Hyperspectral cathodoluminescence imaging and analysis extending from ultraviolet to near infrared.

The measurement of near-infrared (NIR) cathodoluminescence (CL) with sufficient sensitivity to allow full spectral mapping has been investigated through the application of optimized grating spectrometers that allow the ultraviolet (UV), visible, and NIR CL spectra to be measured simultaneously. Two optical spectrometers have been integrated into an electron microprobe, allowing simultaneous collection of hyperspectral CL (UV-NIR), characteristic X-rays, and electron signals. Combined hyperspectral CL spectra collected from two natural apatite (Ca5[PO4]3[OH,F]) samples from Wilberforce (Ontario, Canada) and Durango (Mexico) were qualitatively analyzed to identify the emission centers and then deconvoluted pixel-by-pixel using least-squares fitting to produce a series of ion-resolved CL intensity maps. Preliminary investigation of apatite has shown strong NIR emissions associated primarily with the rare-earth element Nd. Details of growth and alteration were revealed in the NIR that were not discernable with electron-induced X-ray mapping. Intense emission centers from Nd3+ and Sm3+ were observed in the spectra from both apatites, along with minor emissions from other 3+ rare-earth elements. Quantitative electron probe microanalysis was performed on points within the mapped area of the Durango apatite to produce a calibration line relating cathodoluminescent intensity of the fitted peak centered at 1,073 nm (1.156 eV) to the Nd concentration.

Predictive value of dobutamine stress echocardiography for coronary artery disease detection in liver transplant candidates.

Patients with obstructive coronary artery disease (CAD) undergoing orthotopic liver transplantation (OLT) are at increased risk of poor outcomes. The accuracy of dobutamine stress echocardiography (DSE) to detect obstructive CAD is not well established in this population. We retrospectively identified patients with end-stage liver disease who underwent both DSE and coronary angiography as part of risk stratification prior to OLT. One hundred and five patients had both DSE and angiography, of whom 14 had known CAD and 27 failed to reach target heart rate during DSE. Among the remaining 64 patients (45 men; average age 61 +/- 8 years) DSE had a low sensitivity (13%), high specificity (85%), low positive predictive value (PPV) (22%) and intermediate negative predictive value (NPV) (75%) for obstructive CAD. DSE as a screening test for obstructive CAD in OLT candidates has a poor sensitivity. The frequent chronotropic incompetence and low sensitivity in patients who achieve target heart rate, even in those with multiple cardiovascular disease risk factors, suggest that alternative or additional methods of risk stratification are necessary.

Impact of intracoronary aspiration thrombectomy during primary angioplasty on left ventricular remodelling in patients with anterior ST elevation myocardial infarction.

OBJECTIVE: To evaluate prospectively the impact on left ventricular (LV) remodelling of an intracoronary aspiration thrombectomy device as adjunctive therapy in primary percutaneous coronary intervention (PCI) in patients with anterior ST elevation myocardial infarction (STEMI). METHODS: 76 consecutive patients with anterior STEMI (65.3 (11.2) years, 48 men) were randomly assigned to intracoronary thrombectomy and stent placement (n = 38) or to conventional stenting (n = 38) of the infarct related artery. Each patient underwent transthoracic echocardiography immediately after PCI and at six months. At the time of echocardiographic control, major adverse cardiovascular events (MACE) in terms of death, new onset of myocardial infarction, and hospitalisation for heart failure were also evaluated. RESULTS: After a successful primary PCI, patients in the thrombectomy group achieved a higher rate of post-procedure myocardial blush grade 3 (36.8% v 13.1%, p = 0.03) and effective ST segment resolution at 90 minutes (81.6% v 55.3%, p = 0.02). Six months after the index intervention, 19 patients (26.8%) developed LV dilatation, defined as an increase in end diastolic volume (EDV) >or= 20%: 15 in the conventional group and four in the thrombectomy group (p = 0.006). Accordingly, at six months patients treated conventionally had significantly higher end systolic volumes (82 (7.7) ml v 75.3 (4.9) ml, p < 0.0001) and EDV (152.5 (18.1) ml v 138.1 (10.7) ml, p < 0.0001) than patients treated with thrombectomy. No differences in cumulative MACE were observed (10.5% in the conventional group v 8.6% in the thrombectomy group, not significant). CONCLUSION: Compared with conventional stenting, adjunctive aspiration thrombectomy in successful primary PCI seems to be associated with a significantly lower incidence of LV remodelling at six months in patients with anterior STEMI.

450 million years of hemostasis.

In mammalian blood coagulation, five proteases (factor VII [FVII]; factor IX [FIX]; factor X [FX]; protein C [PC] and prothrombin [PT]) act with five cofactors (tissue factor [TF]; factor V [FV]; factor VIII [FVIII]; thrombomodulin and protein S) to control the generation of fibrin. Biochemical evidence, molecular cloning data and comparative sequence analysis support the existence of all components of this network in all jawed vertebrates, and strongly suggest that it evolved before the divergence of teleosts over 430 million years ago. Phylogenetic analysis of the amino acid sequences of the Gla-EGF1-EGF2-SP domain serine proteases (FVII, FIX, FX, PC) and the A domain-containing cofactors (FV and FVIII) strongly supports the evolution of the blood coagulation network through two rounds of gene duplication, and supports the hypothesis that vertebrate evolution benefited from two global genome duplications. The jawless vertebrates (hagfish and lamprey) that diverged over 450 million years ago have a blood coagulation network involving TF, PT and fibrinogen. Preliminary evidence indicates that they may have a smaller complement of Gla-EGF1-EGF2-SP domain proteins, suggesting the existence of a 'primitive' coagulation system in jawless vertebrates.

Predictors of long-term outcomes following direct percutaneous coronary intervention for acute myocardial infarction.

To determine predictors of a long-term major adverse cardiac event (MACE) in unselected patients undergoing direct percutaneous coronary intervention (PCI), 274 consecutive patients presenting within 12 hours of ST-segment elevation acute myocardial infarction (AMI) were evaluated. No patient with ST-segment elevation AMI received intravenous thrombolytic drugs. Chest pain to balloon time was 3.8 hours (range 2.5 to 6.9). percutaneous transluminal coronary angioplasty was successful in 95% of patients. Abciximab was administered to 69% of patients, stents were deployed in 53%, and 17% underwent only catheterization. In-hospital events were death (7%), abrupt closure (2%), emergent coronary artery bypass grafting (CABG) (5%), repeat PCI (3%), and recurrent myocardial infarction (1%). In patients undergoing direct PCI (n = 227), the in-hospital event rate was death 5.3%, abrupt closure 2.2%, emergency CABG 0.9%, repeat PCI 3.1%, and repeat myocardial infarction 1.3%. Median time to last follow-up or death was 20 months (range 11 to 34), and to any event, 0.3 months (range 0.03 to 24.0). Postdischarge MACE included death (5%), AMI (4%), repeat PCI (8%), CABG (9%), and stroke (0.7%). Among those undergoing direct PCI (n = 227), 10% died, 3.5% had a repeat AMI, 9% had a repeat PCI, 5% had CABG, and 1% had a stroke at long-term follow-up. At long-term follow-up, 75% were event free. Multivariate predictors were (hazard ratio [95% confidence interval (CI)]): abciximab use 0.6 (95% CI 0.43 to 0.95), Killip class 2.2 (95% CI 1.1 to 4.4), and number of narrowed coronary arteries 1.7 (95% CI 1.4 to 2.2). In this unselected consecutive series of patients presenting with ST-segment elevation AMI, direct PCI was associated with sustained long-term efficacy. Outcomes were predicted by cardiac impairment at presentation and number of narrowed coronary arteries. MACE is not related to device selection but is significantly improved with abciximab.

Clinical pharmacology of higher dose eptifibatide in percutaneous coronary intervention (the PRIDE study).

This study describes the dose-exploration phase of the PRIDE trial, an investigation of the clinical pharmacology of higher dose eptifibatide in patients who underwent elective percutaneous coronary intervention (PCI). Outcomes of treatment with the platelet glycoprotein IIb/IIIa inhibitors were dependent upon proper dosing selection. In this multicenter, placebo-controlled clinical study, 127 patients were randomized 1:1:2:2 into 1 of the following treatment groups: placebo; eptifibatide as a 135 microg/kg bolus followed by a 0.75 microg/kg/min infusion; eptifibatide as a 180 microg/kg bolus with a 2.0 microg/kg/min infusion; or eptifibatide as a 250 microg/kg bolus with a 3.0 microg/kg/min infusion. Light transmission aggregometry was used to determine platelet aggregation in response to 20 microM adenosine diphosphate, and platelet receptor occupancy was also determined. Eptifibatide exhibited linear pharmacokinetics over the dose range studied. Inhibition of platelet aggregation was greater in samples collected in sodium citrate compared with those collected in D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone. The 180/2.0 dosing regimen achieved 90% inhibition of platelet aggregation immediately (5 minutes) and at steady state (8 to 24 hours). At 1 hour, mean inhibition of platelet aggregation was 80%. Eptifibatide exhibited dose-dependent pharmacodynamics that were dependent upon choice of anticoagulant. A 180 microg/kg bolus followed by a 2.0 microg/kg/min infusion at steady state achieved >80% inhibition of platelet aggregation. With the single-bolus regimen, however, there was an early loss of the inhibition of platelet aggregation before steady state was reached. Additional dose-exploration studies may further optimize eptifibatide dosing.

In-hospital and long-term outcomes of patients with acute myocardial infarction undergoing direct angioplasty during regular and after hours.

Off-hours presentation resulted in a significant increase in the onset of pain to balloon inflation time (approximately 1.3 hours) as well as the emergency room to balloon inflation time (approximately 54 minutes). However, this delay to reperfusion did not result in a difference in clinical outcomes (in-hospital or long-term) in patients undergoing direct percutaneous transluminal coronary angioplasty within 12 hours of the onset of acute myocardial infarction.

Adjunctive therapies in the cath lab. Successful thrombolysis using the combination of tissue plasminogen activator and abciximab in an adult with Kawasaki's disease.

Kawasaki's disease is an acute systemic vasculitic syndrome that primarily affects children. Coronary aneurysms are common vasculitic sequelae of Kawasaki's disease. Intracoronary thrombosis and embolization are potential consequences of coronary aneurysms. We describe our experience of successful thrombolysis using the combination of reduced-dose intravenous tissue plasminogen activator and abciximab as described in the Thrombolysis in Myocardial Infarction 14 trial (TIMI 14) to treat a patient found to have intracoronary thrombus at the site of aneurysm formation due to Kawasaki's disease.

Excimer laser facilitated percutaneous coronary intervention of a nondilatable coronary stent.

A patient is described in which excimer laser percutaneous coronary intervention is performed inside a suboptimally expanded stent due to nondilatable calcified plaque. The use of excimer laser facilitated full expansion of the stent with a balloon.

Resource utilization and clinical outcomes of coronary stenting: a comparison of intravascular ultrasound and angiographical guided stent implantation.

BACKGROUND: Intravascular ultrasound (IVUS) guided stent implantation studies have demonstrated that inadequate stent implantation can occur despite achieving an optimal angiographic result. Furthermore, IVUS-guided stent implantation has been shown to improve lesional acute gain. However, it is unknown whether the use of IVUS guidance during stent implantation is associated with improved acute and long-term clinical outcomes. Moreover, the additional procedural cost and time incurred with the use of IVUS-directed stent implantation has not been evaluated. Thus the purpose of this study was to determine whether IVUS-guided stent implantation is associated with improved clinical outcomes compared with angiographically guided stent implantation and to evaluate the difference in resource utilization between these respective stent deployment strategies. METHODS: Data were collected on 278 consecutive patients in whom 455 stents were deployed in native coronary arteries. High-pressure (> or = 12 atm) balloon inflations were performed until an optimal angiographic result was obtained. In the angiographically guided group, no IVUS imaging was performed. In the IVUS-guided group, IVUS imaging and additional interventions were performed attempting to achieve full apposition, absence of edge tear, and acute gain (lesion lumen area: distal reference lumen area) > or = 0.8 in subsequent IVUS imaging. Total procedure time, fluoroscopy time, contrast media volume, number of balloons, stents, guidewires, guide catheters, and procedural cost were calculated. In hospital abrupt closure rate and 6-month major adverse cardiovascular events (cardiac death, myocardial infarction, target vessel revascularization) rate were obtained. RESULTS: A total of 178 patients underwent IVUS-guided stent placement and 100 patients underwent angiographically guided stent implantation. There was no significant difference in procedure time (107 +/- 49 vs 100 +/- 50 minutes, P = .22), fluoroscopy time (33 +/- 24 vs 30 +/- 18 minutes, P = .36), contrast volume (411 +/- 157 vs 386 +/- 181 mL, P = .23), guide catheters (1.3 +/- 0.8 vs 1.3 +/- 0.6, P = .69), guidewires (1.6 +/- 1.2 vs 1.6 +/- 1.0, P = .99), balloons (2.4 +/- 1.0 vs 2.3 +/- 1.3, P = .58), and stents (1.7 +/- 0.9 vs 1.6 +/- 0.9, P = .42). Intraprocedural cost was significantly higher in the IVUS-guided group, $4142 +/- 1547 verus $3635 +/- 1949 (P = .03), which was primarily related to the cost of the IVUS catheter. However, the in-hospital acute vessel closure rate was significantly lower in the IVUS-guided group, 0.6% versus 4% (P = .04). There was a trend toward lower target vessel revascularization rate in the IVUS-guided group (11% vs 19%, P = .08). By multivariate analysis IVUS use was demonstrated to be an independent negative predictor of cardiac death, myocardial infarction, repeat revascularization, and abrupt stent closure with a relative risk of 0.49 (95% confidence interval of 0.25 to 0.98), and P = .04. CONCLUSIONS: The use of IVUS guidance during stent implantation does not significantly increase procedure time, fluoroscopy exposure, contrast volume, or device utilization. Furthermore, despite the increase in procedural cost, IVUS-guided stent implantation is associated with a significant decrease in the in-hospital abrupt closure rate and a trend toward a lower 6-month target vessel revascularization.

Visualization of discrete microinfarction after percutaneous coronary intervention associated with mild creatine kinase-MB elevation.

BACKGROUND: Mild elevations in creatine kinase-MB (CK-MB) are common after successful percutaneous coronary interventions and are associated with future adverse cardiac events. The mechanism for CK-MB release remains unclear. A new contrast-enhanced MRI technique allows direct visualization of myonecrosis. METHODS AND RESULTS: Fourteen patients without prior infarction underwent cine and contrast-enhanced MRI after successful coronary stenting; 9 patients had procedure-related CK-MB elevation, and 5 did not (negative controls). The mean age of all patients was 61 years, 36% had diabetes, 43% had multivessel coronary artery disease, and all had a normal ejection fraction. Twelve patients (86%) received an intravenous glycoprotein IIb/IIIa inhibitor; none underwent atherectomy, and all had final TIMI 3 flow. Of the 9 patients with CK-MB elevation, 5 had a minor side branch occlusion during stenting, 2 had transient ECG changes, and none developed Q-waves. The median CK-MB was 21 ng/mL (range, 12 to 93 ng/mL), which is 2.3x the upper limit of normal. Contrast-enhanced MRI demonstrated discrete regions of hyperenhancement within the target vessel perfusion territory in all 9 patients. Only one developed a new wall motion abnormality. The median estimated mass of myonecrosis was 2.0 g (range, 0.7 to 12.2 g), or 1.5% of left ventricular mass (range, 0.4% to 6.0%). Hyperenhancement persisted in 5 of the 6 who underwent a repeat MRI at 3 to 12 months. No control patient had hyperenhancement. CONCLUSIONS: Contrast-enhanced MRI provides an anatomical correlate to biochemical evidence of procedure-related myocardial injury, despite the lack of ECG changes or wall motion abnormalities. Mild elevation of CK-MB after percutaneous coronary intervention is the result of discrete microinfarction.

Thrombotic thrombocytopenic purpura associated with clopidogrel.

BACKGROUND: The antiplatelet drug clopidogrel is a new thienopyridine derivative whose mechanism of action and chemical structure are similar to those of ticlopidine. The estimated incidence of ticlopidine-associated thrombotic thrombocytopenic purpura is 1 per 1600 to 5000 patients treated, whereas no clopidogrel-associated cases were observed among 20,000 closely monitored patients treated in phase 3 clinical trials and cohort studies. Because of the association between ticlopidine use and thrombotic thrombocytopenic purpura and other adverse effects, clopidogrel has largely replaced ticlopidine in clinical practice. More than 3 million patients have received clopidogrel. We report the clinical and laboratory findings in 11 patients in whom thrombotic thrombocytopenic purpura developed during or soon after treatment with clopidogrel. METHODS: The 11 patients were identified by active surveillance by the medical directors of blood banks (3 patients), hematologists (6), and the manufacturer of clopidogrel (2). RESULTS: Ten of the 11 patients received clopidogrel for 14 days or less before the onset of thrombotic thrombocytopenic purpura. Although 10 of the 11 patients had a response to plasma exchange, 2 required 20 or more exchanges before clinical improvement occurred, and 2 had relapses while not receiving clopidogrel. One patient died despite undergoing plasma exchange soon after diagnosis. CONCLUSIONS: Thrombotic thrombocytopenic purpura can occur after the initiation of clopidogrel therapy, often within the first two weeks of treatment. Physicians should be aware of the possibility of this syndrome when initiating clopidogrel treatment.

Randomized trial of contrast media utilization in high-risk PTCA: the COURT trial.

BACKGROUND: Previous in vitro and in vivo studies have suggested an association between thrombus-related events and type of contrast media. Low osmolar contrast agents appear to improve the safety of diagnostic and coronary artery interventional procedures. However, no data are available on PTCA outcomes with an isosmolar contrast agent. METHODS AND RESULTS: A multicenter prospective randomized double-blind trial was performed in 856 high-risk patients undergoing coronary artery intervention. The objective was to compare the isosmolar nonionic dimer iodixanol (n=405) with the low osmolar ionic agent ioxaglate (n=410). A composite variable of in-hospital major adverse clinical events (MACE) was the primary end point. A secondary objective was to evaluate major angiographic and procedural events during and after PTCA. The composite in-hospital primary end point was less frequent in those receiving iodixanol compared with those receiving ioxaglate (5.4% versus 9.5%, respectively; P=0.027). Core laboratory defined angiographic success was more frequent in patients receiving iodixanol (92.2% versus 85. 9% for ioxaglate, P=0.004). There was a trend toward lower total clinical events at 30 days in patients randomized to iodixanol (9.1% versus 13.2% for ioxaglate, P=0.07). Multivariate predictors of in-hospital MACE were use of ioxaglate (P=0.01) and treatment of a de novo lesion (P=0.03). CONCLUSIONS: In this contemporary prospective multicenter trial of PTCA in the setting of acute coronary syndromes, there was a low incidence of in-hospital clinical events for both treatment groups. The cohort receiving the nonionic dimer iodixanol experienced a 45% reduction in in-hospital MACE when compared with the cohort receiving ioxaglate.

Exacerbation of radiocontrast nephrotoxicity by endothelin receptor antagonism.

BACKGROUND: Endothelin is a potent vasoconstrictor that has been implicated in the pathogenesis of radiocontrast nephrotoxicity. Endothelin antagonists may reduce the renal hemodynamic abnormalities following radiocontrast administration. METHODS: One hundred fifty-eight patients with chronic renal insufficiency [mean serum creatinine +/- SD = 2.7 +/- 1.0 mg/dL (242. 3 to +/- 92.8 micromol/L)] and undergoing cardiac angiography were randomized to receive either a mixed endothelin A and B receptor antagonist, SB 290670, or placebo. All patients received intravenous hydration with 0.45% saline before and after radiocontrast administration. Serum creatinine concentrations were measured at baseline, 24 hours, 48 hours, and 3 to 5 days after radiocontrast administration. The primary end point was the mean change in serum creatinine concentration from baseline at 48 hours; the secondary end point was the incidence of radiocontrast nephrotoxicity, defined as an increase in serum creatinine of > or =0.5 mg/dL (44 micromol/L) or > or = 25% from baseline within 48 hours of radiocontrast administration. RESULTS: The mean increase in serum creatinine 48 hours after angiography was higher in the SB 209670 group [0.7 +/- 0. 7 mg/dL (63.5 +/- 58.6 micromol/L)] than in the placebo group [0.4 +/- 0.6 mg/dL (33.6 +/- 55.1 micromol/L), P = 0.002]. The incidence of radiocontrast nephrotoxicity was also higher in the SB 209670 group (56%) compared with placebo (29%, P = 0.002). This negative effect of SB 209670 was apparent in both diabetic and nondiabetic patients. Adverse effects, especially hypotension or decreased blood pressure, were more common in the SB 209670 group. CONCLUSIONS: In patients with chronic renal insufficiency who were undergoing cardiac angiography, endothelin receptor antagonism with SB 209670 and intravenous hydration exacerbate radiocontrast nephrotoxicity compared with hydration alone.

Role of intracoronary ultrasound after high-pressure stent implantation.

BACKGROUND: Poststent high-pressure balloon inflation has been shown to improve clinical outcomes. However, it is unknown whether intracoronary ultrasound (ICUS) provides additional clinical guidance after initial high-pressure balloon inflation is used during stent placement. Thus the purpose of this study was to determine if stent deployment techniques are improved with ICUS imaging despite an optimal angiographic result achieved with high-pressure balloon inflation. METHODS AND RESULTS: Prospective data were collected on 96 consecutive patients in whom 151 stents were deployed. Stents and high-pressure balloons were angiographically sized 1:1 by visual estimation. High-pressure (> or =12 atm in all cases) balloon inflations were continued until angiographic completion (<10% residual stenosis), after which index ICUS imaging was performed. Stent apposition, symmetry, and lumen dimensions were evaluated. An optimal ICUS result was defined as full apposition of the stent, symmetry ratio > or =0.80, and acute gain > or =0.80 of the reference lumen area. If inadequate ICUS results were found, further dilations with higher pressures or larger balloons and subsequent stent reevaluation with ICUS were performed. Sixty-nine (46%) stents required additional balloon inflations. Of these stents, 35 (23%) had initial acute gains that were <80% of the reference lumen area. Forty-six (30%) stents were found to have unapposed struts and 24 (16%) had a symmetry ratio <0.80. In patients requiring additional inflations, minimum stent area increased from 7.6 +/- 2.2 mm(2) to 9.2 +/- 2.4 mm(2) (P <.0001). Similarly, complete stent apposition improved from 33% to 68% of total stents (P <.0001). After initial ICUS, higher-pressure dilations were performed in 40 patients, whereas larger balloons greater than or equal to ICUS reference vessel diameter were used in 33 patients. Follow-up was obtained in 95 (99%) patients. The overall major adverse cardiac event rate at 6 months was 9.3%, which consisted of 8 target vessel revascularizations and 1 abrupt closure requiring repeat intervention. CONCLUSIONS: Even when poststent high-pressure balloon inflation achieves an optimal angiographic result, ICUS assists in optimizing acute gain, symmetry, and apposition of intracoronary stents in approximately 50% of patients. Moreover, ICUS guidance is associated with low rates for target vessel revascularization and major adverse cardiac events at 6-month follow-up.

Effect of variability in the interpretation of coronary angiograms on the appropriateness of use of coronary revascularization procedures.

BACKGROUND: Evidence from numerous studies of coronary angiography show differences between observers' assessments of 15% to 45%. The implication of this variation is serious: If readings are erroneous, some patients will undergo revascularization procedures unnecessarily and others will be denied an essential treatment. We evaluated the variation in interpretation of angiograms and its potential effect on appropriateness of use of revascularization procedures. METHODS AND RESULTS: Angiograms of 308 randomly selected patients previously studied for appropriateness of angiography, coronary artery bypass grafting (CABG), and percutaneous transluminal coronary angioplasty (PTCA) were interpreted by a blinded panel of 3 experienced angiographers and compared with the original interpretations. The potential effect on differences on the appropriateness of revascularization was assessed by use of the RAND criteria. Technical deficiencies were found in 52% of cases. Panel readings tended to show less significant disease (none in 16% of vessels previously read as showing significant disease), less severity of stenosis (43% lower, 6% higher), and lower extent of disease (23% less, 6% more). The classification of CABG changed from necessary/appropriate to uncertain/inappropriate for 17% to 33% of cases when individual ratings were replaced by panel readings. CONCLUSIONS: The general level of technical quality of coronary angiography is unsatisfactory. Variation in the interpretation of angiograms was substantial in all measures and tended to be higher in individual than in panel readings. The effect was to lead to a potential overestimation of appropriateness of use of CABG by 17% and of PTCA by 10%. These findings indicate the need for increased attention to the technical quality of studies and an independent second reading for angiograms before recommending revascularization.