Expanding the Differential: What Else Can an Elevated Troponin Signify?

Author: Shyam Sivasankar, MD
Stanford-Kaiser Emergency Medicine

Originally Published: Modern Resident, December-January 2015

We often underestimate the utility of modern laboratory technology—we become shortsighted and we forget that a lab value can tell us more than what we are naturally used to it representing. One such lab value is cardiac troponin.

Instinctively, we assume that an elevated troponin is a sign of a myocardial infarction (MI), but that is not always the case. Troponin is released by cardiac muscle fibers in the setting of irreversible cell injury.

Occasionally, we can be fooled into thinking that all chest pain with an elevated troponin is a definitive diagnosis of MI, but other life-threatening causes of chest pain such as pulmonary embolism (PE) or aortic dissection can also present with an elevated troponin. The ‘troponin leak’ from PE results from right-sided heart strain and from direct myocardial injury in dissection. Elevated troponin can also be seen in pericarditis (which can also present with ST segment changes), myocarditis, blunt chest trauma and arrhythmias. Patients who have suffered from cardiac arrest and undergone CPR can also have elevated troponin levels.

Besides diseases that primarily involve the heart, sepsis can also present with elevated troponins. Although underlying cardiovascular disease can have an impact on the elevation of troponin, the mechanism underlying troponin elevations in sepsis is not very well understood. Chronic diseases may also present with baseline elevations in troponins, such as amyloidosis, chronic kidney disease, renal failure and congestive heart failure (CHF).

The mechanism of troponin elevation in patients with renal failure is still a widely debated topic, but the general consensus is that troponin levels increase secondary to a combination of reduced renal clearance of troponin and troponin leak secondary to uremic muscle tissue. Elevations of troponin in this group should not be ignored, as this population is a particularly high-risk group. Accordingly, these values should be compared to a patient’s baseline and most importantly, be placed into clinical context. The mechanism behind higher than normal troponin levels in CHF is thought to be due to pressure induced ischemia or inflammation. Long-standing disease such as left ventricular hypertrophy and systemic hypertension can also present a rise in troponin levels.

Common causes of elevations in troponin besides acute coronary syndromes (ACS):

• Pericarditis
• Pulmonary Embolism
• Aortic Dissection
• Heart Failure
• Myocarditis
• Blunt Chest Trauma
• Sepsis/SIRS
• Renal Failure
• Strenuous Exercise
• Upper GI Bleed
• LVH
• Systemic Hypertension
• Medication Induced (Cardiotoxic Drugs, such as chemotherapeutic agents)

The bottom line? Not all troponin elevations are due to an MI and when chest pain is the presenting chief complaint, we must rely on the entire clinical picture in addition to an EKG, troponin, and other adjunct studies to make a diagnosis and potentially, to save a life. For example, in the patient with an acute aortic dissection, a diagnosis of ACS based on chest pain with an elevated troponin can be deadly when anticoagulation is initiated. This is by no means an extensive or exhaustive list, but encompasses some of the major alternative diagnosis to consider.

References:

1. Januzzi JL. Cardiac biomarkers. Cardiac Biomarkers. CardioSource, 08 Sept. 2010. Web. 16 Oct. 2014.
2. Korff S. Differential diagnosis of elevated troponins. Heart 92.7 (2006): 987-93. Web.
3. Roongsritong C. Common causes of troponin elevations in the absence of acute myocardial infarction: incidence and clinical significance." Chest 125.5 (2004): 1877-884. Web.