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Small-scale crucible melting tests on simulated waste glass were performed with technetium-99 (Tc-99) introduced as different species in a representative low activity waste simulant. The glass saw an increase in Tc-99 retention when TcO2∙2H2O and various Tc-minerals containing reduced tetravalent Tc were used compared to tests in which pertechnetate with heptavalent Tc was used. We postulate that the increase of Tc retention is likely caused by different reaction paths for Tc incorporation into glass during early stages of melting, rather than the low volatility of reduced tetravalent Tc compounds, which has been a generally accepted idea. Additional studies are needed to clarify the exact mechanisms relevant to the effect of reduced Tc compounds on Tc incorporation into or volatilization from the glass melt.

Technetium (99Tc) immobilization by doping into iron oxide mineral phases may alleviate the problems with Tc volatility during vitrification of nuclear waste. Because reduced Tc, Tc(IV), substitutes for Fe(III) in the crystal structure by a process of Tc reduction from Tc(VII) to Tc(IV) followed by co-precipitation of Fe oxide minerals, two Tc-incorporated Fe minerals (Tc-goethite and Tc-magnetite/maghemite) were prepared and tested for Tc retention in glass melt samples at temperatures between 600 and 1000 °C. After being cooled, the solid glass specimens prepared at different temperatures at 600, 800, and 1000 °C were analyzed for Tc oxidation state using Tc K-edge XANES. In most samples, Tc was partially (95%) oxidized to Tc(VII) at temperature above 800 °C. Tc retention in glass melt samples prepared using Tc-incorporated Fe minerals were slightly higher (∼10%) than in glass prepared using KTcO4 because of limited and delayed Tc volatilization.

BACKGROUND: Platelet glycoprotein IIb/IIIa antagonists reduce complications following percutaneous coronary intervention (PCI). There are limited data comparing different agents. OBJECTIVE: The purpose of this study was to compare in-hospital and 30-day outcomes in 2 sequential cohorts of consecutive patients undergoing PCI at our institution who received abciximab or eptifibatide. METHODS: The first cohort included patients who received abciximab between September 1, 1998, and January 9, 1999, and the second included patients who were treated with eptifibatide between January 11 and April 27, 1999. Per formulary decision, during the latter period, patients with renal insufficiency continued to be treated with abciximab and were ineligible for therapy with eptifibatide. Major adverse cardiac events (MACEs) were evaluated by one or more of the authors and compared. RESULTS: A total of 319 patients were treated with abciximab and 301 with eptifibatide. There were no differences in baseline characteristics between the 2 groups, with the exception of a significantly higher proportion of patients with chronic renal insufficiency in the abciximab-treated group (4% vs 0% with eptifibatide; P = 0.03) The majority of interventions were performed for an acute coronary syndrome. Procedural success was 97% in both groups. Eptifibatide patients were treated for a mean 20.4 (5.2) hours, with 10.1% receiving the drug before the procedure. There were no differences in overall or individual MACEs in hospital or at 30 days. CONCLUSION: Our data suggest similar in-hospital and 30-day outcomes for abciximab- and eptifibatide-treated patients undergoing PCI. [ABSTRACT FROM AUTHOR]

The definition of severe aortic stenosis has undergone significant change casting a wider net to avoid missing patients who could benefit from valve replacement. The presence or absence of symptoms remains the key decision-making element; however, individuals presently undergoing evaluation are older, more likely asymptomatic, and have lower gradients. Due to numerous potential measurement errors, attention to detail when performing diagnostic testing and understanding their limitations are necessary to render appropriate treatment. Exercise testing adds useful information for individuals with severe aortic stenosis felt to be asymptomatic. Dobutamine echocardiography, in low flow-low gradient aortic stenosis, distinguishes between a myopathic and valvular cause of left ventricular dysfunction. Evaluation of patients when normotensive minimizes measurement errors. The amount of aortic valve calcification adds useful information when the degree of aortic stenosis is uncertain. A good history and physical integrated with high-quality imaging data allows for appropriate clinical treatment decisions for patients with aortic stenosis. The goal is simultaneously to provide aortic valve replacement for patients in need while avoiding overdiagnosis and performance of unnecessary procedures., (Copyright © 2022. Published by Elsevier Inc.)

Here, Cr(VI) effects on Tc-immobilization by Fe(OH) 2 (s) are investigated while assessing Fe(OH) 2 (s) as a potential treatment method for Hanford low-activity waste destined for vitrification. Batch studies using simulated low-activity waste indicate that Tc(VII) and Cr(VI) removal is contingent on reduction to Tc(IV) and Cr(III). Furthermore, complete removal of both Cr and Tc depends on the amount of Fe(OH) 2 (s) present, where complete Cr and Tc removal requires more Fe(OH) 2 (s) (∼200 g/L of simulant), than removing Cr alone (∼50 g/L of simulant). XRD analysis suggests that Fe(OH) 2 (s) reaction and transformation in the simulant produces mostly goethite (α-FeOOH), where Fe(OH) 2 (s) transformation to goethite rather than magnetite is likely due to the simulant chemistry, which includes high levels of nitrite and other constituents. Once reduced, a fraction of Cr(III) and Tc(IV) substitute for octahedral Fe(III) within the goethite crystal lattice as supported by XPS, XANES, and/or EXAFS results. The remaining Cr(III) forms oxide and/or hydroxide phases, whereas Tc(IV) not fully incorporated into goethite persists as either adsorbed or partially incorporated Tc(IV)-oxide species. As such, to fully incorporate Tc(IV) into the goethite crystal structure, additional Fe(OH) 2 (s) (>200 g/L of simulant) may be required.

Technetium (Tc) remains a priority remediation concern due to persistent challenges, including mobilization due to rapid reoxidation of immobilized Tc, and competing comingled contaminants, e.g., Cr(VI), that inhibit Tc(VII) reduction and incorporation into stable mineral phases. Here Fe(OH) 2 (s) is investigated as a comprehensive solution for overcoming these challenges, by serving as both the reductant, (Fe(II)), and the immobilization agent to form Tc-incorporated magnetite (Fe 3 O 4 ). Trace metal analysis suggests removal of Tc(VII) and Cr(VI) from solution occurs simultaneously; however, complete removal and reduction of Cr(VI) is achieved earlier than the removal/reduction of comingled Tc(VII). Bulk oxidation state analysis of the final magnetite solid phase by XANES shows that the majority of Tc is Tc(IV), which is corroborated by XPS measurements. Furthermore, EXAFS results show successful, albeit partial, Tc(IV) incorporation into magnetite octahedral sites. Cr XPS analysis indicates reduction to Cr(III) and the formation of a Cr-incorporated spinel, Cr 2 O 3 , and Cr(OH) 3 phases. Spinel (modeled as Fe 3 O 4 ), goethite (α-FeOOH), and feroxyhyte (δ-FeOOH) are detected in all reacted final solid phase samples analyzed by XRD. Incorporation of Tc(IV) has little effect on the spinel lattice structure. Reaction of Fe(OH) 2 (s) in the presence of Cr(III) results in the formation of a spinel phase that is a solid solution between magnetite (Fe 3 O 4 ) and chromite (FeCr 2 O 4 ).

Efficient and cost-effective removal of radioactive pertechnetate anions from nuclear waste is a key challenge to mitigate long-term nuclear waste storage issues. Traditional materials such as resins and layered double hydroxides (LDHs) were evaluated for their pertechnetate or perrhenate (the non-radioactive surrogate) removal capacity, but there is room for improvement in terms of capacity, selectivity and kinetics. A series of functionalized hierarchical porous frameworks were evaluated for their perrhenate removal capacity in the presence of other competing anions., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The efficient removal of pertechnetate (TcO4(-)) anions from liquid waste or melter off-gas solution for an alternative treatment is one of the promising options to manage (99)Tc in legacy nuclear waste. Safe immobilization of (99)Tc is of major importance because of its long half-life (t1/2 = 2.13 × 10(5) yrs) and environmental mobility. Different types of inorganic and solid-state ion-exchange materials have been shown to absorb TcO4(-) anions from water. However, both high capacity and selectivity have yet to be achieved in a single material. Herein, we show that a protonated version of an ultrastable zirconium-based metal-organic framework can adsorb perrhenate (ReO4(-)) anions, a nonradioactive surrogate for TcO4(-), from water even in the presence of other common anions. Synchrotron-based powder X-ray diffraction and molecular simulations were used to identify the position of the adsorbed ReO4(-) (surrogate for TcO4(-)) molecule within the framework.

Technetium mainly forms during artificial nuclear fission; it exists primarily as TcO4(-) in nuclear waste, and it is among the most hazardous radiation-derived contaminants because of its long half-life (t1/2 = 2.13 × 10(5) years) and environmental mobility. The high water solubility of TcO4(-) (11.3 mol L(-1) at 20 °C) and its ability to readily migrate within the upper layer of the Earth's crust make it particularly hazardous. Several types of materials, namely resins, molecular complexes, layered double hydroxides, and pure inorganic and metal-organic materials, have been shown to be capable of capturing TcO4(-) (or other oxoanions) from solution. In this review, we give a brief description about the types of materials that have been used to capture TcO4(-) and closely related oxyanions so far and discuss the possibility of using metal-organic frameworks (MOFs) as next-generation ion-exchange materials for the stated application. In particular, with the advent of ultra-stable MOF materials, in conjunction with their chemical tunability, MOFs can be applied to capture these oxyanions under real-life conditions.

Iron oxides and oxyhydroxides play an important role in minimizing the mobility of redox-sensitive elements in engineered and natural environments. For the radionuclide technetium-99 (Tc), these phases hold promise as primary hosts for increasing Tc loading into glass waste form matrices, or as secondary sinks during the long-term storage of nuclear materials. Recent experiments show that the inverse spinel, magnetite [Fe(II)Fe(III)2O4], can incorporate Tc(IV) into its octahedral sublattice. In that same class of materials, trevorite [Ni(II)Fe(III)2O4] is also being investigated for its ability to host Tc(IV). However, questions remain regarding the most energetically favorable charge-compensation mechanism for Tc(IV) incorporation in each structure, which will affect Tc behavior under changing waste processing or storage conditions. Here, quantum-mechanical methods were used to evaluate incorporation energies and optimized lattice bonding environments for three different, charge-balanced Tc(IV) incorporation mechanisms in magnetite and trevorite (∼5 wt % Tc). For both phases, the removal of two octahedral Fe(II) or Ni(II) ions upon the addition of Tc(IV) in an octahedral site is the most stable mechanism, relative to the creation of octahedral Fe(III) defects or increasing octahedral Fe(II) content. Following hydration-energy corrections, Tc(IV) incorporation into magnetite is energetically favorable while an energy barrier exists for trevorite.

Background: The relationship between culprit vessel, infarct size, and outcomes in non-ST-segment elevation acute coronary syndromes (NSTE ACS) is unclear. In some reports, the left circumflex artery (LCX) was more often the culprit at angiography than the right coronary artery (RCA) or left anterior descending artery (LAD), and infarcts were larger with LCX culprits., Methods: We determined culprit vessel frequency and initial patency (TIMI flow grade), median fold elevation of peak troponin above the upper limit of normal, and outcomes (30-day death or myocardial infarction [MI] and 1-year mortality) by culprit vessel in high-risk NSTE ACS patients in the EARLY ACS trial., Results: Of 9406 patients, 2066 (22.0%) had angiographic core laboratory data. We evaluated 1774 patients for whom the culprit artery was not the left main, a bypass graft, or branch vessel. The culprit was the LCX in 560 (31.6%), LAD in 653 (36.8%), and RCA in 561 (31.6%) patients. There were fewer women (24.1%) and more prior MI (25.5%) among patients with a culprit LCX compared with those with a culprit LAD or RCA. Patients with LCX (21.2%) and RCA (27.5%) culprits more often had an occluded artery (TIMI 0/1) than did those with LAD (11.3%). Peak troponin elevation was significantly higher for LCX than RCA or LAD culprits. LCX culprit vessels were not associated with worse 30-day or 1-year outcomes in adjusted models., Conclusions: Among patients with NSTE ACS, the frequencies of LCX, LAD, and RCA culprits were similar. Although LCX lesions were associated with higher peak troponin levels, there was no difference in short- or intermediate-term outcomes by culprit artery., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The kinetics of the feed-to-glass conversion affects the waste vitrification rate in an electric glass melter. The primary area of interest in this conversion process is the cold cap, a layer of reacting feed on top of the molten glass. The work presented here provides an experimental determination of the temperature distribution within the cold cap. Because direct measurement of the temperature field within the cold cap is impracticable, an indirect method was developed in which the textural features in a laboratory-made cold cap with a simulated high-level waste feed were mapped as a function of position using optical microscopy, scanning electron microscopy, energy dispersive spectroscopy, and X-ray diffraction. The temperature distribution within the cold cap was established by correlating microstructures of cold-cap regions with heat-treated feed samples of nearly identical structures at known temperatures. This temperature profile was compared with a mathematically simulated profile generated by a cold-cap model that has been developed to assess the rate of glass production in a melter.

Introduction: The United States spends a higher percentage of its gross domestic product on health care than any other country. Previous efforts to curtail health care spending have had minimal impact. We hypothesized that informing physicians of the cost of expensive cardiovascular diagnostic tests would change their ordering behavior., Materials and Methods: Hospitalist physicians (n = 38) were randomly assigned to either seeing or not seeing the cost of diagnostic tests, via a computer pop-up screen, at the time of order entry. Patients were inpatients on a general medical service. Cost-aware physicians were shown the cost of the test they ordered as well as the cost of similar tests with different costs. There was a 4-month baseline period prior to randomization followed by a 4-month intervention period. The primary outcome measure was a change in the proportion of imaging stress tests in the study period., Results: Of the total number of stress tests ordered (imaging and nonimaging), cost-aware physicians ordered 89% of their tests with imaging during both the baseline and study periods. Cost-unaware physicians ordered 91% imaging tests during the baseline period and 87% during the study period. There were no significant differences between the groups regarding change in ordering from baseline to study period. Both groups showed a slight increase (P < 0.03) in ordering the more expensive regadenoson nuclear stress tests (cost-aware: 30% baseline, 44% study period; cost-unaware: 36% baseline, 41% study period)., Discussion: Informing physicians of the cost of certain diagnostic tests is not a sufficient intervention to influence their ordering behavior.

Background and Objectives: Eptifibatide is indicated during percutaneous coronary intervention (PCI) with continuation for 18-24 hours post procedure but is associated with bleeding. We examined the efficacy and safety of shorter post-PCI eptifibatide infusions in high-risk non-ST-segment elevation acute coronary syndrome (NSTE ACS) patients., Methods: EARLY ACS patients treated with PCI and eptifibatide were grouped by post-procedure infusion duration: <10, 10-13, 13-17, and 17-25 (per protocol) hours. Adjusted estimated event rates for 96-hour death/myocardial infarction (MI)/recurrent ischaemia requiring urgent revascularization (RIUR), 30-day death/MI, post-PCI packed red blood cell (PRBC) transfusion, and GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) moderate/severe bleeding were obtained using inverse-propensity weighting to account for informative censoring of infusions., Results: Among 3271 eptifibatide-treated PCI patients, there were 66 96-hour death/MI/RIUR events, 94 30-day death/MI events, 127 PRBC transfusions, and 115 GUSTO moderate/severe bleeds. Compared with per protocol, patients receiving post-PCI infusions <10 hours had similar adjusted estimated rates of 96-hour death/MI/RIUR (absolute difference 0.021 higher; 0.040 vs. 0.019, 95% CI -0.023 to 0.064; p=0.35) and 30-day death/MI (0.020 higher; 0.046 vs. 0.026, 95% CI -0.021 to 0.062; p=0.34). There were also no differences in ischaemic outcomes between infusions of 10-17 hours and per-protocol infusions. Adjusted estimated rates of PRBC transfusion were higher for the <10-hour infusion group compared with per protocol (0.048 higher; 0.079 vs. 0.031, 95% CI 0.005 to 0.091, p=0.03) but were similar for other groups. Adjusted GUSTO moderate/severe bleeding rates were similar to per-protocol rates for all groups., Conclusions: In high-risk NSTE ACS patients, post-PCI eptifibatide infusions <18 hours were not associated with worse ischaemic outcomes. Shorter eptifibatide infusions in this population may be feasible.

The immobilization of technetium-99 ((99)Tc) in a suitable host matrix has proven to be a challenging task for researchers in the nuclear waste community around the world. In this context, the present work reports on the solubility and retention of rhenium, a nonradioactive surrogate for (99)Tc, in a sodium borosilicate glass. Glasses containing target Re concentrations from 0 to 10,000 ppm [by mass, added as KReO(4) (Re(7+))] were synthesized in vacuum-sealed quartz ampules to minimize the loss of Re from volatilization during melting at 1000 °C. The rhenium was found as Re(7+) in all of the glasses as observed by X-ray absorption near-edge structure. The solubility of Re in borosilicate glasses was determined to be ~3000 ppm (by mass) using inductively coupled plasma optical emission spectroscopy. At higher rhenium concentrations, additional rhenium was retained in the glasses as crystalline inclusions of alkali perrhenates detected with X-ray diffraction. Since (99)Tc concentrations in a glass waste form are predicted to be <10 ppm (by mass), these Re results implied that the solubility should not be a limiting factor in processing radioactive wastes, assuming Tc as Tc(7+) and similarities between Re(7+) and Tc(7+) behavior in this glass system.

Introduction: Eptifibatide is a glycoprotein IIb/IIIa inhibitor that blocks the final common pathway of platelet aggregation. Its major adverse effect is bleeding. Balancing its safety and efficacy is paramount for its appropriate usage., Areas Covered: The development of eptifibatide and its mechanism of action are explored. Clinical trials evaluating its efficacy and safety in a variety of clinical settings, as well as newer dosing regimens, are discussed. Readers will be able to understand the bleeding risks of eptifibatide in specific patient populations., Expert Opinion: The risk of bleeding with eptifibatide needs to be weighed against the potential benefits. Understanding which patients are at higher risk of bleeding will help the clinician make appropriate decisions.

Background: It is unclear whether patients understand that percutaneous coronary intervention (PCI) reduces only chronic stable angina and not myocardial infarction (MI) or associated mortality., Objective: To compare cardiologists' and patients' beliefs about PCI., Design: Survey., Setting: Academic center., Participants: 153 patients who consented to elective coronary catheterization and possible PCI, 10 interventional cardiologists, and 17 referring cardiologists., Measurements: Patients' and cardiologists' beliefs about benefits of PCI. All cardiologists reported beliefs about PCI for patients in hypothetical scenarios. Interventional cardiologists also reported beliefs for study patients who underwent PCI., Results: Of 153 patients, 68% had any angina, 42% had activity-limiting angina, 77% had a positive stress test result, and 29% had had previous MI. The 53 patients who underwent PCI were more likely than those who did not to have a positive stress test result, but angina was similar in both groups. Almost three quarters of patients thought that without PCI, they would probably have MI within 5 years, and 88% believed that PCI would reduce risk for MI. Patients were more likely than physicians to believe that PCI would prevent MI (prevalence ratio, 4.25 [95% CI, 2.31 to 7.79]) or fatal MI (prevalence ratio, 4.83 [CI, 2.23 to 10.46]). Patients were less likely than their physicians to report pre-PCI angina (prevalence ratio, 0.79 [CI, 0.67 to 0.92]). For the scenarios, 63% of cardiologists believed that the benefits of PCI were limited to symptom relief. Of cardiologists who identified no benefit of PCI in 2 scenarios, 43% indicated that they would still proceed with PCI in these cases., Limitation: The study was small and conducted at 1 center, and information about precatheterization counseling was limited., Conclusion: Cardiologists' beliefs about PCI reflect trial results, but patients' beliefs do not. Discussions with patients before PCI should better explain anticipated benefits., Primary Funding Source: None.

Aims: We report 2-year outcomes in a large unselected drug-eluting stent population (N=7,492) in the TAXUS Express2 ARRIVE post-market surveillance programme (101 U.S. sites)., Methods and Results: No specific inclusion/exclusion criteria were mandated; patients enrolled at procedure initiation. Two-year follow-up was 94%, with independent adjudication of major cardiac events, monitoring of patients with cardiac events and an additional 10-20% sample by site. Most ARRIVE cases (64%, n=4,794) typified expanded use based on patient/lesion characteristics outside the simple use (single vessel/stent) pivotal trial populations. These expanded use patients had higher 2-year rates than simple use patients for mortality (7.8% vs. 4.2%, P<0.001), myocardial infarction (MI, 3.9% vs. 2.2%, P<0.001), target lesion revascularisation (TLR, 9.2% vs. 5.4%, P<0.001), and stent thrombosis (3.3% vs. 1.4%, P<0.001). Among subgroups with renal disease, chronic total occlusion (CTO), lesion >28 mm, reference vessel diameter (RVD) <2.5 mm, multivessel stenting, acute MI, bifurcation, vein graft, or in-stent restenosis, TLR ranged from 3.8% to 8.9% in year one, and from 1.3% to 6.0% during year two., Conclusions: Mortality and stent-related events were higher in expanded use than simple use patients in the pivotal trials. ARRIVE provides a detailed estimate of procedural and 2-year outcomes in such real-world patients.

Background: Clopidogrel is inactive in vitro and is metabolized by hepatic cytochrome P-450-3A4 to produce active metabolites. Unlike pravastatin, atorvastatin is a statin that is subject to metabolism by cytochrome P-450-3A4, and drug-drug interactions with other potent inhibitors of this cytochrome system have been demonstrated. However, the clinical impact of this interaction has created debate., Methods: In the PROVE IT-TIMI 22 study, 4162 patients with an acute coronary syndrome within the preceding 10 days were randomly assigned in a 1:1 fashion to pravastatin 40 mg or atorvastatin 80 mg daily. The primary efficacy outcome measure was the time from randomization until the first occurrence of a component of the primary end point: death from any cause, myocardial infarction, documented unstable angina requiring rehospitalization, revascularization with either percutaneous coronary intervention or coronary artery bypass grafting, or stroke., Results: At 30 days, there was a trend for less occurrence of the primary end point in patients randomized to atorvastatin compared with pravastatin, irrespective of whether they were taking clopidogrel. This becomes significant at 2-year follow-up in clopidogrel-treated patients (21.66 % vs 26.18% P = .0091). There was no evidence of interaction in the clopidogrel/no clopidogrel subgroup for the primary end point (interaction P = .65) or the components of the composite., Conclusion: In conclusion, the beneficial affects of atorvastatin 80 mg in reducing the primary end point at 2 years is independent of coadministration with clopidogrel.

Contrast induced nephropathy (CIN) is the third leading cause of hospital acquired renal failure and is associated with significant morbidity and mortality. Chronic kidney disease is the primary predisposing factor for CIN. As estimated glomerular filtration rate<60 ml/1.73 m2 represents significant renal dysfunction and defines patients at high risk. Modifiable risk factors for CIN include hydration status, the type and amount of contrast, use of concomitant nephrotoxic agents and recent contrast administration. The cornerstone of CIN prevention, in both the high and low risk patients, is adequate parenteral volume repletion. In the patient at increased risk for CIN it is often appropriate to withhold potentially nephrotoxic medications, and consider the use of n-acetylcysteine. In patients at increased risk for CIN the use of low or iso-osomolar contrast agents should be utilized and strategies employed to minimize contrast volume. In these patients serum creatinine should be obtained forty-eight hours post procedure and it is often appropriate to continue withholding medications such as metformin or non steroidal anti-inflammatories until renal function returns to normal., (Copyright (c) 2006 Wiley-Liss, Inc.)

Background: The REPLACE-2 trial demonstrated the noninferiority of bivalirudin with provisional glycoprotein IIb/IIIa (GPIIb/IIIa) blockade as compared with heparin plus planned GPIIb/IIIa blockade among patients undergoing percutaneous coronary revascularization. Provisional drug was used in 374 (6%) of the 6010 patients. We sought to analyze the predictors for provisional drug use and to assess the outcomes in this cohort., Methods: Outcome among the 5.2% of patients in the heparin plus GPIIb/IIIa blockade group and the 7.2% of patients in the bivalirudin group who received provisional placebo or GPIIb/IIIa inhibitor, respectively, was compared against patients without provisional drug use and between randomized arms. Multivariate models identified predictors of provisional drug use and outcome at 30 days, 6 months, and 1 year., Results: Myocardial infarction, repeat revascularization, and bleeding events occurred more frequently among patients who required provisional drug than those who did not, but there were no differences in 1-year mortality. Ischemic and hemorrhagic end points occurred at similar rates among patients receiving provisional drug in either the heparin plus GPIIb/IIIa group compared with the bivalirudin group. Independent predictors of provisional drug use were randomization to bivalirudin, recent infarction, multilesion intervention, impaired pretreatment coronary flow, and lesion complexity. Provisional drug use, but not randomization to bivalirudin, independently predicted 30-day and 6-month ischemic events., Conclusions: Provisional administration of a GPIIb/IIIa inhibitor is associated with more frequent ischemic and bleeding events, reflecting the procedural complications that led to the use of provisional drug. The proportion of bivalirudin-treated patients who will require provisional GPIIb/IIIa blockade, however, is not large enough to have a significant deleterious impact on the overall incidence of ischemic end points or to invalidate the strategy of bivalirudin plus provisional GPIIb/IIIa blockade.

Restenosis following bare metal coronary stenting is common. The location and characteristics of restenotic lesions in patients who have undergone coronary stent implantation is not well described. The purpose of this study was to determine the location, type and temporal distribution of stent-related restenosis. We reviewed the clinical and angiographic characteristics of 203 consecutive patients with stent-related restenosis undergoing a repeat clinically-indicated coronary angiogram, 30 days to 1 year after the index procedure. All lesions within 10 mm of the proximal and distal margins of the stent were included in the analysis. An angiographic classification was developed based on lesion location. Class I lesions were those occurring within the stent, and Class II comprised those lesions occurring within 10 mm of the proximal and distal stent edge. We classified a total of 234 stent-related restenosis lesions. Class I lesions were found in 52% of patients, and Class II in 48%. Three-fifths of the patients who developed new lesions at a stent edge presented 1-3 months following the initial procedure, which was significantly earlier than other lesion types (p < 0.001). A substantial number of patients undergoing repeat angiography after stent placement have lesions proximate, but peripheral, to the stent. This may limit the effectiveness of stent-based efforts to reduce restenosis. The time interval between coronary stenting and symptom recurrence appears to vary according to lesion location.

Objectives: The purpose of this study is to determine whether there is clinical significance to elevated troponin I in patients with suspected acute coronary syndromes (ACS) with non-critical angiographic coronary stenosis., Background: Elevation of troponin in patients admitted with ACS symptoms with non-critical coronary artery disease (CAD) may result from coronary atherothrombosis not evident using standard angiography or from other ischemic and non-ischemic causes that may confer increased risk for future events., Methods: Patients with ACS enrolled in the Treat Angina With Aggrastat and Determine Cost of Therapy With Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction (TACTICS-TIMI)-18 were included. Of 2,220 patients enrolled in the trial, 895 were eligible. Patients were divided into four groups according to troponin status on admission and presence of significant angiographic stenosis. Baseline brain natriuretic peptide (BNP) and C-reactive protein (CRP) were obtained on all patients., Results: The median troponin I levels were 0.71 ng/ml in patients with CAD compared with 0.02 ng/ml in patients without CAD (p <0.0001). Troponin-positive patients with or without angiographic CAD had higher CRP and BNP levels compared with troponin-negative patients (p <0.01 for both). The rates of death or reinfarction at six months were 0% in troponin-negative patients with no CAD, 3.1% in troponin-positive patients with no CAD, 5.8% in troponin-negative patients with CAD, and 8.6% in troponin-positive patients with CAD (p=0.012)., Conclusions: Elevated troponin in ACS is associated with a higher risk for death or reinfarction, even among patients who do not have significant angiographic CAD. The mechanisms conferring this adverse prognosis merit further study.

Background: More complete ST-segment resolution (ST res) in acute myocardial infarction (MI) has been associated with better epicardial and myocardial reperfusion as assessed with the Thrombolysis in Myocardial Infarction (TIMI) flow grade (TFG) and the TIMI myocardial perfusion grade (TMPG), respectively. However, no data exist comparing the speed of ST resolution on continuous electrocardiogram (ECG) monitoring with the TMPG on coronary angiography. We hypothesized that delayed ST res is associated with impaired TMPGs., Methods: Continuous 12-lead ECG recordings and 60-minute angiographic data were analyzed in 120 patients with acute MI who received tenectaplase monotherapy or combination therapy with low-dose tenectaplase and eptifibatide in the Integrilin and Tenecteplase in Acute Myocardial Infarction (INTEGRITI) trial., Results: More rapid ST res on continuous ECG monitoring was associated with improved TMPGs on coronary angiography performed 60 minutes after study drug administration. For TMPG 3, the median time to ST resolution was 53 minutes. For TMPG 2, 1, and 0, the corresponding times were 64 minutes, 80 minutes, and 106 minutes, respectively (P =.01 for trend). Likewise, more rapid ST res was also associated with faster epicardial flow. For TFG 3, the median time to ST resolution was 46 minutes, compared with 109 minutes for TIMI flow grades 0 to 2 (P =.001). The corresponding times for a corrected TIMI frame count < or =40 versus >40 were 52 minutes and 112 minutes, respectively (P <.001)., Conclusions: Although the static ECG has been associated with epicardial and myocardial blood flow in the past, this study extends these observations to demonstrate that more rapid ST res on continuous ECG monitoring is associated with improved myocardial perfusion after thrombolytic administration.

The TIMI 9 Registry set out to assess the management strategies and outcomes of an unselected group of patients with acute myocardial infarction presenting with ST segment elevation (STEMI). Demographic, procedural, and outcome data were collected from 840 consecutive patients with STEMI at 20 hospitals in United States and Canada between February and September 1994. Of them, 60% were treated with thrombolytic therapy, 9% with primary angioplasty, and 31% did not receive reperfusion therapy. Patients who did not receive reperfusion therapy were older, more likely female, and had a higher prevalence of prior myocardial infarction, congestive heart failure, higher Killip class on admission, and longer time from onset of symptoms to presentation. In evaluating the standard contraindications for fibrinolysis, approximately 10% in the thrombolytic group, 40% in the primary percutaneous coronary intervention (PCI), and 34% of those not receiving reperfusion therapy had at least one of these characteristics. Of those patients treated with fibrinolysis, only 20% met the National Heart Attack Alert Program goal of door-to-drug time < or =30 minutes. Likewise, of those treated with primary PCI, only 30% had PCI performed within < or =90 minutes. In-hospital mortality was significantly higher for patients not treated with reperfusion therapy (18.9%), compared with patients treated with fibrinolysis (7.6%) and those treated with primary PCI (10.5%) (P < 0.001). Thus, we found that reperfusion therapy was underused, with only 69% of patients with STEMI receiving this proven treatment, and of those only 25% treated within the recommended timeline. These data suggest that there is room for improvement in the management of these patients.

Earlier studies have suggested that immediate percutaneous coronary intervention (PCI) following thrombolytic therapy for acute myocardial infarction (AMI) is associated with an increase in adverse events and that routine PCI in this setting has offered no advantage over a conservative strategy. To reassess this issue in a more recent era, we evaluated 1,938 patients from the Thrombolysis in Myocardial Infarction (TIMI) 10B and 14 trials of AMI. Patients in TIMI 10B were randomized to receive tissue plasminogen activator or TNK tissue plasminogen activator, whereas patients in TIMI 14B trial were randomized to receive thrombolytic therapy with or without abciximab. All patients underwent angiography 90 minutes after receiving pharmacologic therapy. Patients who underwent PCI were classified as having undergone a rescue procedure (TIMI 0 or 1 flow at 90 minutes), an adjunctive procedure (TIMI 2 or 3 flow at 90 minutes), or a delayed procedure (performed >150 minutes after symptom onset, median of 2.75 days). Among patients with TIMI 0 or 1 flow, there was a trend for lower 30-day mortality among patients who underwent rescue PCI than among those who did not (6% vs 17%, p = 0.01, adjusted p = 0.28). Patients who underwent adjunctive PCI had similar 30-day mortality and/or reinfarction as those who underwent delayed PCI. In a multivariate model both had lower 30-day mortality and/or reinfarction than patients with "successful thrombolysis" (i.e., TIMI 3 flow at 90 minutes) who did not undergo revascularization (p = 0.02). Thus, early PCI following AMI is associated with excellent outcomes. Randomized trials of an early invasive strategy following thrombolysis are warranted.

Pulmonary hemorrhage following percutaneous coronary intervention is a very rare complication that has been previously reported in association with abciximab and tirofiban, but not with clopidogrel. We report the case of a 56-year-old man who developed diffuse alveolar hemorrhage after receiving clopidogrel for placement of a coronary stent. Since clopidogrel is a commonly used medication, clinicians should be aware of this potentially life-threatening complication.

Ad hoc coronary intervention is a percutaneous revascularization procedure performed at the same sitting as diagnostic cardiac catheterization. While this appears to be an efficient strategy, the safety and cost of ad hoc coronary intervention compared with delayed coronary intervention have not been clearly documented. Special preparation and precautions are necessary for patients in whom ad hoc coronary intervention is anticipated. Ad hoc coronary intervention is not appropriate if informed consent has not been previously obtained or if it would pose greater risks than delayed intervention. While ad hoc coronary intervention is often efficient and effective, its use should be individualized. Cathet. Cardiovasc. Intervent. 49:130-134, 2000., (Copyright 2000 Wiley-Liss, Inc.)

Fixed doses of thrombolytic agents are generally administered to patients of varying body weights, and the dose-response relation may be confounded by the variability in patient weight. We hypothesized that higher doses of TNK-tissue plasminogen activator (tPA) per unit body weight would be related to improved flow at 90 minutes after thrombolytic administration. A total of 886 patients with acute myocardial infarction were randomized to receive either a single bolus of 30, 40, or 50 mg of TNK-tPA or front-loaded tPA in the Thrombolysis In Myocardial Infarction (TIMI) 10B trial. The dose of TNK-tPA administered was divided by the patient's weight to arrive at the TNK-tPA dose (mg) per unit body weight (kg), and patients were stratified into tertiles based on mg/kg of TNK-tPA: low dose, 0.2 to 0.39 mg/kg; mid-dose, 0.40 to 0.51 mg/kg; high dose, 0.52 to 1.24 mg/kg. Flow in the culprit and nonculprit arteries was analyzed using the TIMI flow grades and the corrected TIMI frame count (CTFC). The median CTFC in culprit arteries differed between the tertiles (3-way p = 0.007), with the CTFC being 7.2 frames faster in high-dose than in low-dose patients (43.1 +/- 30.1, median 31.2, n = 171 vs 54.6 +/- 34.8, median 38.4, n = 166, 2-way p = 0.002). Patients in the mid- and high-dose tertiles achieved patency more frequently (TIMI grade 2 or 3 flow) by 60 minutes (p = 0.02), and the 90-minute percent diameter stenosis was less severe in patients in the high- versus low-dose tertile (p = 0.03). In nonculprit arteries, the CTFC was faster in high- than in low-dose tertiles (29.6 +/- 13.4, median 26.9, n = 130 vs 34.7 +/- 16.3, median 32.8, n = 108, 3-way p = 0.03, 2-way p = 0.008). In patients who underwent percutaneous transluminal coronary angioplasty (PTCA), the CTFC in culprit arteries after PTCA was fastest in the high- and mid-dose tertiles than in those receiving low doses (2-way p = 0.05). Thus, higher doses per unit body weight of TNK-tPA result in not only faster culprit artery flow, but also faster nonculprit, global, and post-PTCA flow, which may reflect earlier opening, reduced stunning, or improved microvascular function. The greater effectiveness of thrombolysis must be weighed against any increase in risk.

Objectives: This study evaluated the determinants of coronary blood flow following thrombolytic administration in a large cohort of patients., Background: Tighter residual stenoses following thrombolysis have been associated with slower coronary blood flow, but the independent contribution of other variables to delayed flow has not been fully explored., Methods: The univariate and multivariate correlates of coronary blood flow at 90 min after thrombolytic administration were examined in a total of 2,195 patients from the Thrombolysis in Myocardial Infarction (TIMI) 4, 10A, 10B and 14 trials. The cineframes needed for dye to first reach distal landmarks (corrected TIMI frame count, CTFC) were counted as an index of coronary blood flow., Results: The following were validated as univariate predictors of delayed 90-min flow in two cohorts of patients: a greater percent diameter stenosis (p < 0.0001 for both cohorts), a decreased minimum lumen diameter (p = 0.0003, p = 0.0008), a greater percent of the culprit artery distal to the stenosis (p = 0.03, p = 0.02) and the presence of any of the following: delayed achievement of patency (i.e., between 60 and 90 min) (p < 0.0001 for both cohorts), a culprit location in the left coronary circulation (left anterior descending or circumflex) (p = 0.02, p < 0.0001), pulsatile flow (i.e., reversal of flow in systole, a marker of heightened microvascular resistance, p = 0.0003, p < 0.0001) and thrombus (p = 0.002, p = 0.03). Despite a minimal 16.4% residual stenosis following stent placement, the mean post-stent CTFC (25.8 +/- 17.2, n = 181) remained significantly slower than normal (21.0 +/- 3.1, n = 78, p = 0.02), and likewise 34% of patients did not achieve a CTFC within normal limits (i.e., <28 frames, the upper limit of the 95th percent confidence interval previously reported for normal flow). Those patients who failed to achieve normal CTFCs following stent placement had a higher mortality than did those patients who achieved normal flow (6/62 or 9.7% vs. 1/118 or 0.8%, p = 0.003)., Conclusions: Lumen geometry is not the sole determinant of coronary blood flow at 90 min following thrombolytic administration. Other variables such as the location of the culprit artery, the duration of patency, a pulsatile flow pattern and thrombus are also related to slower flow. Despite a minimal 16% residual stenosis, one-third of the patients treated with adjunctive stenting still have a persistent flow delay following thrombolysis, which carries a poor prognosis.

Context: Current management of patients with unstable angina and non-Q wave myocardial infarction generally consists of intensive medical therapy, with angiography and revascularization sometimes limited to those who fail such therapy., Aim: To determine if certain baseline characteristics are predictive of patients who fail medical therapy, since such patients could then be expeditiously directed to a more invasive strategy in a cost-effective manner., Methods: The study cohort consisted of the 733 patients in the Thrombolysis in Myocardial Ischemia (TIMI) IIIB study who were randomized to conservative strategy. Patients were to be treated with bedrest, anti-ischaemic medications, aspirin, and heparin, and were to undergo risk-stratifying tests, consisting of an exercise test with ECG and thallium scintigraphy, scheduled to be performed within 3 days prior to, or 5 days after, hospital discharge and 24 h Holter monitoring scheduled to begin 2-5 days after randomization. Baseline clinical and ECG characteristics were compared between patients who 'failed' medical therapy and those who did not 'fail'. Failure was defined using clinical end-points (death, myocardial infarction, or spontaneous ischaemia by 6 weeks after randomization) or a strongly positive risk-stratifying test. For each test an ordered failure profile of results was calculated and consisted of death, myocardial infarction, or rest ischaemia occurring prior to performance of the test, a markedly abnormal test result, and no abnormality., Results: Clinical end-points occurred in 241 (33%) patients and were more likely to occur in patients who at presentation were older, had ST-segment depression on the qualifying ECG, or were being treated with heparin or aspirin. Characteristics independently predictive of developing a clinical event or an abnormal exercise treadmill test included: ST-segment depression on the qualifying ECG, history of prior angina, family history of premature coronary disease (i.e. onset <55 years of age), prior use of heparin or aspirin, and increasing age. By combining these baseline risk characteristics for each outcome the incidence of developing a clinical event ranged from 8% if none was present to 63% if all six were present, and of developing a markedly abnormal risk stratifying test from 8-21% if none were present to approximately 90% if all six were present., Conclusions: Baseline characteristics associated with developing a clinical event or a markedly abnormal risk stratifying test were similar: rest anginal episode accompanied by ST-segment depression and occurring despite treatment with aspirin and heparin, a history of angina, older age, and family history of coronary disease. Patients with these characteristics are appropriate candidates for expeditious cardiac catheterization and consideration for revascularization, while patients without them may be suitable for medical management alone., (Copyright 1999 The European Society of Cardiology.)

Background: Although studies have documented that randomized, controlled trials (RCTs) have a measurable influence on clinical practice, investigators have uncovered important deficiencies in the application of RCT findings to the management of acute myocardial infarction (AMI). Little is known about the extent to which physicians who design and/or implement clinical trials differ from physicians in routine practice in their translation of the literature., Methods: Our aims were to (1) evaluate recent trends in selected treatments of AMI in relation to the publication of RCTs, statistical overviews, and task-force guidelines, and (2) compare prescribing practices in AMI management between physicians in routine clinical practice and physicians who design and/or implement RCTs. We reviewed the use of aspirin, beta-blockers, angiotensin-converting enzyme inhibitors, and calcium channel blockers on entry and at discharge in patients enrolled in the MILIS, TIMI 1, 2, 4, 5, 6, and 9B trials with ST-elevation (and depression in MILIS) myocardial infarction for a period approaching 2 decades (August 1978 to September 1995). We hypothesized that physicians who participate in RCTs apply the findings of the published literature more promptly and thoroughly than physicians in routine practice., Results: Use of aspirin, beta-blockers, and angiotensin converting enzyme inhibitors exhibited a statistically significant time-related increase at discharge and, excepting beta-blockers, at enrollment across the trials. Prescription of calcium channel blockers showed a statistically significant decrease at discharge only. For all medications under study, increases and decreases in use associated with publication of clinical data occurred earlier and more steeply for the discharge cohort (prescriptions by physicians participating in RCTs) than for the enrollment cohort (prescriptions by physicians in routine practice). Recent prescribing practices (1994 to 1995) among RCT investigators and their colleagues have higher concordance with published findings than those of physicians in routine practice., Conclusions: Physicians who design and/or implement RCTs translate the results of the medical literature more promptly and to a greater extent than physicians in routine clinical practice. Differences between different physician classes need to be studied further amid efforts to reconfigure health care delivery that currently favor more dominant roles for primary care physicians.

Background: Bolus thrombolytic therapy is a simplified means of administering thrombolysis that facilitates rapid time to treatment. TNK-tissue plasminogen activator (TNK-tPA) is a highly fibrin-specific single-bolus thrombolytic agent., Methods and Results: In TIMI 10B, 886 patients with acute ST-elevation myocardial infarction presenting within 12 hours were randomized to receive either a single bolus of 30 or 50 mg TNK-tPA or front-loaded tPA and underwent immediate coronary angiography. The 50-mg dose was discontinued early because of increased intracranial hemorrhage and was replaced by a 40-mg dose, and heparin doses were decreased. TNK-tPA 40 mg and tPA produced similar rates of TIMI grade 3 flow at 90 minutes (62.8% versus 62.7%, respectively, P=NS); the rate for the 30-mg dose was significantly lower (54.3%, P=0.035) and was 65. 8% for the 50-mg dose (P=NS). A prespecified analysis of weight-based TNK-tPA dosing using median TIMI frame count demonstrated a dose response (P=0.001). Similar dose responses were observed for serious bleeding and intracranial hemorrhage, but significantly lower rates were observed for both TNK-tPA and tPA after the heparin doses were lowered and titration of the heparin was started at 6 hours., Conclusions: TNK-tPA, given as a single 40-mg bolus, achieved rates of TIMI grade 3 flow similar to those of the 90-minute bolus and infusion of tPA. Weight-adjusting TNK-tPA appears to be important in achieving optimal reperfusion; reduced heparin dosing appears to improve safety for both agents. Together with the safety results from the parallel Assessment of the Safety of a New Thrombolytic: TNK-tPA (ASSENT I) trial, an appropriate dose of this single-bolus thrombolytic agent has been identified for phase III testing.

The direct antithrombin, bivalirudin, did not reduce angiographic restenosis measured either as the dichotomous restenosis rate of 62% for bivalirudin and 58% for heparin (p = 0.70), or as the late loss in lumen diameter of 0.44 +/- 0.47 mm for bivalirudin and 0.39 +/- 0.53 mm for heparin (p = 0.62). Direct thrombin inhibition with bivalirudin neither reduces angiographic restenosis nor alters the impact of several established risk factors for restenosis.

Although the use of composite end points in clinical trials has increased in recent years, few data are available on the validity of such an approach. In the Thrombolysis In Myocardial Infarction (TIMI) 4 and 5 trials, we set out to validate prospectively the nonfatal components of the "unsatisfactory outcome" end point. This end point consisted of the in-hospital occurrence or observation of new-onset severe congestive heart failure/shock, left ventricular ejection fraction <40% (or <30% for patients with prior myocardial infarction), reinfarction, reocclusion by sestamibi perfusion imaging, TIMI flow grade <2 at 90 minutes or 18 to 36 hours, intracranial hemorrhage, major spontaneous hemorrhage, or anaphylaxis. Among 576 patients in TIMI 4 and 5 with 1-year follow-up, a nonfatal unsatisfactory outcome end point was reached in hospital in 45% of patients. Compared with patients without such an end point, patients with an end point had a relative risk of 1-year mortality of 2.5 (95% confidence interval 1.4 to 5.6, p = 0.001). For individual components, new-onset severe congestive heart failure/shock had a relative risk of 4.6 (p = 0.001), left ventricular ejection fraction <40% had a relative risk of 3.5 (p = 0.006), recurrent myocardial infarction had a relative risk of 2.2 (p = 0.047), and TIMI flow grade <2 at 90 minutes had a relative risk of 2.2 (p = 0.005). Our findings show that these nonfatal in-hospital end points and the composite end point are associated with an increased risk of 1-year mortality and as such are valid predictive survival markers for use in clinical trials.

Background: Although the development of thrombus or dissection during percutaneous transluminal coronary angioplasty (PTCA) increases the risk of abrupt vessel closure, the magnitude of the effect is difficult to define., Objective: The aim of the study was to determine prospectively the effect of the development of thrombus or dissection on PTCA procedural outcome., Methods: Data from 591 consecutive angioplasty procedures involving 756 lesions at 9 clinical centers were included in a prospective registry with a core angiographic laboratory., Results: Clinical success (defined as < 50% stenosis of all target lesions assessed in a core angiographic laboratory, with no major complications of death, Q wave or non-Q wave myocardial infarction or emergency CABG) was achieved in 497 patients (84%). Major complications occurred in 45 (7.6%). Abrupt vessel closure, including both established closure (TIMI grade 0 or I flow) and impending closure (> 50% stenosis, TIMI grade 0-2 flow, plus use of additional interventions) occurred in 65 patients (11%). Angiographically visible dissections developed in 40% of lesions; more severe grades of dissection were associated with reduced success rates, and increased incidence of and abrupt vessel closure and major complication. Angiographic evidence of thrombus (filling defects) developed in 12.3% of lesions; the presence of thrombus was associated with significantly lower procedural success (61% vs. 86%) and significantly higher rates of abrupt vessel closure (28% vs 7%) and major complications (24% vs. 6%). With multivariable analysis, thrombus was identified as an independent predictor of procedural success, abrupt vessel closure, and major complications., Conclusions: The development of severe dissections or thrombus following PTCA is associated with significantly lower procedural success rates and higher rates of abrupt vessel closure and major complications. Patients who develop severe dissection or thrombus may be appropriate candidates for more aggressive forms of therapy.

The purpose of this study was to analyze angiographic findings, clinical course, and follow-up data on 1,752 patients who underwent protocol cardiac catheterization 18 to 48 hours after enrollment in the Thrombolysis in Myocardial Infarction (TIMI) II pilot and randomized trial: 244 patients (14.0%) had < 60% diameter stenosis in the infarct-related artery and TIMI grade 2 or 3 flow, 1,249 (71.2%) had a narrowing > or = 60% in diameter with TIMI grade 2 or 3 flow, and 259 patients (15%) had TIMI grade 0 or 1 flow (total occlusion). Patients with < 60% narrowing in the infarct-related artery were younger (p < 0.001) and more likely to be current smokers than those with more severe narrowings (p < 0.003). Patients with < 60% diameter stenosis in the infarct-related artery were more likely to have a predischarge radionuclide ejection fraction > 55% (p < 0.001) than were other patient groups. The 1-year mortality rate of patients with < 60% diameter stenosis in the infarct-related artery was 1.6% compared with 4.4% for patients with stenosis > or = 60% and TIMI grade 2 or 3 flow (p = 0.05) and 7.0% for patients with total occlusion (p = 0.004). Patients with stenosis < 60% in the infarct-related artery 18 to 48 hours after thrombolytic therapy have a good prognosis. Infarct artery status predicts predischarge ejection fraction and 1-year mortality.

Objectives: The purpose of this study was to assess the value of recombinant desulfatohirudin (hirudin) as adjunctive therapy to thrombolysis in acute myocardial infarction., Background: Failure to achieve initial reperfusion and reocclusion of the infarct-related artery remain major limitations of thrombolytic therapy despite aggressive regimens of heparin and aspirin. Hirudin, a direct thrombin inhibitor, has been shown in experimental models to enhance thrombolysis and reduce reocclusion., Methods: The Thrombolysis in Myocardial Infarction (TIMI) 5 trial was a randomized, dose-ranging, pilot trial of hirudin versus heparin, given with front-loaded tissue-type plasminogen activator and aspirin to 246 patients with acute myocardial infarction. Patients received either intravenous heparin or hirudin at one of four ascending doses for 5 days. Patients underwent coronary angiography at 90 min and at 18 to 36 h, unless rescue angioplasty was performed., Results: The primary end point, TIMI grade 3 flow in the infarct-related artery at 90 min and 18 to 36 h without death or reinfarction before the 18- to 36-h catheterization was achieved in 97 (61.8%) of 157 evaluable hirudin-treated patients compared with 39 (49.4%) of 79 evaluable heparin-treated patients (p = 0.07). All four doses of hirudin led to similar findings in the angiographic and clinical end points. At 90 min, TIMI grade 3 flow was present in 105 (64.8%) of 162 hirudin-treated patients compared with 48 (57.1%) of 84 heparin-treated patients (p = NS). Infarct-related artery patency (TIMI grade 2 or 3 flow) was similar in the two groups (82.1% and 78.6%, respectively). At 18 to 36 h, 129 (97.8%) of 132 hirudin-treated patients had a patent infarct-related artery compared with 58 (89.2%) of 65 heparin-treated patients (p = 0.01). Reocclusion by 18 to 36 h occurred in 2 (1.6%) of 123 hirudin-treated patients versus 4 (6.7%) of 60 heparin-treated patients (p = 0.07). Death or reinfarction occurred during the hospital period in 11 (6.8%) of 162 hirudin-treated patients compared with 14 (16.7%) of 84 heparin-treated patients (p = 0.02). Major spontaneous hemorrhage occurred in 1.2% of hirudin-treated patients versus 4.7% of heparin-treated patients (p = 0.09), and major hemorrhage at an instrumented site occurred in 16.3% and 18.6%, respectively (p = NS)., Conclusions: Hirudin is a promising agent compared with heparin as adjunctive therapy with thrombolysis for acute myocardial infarction, and its evaluation in larger trials is warranted.

Background: Percutaneous transluminal coronary angioplasty (PTCA) of the infarct-related artery was performed within 42 days of recombinant tissue-type plasminogen activator (rt-PA) administration in 1,414 of the 3,534 patients who participated in the Thrombolysis In Myocardial Infarction (TIMI) II study. Primary angiographic success was obtained in 88.7%, with bypass surgery within 24 hours in 3.3% and death within 24 hours in 0.7% of patients. By 1 year, 25.1% of the 1,414 patients had sustained one or more adverse outcomes including death (3.6%), reinfarction (8.4%), or the need for further revascularization (20%)., Methods and Results: Despite these generally favorable results, multivariate testing identified several anatomic and clinical subgroups as having an increased risk ratio (RR) for adverse outcome: Unsuccessful PTCA was more common in patients undergoing protocol-assigned PTCA within 2 hours of rt-PA administration (RR, 2.7; p less than 0.001) and in patients over age 70 years (RR, 1.7; p = 0.034). The need for further revascularization within 1 year was increased in the 30.4% of patients with multivessel disease (RR, 2.5; p less than 0.001), patients with prior angina (RR, 1.4; p less than 0.006), or those undergoing ischemia-driven PTCA within 15 hours of rt-PA administration (RR, 1.7; p = 0.022). The risk of death or recurrent infarction within 1 year was increased by the presence of multivessel disease (RR, 1.6; p = 0.007) or prior angina (RR, 1.5; p = 0.014)., Conclusions: These observations do not necessarily apply to patients undergoing primary PTCA (or PTCA after other thrombolytic agents); however, they do offer a unique yardstick against which to evaluate the results of PTCA in myocardial infarction.

A 65-year-old woman underwent successful percutaneous transluminal coronary angioplasty of a right coronary artery stenosis. Shortly thereafter, she developed chest discomfort and repeat angiography demonstrated a new area of stenosis distal to the area of original angioplasty. An attempt at a second angioplasty resulted in vessel occlusion with subsequent successful bypass surgery. The etiology of the new distal lesion is discussed.

We compared visual estimate and digital caliper measurement of coronary stenoses, utilizing both a 50% and 70% diameter reduction as a definition of significance and both experienced angiographers and cardiology fellows as readers. Ten angiograms were interpreted twice, using the different methods, by four readers, two months apart. The angiograms were divided into 12 vessel segments. Stenoses were judged more severe by visual estimate in 11 segments. Seven of twelve segments had significant differences between readers using the visual estimate, but no significant differences were obtained using caliper measurements. Variability was highest for fellows using the visual method. Interobserver agreement was highest using the digital caliper and the 70% criteria. Intraobserver agreement was most dependent on the amount of time taken in film interpretation. The digital caliper appears to be preferable in interpreting angiograms, particularly for cardiology fellows.

A patient with prolonged duration, bacterial infection, and echocardiographic disappearance of an atrial myxoma following embolization is discussed. Following aortic saddle embolus, all echocardiographic manifestations of the patient's left atrial myxoma disappeared. Previous cases of infected atrial myxomas are reviewed. The necessity of early surgical intervention, despite active infection, is discussed.

Patients with a history of anaphylactoid reaction to radiographic contrast medium (RCM) are at increased risk for subsequent reaction. To date, 275 of these high-risk patients have been studied with use of prophylactic pretreatment with diphenhydramine hydrochloride or prednisone or both without a single severe anaphylactoid reaction on readministration of RCM. This report describes a patient who received pretreatment as described in the literature but suffered a life-threatening anaphylactoid reaction on readministration of RCM. Premedication does not eliminate the possiblity of a fatal reaction on readministration of RCM.