Can angiographically silent coronary atherosclerosis predict mortality after cardiac transplantation?
Explore the source record for details and available documents.
Comment↗
Biomedical subjects
I K Jang
Publications and source records attributed to I K Jang.
Disagreement between formal and medical record criteria for the diagnosis of acute coronary syndrome.
OBJECTIVES: To measure agreement between formal and medical record criteria for the diagnosis of acute coronary syndrome (ACS) among patients undergoing an emergency department evaluation for potential acute coronary symptoms. METHODS: Cases of ACS were determined by both formal (World Health Organization 1984 criteria for acute myocardial infarction [AMI], Braunwald criteria for unstable angina pectoris [UAP]) and medical record criteria. In the latter, a diagnosis was made if providers indicated AMI or UAP anywhere in the medical record. All information included in formal criteria was available to clinicians establishing the medical record diagnosis. The two criteria for diagnosis were compared, and a kappa value was recorded. Two blinded observers adjudicated discordant cases, with a kappa value recorded. Disagreements between these two coinvestigators were resolved by a Delphi technique. RESULTS: A total of 375 eligible subjects were enrolled, of whom 65 (17%; 45 AMI, 20 UAP) had ACS by both sets of criteria. Formal and medical record criteria disagreed in 32 subjects. This represented 9% (95% confidence interval = 6% to 12%) of the overall study population but 33% (95% confidence interval = 23% to 43%) of subjects with possible ACS. Coinvestigators acting as judges and blinded to each other's determinations agreed that 25 of these subjects had ACS and three did not; they disagreed on four subjects (kappa = 0.54). Among these four subjects, a Delphi consensus technique determined that two subjects had AMI and two had no ACS. CONCLUSIONS: In a single-site study, among subjects who have possible ACS as determined by either or both formal and medical record criteria, these two sets of criteria disagree in almost one third of cases. Among discordant cases, even two expert judges frequently disagreed on the final diagnosis. A modified Delphi technique to address these disagreements is described.
Acute Disease↗
The comparison between optical coherence tomography and intravascular ultrasound.
Coronary angiography, despite its long history, has well recognized limitations, arising in part from the inability to image a three dimensional structure in a single plane. Furthermore the angiographic image of the arterial lumen conceals atherosclerotic processes that occur within the arterial wall. Alternative imaging techniques have evolved as an adjunct to angiography in an attempt to overcome these limitations. Two such invasive techniques are intravascular ultrasound and optical coherence tomography. Intravascular ultrasound allows tomographic imaging of long segments of the coronary tree, highlighting the arterial lumen as well as the arterial wall. Over the last 13 years intravascular ultrasound has enhanced our understanding of the pathophysiology of atherosclerosis, and the mechanisms involved in coronary intervention. Optical coherence tomography is an optical analogue of intravascular ultrasound that has recently reached coronary application. Its superior resolution results in improved diagnostic potential, particularly for vulnerable plaque in which the thin fibrous cap often measures 10-50 mm. The similarities, contrasts and applications of these two imaging techniques in terms of design, image interpretation, and future directions forms the subject of this review.
Angioplasty, Balloon, Coronary↗
Visualization of tissue prolapse between coronary stent struts by optical coherence tomography: comparison with intravascular ultrasound.
Explore the source record for details and available documents.
Aged↗
A risk score system for predicting adverse outcomes and magnitude of benefit with glycoprotein IIb/IIIa inhibitor therapy in patients with unstable angina pectoris.
Clinical outcomes of patients with unstable angina are variable. We sought to identify predictors of adverse clinical outcomes in patients with unstable angina and to investigate whether these factors would predict the magnitude of benefit achieved with platelet glycoprotein IIb/IIIa inhibition. We analyzed 20 variables in the 1,915 patients enrolled in the Platelet Receptor Inhibition for Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms trial. Five independent predictors were identified: age >65 years, prior coronary artery bypass grafting, antecedent aspirin use, antecedent beta-blocker use, and ST depressions on the presenting electrocardiogram. A risk score system was created using these predictors in which patients were assigned 1 point for the presence of each risk factor. There was a progressive increase in the rate of the composite end point of death, myocardial infarction, or refractory ischemia at 7 days with an increasing number of risk factors. For patients treated with heparin alone, the composite end point event rate was 6.5% in the group with 0 or 1 predictor, 14.6% in the group with 2 predictors, 22.7% in the group with 3 predictors, and 37.1% in the group with 4 or 5 predictors (p <0.00001). When dividing patients into low- (0 or 1 point), medium- (2 or 3 points), and high-risk (4 or 5 points) groups, the addition of tirofiban to heparin therapy was associated with no significant benefit in the low-risk group, a 5.2% absolute reduction in the medium-risk group (p = 0.05), and a 16% absolute reduction in the high-risk group (p = 0.0055). Thus, we have developed a risk score system using 5 variables that can be used to identify patients at high risk for death and cardiac ischemic events and who experience the greatest benefit from the addition of a glycoprotein IIb/IIIa inhibitor to their treatment regimen.
Adult↗
Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia.
BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an immune-mediated syndrome caused by heparin. Complications range from thrombocytopenia to thrombocytopenia with thrombosis. We report a prospective, historical- controlled study evaluating the efficacy and safety of argatroban, a direct thrombin inhibitor, as anticoagulant therapy in patients with HIT or HIT with thrombosis syndrome (HITTS). METHODS AND RESULTS: Patients with HIT (isolated thrombocytopenia, n=160) or HITTS (n=144) received 2 microgram. kg(-1). min(-1) IV argatroban, adjusted to maintain the activated partial thromboplastin time 1.5 to 3.0 times baseline value. Treatment was maintained for 6 days, on average. Clinical outcomes over 37 days were compared with those of 193 historical control subjects with HIT (n=147) or HITTS (n=46). The incidence of the primary efficacy end point, a composite of all-cause death, all-cause amputation, or new thrombosis, was reduced significantly in argatroban-treated patients versus control subjects with HIT (25.6% versus 38.8%, P=0.014). In HITTS, the composite incidence in argatroban-treated patients was 43.8% versus 56.5% in control subjects (P=0.13). Significant between-group differences by time-to-event analysis of the composite end point favored argatroban treatment in HIT (P=0.010) and HITTS (P=0.014). Argatroban therapy, relative to control subjects, also significantly reduced new thrombosis and death caused by thrombosis (P<0.05). Argatroban-treated patients achieved therapeutic activated partial thromboplastin times generally within 4 to 5 hours of starting therapy and, compared with control subjects, had a significantly more rapid rise in platelet counts (P=0.0001). Bleeding events were similar between groups. CONCLUSIONS: Argatroban anticoagulation, compared with historical control subjects, improves clinical outcomes in patients who have heparin-induced thrombocytopenia, without increasing bleeding risk.
Aged↗
Production of transgenic live-bearing fish and crustaceans with replication-defective pantropic retroviral vectors.
Transgenic fish have been routinely produced by microinjecting or electroporating foreign DNA into one-cell stage embryos or unfertilized eggs. While both techniques are effective in producing transgenic fish species from which unfertilized or newly fertilized eggs can be easily obtained, these techniques are not applicable to live-bearing fish and many crustacean species where unfertilized or newly fertilized eggs are not readily available. In this paper, we describe a new method of introducing foreign DNA into the live-bearing fish, Poeciliposis lucida, and crayfish, Procambarus clarkii, by directly transforming the immature ovary or testis of these animals with replication-defective pantropic retroviral vectors carrying a reporter gene (neo(R)). A significant fraction of the progeny derived from these treated animals contains the neo(R) reporter gene, determined by a PCR-based assay. The PCR-positive individuals were crossed with nontransgenic individuals, and about 50% of the resulting progeny carried the transgene, suggesting that the F(1) animals are germline transgenic. Integration of the transgenes was confirmed by detecting the junction fragments of the genomic DNA associated with transgene constructs. The expression of reporter genes was detected by reverse transcription (RT) PCR assay. These results showed that foreign genes could be reproducibly transferred into live-bearing fish and crustaceans by directly transforming the immature gonads with replication-defective pantropic retroviral vectors.
Journal Article↗
Transgenic live-bearing fish and crustaceans produced by transforming immature gonads with replication-defective pantropic retroviral vectors.
Transgenic animals have been routinely produced by microinjecting or electroporating naked DNA into 1-cell-stage embryos or unfertilized eggs. However, these techniques are inapplicable to live-bearing fish and many crustacean species for which unfertilized or newly fertilized eggs are not readily obtainable. In the present study, replication-defective pantropic retroviral vectors carrying a reporter gene (neo(R) or beta-gal) were used to directly transform the immature ovary or testis of a live-bearing fish (Poeciliopsis lucida) and crayfish (Procambarus clarkii). The fraction of the progeny derived from these treated individuals shown to contain the neo(R) reporter gene by an assay based on polymerase chain reaction (PCR) was significant. The PCR-positive individuals were crossed with nontransgenic individuals, and about 50% of the resulting progeny carried the transgene, suggesting that the F(1) animals are germline transgenic. Integration of the transgenes was confirmed by detecting the junction fragments of the genomic DNA associated with transgene constructs. Expression of reporter genes was detected by a reverse transcription-nested PCR assay. These results showed that transgenic live-bearing fish and crustaceans could be easily produced by directly transforming the immature gonads with replication-defective pantropic retroviral vectors.
Journal Article↗
Elevation in serum troponin I predicts the benefit of tirofiban.
BACKGROUND: Elevations in serum troponins among patients with acute coronary syndromes have been shown to identify those patients who are at high risk for poor outcome and who accrue larger relative benefits from aggressive antiplatelet and antithrombotic therapies. We studied a group of patients from the PRISM-PLUS trial to explore whether simply using serum troponin I, a serum marker of cardiac injury, could predict benefit of GP IIb/IIIa receptor antagonism with tirofiban. METHODS AND RESULTS: For this study, the subjects consisted of 55 patients receiving the combination therapy of tirofiban/heparin, and 55 receiving heparin alone. The baseline characteristics were similar between the two treatment groups. Serial blood samples were obtained over the first 24-hour period following randomization to study drug, and were analyzed for troponin I (TnI) levels. Among those patients with elevated serum TnI (>0.5 ng/ml), the 30-day event rate for death or myocardial infarction (MI) was reduced from 20.6% among the heparin only group to 3.6% for those treated with the combination of tirofiban/heparin, an absolute risk reduction of 17% and relative risk reduction of 83% (p=0.06). Among the TnI negative patients, the rates of death/MI at 30 days were 9.5% and 11.1% among the combination and heparin treated groups respectively (p=NS). CONCLUSION: Irrespective of high-risk clinical factors, including ST segment depression, these data support the hypothesis that serum troponins identify those who benefit from aggressive antiplatelet therapy with tirofiban.
Acute Disease↗
Vascular complications after hemostatic puncture closure device (Angio-Seal) are not higher in overweight patients.
BACKGROUND: Angio-Seal (Daig Corporation, Minnetonka, Minnesota) allows earlier discharge from the hospital after coronary angiography. Manual compression in overweight patients after percutaneous procedures is associated with a higher incidence of groin complications. The purpose of this study was to determine if a vascular closure device could be safely used without increasing the risk of vascular complications in overweight patients. METHODS: A total of 198 patients who received the 6 French Angio-Seal device after diagnostic coronary angiography were divided into 3 groups. Group A included patients with a body mass index (BMI) of < or = 25, group B with BMI between 25 and 30, and group C with BMI > or = 30. Patients were followed for groin complications during their hospital stay. RESULTS: Complication rates were comparable between the 3 groups. Groin complications occurred in 11% in group A, 5% in group B and 6% in group C. CONCLUSION: After diagnostic cardiac catheterization, a vascular closure device such as Angio-Seal can be safely used in overweight patients.
Aged↗
Effects of tirofiban plus heparin versus heparin alone on troponin I levels in patients with acute coronary syndromes.
Elevated serum troponins following an acute coronary syndrome (ACS) predict a poor clinical outcome. Glycoprotein (GP) IIb/IIIa inhibitors reduce adverse clinical outcomes in patients with ACS, although their effect on serum troponin I (TnI) in this setting has not been described. We therefore studied the effects of the GP IIb/IIIa inhibitor tirofiban on serum TnI levels in a group of patients in the Platelet Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms trial. Serial blood samples were obtained in 53 patients receiving the combination therapy of tirofiban/heparin and in 52 receiving heparin alone, and were analyzed for baseline, peak, and mean concentrations of TnI. Baseline TnI levels were not different between the combination therapy and heparin-only groups (1.6 +/- 3.0 vs 3.1 +/- 6.7 ng/ml, p = 0.15). The peak TnI level was significantly lower in the combination therapy group than in the heparin group (5.2 +/- 8.3 vs 15.5 +/- 29.1 ng/ml, p = 0.017), and mean levels over the initial 24-hour period were also significantly lower in the combination therapy group (3.2 +/- 5.0 vs 8.5 +/- 14.8 ng/ml, p = 0.016). In univariate analysis, combination therapy was associated with lower TnI levels, whereas in a multivariate model, the lower peak and mean TnI levels as a consequence of tirofiban/heparin compared with heparin monotherapy remained significant (peak, p = 0.029; mean, p = 0.035). Among patients with negative TnI at baseline, treatment with the combination of tirofiban/heparin compared with heparin monotherapy still resulted in significantly lower peak (2.5 +/- 5.4 vs 14.6 +/- 32.8 ng/ml, p = 0.024) and mean (1.2 +/- 2.6 vs 6.9 +/- 15.8 ng/ml, p = 0.029) TnI levels. In patients with ACS, therapy with the combination of tirofiban and heparin (compared with heparin treatment alone) resulted in lower serum TnI levels, suggesting reduced myocardial injury.
Angina, Unstable↗
The use of glycoprotein IIb/IIIa inhibitors in patients with coronary artery disease.
Platelet membrane glycoprotein IIb/IIIa inhibitors, a new class of potent antiplatelet agents, have been used in the treatment of acute coronary syndromes as well as in the prevention of complications after percutaneous coronary interventions. Approximately 50,000 patients with coronary artery disease have been enrolled in randomized studies of glycoprotein IIb/IIIa inhibitors. The purpose of this article is to review the pharmacology of glycoprotein IIb/IIIa inhibitors, the results of the clinical trials using these agents, and their current use in percutaneous coronary interventions and the treatment of acute coronary syndromes.
Abciximab↗
Cbl-b regulates the CD28 dependence of T-cell activation.
Whereas co-stimulation of the T-cell antigen receptor (TCR) and CD28 triggers T-cell activation, stimulation of the TCR alone may result in an anergic state or T-cell deletion, both possible mechanisms of tolerance induction. Here we show that T cells that are deficient in the adaptor molecule Cbl-b (ref. 3) do not require CD28 engagement for interleukin-2 production, and that the Cbl-b-null mutation (Cbl-b(-/-)) fully restores T-cell-dependent antibody responses in CD28-/- mice. The main TCR signalling pathways, such as tyrosine kinases Zap-70 and Lck, Ras/mitogen-activated kinases, phospholipase Cgamma-1 and Ca2+ mobilization, were not affected in Cbl-b(-/-) T cells. In contrast, the activation of Vav, a guanine nucleotide exchange factor for Rac1/Rho/CDC42, was significantly enhanced. Our findings indicate that Cbl-b may influence the CD28 dependence of T-cell activation by selectively suppressing TCR-mediated Vav activation. Mice deficient in Cbl-b are highly susceptible to experimental autoimmune encephalomyelitis, suggesting that the dysregulation of signalling pathways modulated by Cbl-b may also contribute to human autoimmune diseases such as multiple sclerosis.
Adaptor Proteins, Signal Transducing↗
Balloon deflection technique: A method to facilitate entry of a balloon catheter into a deployed stent.
The entry of an angioplasty balloon into a coronary stent is occasionally difficult due to poorly expanded stent struts or calcified tissue blocking balloon passage. We describe a simple technique using a second guidewire and balloon to facilitate entry into the stent. Cathet. Cardiovasc. Intervent. 51:312-313, 2000.
Aged↗
Prevalence of early left ventricular thrombus after primary coronary intervention for acute myocardial infarction.
The prevalence of left ventricular (LV) thrombus after acute myocardial infarction (AMI) has been reported high at 20-60%. Current reperfusion therapies such as thrombolysis have shown a trend toward reducing the incidence of LV thrombosis. However, the prevalence of LV thrombus after primary percutaneous coronary intervention (PCI) for AMI has not been systematically studied. At Massachusetts General Hospital 71 consecutive patients who underwent primary PCI for acute ST elevation MI were reviewed for the prevalence of LV thrombus evaluated by echocardiography. Echocardiography was performed within 5 days of infarction. PCI was successful in all patients. The time delay from symptom onset to intervention was 191 minutes. Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow was achieved in more than 80% of cases. Only 3 patients (4%) had echocardiographic evidence of LV thrombus. All 3 patients had anterior infarctions. The incidence among patients with anterior MI was 10% (3 of 30 patients). The prevalence of LV thrombus in patients treated with primary PCI for AMI is low (4%).
Echocardiography↗
Combination of a direct thrombin inhibitor and a platelet glycoprotein IIb/IIIa blocking peptide facilitates and maintains reperfusion of platelet-rich thrombus with alteplase.
We sought to determine the efficacy of the combination of argatroban, a direct thrombin inhibitor, and G4120, a platelet glycoprotein (GP) IIb/IIIa blocker, to enhance thrombolysis with alteplase. Platelet-rich thrombus in the rabbit arterial thrombosis model is relatively resistant to alteplase despite the addition of aspirin and heparin. The adjunctive use of either direct thrombin inhibitors or GP IIb/IIIa inhibitors in thrombolysis has been investigated with encouraging, but limited, success. The usefulness of combining both agents as adjunctive therapy to thrombolysis has not been fully explored. Following platelet-rich thrombus formation in the rabbit, argatroban (3 mg/kg), G4120 (0.5 mg/kg), G4120 plus heparin (200 U/kg), or G4120 plus argatroban were intravenously infused over 60 minutes. Alteplase was given as intravenous boluses (0.45 mg/kg) at 15-minute intervals up to 4 doses or until reperfusion. Blood flow and bleeding time were monitored for 2 hours. The combination of G4120 plus argatroban resulted in a persistent patency in 5 of 7 animals compared with 0 of 6 for argatroban alone (p=0.02), 1 of 6 for G4120 alone (p=0.08), and 2 of 6 for G4120 plus heparin (p=0.2). Although during the infusion the bleeding times were longer in the groups that received G4120 (26+/-7.7 minutes vs. 14+/-10 minutes, p<0.05), by the end of the experiment there were no statistically significant differences. Similarly, during the infusion the activated partial thromboplastin times (aPTT) was higher in groups that received heparin or argatroban (99+/-51 seconds vs. 32+/-7.6 seconds, p<0.001), but by the end of the experiment the aPTTs had returned to close to baseline in all groups except the G4120 plus heparin group. These results suggest that lysis of platelet-rich thrombus with alteplase requires the addition of both potent platelet and thrombin inhibitors. Specifically designed agents, G4120 and argatroban, are effective without additional increased risk for bleeding.
Animals↗
Fundamental concepts in the pathobiology of heparin-induced thrombocytopenia.
Heparin-induced thrombocytopenia (HIT) is among the most common causes of drug-related immune-mediated thrombocytopenia. It is a unique syndrome, in that despite the fact that thrombocyto-penia is the major laboratory manifestation of HIT, its major complication is a highly morbid (and commonly fatal) thrombotic diathesis, known as the HIT with thrombosis syndrome (HITTS). The pathogenesis of HIT and HITTS has been recently elucidated, and involves an immune response against epitopes within circulating heparin-platelet factor-4 (PF4) complexes. This leads to cross-linking and activation of platelets, increasing the risk for thromboses. Furthermore, significant immunological cross-reactivity occurs between endothelial-cell bound PF4 and the HIT antibody, which may lead to endothelial damage, activation, and hyperplasia. This complex process leads to a hypercoagulable state, which may lead to overt thromboses.
Anticoagulants↗
Primary versus rescue percutaneous coronary intervention in patients with acute myocardial infarction.
OBJECTIVE: To compare angiographic and clinical outcomes of patients with acute myocardial infarction (AMI) who underwent primary percutaneous coronary intervention (PCI) versus rescue PCI following failed thrombolysis. BACKGROUND: Patients presenting with AMI are treated either with primary PCI or with thrombolysis. When thrombolysis fails, rescue PCI is performed. METHODS AND RESULTS: We compared the outcome of 105 consecutive patients with AMI who underwent either primary PCI (60 patients) or rescue PCI (45 patients) between January 1997 and January 1999. The patients were followed for up to 6 months. Time delay to reperfusion was significantly longer in the rescue PCI group (354 vs. 189 min; p < 0.001). The majority of patients received a stent (93%). Glycoprotein (GP) IIb/IIIa inhibitors were used in 53% of patients in the primary PCI group and in 22% in the rescue group. TIMI grade 3 flow was achieved in 93.3% of patients in the primary PCI group and in 88.8% in the rescue group (p = 0.08). Post-procedure ejection fraction was 53% in the primary PCI group and 47% in the rescue group (p = 0.014). A composite endpoint of death, recurrent MI, repeat PCI, coronary artery bypass grafting (CABG) and recurrent angina at 6 months occurred in 35% of the patients in the primary PCI group and 26.7% in the rescue group (p = 0.36). CONCLUSION: Despite a significant delay to reperfusion and a lower immediate post-procedure ejection fraction, the clinical outcome of patients treated with rescue PCI following failed thrombolysis appears to be similar to that of patients treated with primary PCI at 6 months.
Angioplasty, Balloon, Coronary↗