirolimus-eluting stents (SES) and bare metal stents (BMS).

Adult↗

Intracoronary radiation therapy using a novel beta emitter for in-stent restenosis Tungsten WRIST.

BACKGROUND: Intracoronary beta-radiation therapy reduces in-stent restenosis (ISR). We aimed to determine the safety and feasibility of intracoronary radiation therapy (IRT) utilizing tungsten (188W), a beta emitter. METHODS: A total of 30 patients with angiographic evidence of ISR in a previously treated native coronary artery underwent percutaneous coronary intervention (PCI; balloon angioplasty, ablation by atherectomy, or laser angioplasty). After the intervention, a noncentered delivery catheter with a side guide 0.014-in. wire carrying a tungsten (188W) coil, with an active length of 33 mm, was inserted. Patients were randomized to a radiation dose of 18, 22, or 25 Gy at 2 mm from the center of the source. Aspirin and Plavix, at 300 mg loading dose, were administered prior to intervention. Plavix 75 mg/day was prescribed for 6 months after the procedure. RESULTS: At 6 months follow-up, the overall binary angiographic restenosis rate was 18.8%. Target vessel revascularization (TVR) was 23% and target lesion revascularization related major adverse cardiac events (TLR-MACE) was 13.3%, without any intergroup differences. A comparison with the original Washington Radiation for In-stent restenosis Trial (WRIST) radiation cohort utilizing an 192Iridium source (prescription dose 15 Gy at 2 mm from the source) showed similar TVR and TLR-MACE rates of 30% and 18%, respectively. The TVR and TLR-MACE rates in the WRIST placebo cohort were 70% and 66%, respectively. CONCLUSIONS: Vascular brachytherapy with tungsten (188W) is feasible and safe. The 6-month clinical outcomes are similar to the original WRIST radiation group.

Anti-Inflammatory Agents, Non-Steroidal↗

Estimation of radiation dose received during treatment of in-stent restenosis using ionizing radiation.

BACKGROUND: Angioplasty is a widely accepted procedure for the treatment of coronary artery disease. However, restenosis of the treated vessel occurs in 30% of patients within 6 months. Intravascular brachytherapy (IVB) is used to inhibit the formation of new tissue growth at the vessel treatment site. IVB protocols using either gamma ray or beta particle emitting isotopes have been tested and approved. However, very little data are available on resultant whole-body dose and the potential for long-term radiation effects. METHODS: Using thermoluminescence dosimetry (TLD) devices, specifically lithium fluoride (LiF) doped with Mg, Cu, and P, the radiation dose on the surface of patients undergoing IVB was measured. The TLDs were positioned on the body to obtain a measure of the gamma dose at selected anatomic locations. Additionally, the skin dose from fluoroscopy was estimated. RESULTS: Measurements indicate that the average body dose on the skin surface from all TLDs, clinical requirements, and gamma source configurations varies from 0.95 mSv (95 mrem) at the head to 27.06 mSv (2706 mrem) at the sternal notch. For beta sources, the dose varied from 0.11 mSv (11.4 mrem) at the head to 0.49 mSv (49.5 mrem) at the sternal notch. The fluoroscopy contribution of dose to the body dose (15-min exposure time) was 0.10 mSv (10 mrem) at the head and 2.57 mSv (257 mrem) to the sternal notch. CONCLUSIONS: The results suggest that surface skin exposures from gamma sources used in IVB pose acceptable risks considering the medical benefits of the procedures.

Brachytherapy↗

Drug-eluting stents for the treatment of in-stent restenosis: a clinical review.

Treatment of in-stent restenosis (ISR) remains problematic despite the widespread application of drug-eluting stents (DES). Challenging lesion cohorts such as diffuse ISR and restenosis after failed intracoronary radiation therapy (IRT) maybe best treated with DES. The overall benefit of DES appears inferior to their utility in treating de novo coronary lesions. Randomised trials comparing DES and IRT will soon be available to determine the optimal therapy for ISR. The challenge to treat ISR in the DES era is the next frontier of interventional cardiology.

Antibiotics, Antineoplastic↗

Optimizing dosimetry with high-dose intracoronary gamma radiation (21 Gy) for patients with diffuse in-stent restenosis.

BACKGROUND: The efficacy of intracoronary gamma radiation (IRT-gamma) in reducing recurrent in-stent restenosis (ISR) is well established using doses of 14-18 Gy. We sought to examine whether an escalation in dose to 21 Gy is safe and confers additional benefit in reducing repeat revascularization and major adverse cardiac events (MACE) in patients with diffuse ISR. METHODS: Forty-seven patients with diffuse ISR (lesion length 20-80 mm) in native coronary arteries (n=25) and saphenous vein grafts (n=22) underwent percutaneous transluminal coronary angioplasty and/or additional stents followed by IRT-gamma using the Checkmate system (Cordis) with a dose of 21 Gy. All patients were discharged with clopidogrel for 12 months and aspirin indefinitely. Six-month angiographic and 12-month clinical outcomes of these patients were compared to 120 patients treated with 18 Gy using the same system. RESULTS: At baseline, patients in the 21-Gy group had more multivessel, vein graft disease and history of prior myocardial infarctions and coronary artery bypass grafts (P<.001). The use of debulking devices and stents was less in this group (P<.001). Procedural and in-hospital complications were similar. Follow-up at 6 months revealed nonsignificant but lower late loss (in-stent, 0.33+/-0.7 mm; in-lesion, 0.41+/-0.6 mm) in the 21-Gy group compared to the 18-Gy group; follow-up at 12 months revealed a trend toward less overall myocardial infarction, although repeat revascularization and MACE rates were similar. CONCLUSIONS: IRT-gamma therapy for diffuse ISR lesions with a 21-Gy dose is clinically safe and feasible with marked reduction in late loss but does not confer additional benefit with regard to repeat revascularization and MACE when compared to a dose of 18 Gy.

Adult↗

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.

Anticoagulants↗

Impact of vessel calcification on outcomes after coronary stenting.

BACKGROUND: Calcified coronary arteries have few viable smooth muscle cells capable of proliferating, and, subsequently, might exhibit less in-stent restenosis. We therefore studied the outcome of stenting in patients with different amounts of coronary calcification. METHODS: Six hundred twenty-one patients who underwent bare metal stenting of calcific native coronary arteries were studied retrospectively. Pre- and postinterventional intravascular ultrasound (IVUS) and qualitative and quantitative coronary angiography (QCA) were performed in 662 lesions. The arc of calcium was measured, and arteries were grouped (A, B, C, and D) according to the calcium arc in IVUS (0-90 degrees , 91-180 degrees , 181-270 degrees , and 271-360 degrees , respectively). Arteries with a superficial calcium arc of < or =270 degrees (Group E) were compared to arteries with >270 degrees calcification (Group F). RESULTS: Clinical and lesion characteristics were similar, and the major complication rate was low (1.9%) in all groups. In Groups A, B, C, and D, patients with more calcific arteries had more non-Q-wave myocardial infarction (MI) (P=.04-.002). Patients in Group F (more extensive superficial calcification) had an increased frequency of non-Q-wave MI compared to Group E. Malapposition of stents to vessel wall and use of rotational atherectomy were more frequent in Group F (P=.001). Late events including death, MI, and revascularization with either coronary artery bypass grafting or percutaneous coronary intervention (PCI) were not different among the groups. Extensive calcification of coronary arteries is associated with more frequent peri-procedural non-Q-wave MI. CONCLUSION: Despite the scarcity of viable cells, the late event rate in severely calcified arteries is not different from mildly calcified arteries. This may be due to more frequent malapposition of stents to vessel wall and augmented trauma during PCI in severely calcified arteries.

Adult↗

Dose mapping of porcine coronary arteries using an optical fiber dosimeter.

BACKGROUND: This study is about the measurement of radiation dose contribution to the coronary arteries during intravascular brachytherapy with beta and gamma emitters utilizing in vivo optical fiber dosimeters. METHODS AND MATERIALS: Domestic pigs were used. With each measurement, catheters were introduced into two different coronary arteries, including the left circumflex (LCX), the left anterior descending (LAD), the first diagonal, and/or the right coronary artery (RCA). A radioactive source (192Ir, 90Sr/Y, or 32P) and the dosimeter were loaded in each of these catheters. Data were collected as the dosimeter was being retracted at a constant rate via computer control. RESULTS: The radiation dose was normalized to 100% at a 2-mm radial distance from the source. When radiating a branching artery, the dose to the bifurcation at 5 mm from the source was 35%, 10%, and 3% for the 192Ir (10 seeds), 90Sr/Y (40 mm), and 32P sources, respectively. When utilizing a 23-seed 192Ir source, the dose is 40% at a 5-mm distance. However, radiation of the RCA did not result in dosing to the LAD or LCX using any source. CONCLUSIONS: The dose to adjacent artery segments is less with beta than with gamma emitters. Significant dose exposition is noted when using gamma emitters at a distance of 5 mm. The results can serve as a guideline for establishing prescription doses and safety margins for the treatment of bifurcation lesions and retreatment of the arteries.

Animals↗

Metabolic syndrome in patients with acute myocardial infarction is associated with increased infarct size and in-hospital complications.

BACKGROUND: Metabolic syndrome (MS), the combination of hypertension, obesity, dyslipidemia, and insulin resistance, is a precursor of diabetes mellitus (DM) and highly prevalent among patients with acute myocardial infarction (AMI). Diabetes mellitus is associated with larger infarct size and worse outcomes after AMI. This study examined infarct size and short-term outcomes among nondiabetic patients with MS following contemporary treatment of AMI. METHODS: Four hundred five consecutive patients with AMI treated with primary percutaneous coronary intervention were evaluated. Patients with diabetes (n=105) were excluded. Those with MS (n=167) included patients with three or more of the following criteria: hypertension, elevated fasting blood glucose, hypertriglyceridemia, low high-density lipoprotein, and obesity [body mass index (BMI)> or =30]. The control group (n=133) included patients without MS or DM. RESULTS: Baseline characteristics were similar except for hypertension, BMI, and dyslipidemia, which by study design were higher in the MS group. The MS group had larger infarct size as determined by peak creatine kinase-MB (79.8+/-133.8 vs. 30.84+/-51.5, P<.001). Overall in-hospital complications were higher in patients with MS (21.1% vs. 9.2%, P=.003). Metabolic syndrome is associated with a 10-fold increased risk of acute renal failure after myocardial infarction (7.9% vs. 0.8%, P=.007). CONCLUSION: Metabolic syndrome in nondiabetic patients with AMI is associated with larger infarct size, more in-hospital complications, and a marked increase of acute renal failure. Awareness of MS and preventative measures is crucial in this population to minimize infarct size and decrease morbidity after AMI.

Acute Kidney Injury↗