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Biomedical subjects

Ron Waksman

Publications and source records attributed to Ron Waksman.

At least 163 records · Page 9Linked to original sources
PubMed2002

The impact of obesity on the short-term and long-term outcomes after percutaneous coronary intervention: the obesity paradox?

OBJECTIVES: The purpose of this study was to assess the impact of body mass index (BMI) on the short- and long-term outcomes after percutaneous coronary intervention (PCI). BACKGROUND: Obesity is associated with advanced coronary artery disease (CAD). However, the relation between BMI and outcome after PCI remains controversial. METHODS: We studied 9,633 consecutive patients who underwent PCI between January 1994 and December 1999. Patients were divided into three groups according to BMI: normal, BMI between 18.5 and 24.9 (n = 1,923); overweight, BMI between 25 and 30 (n = 4,813); and obese, BMI >30 (n = 2,897). RESULTS: Obese patients were significantly younger and had consistently worse baseline clinical characteristics than normal or overweight patients, with a higher incidence of hypertension, diabetes, hypercholesterolemia and smoking history (p < 0.0001). Despite similar angiographic success rates among the three groups, normal BMI patients had a higher incidence of major in-hospital complications, including cardiac death (p = 0.001). At one-year follow-up, overall mortality rates were significantly higher for normal BMI patients compared with overweight or obese patients (p < 0.0001). Myocardial infarction and revascularization rates did not differ among the three groups. By multivariate Cox regression analysis, diabetes, hypertension, age, BMI and left ventricular function were independent predictors of long-term mortality. CONCLUSIONS: In patients with known CAD who undergo PCI, very lean patients (BMI <18.5) and those with BMI within the normal range are at the highest risk for in-hospital complications and cardiac death and for increased one-year mortality.

Age Factors↗
PubMed2002

Use of localised intracoronary beta radiation in treatment of in-stent restenosis: the INHIBIT randomised controlled trial.

BACKGROUND: In-stent restenosis is a major limitation of intracoronary stenting. Ionising gamma radiation has been shown to reduce recurrence of restenosis after stent placement. We aimed to compare the effects of intracoronary beta radiation treatment with those of placebo for clinical and angiographic outcomes of patients with diffuse in-stent restenosis. METHODS: 332 patients with in-stent restenosis underwent successful coronary intervention, and were then randomly allocated to intracoronary beta radiation with a phosphorus-32 source (n=166) or placebo (166) delivered into a centreing balloon catheter through an automatic afterloader. Longer lesions (>22 mm of dilated length) were treated with tandem positioning of the study wire. The primary safety endpoint was major adverse cardiac events, defined as death, myocardial infarction, and repeat target-lesion revascularisation at 9 months. The primary efficacy endpoint was binary angiographic restenosis rate in the analysis segment during 9-months' follow-up. Analysis was by intention to treat. FINDINGS: Procedural success, and in-hospital and 30-day complications were similar among the two groups. 24 (15%) patients in the radiated group had the primary safety endpoint of death, myocardial infarction, or repeat target-lesion revascularisation over 290 days compared with 51 [corrected] (31%) in the placebo group (difference 16% [95% CI 7-25], p = 0.0006). Binary angiographic restenosis rate was lower in the radiated group than the placebo group for the entire analysed segment (difference 25% [14--37], p < 0.0001). INTERPRETATION: Vascular brachytherapy using pure beta-emitter 32P delivered into a centreing catheter via an automatic afterloader can be used to reduce overall revascularisation in patients undergoing treatment for diffuse in-stent restenosis.

Brachytherapy↗
PubMed2002

Quantitative angiographic methods for appropriate end-point analysis, edge-effect evaluation, and prediction of recurrent restenosis after coronary brachytherapy with gamma irradiation.

OBJECTIVES: The study was done to investigate the relationship between clinical restenosis and the relative angiographic location of the recurrent restenotic lesion, after treatment of in-stent restenosis with vascular brachytherapy in the Washington Radiation for In-Stent Restenosis Trial (WRIST). BACKGROUND: Intracoronary radiation therapy reduces recurrence of in-stent restenosis. We investigated the above objective in patients enrolled in WRIST. METHODS: The WRIST study randomized 130 patients to double-blinded therapy with gamma irradiation (iridium-192 [(192)Ir]) versus placebo after interventional treatment of diffuse in-stent restenosis. After the intervention and at follow-up, three vessel segments were individually analyzed with quantitative coronary angiography: 1) the "stent," 2) the "radiation ribbon," and 3) the "ribbon+margin" segment (including 5 mm on either end of the injured or radiation-ribbon segment). Receiver operator curves (ROC) were used to assess the value of the follow-up percent diameter stenosis (DS) for each of the three analyzed segments in predicting target vessel revascularization (TVR). RESULTS: (192)Ir reduced recurrent restenosis (23.7% vs. 60.7%, p < 0.001) and the length of recurrent restenosis (8.99 +/- 4.34 mm vs. 17.54 +/- 10.48 mm, p < 0.001) at follow-up compared to placebo. Isolated stent edge (3.4%) and ribbon edge (1.7%) restenoses were infrequent in both groups. The best angiographic surrogate of TVR was the 50% follow-up DS obtained from the ribbon+margin analysis (ROC area 0.806). CONCLUSIONS: In WRIST, not only was (192)Ir therapy effective in reducing restenosis, but it also reduced the lesion length of treatment failures by 50%, and it was not associated with edge proliferation. The restenosis rate obtained from the vessel segment inclusive of the dose fall-off zones was the best correlate of TVR and should become a standard analysis site in all vascular brachytherapy trials.

Brachytherapy↗
PubMed2002

Device selection in the treatment of in-stent restenosis with and without radiation (from the Gamma Radiation Trials).

In-stent restenosis (ISR) is a major limitation of coronary stenting and is associated with high recurrence rates after intervention with all available devices. Intracoronary gamma (gamma) radiation was proved to reduce the recurrence rate after conventional therapy. The purpose of this study was to compare the different devices utilized for the treatment of ISR with and without gamma radiation. To search for the optimal device for the treatment of ISR, 685 patients from the radiation trials for ISR who were randomized to either iridium-192 gamma radiation (559 patients) or placebo (126 patients) following intervention were evaluated. Devices used included balloon percutaneous transluminal coronary angioplasty, excimer laser coronary angioplasty (ELCA), rotational atherectomy, and additional stent implantation. Baseline clinical and angiographic characteristics were similar between the gamma radiation and placebo groups. One- and 6-month clinical and angiographic outcomes were compared. The use of stenting compared with other devices was associated with increased late loss. Device selection used as adjunctive therapy did not influence the 30-day outcome. Patients treated with gamma radiation and placebo therapy had similar rates of composite major adverse coronary events (MACE) (death, Q-wave myocardial infarction, target vessel revascularization) (3% vs 2%, p = NS). At 6 months, MACE rates in irradiated patients were similar among POBA (29%), ELCA (28%), rotational atherectomy (18%), and additional stent implantation (30%, p = NS), and were significantly lower compared with placebo for the entire cohort and for each device subgroup. The overall recurrence rate of ISR was lower in patients treated with gamma radiation using iridium-192 compared with placebo. Device selection did not influence late clinical outcomes in irradiated and nonirradiated groups.

Aged↗
PubMed2002

Prognostic value of cardiac troponin I elevation after percutaneous coronary intervention in patients with chronic renal insufficiency: a 12-month outcome analysis.

Serum cardiac troponin I (cTnI) is a highly specific marker for myocardial damage in patients with chronic renal insufficiency (CRI), unlike creatine kinase myocardial band fraction (CK-MB), which may be elevated in the absence of myocardial injury in patients with CRI. We studied 116 consecutive CRI patients (serum creatinine +/- 1.8 mg/dL, not on dialysis) with normal baseline cTnI levels who underwent successful percutaneous coronary intervention (PCI). Patients were divided into two groups: group 1, elevated postprocedural cTnI (n = 50), and group 2, normal cTnI (n = 66). Patients with elevated cTnI were older and had a higher incidence of postinfarction angina and lower creatinine clearance compared to patients who did not have cTnI elevation. Atheroablative devices (rotational and directional atherectomy and excimer laser coronary angioplasty) were more frequently used in group 1 patients (27.1% vs. 18.5%; P = 0.04). In-hospital mortality, cardiac mortality, and Q-wave myocardial infarction rates did not differ between the two groups. At 12-month follow-up, total mortality rates were significantly higher in group 1 (28.0% vs. 9.9%; P = 0.002). Multivariate analysis showed that cTnI was an independent predictor of late mortality (OR = 2.26; CI = 1.07-4.77; P = 0.03). Thus, in patients with CRI, elevated cTnI levels after successful PCI is an important predictor of poor long-term outcome. Our data suggest that patients with cTnI elevation > 3 times above normal values are particularly at higher risk.

Age Factors↗
PubMed2002

Elderly patients have a favorable outcome after intracoronary radiation for in-stent restenosis.

Intracoronary radiation therapy (IRT) reduces recurrent in-stent restenosis (ISR) by inhibition of smooth muscle cell proliferation. The ability of these cells to replicate is limited with age due to changes in the telomeres. The purpose of this study was to assess the effect of age on outcomes following IRT for ISR. We evaluated 1,088 patients with 6-month clinical follow-up who were enrolled in radiation trials for ISR using gamma- and beta-emitters. Patients were analyzed within and between IRT (n = 861) or placebo therapy (n = 227) in four age groups (< 55, 55-65, 66-75, > 75 years). Baseline characteristics were similar within each age group of IRT patients, except elderly patients (> 75 years) had a lower rate of diabetes (28% in patients > 75 years; P = 0.008) and a higher rate of previous CABG (59% in patients > 75 years; P < 0.001). The rate of target lesion revascularization (TLR) was reduced in the elderly. TLR at 6 months was 18% in patients < 55 years, 21% in 55-65 years, 12% in 66-75 years, and 10% in patients > 75 (P = 0.009). The MACE rate at 6 months was 21% in patients < 55 years, 29% in 55-65 years, 26% in 66-75 years, and 17% in patients > 75 (P = 0.03). No effect of age was seen in placebo patients. IRT-treated patients had reduced MACE compared to placebo in all age groups, driven by reduced target vessel revascularization. Age was an independent predictor of MACE at 6 months (OR = 0.8; CI = 0.70-0.93; P = 0.004). Angiographic restenosis was not clearly associated with need for TLR in patients > 75 years. In elderly patients (> 75 years) treated with IRT for ISR, the rate of TLR was significantly reduced compared to younger patients. However, this reduction in TLR was not associated with a reduction in angiographic restenosis, suggesting that TLR should not be used as a surrogate for angiographic evaluation.

Age Factors↗
PubMed2002

Balloon-based radiation therapy for treatment of in-stent restenosis in human coronary arteries: results from the BRITE I study.

Catheter-based intracoronary radiation therapy demonstrated reduction of the recurrence rate of in-stent restenosis by 35%-50% when compared to conventional therapy. The objectives of this study were to determine the safety and feasibility of a new balloon-shaped source design and a higher applied dose to reduce the restenosis rates. Thirty-two patients with in-stent restenosis who met study eligibility criteria were successfully treated with standard PCI techniques. Following a successful intervention, a P-32 beta-balloon source was positioned to cover the angioplasty site and a dose of a 20 Gy at 1 mm from the surface of the source was administered. The primary endpoint was a composite of major adverse cardiac events (any death, MI, emergent CABG, or repeat target vessel revascularization) during 6 months of follow-up. At 6 months, only one patient underwent repeat PTCA to the target vessel (3%). There were no instances of death, emergency surgery, late thrombosis, total occlusions, or MI. Binary restenosis measured by QCA at the stented segment was 0% and for the whole analysis vessel was 7.5%. Beta-radiation delivered with a balloon P-32 source design for patients with in-stent restenosis results in lower than expected rate of angiographic and clinical restenosis and the absence of late complications.

Aged↗
PubMed2002

The WRIST series--what have we learnt?

BACKGROUND: The evolution of the WRIST (Washington Radiation for In-Stent Restenosis Trial) series has reflected the progress that has been made in intracoronary radiation for In-stent restenosis of coronary artery and saphenous vein graft disease. We have enrolled over 1,500 patients in eleven WRIST series performed at the Washington Hospital Center, providing a unique and powerful data set that is pivotal in our understanding of vascular brachytherapy. AIM: This review is intended to give an overview of the individual trials, summarize pertinent lessons that have been learned and give insight into future of intracoronary radiation.

Aged↗
PubMed2002

Peripheral vascular brachytherapy.

Ongoing advances in peripheral endovascular technology have been met with disappointing results because of restenosis within the treated vessel. In particular, stent balloon angioplasty of peripheral vessels has yet to achieve patency rates that approximate conventional treatment in the long term. Recent advances in stent, balloon, and wire construction include the incorporation of radioactive substances in an attempt to ameliorate the inflammatory response provoked by typical endovascular manipulation, a technique termed vascular brachytherapy. gamma- and beta-isotopes and external beam radiation target the very cell population whose activity results in the development of neointimal hyperplasia. Although most clinical research examining the efficacy of vascular brachytherapy has emerged from the coronary artery literature, the use of vascular brachytherapy also has been examined in the peripheral arterial tree and has shown promising results. Current data indicate that vascular brachytherapy is a safe and accessible adjunctive endovascular maneuver that may improve the short-term patency rate of peripheral endovascular applications. The effects on long-term patency rates remain indeterminate compared to conventional therapy.

Brachytherapy↗
PubMed2002

Contemporary revascularization strategies in 2002.

This review analyzes important facets of contemporary percutaneous coronary interventions. The optimal strategy of acute myocardial infarction and shock is addressed, as is the role of angioplasty in multivessel coronary disease. Vascular Brachytherapy is essentially the sole available treatment modality for in-stent restenosis. The WRIST trials have provided the foundation for clinical experience and are discussed in detail. Finally, drug-eluting stents may become the next revolution in interventional cardiology and offer the hope of a "cure" for restenosis.

Angioplasty, Balloon↗
PubMed2002

Influence of device selection on angiographic outcomes for the treatment of in-stent restenosis. A sub analysis from the Washington Radiation for In-Stent restenosis Trial (WRIST).

BACKGROUND: Treatment of in-stent restenosis is still a challenge. Despite promising results obtained with intracoronary brachytherapy (ICB), the ideal strategy of device selection has not been identified. The aim of this study was to evaluate the influence of device selection on ICB for the treatment of instant restenosis. METHODS: The outcomes of 130 patients from the Washington Radiation for In-Stent restenosis Trial (WRIST) were studied. Patients were analyzed on the basis of device selection, prior to randomization to gamma-radiation (n = 65) or placebo (n = 65): balloon angioplasty (PTCA) (n = 15, 12%), rotational atherectomy (RA) (n = 40, 31%), excimer laser coronary angioplasty (ELCA) (n = 28, 22%) or additional stent implantation (n = 47, 36%). RESULTS: PTCA was less frequently used in lesions with prior in-stent restenosis (14.8%, p < 0.05); ELCA was less frequently used in saphenous vein grafts (57.1%, p < 0.05). The procedural outcomes and restenosis rates were similar among groups. In the RA group, patients assigned or Ir192 had a larger minimal lumen diameter (1.6 +/- 0.5 vs 0.9 +/- 0.4 mm, p < 0.05) and lower diameter stenosis (39 +/- 7 vs 65 +/- 16%, p < 0.05) at follow-up angiography and a reduced late loss (0.2 +/- 0.5 v 0.9 +/- 0.5 mm, P < 0.05) and loss index (0 +/- 0.4 vs 0.8 +/- 0.4, p < 0.05) when compared to placebo. The incidence of delayed thrombosis was 7.7% in the ICB and 4.6% in the placebo group (p = 0.71); additional stenting, either alone (relative risk 12.36, 95% confidence interval 1.56 divided by 94.43) or followed by ICB (relative risk 3.80, 95% confidence interval 1.02 divided by 14.27), was correlated with an increased risk of late thrombosis. CONCLUSIONS: ICB reduces the recurrence of in-stent restenosis through a reduction in late loss. In view of the higher risk of delayed thrombosis, additional stenting, either alone or followed by ICB, should be used with caution.

Angioplasty, Balloon, Coronary↗
PubMed2002

Clinical trials of intracoronary gamma radiation therapy for in-stent restenosis.

The only gamma emitter used in clinical trials for in-stent restenosis is 192Iridium (192Ir). The efficacy of intracoronary gamma radiation therapy in reducing clinical and angiographic restenosis in patients with in-stent restenosis has been established. This review is intended to give an overview of the clinical trials utilizing gamma vascular brachytherapy in patients with in-stent restenosis and give insight into the future of intracoronary radiation therapy.

Angioplasty, Balloon, Coronary↗
PubMed2002

Vascular brachytherapy: applications in the era of drug-eluting stents.

Vascular brachytherapy using beta and gamma emitters has revolutionized treatment of in-stent restenosis. We are witnessing a near-abolition of the restenosis problem for simple lesions, but the future of vascular brachytherapy depends on our success in improving efficacy and reducing complications such as late thrombosis and edge effects. Optimizing dosimetry, applying adequate radiation margins, and prolonging antiplatelet therapy should equalize brachytherapy results with those of drug-eluting stents. In this overview we examine issues related to progress and optimization of outcomes derived from the use of vascular brachytherapy. We also examine its potential to expand to other applications beyond in-stent restenosis, such as the treatment of de novo lesions and peripheral vascular disease

Angioplasty, Balloon, Coronary↗
PubMed1998

Low-energy X-radiation for prevention of restenosis results in localized inhibition of V79 fibroblast cell proliferation.

Local delivery of high-energy ionizing radiation by using 3 or 3 emitters to injured vessels demonstrated inhibition of cell proliferation (CP) and neointima formation. Low-energy ('soft') X-radiation (LEXR) offers logistic and safety advantages over the use of disposable radioisotopes. This study evaluated the efficacy of LEXR in penetration and inhibition of CP at doses similar to those prescribed for the use of radioisotopes for prevention of restenosis. Serial measurements in an ion chamber detected the attenuation of LEXR using potentials of 17 and 40 kV at a distance of 17 cm of air through 0-10 mm depths of serum-containing tissue culture medium. The effect of inhibition on CP was determined by exposing V79 fibroblasts to a potential of 17 kV in order to deliver a prescribed dose of 13 Gy at a dose rate of 2.17 Gy/min to the surface of the cells. Complete inhibition of CP at a height of 0.00 mm occurred with 13 Gy; however, a 50% attenuation of the dose was measured at a medium depth of 1.22 mm and was associated with a reduction of 60% of the CP. LEXR demonstrated an ability to inhibit CP at doses equivalent to those used in techniques involving 3 and 3 irradiation. Under such conditions, the dose gradient is too high, especially for large vessels. However, a catheter-based LEXR that could be inserted into the artery with the capability of varying effective energy would be ideal for intravascular applications.

Journal Article↗