Cardiac troponin T in chest pain unit patients without ischemic electrocardiographic changes: angiographic correlates and long-term clinical outcomes

OBJECTIVES

We prospectively evaluated the relation between cardiac troponin T (cTnT) level, the presence and severity of coronary artery disease (CAD) and long-term prognosis in patients with chest pain but no ischemic electrocardiographic (ECG) changes who had short-term observation.

BACKGROUND

Cardiac TnT is a powerful predictor of future myocardial infarction (MI) and death in patients with ECG evidence of an acute coronary syndrome. However, for patients with chest pain with normal ECGs, it has not been determined whether cTnT elevation is predictive of CAD and a poor long-term prognosis.

METHODS

In 414 consecutive patients with no ischemic ECG changes who were triaged to a chest pain unit, cTnT and creatine kinase, MB fraction (CK-MB) were evaluated ≥10 h after symptom onset. Patients with adverse cardiac events, including death, MI, unstable angina and heart failure were followed for as long as one year.

RESULTS

A positive (>0.1 ng/ml) cTnT test was detected in 37 patients (8.9%). Coronary artery disease was found in 90% of 30 cTnT-positive patients versus 23% of 144 cTnT-negative patients who underwent angiography (p < 0.001), with multivessel disease in 63% versus 13% (p < 0.001). The cTnT-positive patients had a significantly (p < 0.05) higher percent diameter stenosis and a greater frequency of calcified, complex and occlusive lesions. Follow-up was available in 405 patients (98%). By one year, 59 patients (14.6%) had adverse cardiac events. The cumulative adverse event rate was 32.4% in cTnT-positive patients versus 12.8% in cTnT-negative patients (p = 0.001). After adjustment for baseline clinical characteristics, positive cTnT was a stronger predictor of events (chi-square = 23.56, p = 0.0003) than positive CK-MB (>5 ng/ml) (chi-square = 21.08, p = 0.0008). In a model including both biochemical markers, CK-MB added no predictive information as compared with cTnT alone (chi-square = 23.57, p = 0.0006).

CONCLUSIONS

In a group of patients with chest pain anticipated to have a low prevalence of CAD and a good prognosis, cTnT identifies a subgroup with a high prevalence of extensive and complex CAD and increased risk for long-term adverse outcomes.     

Real-time three-dimensional dobutamine stress echocardiography in assessment stress echocardiography in assessment of ischemia: comparison with two-dimensional dobutamine stress echocardiography

OBJECTIVES: This study was designed to test the feasibility and efficacy of using real-time three-dimensional echocardiography (RT-3D) to detect ischemia during dobutamine-induced stress (DSE) and compares the results with conventional two-dimensional echocardiography (2D). BACKGROUND: Real-time three-dimensional echocardiography, a novel imaging technique, offers rapid acquisition with multiple simultaneous views of the left ventricle (LV). These features make it attractive for application during stress. METHODS: Of 279 consecutive patients screened for image quality by 2D, 253 patients with adequate images underwent RT-3D and 2D within 30 s of each other at baseline and at peak DSE. RESULTS: Real-time three-dimensional echocardiography and 2D showed good concordance in detection of abnormal LV wall motion at baseline (84%: Kappa = 0.59) and at peak DSE (88.9%: Kappa = 0.72). Left ventricular wall motion scores were similar at baseline and peak DSE using both techniques. Interobserver agreements for detection of ischemia at peak DSE were superior for RT-3D, 92.7% compared with 84.6% for 2D (p < 0.05). Mean scanning time at peak stress by RT-3D in 50 randomly selected patients was shorter, 27.4 +/- 10.7 s compared with 62.4 +/- 20.1 s by 2D (p < 0.0001). In 90 patients with coronary angiograms, RT-3D had a sensitivity of 87.9% in the detection of coronary artery disease (CAD) compared with 79.3% by 2D. CONCLUSIONS: Real-time three-dimensional dobutamine stress echocardiography is feasible and sensitive in the detection of CAD. The procedure offers shorter scanning time, superior interobserver agreements and unique new views of the LV.     

Varying the number of telomere-bound proteins does not alter telomere length in tel1Delta cells

Yeast telomere DNA consists of a continuous, approximately 330-bp tract of the heterogeneous repeat TG(1-3) with irregularly spaced, high affinity sites for the protein Rap1p. Yeast monitor, or count, the number of telomeric Rap1p C termini in a negative feedback mechanism to modulate the length of the terminal TG(1-3) repeats, and synthetic telomeres that tether Rap1p molecules adjacent to the TG(1-3) tract cause wild-type cells to maintain a shorter TG(1-3) tract. To identify trans-acting proteins required to count Rap1p molecules, these same synthetic telomeres were placed in two short telomere mutants: yku70Delta (which lack the yeast Ku70 protein) and tel1Delta (which lack the yeast ortholog of ATM). Although both mutants maintain telomeres with approximately 100 bp of TG(1-3), only yku70Delta cells maintained shorter TG(1-3) repeats in response to internal Rap1p molecules. This distinct response to internal Rap1p molecules was not caused by a variation in Rap1p site density in the TG(1-3) repeats as sequencing of tel1Delta and yku70Delta telomeres showed that both strains have only five to six Rap1p sites per 100-bp telomere. In addition, the tel1Delta short telomere phenotype was epistatic to the unregulated telomere length caused by deletion of the Rap1p C-terminal domain. Thus, the length of the TG(1-3) repeats in tel1Delta cells was independent of the number of the Rap1p C termini at the telomere. These data indicate that tel1Delta cells use an alternative mechanism to regulate telomere length that is distinct from monitoring the number of telomere binding proteins.     

Management of Infrapopliteal Peripheral Arterial Occlusive Disease

The management of infrapopliteal peripheral arterial occlusive disease (PAD) is challenging. For patients with asymptomatic disease or claudication, exercise and optimal medical management, including antiplatelet agents, blood pressure control, statin therapy and tight glucose control for patients with diabetes mellitus, are the mainstays of therapy. However, patients with isolated tibial artery occlusive disease often have diabetes mellitus or renal insufficiency and present with critical limb ischemia (CLI). CLI is advanced occlusive disease marked by the development of rest pain, ischemic ulceration, or gangrene and is associated with a high mortality rate. Limb salvage requires an intervention in cases of CLI, but careful operative planning is required as patients often have multilevel disease and limited options for revascularization. A surgical bypass with a vein graft remains the best treatment for infrapopliteal PAD, especially in patients with a life expectancy of over 2 years. Balloon angioplasty can play an important role in limb salvage, especially for patients lacking adequate vein for bypass, at high operative risk, or with a life expectancy of less than 2 years. However, a lack of rigorous trials has left unanswered questions as to the efficacy of infrapopliteal angioplasty with or without stents compared to bypass surgery. As such, endovascular therapy is currently not a proven treatment for intermittent claudication. Patients who are unable to undergo a revascularization procedure for infrapopliteal CLI have few options besides amputation or palliation. New therapies, such as drug-eluting stents, drug-coated balloons, and stem cell therapy are under development, but their efficacy and effectiveness remain unproven.     

Vergleich des Kontrastverhaltens von Gadobenat-Dimeglumine und Gd-DTPA bei intraaxialen Hirntumoren Eine doppelblinde randomisierte intraindividuelle Cross-over-Studie Eine doppelblinde randomisierte intraindividuelle Cross-over-Studie

In einer doppelt verblindeten randomisierten intraindividuellen Cross-Over Vergleichsuntersuchung wurden 27 Patienten mit intraaxialen Hirntumoren mittels der MR-Kontrastmittel Gadobenat-Dimeglumine (Multihance^?) und Gd-DTPA (Magnevist^?) untersucht.     

3-D imaging of the CNS

Summary 3-D gradient echo techniques, and in particular FLASH, represent a significant advance in MR imaging strategy allowing thin section, high rsolution imaging through a large region of interest. Anatomical areas of application include the brain, spine, and extremities, although the majority of work to date has been performed in the brain. Superior T1 contrast and thus sensitivity to the presence of Gd DTPA is achieved with 3-D FLASH when compared to 2-D spin echo technique. There is marked arterial and venous enhancement following Gd DTPA administration on 3-D FLASH, a less common finding with 2-D spin echo. Enhancement of the falx and tentorium is also more prominent. From a single data acquisition, requiring less than 11 min of scan time, high resolution reformatted sagittal, coronal, and axial images can obtained in addition to sections in any arbitrary plane. Tissue segmentation techniques can be applied and lesions displayed in three dimensions. These results may lead to the replacement of 2-D spin echo with 3-D FLASH for high resolution T1-weighted MR imaging of the CNS, particularly in the study of mass lesions and structural anomalies. The application of similar T2-weighted gradient echo techniques may follow, however the signal-to-noise ratio which can be achieved remains a potential limitation.     

Bispecific monoclonal antibodies produced by somatic cell fusion increase the potency of tissue plasminogen activator

Bispecific monoclonal antibodies that bind simultaneously to human fibrin and tissue plasminogen activator (tPA) enhance the fibrinolytic potency of tPA. Two bispecific antibodies (F36.23 and F32.1) were generated by somatic cell fusion. Antibody F36.23 derives its tPA binding from monoclonal anti-tPA antibody TCL8 and its fibrin binding from monoclonal antifibrin antibody 59D8. After purification from cell supernatants and ascites by two steps of affinity chromatography, hybrid-hybridoma bispecific antibody F36.23 simultaneously bound tPA and fibrin in solution and in solid-phase assays. In an assay for the lysis of human fibrin monomer, F36.23 increased the fibrinolytic potency of tPA by 5 to 10 fold, regardless of whether the bispecific antibody had been combined with the tPA before or during the assay. Bispecific F36.23 F(ab')2 also bound tPA and fibrin simultaneously, and the enhancement in fibrinolysis in the presence of F36.23 F(ab')2 was identical to that in the presence of intact F36.23. The second bispecific antibody, F32.1, was produced by an alternative strategy that has a wider potential for application in other systems. Hybridoma bispecific antibody F32.1 was derived from the fusion of immune splenocytes (in mice immunized with a synthetic oligopeptide representing the amino terminus of the alpha-chain of human fibrin) with the anti-tPA cell line TCL8. The properties of hybridoma bispecific antibody F32.1 and its F(ab')2 were indistinguishable from those of hybrid-hybridoma bispecific antibody F36.23 in solid-phase binding assays and in assays of fibrinolysis. Bispecific antibodies produced by somatic cell fusion, particularly in the form of F(ab')2, may have potential for use in clinical thrombolysis.     

Preload-responsive, pulsatile-flow, externally valved pump: cardiopulmonary bypass

Currently two pumps are used for cardiopulmonary bypass, the roller pump and the centrifugal or vortex pump. Both are steady-flow pumps. The procedure of cardiopulmonary bypass possesses a finite morbidity and mortality. The degree to which steady flow is responsible for this morbidity and mortality remains to be clarified, but investigators have established the fact that a physiologic degree of pulsatile flow must be achieved before its beneficial results, such as normal systemic resistance and absence of lactate production, can be demonstrated. Availability of a satisfactory pulsatile pump for cardiopulmonary bypass has been a problem in the past but the pump presented here may satisfy this need. It produces physiologic pulsatility with rate dependent ejection time equal to or less than that of humans (413 microseconds minus 1.7 times heart rate), and it is preload-responsive, varying its pumping rate and output with filling pressure. The pump is externally valved to minimize hemolysis, which has been demonstrated in two laboratory studies to be significantly less than with the roller pump. It produces pulsatile flow through membrane oxygenators. The pump is thought to have potential for several clinical applications in addition to (1) pulsatile-flow cardiopulmonary bypass, including (2) left, right, or combined transthoracic QRS synchronized ventricular assist, (3) femoral vein to femoral artery QRS synchronized left ventricular assist, (4) adult or infant ECMO, (5) pulsatile flow hemodialysis. In the latter, spallation and embolization of hemodialysis tubing particles should not be a problem as has proved to be the case with the present hemodialysis pump.