In patients with suspected ACS, implementation of a sensitive troponin assay increased the diagnosis of MI and identified patients at high risk of recurrent MI and death. Lowering the diagnostic threshold of plasma troponin was associated with major reductions in morbidity and mortality.
Objective-Using a clinical model of deep arterial injury, we assessed the ability of exogenous and endogenous tissue plasminogen activator (t-PA) to limit acute in situ thrombus formation. Approach and Results-Ex vivo thrombus formation was assessed in the Badimon chamber at low and high shear rates in 2 double-blind randomized cross-over studies of 20 healthy volunteers during extracorporeal administration of recombinant t-PA (0, 40, 200, and 1000 ng/mL) or during endogenous t-PA release stimulated by intra-arterial bradykinin infusion in the presence or absence of oral enalapril. Recombinant t-PA caused a dose-dependent reduction in thrombus area under low and high shear conditions (P<0.001 for all). Intra-arterial bradykinin increased plasma t-PA concentrations in the chamber effluent (P<0.01 for all versus saline) that was quadrupled in the presence of enalapril (P<0.0001 versus placebo). These increases were accompanied by an increase in plasma D-dimer concentration (P<0.005 for all versus saline) and, in the presence of enalapril, a reduction in thrombus area in the low shear (16±5; P=0.03) and a trend toward a reduction in the high shear chamber (13±7%; P=0.07). Conclusions-Using a well-characterized clinical model of coronary arterial injury, we demonstrate that endogenous t-PA released from the vascular endothelium enhances fibrinolysis and limits in situ thrombus propagation. These data support a crucial role for the endogenous fibrinolytic system in vivo and suggest that continued exploration and manipulation of its therapeutic potential are warranted.
Introduction Troponin is frequently measured on admission to hyperacute stroke units (HASUs). Modest elevations in stroke are common but whether patient management changes in response to the blood test is unclear. Raised troponin without chest pain or dynamic ECG changes create diagnostic dilemmas. Management strategies were assessed with the introduction of the Imperial HASU covering North West London. Methods Consecutive HASU admissions over 6 months were assessed for measurement of troponin, the result, and the cardiac investigations performed. Clinical parameters guided investigations lead by two Consultant Cardiologists (KF, SC) rather than strict research protocol. Results 412 patients were admitted: 245 patients had a total of 435 troponin-I levels measured, without chest pain or dynamic ischaemic ECG changes. 70 (29%) patients had positive levels (>0.032 ng/l): 53 (22%) were "low" (0.032e0.3 ng/l), 17 (7%) were "high" (>0.3 ng/l). 237 had diagnoses readily available: 170 had stroke (ischaemic or haemorrhagic), 67 had non-stroke (eg, seizure). Troponin was more likely to be raised if stroke, OR 4.3 (2.0e9.7, p¼0.0001). Five patients with "high" troponins had non-invasive stress testing (1 perfusion scan and 4 stress echos): all were negative. All positive troponins had echocardiography and cardiology review with no change in management in 91% of cases. 6 patients had invasive coronary angiography: 3 "high" and 3 "low" troponin. Only 2 patients (3% of those with positive troponin) required percutaneous coronary intervention (PCI); both had troponin >0.3 and multiple cardiac risk factors. Patients with troponin <0.3 did not require PCIeall three had normal coronary arteries. Conclusions Every positive troponin necessitated a review and additional tests, increasing demand on cardiology services without increase in resources. However only 2 patients required PCI with the majority medically managed. We propose a pragmatic pathway for when troponin is performed as a routine test. Raised troponins >0.3 ng/l should be assessed for chest pain and ECG changes suggesting true myocardial infarction. Without these, non-invasive assessment and optimal medical therapy is sufficient in the majority. Minor troponin rise (0.032e0.3 ng/l) represents myocytolysis: cerebral insular damage causes sympathoadrenal activation and patchy myocyte damage. Without chest pain or ECG changes, optimal medical management without further investigation is appropriate. Since this does not represent true acute coronary syndrome, an early invasive strategy confers no additional benefit over medical therapy. In contrast, aspirin and statins benefit both stroke and any coronary disease present. The financial and medical implications of performing non-indicated tests in a routine manner when the result will be disregarded is significant. Therefore, we caution against routine measurement of troponin in stroke.
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