Etiology of Elevated Troponin Levels Other Than in Acute Coronary Syndromes
abstract & commentary
By Harold L. Karpman, MD
Clinical Professor of Medicine, UCLA School of Medicine Dr. Karpman reports no financial relationship to this field of study.
Contemporary troponin assays are extremely sensitive and therefore quite capable of detecting very small episodes of myocardial necrosis. Some guidelines have suggested that any increase in cardiac troponin levels above the 10% coefficient of variation should be considered indicative of myocardial injury1 and, in fact, The Joint European Society of Cardiology/American College of Cardiology redefinition of myocardial infarction published in 2000 suggested that there is "no discernible threshold below which an elevated value of cardiac troponin would be deemed harmless."2 This conclusion was confirmed in 2002 by the updated ACC/AHA practice guidelines for the management of patients with unstable angina and non-ST segment elevation myocardial infarction.3 These recent guidelines have led to a substantial increase in the frequency of myocardial infarction diagnosis.4
Jeremias and Gibson carefully reviewed the potential causes of troponin elevation that are
unrelated to coronary thrombosis.5 They noted that the diagnostic and prognostic value of troponin
elevations in patients with a high pretest probability or clinical suspicion of thrombotic coronary artery
disease was extremely robust. However, since this marker may be found to be abnormal even in the absence of thrombotic acute coronary syndromes (see Table), the high sensitivity but low specificity of this test among patients with a low pretest probability of disease may divert attention from an underlying nonthrombotic clinical problem thereby leading to unnecessary cardiac evaluation including invasive testing in patients who demonstrate even a
minimal troponin elevation. In fact, troponin may be increased because of increased membrane
permeability without myocardial necrosis in patients with unstable angina with values returning to baseline
within a few hours.6
| Table | |
| Nonthrombotic Causes and Presumed Mechanism for Elevated Cardiac Troponin Level | |
| Diagnosis Demand Ischemia Sepsis/systemic inflammatory response syndrome mismatch Hypotension Hypovolemia Supraventricular tachycardia/ atrial fibrillation Left ventricular hypertrophy Myocardial Ischemia Coronary vasospasm Intracranial hemorrhage or stroke Ingestion of sympathomimetic agents Direct Myocardial Damage Cardiac contusion Direct current cardioversion Cardiac infiltrative disorders Chemotherapy Myocarditis Pericarditis Cardiac transplantation Myocardial Strain Congestive heart failure Pulmonary embolism Right Pulmonary hypertension or Right emphysema Chronic renal insufficiency |
Mechanism Myocardial depression/supply demand Decreased perfusion pressure Decreased filling pressure/output Supply demand mismatch Subendocardial ischemia Prolonged ischemia with myonecrosis Imbalance of autonomic nervous system Direct adrenergic effects Traumatic Traumatic Myocyte compression Cardiac toxicity Inflammatory Inflammatory Inflammatory/immune-mediated Myocardial wall stretch ventricular stretch ventricular stretch Strenuous exercise Ventricular stretch Unknown |
| Adapted from: Jeremias A, Gibson CM. Narrative Review: Alternative Causes for Elevated Cardiac Troponin Levels When Acute Coronary Syndromes are Excluded. Ann Intern Med. 2005;142:786-791. | |
Commentary
So-called demand ischemia without significant coronary artery disease refers to a mismatch between myocardial oxygen demand and supply in the absence of hemodynamically significant coronary artery stenosis.
Myocardial oxygen demand increases in the settings of
sepsis,7-8 hypotension or hypovolemia,9 and arrhyth- mias.10,11 Multiple
reports10,11 have demonstrated that troponin levels may be increased as a consequence of
tachycardia alone in the absence of coronary artery stenosis, myodepressive factors and/or inflammatory
mediators. In fact, among patients admitted to the intensive care unit for diagnoses other than acute coronary
syndromes,12 significant coronary artery disease was excluded in 72% of the patients with elevated serum tro-
ponin levels.
Elevated troponin levels have been demonstrated to be present in patients with an acute stroke or intracranial hemorrhage, usually in patients whose electrocardiograms demonstrate ischemic abnormalities.13,14 It has been speculated that the enzyme elevation in these circumstances is associated with myocardial damage due to an imbalance of the autonomic nervous system with resulting excess of sympathetic activity and increased catecholamine effect on the myocardial cells rather then due to pre-existing coronary artery disease.15 Elevated troponin levels are not infrequently found in patients with right-heart strain due to acute pulmonary embolism, chronic pulmonary hypertension and/or chronic pulmonary obstructive disease.16-18 Finally, persistently elevated serum troponin levels have been demonstrated in patients with any stage of renal disease.19-20
In summary, the serum troponin level is an extremely sensitive biomarker that aids in the detection of myocardial damage caused by impaired myocardial perfusion, usually due to thrombotic coronary artery occlusion. However, it must be clearly recognized that this marker is frequently elevated in other disease states in the absence of thrombotic acute coronary syndromes. As a result, elevation of this enzyme in the bloodstream is a sensitive test to help rule out non-ST segment elevation myocardial infarction, but is less sensitive to rule in this event because it is not specific for AMI. Its positive predictive value is greatly diminished when it is applied indiscriminately in broad populations which have a low pretest probability of thrombotic disease. In the final analysis, troponin screening is appropriate because it aids in guiding management decisions in patients with suspected ACS and, in addition, it provides prognostic value in patients both with an acute AMI and in the absence of a thrombotic ACS.
References
1. Apple FS, et al. European Society of Cardiology and American College of Cardiology guidelines for redefinition of myocardial infarction: how to use existing assays clinically and for clinical trials. Am Heart J. 2002;144:981-986.
2. Alpert JS, et al. Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol. 2000;36:959-969.
3. Braunwald E, et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction—summary article: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol. 2002;40:1366-1374.
4. Kontos MC, et al. Impact of the troponin standard on the prevalence of acute myocardial infarction. Am Heart J. 2003;146:446-452.
5. Jeremias A, Gibson CM. Narrative review: alternative causes for elevated cardiac troponin levels when acute coronary syndromes are excluded. Ann Intern Med. 2005;142:786-791.
6. Hamm CW, et al. The prognostic value of serum troponin T in unstable angina. N Engl J Med. 1992;327:146-150.
7. Guest TM, et al. Myocardial injury in critically ill patients. A frequently unrecognized complication. JAMA. 1995;273:1945-1949.
8. Ammann P, et al. Elevation of troponin I in sepsis and septic shock. Intensive Care Med. 2001;27:965-969.
9. Arlati S, et al. Myocardial necrosis in ICU patients with acute non-cardiac disease: a prospective study. Intensive Care Med. 2000;26:31-37.
10. Bakshi TK, et al. Causes of elevated troponin I with a normal coronary angiogram. Intern Med J. 2002;32:520-525.
11. Zellweger MJ, et al. Elevated troponin levels in absence of coronary artery disease after supraventricular tachycardia. Swiss Med Wkly. 2003;133:439-441.
12. Ammann P, et al. Troponin as a risk factor for mortality in critically ill patients without acute coronary syndromes. J Am Coll Cardiol. 2003;41:2004-2009.
13. Trooyen M, et al. Myocardial injury in acute stroke assessed by troponin I. Tidsskr Nor Laegeforen. 2001;121:421-5.
14. Tung P, et al. Predictors of neurocardiogenic injury after subarachnoid hemorrhage. Stroke. 2004;35:548-551.
15. Homma S, Grahame-Clark C. Editorial comment—myocardial damage in patients with subarachnoid hemorrhage. Stroke. 2004;35:552-553.
16. Yalamanchili K, et al. Prevalence of increased cardiac troponin I levels in patients with and without acute pulmonary embolism and relation of increased cardiac troponin I levels with in-hospital mortality in patients with acute pulmonary embolism. Am J Cardiol. 2004;93:263-264.
17. Torbicki A, et al. Detectable serum cardiac troponin T as a marker of poor prognosis among patients with chronic precapillary pulmonary hypertension. Circulation. 2003;108:844-848.
18. Baillard C, et al. Cardiac troponin I in patients with severe exacerbation of chronic obstructive pulmonary disease. Intensive Care Med. 2003;29:584-589.
19. Apple FS, et al. Predictive value of cardiac troponin I and T for subsequent death in end-stage renal disease. Circulation. 2002;106:2941-2945.
20. Freda BJ, et al. Cardiac troponins in renal insufficiency: review and clinical implications. J Am Coll Cardiol. 2002;40:2065-2071.
By Harold L. Karpman, MD Clinical Professor of Medicine, UCLA School of Medicine Dr. Karpman reports no financial relationship to this field of study.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content