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Biomedical subjects

Ron Waksman

Publications and source records attributed to Ron Waksman.

At least 91 records · Page 5Linked to original sources
PubMed2004

Usefulness of periprocedural creatinine phosphokinase-MB release to predict adverse outcomes after intracoronary radiation therapy for in-stent restenosis.

We aimed to analyze periprocedural creatinine phosphokinase (CPK)-MB elevation in patients treated with intracoronary radiation therapy (IRT) for in-stent restenosis (ISR) to risk stratify these patients. The clinical significance of periprocedural CPK-MB elevation after IRT for ISR is unknown. An elevated CPK-MB has been associated with increased mortality after conventional angioplasty. We evaluated 1,326 patients who were enrolled in radiation trials for ISR at the Washington Hospital Center using gamma- and beta-emitters. Patients were analyzed according to degree of CPK-MB increase within 24 hours of the index IRT procedure (normal CPK-MB, CPK-MB 1 to 3 times the upper limit of normal, or CPK-MB >3 times the upper limit of normal). Patients with CPK-MB >3 times the upper limit of normal were older (64 +/- 12 years, p = 0.04), more likely to be smokers (64%, p = 0.04), hypertensive (85%, p <0.01), and diabetic (49%, p = 0.04). The cohort with the highest CPK-MB release (CPK-MB >3 times the upper limit of normal) had significantly higher rates of adverse clinical events at 12 months (major adverse cardiac events 40%, p <0.01), including death (9.3%, p <0.01) and late thrombosis (6.3%, p <0.01). Periprocedural CPK-MB elevation is of prognostic importance in patients treated with IRT for ISR, and its analysis appears to be mandatory to risk stratify these patients. The impact of glycoprotein IIb/IIIa antagonists in reducing periprocedural CPK-MB release awaits evaluation.

Aged↗
PubMed2004

Five-year follow-up after intracoronary gamma radiation therapy for in-stent restenosis.

BACKGROUND: The Washington Radiation for In-Stent Restenosis Trial is a double-blinded randomized study evaluating the effects of intracoronary radiation therapy (IRT) in patients with in-stent restenosis (ISR). METHODS AND RESULTS: One hundred thirty patients with ISR (100 native coronary and 30 vein grafts) underwent percutaneous transluminal coronary angioplasty, laser ablation, rotational atherectomy, or additional stenting (36% of lesions). Patients were randomized to either 192-Iridium IRT or placebo, with a prescribed dose of 15 Gy to a 2-mm radial distance from the center of the source. Angiographic restenosis (27% versus 56%, P=0.002) and target vessel revascularization (26% versus 68%, P<0.001) were reduced at 6 months in patients treated with IRT. Between 6 and 60 months, patients treated with IRT compared with placebo had more target lesion revascularization (IRT, 21.6% versus placebo, 4.7%; P=0.04) and target vessel revascularization (IRT, 21.5% versus placebo, 6.1%; P=0.03). At 5 years, the major adverse cardiac event rate was significantly reduced with IRT (46.2% versus 69.2%, P=0.008). CONCLUSIONS: In the Washington Radiation for In-Stent Restenosis Trial, patients with ISR treated with IRT using 192-Iridium had a reduction in the need for repeat target lesion and vessel revascularization at 6 months and 5 years.

Cardiac Catheterization↗
PubMed2004

Effects of gamma radiation on the noninjured and unprotected left main.

The aim of this study was to evaluate the effect of gamma radiation on the noninjured, unprotected left main coronary artery. Noninjured vessel segments are often radiated during treatment of in-stent restenosis with PCI and gamma radiation. Angiographic analysis using QCA methods was performed on 55 left main arteries of patients (32 with radiation of the left main compared to 23 controls) who participated in the Washington Radiation for In-Stent Restenosis Trials (WRIST). Baseline demographics and follow-up were comparable between the two groups, concluding that gamma radiation with long radiation safety margins is feasible and safe. Gamma radiation of noninjured irradiated left main vessels when used to facilitate wide radiation margins for proximal irradiated injured LAD and LCx is safe and does not compromise the vessel integrity and its lumen.

Aged↗
PubMed2004

Gamma radiation for in-stent restenosis: effect of lesion length on angiographic and clinical outcomes.

The relation between lesion length and effectiveness of gamma radiation treatment (gamma-RT) has not been well described. We evaluated the acute and long-term outcome according to baseline lesion length in 130 patients treated with (192)Ir in the Washington Radiation for In-Stent Restenosis Trial; 44 (35.5%) had baseline short in-stent restenosis (ISR) lesions (length < 15 mm) and 80 (64.5%) long ISR lesions (length > or = 15 mm). At 6-month follow-up after gamma-RT, the short ISR group had larger lumen dimensions and lower late loss than the long ISR group. Restenosis rate was significantly higher in patients with long ISR for both the placebo (74% vs. 39%; P = 0.01) and the gamma-RT arm (31% vs. 5.3%; P = 0.04). gamma-RT significantly improved the angiographic outcome in the short-lesion groups but had the more pronounced effect on the reduction of clinical events after treatment of long ISR group. Lesion length remains a powerful predictor of recurrent ISR and clinical events after treatment of ISR even with gamma-RT.

Brachytherapy↗
PubMed2004

Advanced c-myc antisense (AVI-4126)-eluting phosphorylcholine-coated stent implantation is associated with complete vascular healing and reduced neointimal formation in the porcine coronary restenosis model.

An advanced six-ring morpholino backbone c-myc antisense (AVI-4126) was shown to inhibit c-myc expression and intimal hyperplasia after local catheter delivery in a porcine balloon injury model. The purpose of this study was to investigate the effects of an AVI-4126-eluting phosphorylcholine-coated (PC) stent on c-myc expression restenosis and vascular healing after stent implantation in porcine coronary arteries. PC stents were loaded with AVI-4126 using soak trap. Nine pigs underwent AVI-4126 PC coronary stent implantation (two stents/animal). Two to six hours postprocedure, three pigs were sacrificed and stented segments were analyzed by Western blot for c-myc expression. In chronic experiments, six pigs (12 stent sites) were sacrificed at 28 days following intervention and vessels were perfusion-fixed. High-performance liquid chromatography analysis of plasma samples showed minimal presence of the antisense. Western blot analysis of the stented vessels demonstrated inhibition of c-myc expression at 2 and 6 hr after procedure. Quantitative histologic morphometry showed that the neointimal area was significantly reduced (by 40%) in the antisense-coated group compared with control (2.3 +/- 0.7 vs. 3.9 +/- 0.8 mm(2), respectively; P = 0.0077). Immunostaining and electron microscopy demonstrated complete endothelialization, without fibrin deposition, thrombosis, or necrosis in all implanted stents. In the porcine coronary model, an advanced c-myc-eluting PC stent blocked c-myc expression and significantly inhibited myointimal hyperplasia and allowed complete reendothelialization and healing response.

Animals↗
PubMed2004

Use of IIb/IIIa inhibitors in patients with in-stent restenosis treated with intracoronary gamma-radiation. Integrilin WRIST.

The Integrilin Washington Radiation for In-Stent Restenosis Trial (WRIST) aimed to study the impact of IIb/IIIa inhibitors as adjunct therapy to intracoronary radiation therapy (IRT) for patients with in-stent restenosis (ISR). The impact of GP IIb/IIIa inhibitor (eptifibatide) as adjunct therapy to vascular brachytherapy using (192)Ir emitter was examined in patients with in-stent restenosis. In the study, 150 patients were assigned to eptifibatide (Integrilin) and 150 patients to heparin only. Clinical composite endpoints at 30 days were similar between the patients treated with and without eptifibatide (4.7% vs. 4.0%; P = 0.78). There was a similarity in the non-Q-wave myocardial infarction (MI) rates between the eptifibatide and the control group. Major bleeding was similar in patients treated with and without eptifibatide. Overall, the use of eptifibatide as adjunct therapy for patients with ISR that are treated with IRT did not impact the clinical outcome at 30 days.

Aged↗
PubMed2004

Bivalirudin-associated intracoronary thrombosis during gamma-brachytherapy and its experimental validation in acute swine model.

Bivalirudin is indicated for use as an anticoagulant in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty. Cases of intracoronary thrombosis have been reported with beta-radiation when bivalirudin is used as an anticoagulant. We report two cases of intracoronary thrombosis with gamma-radiation when bivalirudin is used.

Aged↗
PubMed2004

Vascular complications following coronary intervention correlate with long-term cardiac events.

We aimed to study the consequences and late outcomes of patients who experienced peripheral vascular complications (PVCs) following percutaneous coronary interventions (PCI). A retrospective analysis of the medical records of 10,669 patients who underwent PCI and experienced PVC between 1995 and 2002 was conducted. One thousand ninety-six patients (10.27% of the study cohort) had PVC post-PCI. After PCI, patients with PVC had higher rates of in-hospital complications (P < 0.001) when compared to patients without PVC, including Q-wave myocardial infarction (MI; 1.2% vs. 0.3%), coronary artery bypass grafting (CABG; 3.8% vs. 0.6%), and death (4.0% vs. 1.0%). At 1-year follow-up, late complications of MI (37.4% vs. 25.4%), non-Q-wave MI (34.9% vs. 22.7%), death (12.9% vs. 5.9%), and CABG (5.7% vs. 4.5%) were higher (< 0.001) in patients with PVC compared to those without. Multivariate analysis identified PVC as a significant predictor of 1-year mortality (P = 0.045). This study underscores the need to make diligent efforts to minimize PVC and follow up these patients for future coronary events.

Aged↗
PubMed2004

Favorable effect of gamma-radiation for in-stent restenosis: effect of diabetes on angiographic and clinical outcomes.

The purpose of this study was to examine the effect of vascular brachytherapy with gamma-radiation (gamma-RT) in patients with diabetes mellitus (DM) with coronary in-stent restenosis (ISR). In the Washington Radiation for In-Stent Restenosis (WRIST) trial, 130 patients with ISR were treated with (192)Ir or placebo. Of the patients enrolled, 44 (34%) had DM (18 of them treated with gamma-RT and 26 with placebo). Gamma-radiation therapy of ISR in diabetics resulted in similar procedural success and in-hospital outcome compared to nondiabetics. At 6-month follow-up, both DM and non-DM patients treated with gamma-RT had significantly lower target lesion revascularization (TLR), target vessel revascularization, and major adverse cardiac event rates compared to placebo. DM remains a powerful predictor of TLR and major adverse cardiac events even after treatment of ISR with gamma-RT.

Adult↗
PubMed2004

Impact of radiation dose on late clinical outcome after intracoronary radiation therapy: three-year follow-up of Long WRIST.

To determine the safety and efficacy, including the impact, on the late recurrence rate of an incremental gamma-radiation dose from 15 to 18 Gy, we report the 3-year clinical outcome of Washington Radiation for In-Stent Restenosis Trial for Long Lesions (Long WRIST). One hundred eighty patients with recurrent in-stent restenosis (ISR) were enrolled in the Long WRIST series and treated with (192)Ir with 1 month of antiplatelet therapy. Between 6 months and 3 years, the need for repeat revascularization was low and similar among the three groups. At 3 years, target lesion revascularization (TLR) and major adverse cardiac events (MACE) were less frequent in the 18 Gy group than in the 15 Gy group (P = 0.12 for TLR, P < 0.05 for MACE) and less frequent in the 15 Gy group as compared to the placebo group (P < 0.05 for TLR and MACE). At 3 years, a higher dose of 18 Gy with (192)Ir continues to improve the outcome of patients treated for ISR when compared to patients treated with 15 Gy or placebo.

Analysis of Variance↗
PubMed2004

Effects of contrast media on porcine bone marrow-derived mononuclear cells and calf myoblast viability and secretion of VEGF and MCP-1.

We investigated the effect of contrast media on bone marrow-derived cell viability, growth factor secretion, and myoblast viability. Bone marrow was exposed to contrast media, mononuclear cells were isolated, viability was assessed by Trypan blue exclusion or cultured for 4 weeks, and conditioned medium was assayed for vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1). Skeletal myoblasts viability was assessed after exposing them to contrast media. In separate experiments, bone marrow or bone marrow-derived mononuclear cells were exposed to contrast media, cultured for 40 hr, then assessed for viability. None of the contrast media tested had any effect on bone marrow-derived cell viability. Hypaque or Hexabrix increased myoblasts viability by 8-10%. VEGF and MCP-1 concentrations in the conditioned medium increased in a time-related manner. These findings support the concept that for cell therapy, bone marrow cells or myoblasts may be mixed with contrast media and injected into ischemic myocardium without compromise in viability or function.

Animals↗
PubMed2004

Major noncardiac surgery following coronary stenting: when is it safe to operate?

The optimal timing for elective noncardiac surgery (NCS) after coronary stenting is uncertain. We identified 47 patients who underwent elective NCS within 90 days of coronary stent placement between January 1995 and December 2000. Twenty-seven patients had NCS within 3 weeks of coronary stenting. Six of the seven in whom thienopyridine antiplatelet therapy was discontinued died postoperatively in a manner suggestive of stent thrombosis. In contrast, only 1 of the 20 patients in whom the thienopyridine was continued through the NCS died. The frequency of perioperative hemorrhage was similar whether or not the antiplatelet agent was continued. Only 1 perioperative death occurred in the 20 patients with NCS more than 3 weeks following stenting.

Aged↗
PubMed2004

Therapeutic potential of oral antiproliferative agents in the prevention of coronary restenosis.

The treatment of coronary artery disease has reached many milestones - from balloon angioplasty to drug-eluting stents. The last decade witnessed the revolution of bare metal stents with new designs, alloys and strut thicknesses. Yet restenosis, the aphorismic 'Achilles heel', remains to be conquered. The restenosis rates with balloon angioplasty alone are 30-40% and are reduced to 20-30% with stents. Although intravascular brachytherapy proved to be a durable and safely used technique to treat in-stent restenosis, clinical event rates were not reduced to single digits.Drug-eluting stents are showing positive results in this direction, but it is too early to predict their efficacy in various subsets of lesions. With the increased usage of these stents, there are reports of problems such as late stent malapposition, subacute and late thromboses, and aneurysm formations due to the vessel toxicity associated with this method of treatment. Furthermore, when multivessel stenting is considered, the cost of drug-eluting stents is a significant problem given the fact that these are no longer 'zero restenosis' devices. There is a definite need for a simple, safe and durable solution to restenosis. Oral agents are an alternative delivery strategy that can target multiple coronary lesions, which are targets for catheter-based revascularisation with any approved metal stent and with potentially lower cost. Although oral agents have been an interesting option to treat restenosis and several agents have been tested in trials since the 1980s, the results were disappointing. The development of devices such as intravascular ultrasound has led to a greater understanding of restenosis mechanisms, and the focus on pathophysiological mechanisms, which centred mainly on platelets, growth factors and lipids, has changed to inflammation, endothelium and smooth muscle cell proliferation.Accordingly, the targets of pharmaceutical agents have shifted from platelets to cell cycle inhibition, smooth muscle cell proliferation and migration, synthesis of extra cellular matrix, and inflammatory mediators. Initial encouraging results with oral drugs such as cilostazol, sirolimus (rapamycin) and thiazolidinediones indicate a definite place for this strategy to reduce restenosis. A desirable oral agent would be anti-inflammatory, inhibit smooth muscle cell migration and proliferation, promote endothelial growth, and be well tolerated and free from significant adverse effects. It may be useful to start with a high loading dose before stent implantation and then follow with a short-term lower maintenance dose. Future trials should be aimed at finding an ideal agent, effective loading dose, maintenance dose and optimum duration of therapy.

Administration, Oral↗
PubMed2004

Intravascular ultrasound predictors of subacute vessel closure after balloon angioplasty or atherectomy.

BACKGROUND: Factors leading to subacute vessel closure after percutaneous coronary intervention (PCI) have not been well established in lesions treated with balloon angioplasty or atherectomy. METHODS AND RESULTS: We used intravascular ultrasound (IVUS) to determine the pre- and post-PCI characteristics involved in subacute vessel closure after PCI. Of 3,403 patients undergoing IVUS imaging during coronary balloon angioplasty or atherectomy, 8 patients (0.2%) developed angiographically documented subacute vessel closure within 1 week post-PCI and were compared to a group matched by procedure date (within 6 months), age, gender, stable or unstable angina, lesion location and treatment (balloon angioplasty or atherectomy). IVUS identified at least one cause for subacute vessel closure in 87% of patients (vs 25% in matched lesions, p < 0.01). Causes were all procedure-related and included inadequate final lumen (60%), dissection (50%) and thrombus (25%). Pre-procedure lesion characteristics were not different from matched lesions. CONCLUSIONS: Subacute vessel closure after balloon angioplasty or atherectomy is mostly related to insufficient post-procedure lumen dimension or dissection.

Aged↗
PubMed2004

Safety of percutaneous coronary intervention alone in symptomatic patients with moderate and severe valvular aortic stenosis and coexisting coronary artery disease: analysis of results in 56 patients.

Whether percutaneous coronary intervention (PCI) alone is safe in patients with moderate or severe aortic stenosis (AS) and coexisting coronary artery disease (CAD), and whether aortic valve replacement (AVR) can be deferred in patients with moderate AS by undergoing PCI alone is not known. We conducted a retrospective study of surgically inoperable patients with AS who underwent PCI (moderate AS, n = 28; and severe AS, n = 28) and compared to those with AVR (n = 55). The clinical characteristics, procedural complications, in-hospital and long-term clinical outcomes of PCI were compared. Baseline and procedural characteristics were similar except that lower age, hypertension, and renal impairment were seen in the AVR group. In-hospital complications were comparable among the 3 groups. Six-month and 1-year rates of myocardial infarction (MI), non-Q-wave MI, death and out-of-hospital death were similar between AVR and moderate AS patients (p = NS) and significantly high (p < 0.04) in patients with severe AS. On multivariate analysis, severe AS was the only significant predictor of 6-month and 1-year mortality. Our study suggests that PCI is safe in patients with moderate AS and coexisting CAD but is associated with poor outcomes in patients with severe AS.

Aged↗
PubMed2003

Comparison of the angiographic outcomes after beta versus gamma vascular brachytherapy for treatment of in-stent restenosis.

This study was designed to compare the angiographic outcomes of beta versus gamma vascular brachytherapy (VBT). We reviewed the angiographic results of 636 lesions (212 that underwent beta and 212 that underwent gamma VBT, and 212 that received placebo) with native coronary in-stent restenosis matched for lesion length, vessel size, preprocedure minimum lumen diameter (MLD), and time to angiographic follow-up in the various randomized clinical trials and studies. Baseline lesion complexity was similar in these 3 groups. Final MLD was smaller in the beta VBT group than in the gamma VBT or placebo group. At follow-up, beta and gamma VBT significantly reduced both angiographic restenosis (34.4% for beta VBT, 26.4% for gamma VBT, and 50.9% in the placebo group; p <0.0001) and recurrent lesion length (9.2 mm for beta VBT, 8.4 mm for gamma VBT, and 15.5 mm placebo, p <0.0001) compared with placebo. Gamma VBT was associated with a greater reduction in restenosis outside the stent than beta VBT. By multivariable analysis, independent angiographic predictors of treated segment restenosis included beta or gamma VBT, lesion length, and vessel size. In matched lesions, beta and gamma VBT achieved similar reductions in treated segment restenosis and recurrent lesion length compared with placebo.

Adult↗
PubMed2003

Comparison of effectiveness and safety of three different antithrombotic regimens (bivalirudin, eptifibatide, and heparin) in preventing myocardial ischemia during percutaneous coronary intervention.

The aim of this retrospective, observational analysis was to compare the efficacy and safety of 3 antithrombotic regimens: bivalirudin, eptifibatide plus heparin, and heparin alone, with emphasis on preventing interventional procedural creatinine kinase-MB fraction (CK-MB) release, and consequently, myocardial necrosis.

Aged↗