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Biomedical subjects

Daniel Canos

Publications and source records attributed to Daniel Canos.

At least 19 recordsLinked to original sources

Impact of renal function on coronary plaque morphology and morphometry in patients with chronic renal insufficiency as determined by intravascular ultrasound volumetric analysis.

The aim of the present study was to use intravascular ultrasonography (IVUS) to assess plaque morphology and morphometry in patients with varying degrees of chronic renal insufficiency, including end-stage renal disease (ESRD) on dialysis replacement. Cardiovascular disease is the main cause of death for patients with chronic renal insufficiency, particularly in patients with ESRD. The impact of several degrees of renal insufficiency (including ESRD) on coronary plaque characteristics has not been determined. A total of 142 patients who underwent IVUS imaging of a de novo native coronary artery stenosis before percutaneous intervention were matched for age, gender, and diabetes and were grouped according to calculated creatinine clearance (CrCl): CrCl >70 ml/min (n = 39); CrCl 50 to 69 ml/min (n = 41); CrCl <50 ml/min, (n = 37), and ESRD (n = 25). Standard clinical, angiographic, and IVUS parameters were measured. The ESRD group had more African-American (p = 0.002) and hypertensive (p = 0.002) patients. No significant difference was found in any of the IVUS measurements among patients with CrCl >70, 50 to 69, and <50 ml/min: reference and lesion site arterial, lumen, and plaque areas and volumes, and arterial calcium (p = NS for all comparisons). Conversely, patients with ESRD had larger reference segment arterial and lumen areas and volumes; larger lesion site arterial, lumen, and plaque areas; and larger arcs of calcium (p <0.05 for all post hoc comparisons between patients with ESRD and patients with CrCl >70, 50 to 69, and <50 ml/min). Thus, chronic renal insufficiency in the absence of dialysis is not associated with increased reference segment or lesion site plaque burden and calcium. However, the transition to the need for dialysis is associated with progressive calcific atherosclerosis (larger lesion plaque area and calcium).

Aged↗

Serial intravascular ultrasound comparison of the extent and distribution of intimal hyperplasia six months after stent implantation for de novo versus in-stent restenosis lesions.

The aim of this study was to compare intimal hyperplasia (IH) growth at 6 months in patients with de novo lesions treated with stents versus IH regrowth in patients with treated in-stent restenosis. Intravascular ultrasound was performed after intervention and at the 6-month follow-up visit as part of a standardized protocol across several clinical trials. At 6 months, the lumen was larger in the de novo group (mean lumen cross-sectional area [CSA] 6.31 +/- 2.2 vs 4.48 +/- 1.9 mm(2), p = 0.0001; minimum lumen CSA 4.2 +/- 1.8 vs 2.59 +/- 1.5 mm(2), p = 0.0001). However, the total increase in the mean IH CSA volume was the similar in the de novo and ISR groups (2.89 +/- 1.6 vs 2.64 +/- 1.94 mm(2), respectively; p = 0.11). We found that IH regrowth in restented in-stent restenosis lesions was similar to that in de novo stent implantation and that the final lumen CSA was an important component of in-stent restenosis recurrence.

Coronary Restenosis↗

Impact of treatment of coronary artery disease with sirolimus-eluting stents on outcomes of diabetic and nondiabetic patients.

Patients with diabetes mellitus are at increased risk for repeat interventions and mortality after coronary angioplasty and stenting. The efficacy of sirolimus-eluting stents (SESs) to improve the outcomes of these patients is a focus of interest. In the first 1,407 patients treated with SESs at our institution, 492 were diabetic (insulin dependent diabetes mellitus [IDDM], n = 160 and non-insulin-dependent DM [NIDDM], n = 332). The in-hospital and 1- and 6-month clinical outcomes were compared with those of 915 patients without DM (non-DM). The baseline characteristics were similar, except for more women, obesity, previous myocardial infarction, coronary artery bypass grafting, and renal insufficiency in the DM group (p <0.001). Compared with non-DM patients, DM patients had higher in-hospital (p <0.05) and 1-month mortality (p = 0.02). IDDM patients had more in-hospital renal failure (p = 0.04) and Q-wave myocardial infarctions (1.6% vs 0%, p = 0.04) compared with NIDDM patients, and higher mortality (3.1% vs 0.8%, p = 0.04) and subacute stent thromboses (2.3% vs 0.5%, p = 0.07) than non-DM patients at 30 days. At 6 months, DM patients had a higher incidence of Q-wave myocardial infarction, target lesion revascularization-major adverse cardiac events, and composite of death and Q-wave myocardial infarction than non-DM patients (6.0% vs 2.7%, p = 0.01). Late outcomes between the IDDM and NIDDM groups were similar. Multivariate analysis showed diabetes and acute renal failure as independent predictors of target lesion revascularization-major adverse cardiac events. In conclusion, our data showed that, despite a reduction in repeat revascularization, coronary intervention with SESs in diabetic patients is limited by higher mortality at 1 month and a higher incidence of Q-wave myocardial infarction and target lesion revascularization-major adverse cardiac events at 6 months compared with non-DM patients. Careful surveillance is required in IDDM patients undergoing SES implantation.

Angioplasty, Balloon, Coronary↗

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.

Angioplasty, Balloon, Coronary↗

The potential role of resistin in atherogenesis.

Resistin, an adipocyte-derived cytokine linked to insulin resistance and obesity, has recently been shown to activate endothelial cells (ECs). Using microarrays, we found that along with numerous other pro-atherosclerotic genes, resistin expression levels are elevated in the aortas of C57BL/6J apoE-/- mice; these findings led us to further explore the relation between resistin and atherosclerosis. Using TaqMan PCR and immunohistochemistry, we found that ApoE-/- mice had significantly higher resistin mRNA and protein levels in their aortas, and elevated serum resistin levels, compared to C57BL/6J wild-type mice. Incubation of murine aortic ECs with recombinant resistin increased monocyte chemoattractant protein (MCP)-1 and soluble vascular cell adhesion molecule (sVCAM)-1 protein levels in the conditioned medium. Furthermore, human carotid endarterectomy samples stained positive for resistin protein, while internal mammary artery did not show strong staining. Patients diagnosed with premature coronary artery disease (PCAD) were found to have higher serum levels of resistin than normal controls. In summary, resistin protein is present in both murine and human atherosclerotic lesions, and mRNA levels progressively increase in the aortas of mice developing atherosclerosis. Resistin induces increases in MCP-1 and sVCAM-1 expression in murine vascular endothelial cells, suggesting a possible mechanism by which resistin might contribute to atherogenesis. Finally, PCAD patients exhibited increased serum levels of resistin when compared to controls. These findings suggest a possible role of resistin in cardiovascular disease.

Adult↗

Oral rapamycin to inhibit restenosis after stenting of de novo coronary lesions: the Oral Rapamune to Inhibit Restenosis (ORBIT) study.

OBJECTIVES: The aim of this study was to establish safety and feasibility of oral Rapamycin at two doses-2 mg and 5 mg-in achieving low rates of repeat target lesion revascularization (TLR) in de novo native coronary artery lesions. BACKGROUND: Drug-eluting stents have shown the ability to limit restenosis. Oral Rapamycin is an alternative strategy that can target multiple coronary lesions suitable for treatment with any approved metal stent and at potentially lower cost. METHODS: The Oral Rapamune to Inhibit Restenosis (ORBIT) study is an open-label study of 60 patients with de novo lesions treated with bare metal stents in up to two vessels. After a loading dose of 5 mg, patients received a daily dose of 2 mg (n = 30) and 5 mg (n = 30) for 30 days. Six-month angiographic, intravascular ultrasound (IVUS), and clinical follow-up were conducted. RESULTS: Baseline clinical and procedural characteristics were similar: 10% of patients in the 2-mg group and 30% in the 5-mg group did not complete the course; 43% in the 2-mg group and 66% in the 5-mg group had side effects. At six-month follow-up, late loss (0.6 +/- 0.5 mm vs. 0.7 +/- 0.5 mm; p = NS), in-stent binary restenosis (7.1% vs. 6.9%; p = NS), in-stent percent volume obstruction by IVUS (29% vs. 24%; p = NS), and clinically driven TLR (14.3% vs. 6.9%; p = NS) were similar in 2-mg and 5-mg groups. CONCLUSIONS: Oral Rapamycin for the prevention of restenosis is safe, feasible, and associated with low rates of repeat revascularization. Although associated with certain side effects, it may be considered for patients undergoing multivessel stents if proven in larger randomized studies.

Administration, Oral↗

Value of monitoring activated clotting time when bivalirudin is used as the sole anticoagulation agent for percutaneous coronary intervention.

Anticoagulation during percutaneous coronary intervention (PCI) requires the monitoring of activated clotting time (ACT) to protect from periprocedural ischemic and bleeding complications; however, the optimal ACT values have not been established when PCI is performed with bivalirudin. After 495 consecutive patients treated for coronary artery disease with PCI received bivalirudin as a single anticoagulation agent, it was found that ACT is reproducible when bivalirudin is used during PCI and does not correlate with clinical events.

Aged↗

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↗

Predictors of subacute stent thrombosis: results of a systematic intravascular ultrasound study.

BACKGROUND: Factors leading to subacute stent thrombosis after percutaneous coronary intervention (PCI) have not been well established. We assessed the pre- and post-PCI intravascular ultrasound (IVUS) characteristics of subacute stent thrombosis. METHODS AND RESULTS: We analyzed 7484 consecutive patients without acute myocardial infarction who were treated with PCI and stenting and underwent IVUS imaging during the intervention. Twenty-seven (0.4%) had angiographically documented subacute closure <1 week after PCI (median time to subacute closure, 24 hours). Subacute closure lesions were compared with a control group (selected to be 3 times the abrupt closer group) matched by procedure date (within 6 months), age, gender, stable or unstable angina, lesion location, and additional treatment (balloon angioplasty or atherectomy). Postintervention IVUS did not identify a cause in 22% and did identify at least 1 cause for abrupt closure in 78% of patients (versus 33% in matched lesions, P=0.0002). In 48% of the patients, there were multiple causes in 48% (versus 3% in matched lesions, P<0.0001). Causes included dissection (17%), thrombus (4%), and tissue protrusion within the stent struts leading to lumen compromise lumen (4%). A total of 83% of patients with >1 of these abnormal morphologies also had reduced lumen dimensions post-PCI (final lumen <80% reference lumen). Preprocedural lesion characteristics were not different from matched lesions. CONCLUSIONS: Subacute stent thrombosis is infrequently related to the preintervention lesion characteristics. Inadequate postprocedure lumen dimensions, alone or in combination with other procedurally related abnormal lesion morphologies (dissection, thrombus, or tissue prolapse), contribute to this phenomenon.

Angioplasty, Balloon, Coronary↗

Impact of the acute results on the long-term outcome after the treatment of in-stent restenosis: a serial intravascular ultrasound study.

The current study used serial (postintervention and follow-up) intravascular ultrasound (IVUS) to assess the impact of acute results on long-term follow-up of patients with in-stent restenosis (ISR). All patients (n = 180) with serial IVUS studies of ISR lesions from the following gamma-irradiation brachytherapy trials were included: Washington Radiation for In-Stent Restenosis Trial (WRIST), Gamma-1, and Angiorad Radiation Technology for In-Stent Restenosis Trial in Native Coronaries (ARTISTIC). There were 106 irradiated and 74 placebo patients. Quantitative analysis was performed according to the American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of IVUS. Images were acquired using motorized transducer pullback, cross-sectional analysis was performed every 1 mm, and volumetric and mean planar dimensions were calculated. The independent predictors for the absolute follow-up minimum lumen area (MLA) were the postintervention MLA, the postintervention minimum stent area, and the use of brachytherapy. Placebo patients lost 45% of the postintervention MLA while irradiated patients lost only 17% of the MLA. The independent predictors of the follow-up percent intimal hyperplasia (intimal hyperplasia volume divided by stent volume) and the independent predictors of the absolute increase in intimal hyperplasia were the postintervention percent intimal hyperplasia and the use of brachytherapy. Serial IVUS analysis shows that the follow-up MLA and percent intimal hyperplasia are dependent on the results obtained during the treatment of ISR lesions.

Brachytherapy↗

Effect of direct stenting on clinical outcome in patients treated with percutaneous coronary intervention on saphenous vein graft.

BACKGROUND: Percutaneous coronary intervention (PCI) of saphenous vein graft (SVG) is associated with frequent postprocedural enzyme elevation and late cardiac events. New strategies are proposed to minimize distal embolization and to improve the outcome of patients treated with stenting for SVG lesions. The objectives of the current study were to examine direct stenting (DS) strategy of PCI in SVG lesions and its effects on creatine-kinase (CK) release, major adverse cardiac events (MACE), and late outcome when compared to conventional stenting (CS). METHODS: A consecutive series of 527 patients treated with stent implantation for SVG stenosis was analyzed. In this cohort, 170 patients with 229 lesions were treated with DS and 357 patients with 443 lesions were treated with CS. The inhospital and 12-month follow-up events were recorded and reported. RESULTS: Baseline clinical and postprocedural angiographic characteristics were similar between the 2 groups except for higher preprocedural prevalence of thrombus-containing lesions in the DS group. Patients in the DS group had less CK-MB release (P <.001), and less non-Q-wave myocardial infarction (P =.024). Multivariate analysis detected unstable angina (odds ratio [OR] = 1.8, P =.03) as a correlate for non-Q-wave MI; DS was inversely associated with non-Q-wave myocardial infarction (OR = 0.65, P =.04). At 1 year, the target lesion revascularization-MACE was significantly lower in the DS group (P =.021). Multivariate analysis showed that DS (OR = 0.47, P =.007) was associated with reduction of the target lesion revascularization-MACE. CONCLUSIONS: When feasible, DS may be the best approach for treating SVG stenosis.

Aged↗

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↗

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↗

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↗