Single Troponin for Atypical Symptoms? – PART I

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    Single Troponin for Atypical Symptoms? – PART I

    You’re working in Geri and have 10 elderly patients with dizziness and/or SOB on your board. None of them can reliably recall when their symptoms started. You are about to order “just one trop” on all of them. After all, elderly patients have atypical presentations of ACS, right? And most of them have cardiac risk factors including hypertension or hyperlipidemia. But there’s no acute time frame, and your suspicion for ACS is (to be honest) fairly low. But does it make sense to forgo the serial troponin gold standard and order just a single troponin for atypical symptoms?

    Given the complexity of this question, we’ll answer it in three parts: 1) a discussion of troponins; 2) a discussion of atypical symptoms or anginal equivalents; and 3) a discussion of what it means to put these two together.

    PART I – THE POWER AND PITFALLS OF TROPONIN


    Troponin is a complex of three proteins (troponin C, troponin I, and troponin T) involved in calcium processing in skeletal and cardiac muscle. While skeletal and cardiac muscle share troponin C isoforms, the troponin I and T isoforms are found exclusively in cardiac muscle. Cardiac Troponin I, also known as cTnI, exists in myocytes in two forms: bound and cytoplasmic. When myocytes are damaged or undergo apoptosis, the cytoplasmic cTnI spills into the blood, where it can be measured by assay. Modern cTnI assays are highly sensitive for myocardial damage, to the point where serum cTnI measurement has become the gold standard for differentiating unstable angina from NSTEMI in patients undergoing an ACS workup.

    As powerful as cardiac troponin I has become, it is crucial to note that it has poor specificity. That is, a “positive troponin,” or cTnI levels above the 99th percentile of normal as defined by ACC/AHA guidelines, does not equal a diagnosis of MI. I’ll say that again: a positive troponin does not equal MI. It is only one component of a multi-factorial risk assessment for ACS, and as such does not substitute for clinical suspicion, EKG findings, or concerning history. A positive troponin should certainly alert you that the patient may be at higher risk of MI or ischemic heart disease, but it is not diagnostic. This is because there are a myriad of other conditions that can cause elevated serum troponin. In other words, cTnI indicates the presence of myocardial damage but not the cause. While it’s certainly true that ischemic heart disease/ACS is a major cause of elevated serum cTnI, there are a host of others. Some are intuitive (pericarditis/myocarditis, cardiac contusion, cardiomyopathy), but others are not as obvious (sepsis, drug toxicity, hypothyroidism, rhabdomyolysis, renal failure). This shortcoming of cTnI has not been lost on researchers, who are looking into different biomarkers that are specific for MI or specific for cardiac ischemia in the absence of cardiac injury.
    On the flip side, a negative troponin does not equal the absence of MI. Patients can present very early in their course, before they had a chance to spill cTnI into their blood, and therefore may have a negative initial cTnI assay. Again, troponins are a risk assessment tool and not a diagnosis. This is why troponins should be repeated based on your risk stratification of the patient, and not based on set “diagnostic rules.” If a patient is at very high risk of an active ischemic process, it may be prudent to repeat troponins every hour for 4-6 hours. If a patient is at relatively low risk, two negative troponins 6 hours apart may be more than sufficient. Also, remember that negative troponin can never rule out unstable angina, since this is by definition the absence of serum troponin.
    While it’s common practice to order troponins as we see fit based on our risk assessment and clinical judgement, remember that troponin I assays were originally developed to reflect an evolving process. That is, the troponin assay is most powerful when obtained serially. In fact, all the beautiful literature supporting cTnI used serial rather than single measurements. Depending on the type of assay, blood cTnI is detectable within 4-6 hours of coronary occlusion, and remains elevated in the blood for up to 10 days. According to the ACC/AHA guidelines, it is necessary to obtain two troponin assays spaced 6 hours apart in order to rule out acute MI. However, studies have shown that this spacing can be shortened to 3-4 hours without significantly increasing the risk of missed early presentations. In fact, some studies show that two troponins can even be spaced just 1 hour apart and still rule out acute MI, as long as one troponin measurement is obtained 6 hours after symptom onset.
    So what about obtaining a single troponin if patients report symptoms well beyond the 6 hour window? Unfortunately, there are no good studies or trials to support the prognostic value of a single troponin measurement. Because of this, a single cTnI measurement is not recommended by the ACC/AHA or any other clinical guidelines, and the clinical practice of doing so is not evidence-based.
    So far, the idea of a single measurement is not looking so hot…but stay tuned for Part II tomorrow!
    References
    1. Macrae AR1, Kavsak PA, Lustig V, Bhargava R, Vandersluis R, Palomaki GE, Yerna MJ, Jaffe AS Assessing the requirement for the 6-hour interval between specimens in the American Heart Association Classification of Myocardial Infarction in Epidemiology and Clinical Research Studies. Clin Chem. 2006 May;52(5):812-8. Epub 2006 Mar 23.
    2. Jaffe AS1. Use of biomarkers in the emergency department and chest pain unit. Cardiol Clin. 2005 Nov;23(4):453-65, vi.
    3. Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE 2nd, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED,Theroux P, Wenger NK, Wright RS, Smith SC Jr, Jacobs AK, Halperin JL, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura R, Ornato JP, Page RL,Riegel B. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. Circulation. 2007 Aug 14;116(7):e148-304. Epub 2007 Aug 6.
    Jean Sun

    Jean Sun

    PGY2 Resident

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