Troponin - Non-MI Causes of Troponin Elevation

published. 25–28 Ammann et al 25 evaluated patientswith sepsis, 40% of whom were in shock. Seventeenof their 20 patients (85%) had TnI elevation. TnIlevels ranged from 0.17 to 15.4 ng/mL, with amedian value of 0.57 ng/mL. ver Elst et al 26 foundTnI levels of at least 0.4 ng/mL in 50% of their 46patients with early septic shock. Similarly, a relativelylow median level (1.4 ng/mL) of the peak concentrationsof TnI was observed in this study. In patientswith severe sepsis, septic shock, or hypovolemicshock, Arlati et al 27 found elevated TnI elevation in74% of the cases. All of their 12 patients withhypovolemic shock and 58% of those with severesepsis or septic shock had elevated TnI.Elevation of TnT in sepsis has also been reported.26,28 ver Elst et al 26 found cardiac TnT elevations( 0.1 ng/mL) in 36% of their cases. A muchhigher incidence of TnT elevation was reported bySpies et al 28 ; in their 26 patients with sepsis, 69% hadTnT levels 0.2 ng/mL.Furthermore, elevations of troponin in these patientsappear to correlate with severity of the diseaseprocess. TnI levels were found to correlate with thedegree of hypotension 27 and APACHE (acute physiologyand chronic health evaluation) II score. 26The causes of troponin elevations in these criticallyill patients are not well understood. Thesereports, in general, had a relatively small sample sizeand included a heterogeneous group of patients.Some of these patients had CAD, and stress-inducedMI may have been responsible for troponin releasein this particular subgroup of patients. Acute coronaryevents have, however, been excluded in some ofthese patients. For example, Ammann et al 25 wereable to exclude CAD in 10 of 17 TnI-positivepatients. These findings indicated that other mechanismsare also involved.In one study, 26 patients with elevated troponinlevels are older and more likely to have hypertensionor previous history of MI, suggesting that theirunderlying cardiovascular disease may, to some degree,contribute to troponin elevation. However,these findings were not observed in another study. 28It also remains unclear whether infection with anyspecific pathogens is more likely to result in troponinelevations. Streptococcal pneumoniae infection wasthe cause of sepsis in 41% of TnI-positive patients inone study, 25 whereas Gram-negative bacteria werethe offending pathogens in 63% of cases in anotherstudy. 26 Spies et al 28 found no difference in terms ofthe causes of sepsis between patients with or withouttroponin elevation.Nevertheless, there are several potential mechanisms,other than acute MI, for troponin release inseptic patients. First, it is well known that a numberof local and circulating mediators (eg, cytokines orreactive oxygen species) possess direct cardiac myocytoxicproperties. 26 Secondly, myocardial injuryfrom the effect of bacterial endotoxins has beendemonstrated. Finally, dysfunction of the microcirculationhas been described in sepsis. 29 This microvasculardysfunction can lead to ischemia and reperfusioninjury of the myocardial cell.More importantly, troponin measurements inthese patients appear to provide valuable prognosticinformation. ver Elst et al 26 reported that both TnIand TnT were independent markers of left ventriculardysfunction in patients with sepsis. They detectedleft ventricular dysfunction by transesophagealechocardiography in 78% and 9% of patientswith and without TnI elevation, respectively(p 0.001). Several studies 26,28,30 also found a weakcorrelation between elevated cardiac troponin andhospital mortality.Renal FailureThe prevalence and clinical significance of elevatedtroponins in patients with renal failure havebeen recently reviewed elsewhere. 31 In brief, TnT ismore commonly elevated in patients with renalfailure than TnI. Although the exact causes of troponinelevation in renal failure remain debatable,patients with elevated troponin generally have worseclinical outcome than those without it.False-Positive TroponinTroponin complex is located on the thin filamentof skeletal and myocardial muscle. An importantfeature of troponin complex is that its I and Tsubunits are sufficiently unique so that specificantisera can differentiate these two tissue forms. Thehigh sensitivity and specificity of cardiac troponin fordetecting myocardial injury is well documented. 32–33However, various factors can interfere with the TnIassay, leading to falsely elevated levels (Table 3).These include heterophilic antibodies, 34 rheumatoidfactor, 35 fibrin clots, 36 microparticles, 36 and malfunctionof the analyzer itself. 37The role of heterophilic antibodies in causinginterference in immunoassays has been reported in aTable 3—Common Causes of False-Positive TroponinHeterophilic antibodiesRheumatoid factorFibrin clotsMicroparticlesAnalyzer malfunctionwww.chestjournal.org CHEST / 125 /5/MAY, 2004 1881