LabMed

Myocarditits (Non-infectious)

At a Glance

Myocarditis is an inflammatory condition of the myocardium associated with damage to the cardiomyocytes. In developed countries, viral infections, such as adenovirus, coxsackievirus, cytomegalovirus, influenza, Borrelia, herpes simplex, and Epstein-Barr, are the most frequent causes of myocarditis.

Non-infectious myocarditis is primarily immune mediated and associated with rheumatic fever, systemic lupus erythmatoses, drug-induced hypersensitivity reactions, and systemic hypereosinophilic syndromes. Regardless of cause, there is no common presentation associated with myocarditis, as some patients remain asymptomatic and others present with fulminant heart failure. Myocarditis should be suspected in individuals (particularly males) who are otherwise healthy but present with new or subacute congestive heart failure, chest pain, or unexplained arrhythmias.

Pericarditis involves inflammation of the pericardium, and patients present with a primary complaint of chest pain, which ranges in intensity from severe to minor pain. There are no absolute criteria established for the diagnosis of acute pericarditis; however, generally, the presence of two out of the following four clinical criteria is considered diagnostic

  • characteristic chest pain

  • pericardial friction rub

  • electrocardiogram (ECG) changes/abnormalities and/or widespread ST-segment elevations

  • new or worsening pericardial effusion

Approximately 80-85% of cases of pericarditis are idiopathic in nature and thought to arise from undiagnosed viral infections; however, there are no clinical features distinguishing viral from idiopathic pericarditis. It is often not of importance to decipher the cause of the pericarditis, as a majority of the time there will be no cause determined despite extensive testing. Patients, in particular males, with pericarditis often have myocardial involvement (myopericarditis) and can present with acute, severe dyspnea/tachypnea. Clinically, the diagnosis of myopericarditis can be made once pericarditis has been definitively diagnosed and there is evidence of increased cardiac biomarkers (troponin) or loss of left ventricular (LV) function noted on imaging.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

There is no gold standard laboratory test(s) for myocarditis, pericarditis, or myopericarditis that offers either absolute sensitivity or specificity for the diseases, making their diagnoses particularly challenging. However, the following tests are helpful in the assessment of myocarditis, pericarditis, and myopericarditis.

Troponin

Myocarditis may mimic acute myocardial infarction (MI); therefore, cardiac enzymes (preferably cardiac troponin) should be ordered. Troponin offers improved sensitivity and specificity over CK-MB and myoglobin; therefore, ordering either in conjunction with troponin offers no additional value to the diagnosis of myocarditis. Troponin T or troponin I assays can be used to rule out MI, provided appropriate cutoffs are utilized and are used along with clinical criteria. Point-of-care troponin assays do not have sufficient precision or sensitivity for widespread use; therefore, laboratory-based troponin assays are preferred if the turnaround time is acceptable (<60 minutes to reporting results).

Contemporary cardiac troponin assays are both sensitive and specific for myocardial damage, and elevations are commonly present in acute and fulminant myocarditis. This is indicative of an ongoing, low-grade myocardial necrosis, and elevations above the normal range are seen in myocarditis, which is similar to patients with acute coronary syndrome (ACS).

Myocarditis now appears to be the most common imitator of acute MI and the most common cause of an elevated cTn in patients with ACS and normal coronary arteries. Values can be increasing or stable. However, in general, cases of non-infectious myocarditis can be differentiated from acute MI by examination of results from serial troponin samples. In non-infectious myocarditis, troponin is typically elevated but does not change acutely over time, whereas, in acute MI, a significant changing pattern is observed in patients.

There is no absolute agreement about the timing of serial samples; cardiology guidelines recommend baseline and 6-hour samples, with a 12-hour sample drawn in patients with a high suspicion or risk of MI. However, it is widely recognized that baseline and another sample between 3 and 6 hours is sufficient for rule in/rule out purposes, depending on the assay and cutoffs used.

Troponin elevations may be seen in acute pericarditis, indicative of myopericarditis, although to a much lesser extent than seen in myocarditis alone. If elevated, troponin will be elevated and not change acutely; a majority of patients with an elevated troponin and myopericarditis have normal findings on coronary angiography. These elevations generally become undetectable within 1-2 weeks and are not prognostic of future adverse events. If there is concurrent myocardial involvement, troponin elevations mimic and express the extent of myocardial damage.

Inflammatory Markers

Elevations of inflammatory markers, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), may be noted and considered confirmatory, although both tests are nonspecific indicators of inflammation. Measurement of CRP is preferred over ESR, however, because of its improved analytical and clinical sensitivity for detecting inflammatory processes, likely because of the direct involvement of CRP in complement activation. Abnormal results will not indicate further information about the underlying cause(s). Given the low frequency of autoimmune diseases or drugs as the cause of non-infectious myocarditis, the overall yield of testing for various antibodies or drugs is low, unless the clinical presentation is suggestive or suspicious.

CRP and ESR may be more useful in patients with pericarditis, and they generally have marked elevations that normalize following appropriate therapeutic measures (approximately 7-14 days). A small percentage of patients with pericarditis have normal or only mildly elevated CRP/ESR, typically in the hyperacute phase of pericarditis.

Complete Blood Count (CBC)

A CBC with differential may be ordered to evaluate for leukocytosis and eosinophilia; if present, results may provide guidance toward the diagnosis of non-infectious myocarditis.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

Several OTC and prescription drugs are known to be causative of non-infectious myocarditis, thus, careful consideration should be taken to obtain an accurate and thorough medical/lifestyle history. However, none of these interfere with the diagnostic laboratory assay itself.(Table 1)

Analytical false-positive troponin elevations are rare but should be suspected when values are elevated, do not change over time, and/or do not fit the clinical situation. The most common problem is fibrin interference in plasma specimens that can be easily investigated and remedied by the clinical laboratory. Other interferences in troponin assays exist, such as a variety of heterophile antibodies or autoantibodies that may cause false-positive or false-negative results, although these are extremely rare.

Table 1

Drugs Most Commonly Associated with Non-Infectious Myocarditis
Drug Class Examples
Antibiotics sulfonamides, beta-lactams, tetracycline, aminoglycosides
Cardiac drugs methyldopa, catecholamines, cocaine, thiazides, furosemide
Antiepileptics phenytoin, carbamazepine
Psychotropics tricyclic antidepressants, phenothiazine antipsychotics, clozapine
Antimycobacterials streptomycin
Heavy metals copper, lead, iron, arsenic
Other non-steroidal anti-inflammatory drugs, sulfonylureas, carbon monoxide

What Lab Results Are Absolutely Confirmatory?

None of the laboratory results are confirmatory when utilized independently and, therefore, must be interpreted with other clinical diagnostic modalities (i.e., ECG changes, echocardiography, cardiac magnetic resonance imaging, and/or endomyocardial biopsy). Troponin is the superior blood based biomarker and provides the best evidence of myocardial necrosis.

Additional Issues of Clinical Importance

It is critical that appropriate cutoffs for cardiac troponin are used for proper clinical interpretation. A single troponin provides little to no information on its own, and serial samples should always be ordered 3-6 hours and 9-12 hours after the baseline sample to evaluate for acute versus chronic changes/elevations to help differentiate patterns seen in non-infectious myocarditis, pericarditis, and myopericarditis from MI, while correlating with the ECG and imaging results.

The 99th percentile value of the reference population should be used to designate an abnormal cardiac troponin, and it is important to know the 99th percentile for the assay used locally, because there is wide variability in assay sensitivity. However, it is important to remember that an elevated troponin is not specific for an acute MI, only the process of myocyte necrosis.

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