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Ron Waksman

Publications and source records attributed to Ron Waksman.

At least 145 records · Page 8Linked to original sources
PubMed2003

Repeat radiation for recurrent in-stent restenosis in patients who failed initial brachytherapy.

In-stent restenosis (ISR) is due to neointimal hyperplasia and is shown to be effectively inhibited by vascular brachytherapy (VBT). Despite its efficacy, 20-25% of patients present with recurrent ISR following failed initial VBT. Although conventional percutaneous coronary intervention (PCI) is offered in a majority of patients to treat failed brachytherapy, the requirement for repeat revascularization is about 50%. PCI with repeat radiation to treat this difficult subset of patients is safe and feasible with target lesion revascularization (TLR) rates less than 25%. The lessons learned from randomized trials of brachytherapy, including prevention of edge effect, prolonged antiplatelet therapy and the prescription of a higher mean dose, should be applied to treat these patients with repeat radiation.

Brachytherapy↗
PubMed2002

How to fix the edge effect of catheter-based radiation therapy in stented arteries.

BACKGROUND: Edge stenosis remains a serious limitation of catheter-based vascular brachytherapy (VBT). This study aims to identify the mechanisms and evaluate strategies to minimize edge restenosis in patients treated with VBT. METHODS AND RESULTS: Thirty-four porcine stented coronary arteries were irradiated (doses of 15 or 22 Gy) with (192)Ir trains of either 6 seeds (23 mm) with 0 mm coverage at the distal stent edge and 10 mm at the proximal stent edge or 14 seeds (55 mm) centered at the distal edge of the stent with 27.5 and 14.5 mm coverage at the distal and proximal edges, respectively. After VBT, an additional 13-mm stent was positioned overlapping the distal margin of the first stent. Animals were killed at 28 days, and arteries were analyzed. Longer radiation margins were associated with reduced intimal area (IA) at the stent edge: 2.3+/-0.9, 3.6+/-2.0, and 5.3+/-2.2 mm(2) with 15 Gy for a radiation margin of 14.5, 10, and -13 mm (-13 versus 10, P=0.06; 10 versus 14.5, P=0.06). Additional stenting was associated with an increase of IA: 4.0+/-2.3 mm(2) at the overlapped segment. Increasing the dose to 22 Gy resulted in a reduction of the IA at the overlap segment to 1.31+/-0.57 mm(2) with 14 seeds (27.5 mm coverage) but was not helpful with 6 seeds (0 mm coverage): IA, 5.56+/-2.28 mm(2). CONCLUSIONS: Extending the radiation margins to 14.5 mm from each end of the stent minimized the edge-effect phenomenon. A higher dose is essential to eliminate further increases in IA at the overlapped segment with additional stents.

Animals↗
PubMed2002

Morphologic and angiographic features of coronary plaque rupture detected by intravascular ultrasound.

OBJECTIVES: This study was designed to report the clinical and angiographic correlates of plaque rupture detected by intravascular ultrasound (IVUS). BACKGROUND: Acute coronary syndromes result from spontaneous plaque rupture and thrombosis. METHODS: We report 300 plaque ruptures in 257 arteries in 254 patients. Plaque ruptures were detected during pre-intervention IVUS. Standard clinical, angiographic, and IVUS parameters were collected and/or measured. One lesion per patient was analyzed. RESULTS: Multiple ruptures were observed in 39 of 254 patients (15%), 36 in the same artery. Plaque rupture occurred not only in patients with unstable angina (46%) or myocardial infarction (MI, 33%), but also stable angina (11%) or no symptoms (11%). The tear in the fibrous cap could be identified in 157 of 254 patients; 63% occurred at the shoulder of the plaque and 37% in the center of the plaque. Thrombi were more common in patients with unstable angina or MI (p = 0.02) and in multiple ruptures (p = 0.04). The plaque rupture site contained the minimum lumen area (MLA) site in only 28% of patients; rupture sites had larger arterial and lumen areas and more positive remodeling than MLA sites. Intravascular ultrasound plaque rupture strongly correlated with complex angiographic lesion morphology: ulceration in 81%, intimal flap in 40%, thrombus in 7%, and aneurysm in 7%. CONCLUSIONS: Plaque ruptures occur with varying clinical presentations, strongly correlate with angiographic complex lesion morphology, may be multiple, and usually do not cause lumen compromise.

Angina Pectoris↗
PubMed2002

Effectiveness of radioactive tungsten source in the prevention of restenosis in stented porcine coronary arteries.

PURPOSE: Intracoronary radiation has shown the potential to inhibit neointimal proliferation in porcine models of restenosis. The objective of this study was to determine whether intracoronary radiation using a new coiled wire of tungsten-188 ((188)W), a pure beta emitter (half-life 69.4 days) is safe. In addition, a dose of 0 Gy, 18 Gy, or 25 Gy prescribed to 2 mm from the center of the source and delivered intraluminally is sufficient to prevent restenosis and free from adverse effects. METHODS AND MATERIALS: Ten domestic swine underwent 13-mm stent implantation (SI) into two arteries, left anterior descending plus either the left circumflex or right coronary artery. After SI, a closed-end lumen radiation catheter was inserted to the treated artery and a 40-mm coiled (188)W source was manually delivered to cover the stented segment and its margins. A total of 20 arteries were randomized to treatment with a radiation dose of 0, 18 Gy, or 25 Gy delivered to 2 mm depth from the center of the source. Four weeks after the procedure, the swine underwent angiography and intravascular ultrasound using automated pullback at 0.5 mm/s. before being killed and the arteries perfusion fixed. Histopathologic and histomorphometric analyses were performed at 28 days after injury and radiation. RESULTS: Irradiation with (188)W at a dose of 25 Gy after SI significantly inhibited neointima formation (intimal area: 1.05 +/- 0.64 vs. 2.75 +/- 0.99 mm(2), p < 0.01) and at an 18 Gy dose of radiation (intimal area: 1.73 +/- 0.49 vs. 2.75 +/- 0.99 mm(2)), as compared to controls. One artery receiving 18 Gy and two arteries receiving 25 Gy were totally occluded at follow-up due to thrombus formation but no edge stenosis was observed in any of the irradiated arteries. CONCLUSIONS: Intracoronary radiation therapy using a new coiled wire of (188)W source delivered after SI appeared to be safe and well tolerated. The radiation doses demonstrated efficacy in reducing neointima formation in the porcine coronary stent injury model.

Animals↗
PubMed2002

Twelve versus six months of clopidogrel to reduce major cardiac events in patients undergoing gamma-radiation therapy for in-stent restenosis: Washington Radiation for In-Stent restenosis Trial (WRIST) 12 versus WRIST PLUS.

BACKGROUND: Intracoronary gamma-radiation reduces recurrent in-stent restenosis (ISR). Late thrombosis was attenuated with 6 months of aspirin and clopidogrel. We aimed to find out whether 12 months of aspirin plus clopidogrel is superior to a strategy of 6 months after radiation therapy for patients with ISR. METHODS AND RESULTS: One hundred twenty consecutive patients with diffuse ISR in native coronaries and vein grafts with lesions <80 mm in length underwent PTCA, laser ablation, or rotational atherectomy. Additional stents were placed in 39 patients (33%). After the intervention, a ribbon with different trains of radioactive 192Ir seeds was positioned to cover the treated site, and a dose of 14 Gy to 2 mm was prescribed. Patients were discharged with clopidogrel and aspirin for 12 months and followed up clinically. The cardiac clinical event rates at 15 months were compared with the gamma-treated (n=120) patients of the WRIST PLUS study (only 6 months of antiplatelet therapy). Whereas the late thrombosis rates were similar (3.3% for the group given 12 months of antiplatelet therapy versus 4.2% for the group given 6 months, P=0.72), the group treated with 12 months of antiplatelet therapy had a rate of 21% for major adverse cardiac events and 20% for target-lesion revascularization compared with 36% (P=0.01) and 35% (P=0.009), respectively, in patients who were treated with only 6 months of clopidogrel. CONCLUSIONS: Twelve months of clopidogrel is superior to 6 months in reducing overall major cardiac events and revascularization rates at 15 months for patients with ISR treated with gamma-radiation. At least 12 months of clopidogrel therapy should be recommended for patients undergoing radiation therapy for ISR.

Aspirin↗
PubMed2002

Radioactive 133-Xenon gas-filled balloon to prevent restenosis: dosimetry, efficacy, and safety considerations.

BACKGROUND: Ionizing radiation administered intraluminally via catheter-based systems using solid beta and gamma sources or liquid-filled balloons has shown reduction in the neointima formation after injury in the porcine model. We propose a novel system that uses a 133-Xenon (133Xe) radioactive gas-filled balloon catheter system. METHODS AND RESULTS: Overstretch balloon injury was performed in the coronary arteries of 33 domestic pigs. A novel 133Xe radioactive gas-filled balloon (3.5/45 mm) was positioned to overlap the injured segment with margins. After vacuum was obtained in the balloon catheter, approximately 2.5 cc of 133Xe gas was injected to fill the balloon. Doses of 0, 7.5, 15, and 30 Gy were delivered to a distance of 0.25 mm from the balloon surface. The dwell time ranged from 1.0 to 4.0 minutes, depending on the dose. Localization of 133Xe in the balloon was verified by a gamma camera. The average activity in a 3.5/45-mm balloon was measured at 67.7+/-12.1 mCi, and the total diffusion loss of the injected dose was 0.26% per minute of the injected dose. Bedside radiation exposure measured between 2 and 6 mR/h, and the shallow dose equivalent was calculated as 0.037 mrem per treatment. Histomorphometric analysis at 2 weeks showed inhibition of the intimal area (intimal area corrected for medial fracture length [IA/FL]) in the irradiated segments of 0.26+/-0.08 with 30 Gy, 0.07+/-0.24 with 15 Gy, and 0.12+/-0.89 with 7.5 Gy versus 0.76+/-0.08 with control P<0.001. CONCLUSIONS: 133Xe gas-filled balloon is feasible and effective in the reduction of neointima formation in the porcine model and safe for use in coronary arteries.

Angioplasty, Balloon, Coronary↗
PubMed2002

Dose heterogeneity may not affect the neointimal proliferation after gamma radiation for in-stent restenosis: a volumetric intravascular ultrasound dosimetric study.

OBJECTIVES: The goal of this study was to use serial (postirradiation and follow-up) volumetric intravascular ultrasound (IVUS): 1) to evaluate the actual distribution of gamma radiation in human in-stent restenosis (ISR) lesions, and 2) to analyze the relationship between neointimal regrowth and the delivered radiation dose. BACKGROUND: The relationship between the neointimal regrowth and delivered dose during the treatment of ISR remains unknown. METHODS: We analyzed 20 actively (gamma emitter) treated, native artery ISR patients from the Washington Radiation for In-Stent restenosis Trial (WRIST) that met the following criteria: on both postirradiation and six-month follow-up IVUS imaging, > or =80% of the external elastic membrane circumference could be identified throughout the treated length including the lesion and proximal and distal reference segments. Intravascular ultrasound images were digitized every 1 mm. Proximal and distal reference and stented segment luminal and adventitial contours were imported and reconstructed. The source was placed circumferentially at the site of the IVUS catheter and longitudinally according to the relationship between the radioactive seeds and stent edges. Using Monte Carlo simulations, dose volume histograms for the adventitia and intima were calculated. The relationship between the neointimal regrowth and calculated doses were evaluated. RESULTS: There was large dose heterogeneity at both the intimal and adventitial levels. Most of the sites (93%) received >4 Gy at the adventitia, and all of the sites received >4 Gy at the intima. There was no relationship between neointimal regrowth and radiation dose. CONCLUSIONS: Although there may be large dose heterogeneity, gamma irradiation (using a fixed dose prescription) appears to deliver a sufficient dose to prevent neointimal regrowth.

Aged↗
PubMed2002

The effect of intracoronary radiation for the treatment of recurrent in-stent restenosis in patients with diabetes mellitus.

OBJECTIVES: The purpose of this study was to examine the effect of intracoronary radiation therapy (IRT) in diabetic patients with in-stent restenosis (ISR). BACKGROUND: Diabetic patients are at an increased risk for restenosis, repeat revascularization procedures and late mortality after percutaneous coronary interventions and stenting. Intracoronary radiation therapy, utilizing both gamma and beta-emitters, has been shown to reduce the rate of ISR. METHODS: The study group consisted of 749 consecutive patients with ISR who were treated with either IRT or placebo in randomized trials and registries at our center. Diabetic patients (252 radiation and 51 placebo) were compared with nondiabetic patients (371 radiation and 75 placebo). RESULTS: In-hospital outcomes were similar between diabetic and nondiabetic patients treated with and without radiation. At six-month clinical and angiographic follow-up, there was a significant reduction in the binary restenosis (63.8% vs. 15.7%, p < 0.0001), target lesion revascularization (66.7% vs. 17.6%, p < 0.0001) and target vessel revascularization (TVR) (70.6% vs. 22.9%, p < 0.0001) rates in diabetic patients treated with radiation compared to placebo. Comparisons between the placebo arms detected a trend towards higher restenosis (63.8% vs. 48.4% p = 0.13) and TVR (70.6% vs. 56.0%, p = 0.14) in diabetic versus nondiabetic patients. In contrast, diabetic and nondiabetic patients treated with IRT experienced similar restenosis (15.6% vs. 10.7% p = 0.33) and TVR (22.9% vs. 28.2% p = 0.41) rates. CONCLUSIONS: In diabetic patients with ISR, intracoronary radiation significantly reduced the recurrence of ISR compared to placebo. Additionally, similar rates of restenosis and revascularization procedures were achieved in irradiated diabetic and nondiabetic patients. In view of these results, IRT should be considered as a valuable therapeutic alternative in all diabetic patients with ISR.

Aged↗
PubMed2002

Late vascular response to repeat stenting for in-stent restenosis with and without radiation: an intravascular ultrasound volumetric analysis.

BACKGROUND: Re-stenting of in-stent restenosis (ISR) improves acute angiographic results. Methods and Results- Volumetric intravascular ultrasound analysis was performed in 70 ISR lesions that received either placebo (n=36) or (192)Ir radiation (n=34). ISR lesions treated by re-stenting were divided into 3 groups: old stent not re-stented (A), old/new stent overlap (B), and new stent only (C). ISR lesions treated without re-stenting were categorized as D. In placebo patients, postintervention lumen volume index (LVI) was significantly greater in re-stented segments B and C than in non-re-stented segment A (P<0.05).At follow-up, however, LVI was similar in all 4 segments secondary to the increased intimal hyperplasia (IH) reaccumulation within the re-stented segments. In patients treated with (192)Ir radiation, LVI was maintained from baseline to follow-up only in non-re-stented segments A and D. Conversely, there was a significant decrease in LVI in re-stented segments B and C (P<0.05). Qualitatively, 79% of patients in the irradiated group had stent struts with undetectable neointimal versus only 27% in the placebo group (P<0.001). Coefficient of variation of IH reaccumulation was greater in re-stented segments of (192)Ir patients (B=57.3% and C=58.9%) than in re-stented segments in placebo patients (B=27.3% and C 26.8%) and non-re-stented segments in irradiated patients. CONCLUSIONS: Additional lumen gain from re-stenting ISR lesions is counteracted by exaggerated neointimal proliferation in placebo patients. Maximum effectiveness and safety of radiation can be achieved for ISR lesions when treated without re-stenting. Thus, regardless of supplementary intravascular brachytherapy, repeat stenting strategies provided little long-term advantage.

Blood Vessel Prosthesis Implantation↗
PubMed2002

Incidence, morphology, angiographic findings, and outcomes of intramural hematomas after percutaneous coronary interventions: an intravascular ultrasound study.

BACKGROUND: Intramural hematomas during percutaneous coronary intervention (PCI) have not been well studied. METHODS AND RESULTS: We used intravascular ultrasound to determine the incidence, morphology, and clinical features of post-PCI intramural hematomas. In 905 patients with 1025 consecutive native coronary artery, non-in-stent restenosis lesions undergoing PCI, 72 hematomas were detected in 69 arteries in 68 patients. The incidence of intramural hematomas per artery was 6.7% (69 of 1025); 36% (26 of 72) involved the proximal reference artery, 18% (13 of 72) were confined to the lesion, and 46% (33 of 72) involved the distal reference artery. The entry site from the lumen into the hematoma was identified in 86% of hematomas (62 of 72) and had the appearance of a dissection into the media. Conversely, a re-entry site was identifiable in only 8% (6 of 72). The axial extension of the hematoma was distal in 63% and proximal in 37%. In 60% of the hematomas (42 of 72) the angiogram had the appearance of a dissection; in 11% (8 of 72), it appeared to be a new stenosis; and in 29% (22 of 72), no significant abnormality was detected. Non-Q-wave myocardial infarctions occurred in 26% of patients (17 of 65). In 3 patients, the creatine kinase-MB was not measured during the hospital stay. Repeat revascularization occurred in 2 patients in-hospital, 2 additional patients at 1 month, and 8 additional patients at 1 year. There were 3 sudden deaths at 1 year. CONCLUSIONS: Intravascular ultrasound identified intramural hematomas after 6.7% of PCIs. The mechanism appeared to be a dissection into the media where blood accumulated because of a lack of re-entry. A third of ultrasound-identified hematomas showed no angiographic abnormalities. There was a high rate of non-Q-wave myocardial infarction, need for repeat revascularization, and sudden death in patients with hematomas.

Angioplasty, Balloon, Coronary↗
PubMed2002

Intravascular gamma radiation for in-stent restenosis in saphenous-vein bypass grafts.

BACKGROUND: Intracoronary radiation therapy is effective in reducing the recurrence of in-stent stenosis in native coronary arteries. We examined the effects of intravascular gamma radiation in patients with in-stent restenosis of saphenous-vein bypass grafts. METHODS: A total of 120 patients with in-stent restenosis in saphenous-vein grafts, the majority of whom had diffuse lesions, underwent balloon angioplasty, atherectomy, additional stenting, or a combination of these procedures. If the intervention was successful, the patients were randomly assigned in a double-blind fashion to intravascular treatment with a ribbon containing either iridium-192 or nonradioactive seeds. The prescribed dose, delivered at a distance of 2 mm from the source, was 14 to 15 Gy in vessels that were 2.5 to 4.0 mm in diameter and 18 Gy in vessels with a diameter that exceeded 4.0 mm. The primary end points were death from cardiac causes, Q-wave myocardial infarction, revascularization of the target vessel, and a composite of these events at 12 months. RESULTS: Revascularization and radiation therapy were successfully accomplished in all patients. At six months, the restenosis rate was lower in the 60 patients assigned to the iridium-192 group than in the 60 assigned to the placebo group (21 percent vs. 44 percent, P=0.005). At 12 months, the rate of revascularization of the target lesion was 70 percent lower in the iridium-192 group than in the placebo group (17 percent vs. 57 percent, P<0.001), and the rate of major cardiac events was 49 percent lower (32 percent vs. 63 percent, P<0.001). CONCLUSIONS: The results of our study support the use of gamma-radiation therapy for the treatment of in-stent restenosis in patients with bypass grafts.

Aged↗
PubMed2002

The impact of lesion length and reference vessel diameter on angiographic restenosis and target vessel revascularization in treating in-stent restenosis with radiation.

OBJECTIVES: The study assessed the influence of lesion length and reference vessel diameter (RVD) on recurrent restenosis after gamma intracoronary radiation therapy (ICRT) for in-stent restenosis (IRS). BACKGROUND: Intracoronary radiation therapy reduces angiographic and clinical restenosis in patients with ISR. The impact of ICRT on challenging subgroups, such as long lesions and small vessels, has not been established. METHODS: Six-month quantitative coronary angiography and clinical follow-up were conducted to evaluate the influence of lesion length and RVD in patients with ISR treated with ICRT who were enrolled in gamma radiation trials. Angiographic binary restenosis (>50% diameter stenosis) and clinical events were assessed in 311 patients treated with gamma ICRT and 105 patients who received placebo. RESULTS: Baseline demographic, angiographic and procedural details were similar in the two treatment groups. The ICRT group had reduced binary restenosis in vessels of all sizes (30% vs. 66%, p < 0.001), with the most benefit seen in small vessels. A trend toward reduced restenosis with ICRT was found across all lesion lengths. At six months, major adverse cardiac events (MACE) were reduced in the ICRT group compared to placebo (34% vs. 71%, p < 0.0001), driven by reduced target vessel revascularization (27% vs. 71%, p < 0.0001). The independent predictors of angiographic restenosis include ICRT (OR [odds ratio] 0.16; CI [confidence interval] 0.10 to 0.28, p < 0.001), lesion length (OR 1.03; CI 1.01 to 1.05, p = 0.004) and RVD (OR 0.40; CI 0.23 to 0.67, p < 0.001). CONCLUSIONS: Intracoronary radiation therapy, compared to placebo, results in a significant reduction of angiographic restenosis across all vessel sizes, with a trend toward reduction of angiographic restenosis across all lesion lengths; this effect is seen predominantly in small vessels and diffuse lesions.

Aged↗
PubMed2002

Clinical and angiographic outcomes after use of 90Strontium/90Yttrium beta radiation for the treatment of in-stent restenosis: results from the Stents and Radiation Therapy 40 (START 40) registry.

PURPOSE: To evaluate the safety and efficacy of a 40-mm 90Strontium/90Yttrium source train in the management of in-stent restenosis within native coronary arteries. MATERIALS AND METHODS: This multicenter, prospective registry was designed to compare the results of patients with in-stent restenosis treated with a 40-mm source train to the placebo arm of the previously reported randomized Stents and Radiation Trial (START). All patients entered in the registry were treated with repeat balloon angioplasty followed by intravascular brachytherapy. Radiation dose was prescribed based on vessel size. 18 Gy was delivered at 2 mm for vessel diameters between 2.75 and 3.35 mm, and 23 Gy was used for vessels between 3.36 and 4.0 mm. The efficacy endpoints for the START 40 registry included a reduction in the target lesion revascularization (TLR) rate, target vessel revascularization rates, and target vessel failure (TVF) at 8 months. Secondary angiographic efficacy endpoints were binary restenosis at 8 months, in-stent minimum luminal diameter (MLD), and late loss. The safety endpoints included major adverse cardiac events as well as late aneurysm formation. The registry was designed to allow a statistically valid comparison of these results to the placebo group of the START 30 trial. Quantitative angiographic analysis was performed on the 8-month follow-up examination. Rates of restenosis were evaluated for various segments of the treated vessel. A separate analysis was performed to evaluate the relationship between vessel injury length and the radiated segment. RESULTS: A total of 207 patients were entered into the START 40 registry. The postprocedure angiographic results, including the postprocedure MLD and percent diameter stenosis, were similar between the START 40 patients and the placebo group from the START trial in the stented segment of the treated vessel. Eight-month angiographic follow-up was available on 150 patients from the registry. The TLR rate was significantly reduced when compared to the placebo group (11% vs. 22.4% respectively, p = 0.008). A similar reduction was seen in terms of target vessel revascularization (15.9% vs. 24.1%, p = 0.03). The 8-month MLD was found to be significantly larger in the START 40 patients (1.85 mm vs. 1.47 mm, p < 0.0001). The difference seen in the clinical endpoint of TVF (19.3% vs. 25.9%) did not reach statistical significance (p = 0.1). Analysis of the procedural angiograms revealed mismatch between the length of vessel injured and the location of the 90% isodose in 46% of the treated cases. Angiographic analysis revealed that geographic miss was associated with a higher rate of binary restenosis (32% vs. 18% p = 0.04) in the analysis segment. CONCLUSIONS: This multicenter registry demonstrates the safety and efficacy of a 40-mm 90Strontium/90Yttrium source train in the management of patients with in-stent restenosis. Restenosis rates were lowered with the use of this longer source train when compared to the placebo arm of the START trial for lesions with a maximum vessel injury length of 20 mm. Angiographic analysis identified the importance of the accurate delineation of injury length and correct source positioning. These results support the continued use of beta radiation for the treatment of this disease process.

Brachytherapy↗