From the Guidelines
Elevated troponin levels can occur due to several non-cardiac causes, including severe infections, renal failure, pulmonary embolism, strenuous exercise, critical illnesses, and certain drugs or toxins, as noted in the 2021 ESC guidelines for the management of acute coronary syndromes 1.
Non-Cardiac Causes of Elevated Troponin
The following are some of the non-cardiac causes of elevated troponin levels:
- Severe infections or sepsis, which can damage heart muscle through inflammatory mediators and oxygen supply-demand imbalance
- Renal failure, as decreased kidney function reduces troponin clearance, leading to accumulation in the bloodstream
- Pulmonary embolism, which can elevate troponins through right heart strain and hypoxemia
- Strenuous exercise, particularly endurance activities like marathons, can cause transient troponin elevations due to increased cardiac workload
- Critical illnesses such as respiratory failure, shock, or severe burns may elevate troponins through systemic inflammation and metabolic derangements
- Certain drugs and toxins, including chemotherapeutic agents (especially anthracyclines), cocaine, and carbon monoxide, can directly damage cardiac myocytes
- Neurological emergencies like stroke or subarachnoid hemorrhage can cause troponin release through catecholamine surges
- Other causes include severe anemia, tachyarrhythmias, direct cardiac trauma, and inflammatory conditions like myocarditis or pericarditis
Importance of Considering Non-Cardiac Causes
When evaluating elevated troponin levels, it's essential to consider these non-cardiac causes alongside potential acute coronary syndromes, especially in patients with atypical symptoms or known non-cardiac acute illnesses, as highlighted in the 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 1 and the 2012 third universal definition of myocardial infarction 1.
Clinical Approach
In clinical practice, a comprehensive approach is necessary to differentiate between cardiac and non-cardiac causes of elevated troponin levels, taking into account the patient's medical history, physical examination, and laboratory results, including cardiac troponin, blood urea nitrogen, creatinine, electrolytes, and liver function tests, as recommended in the 2011 ESC guidelines for the management of acute coronary syndromes 1.
From the Research
Non-Cardiac Causes of Elevated Troponin Levels
Elevated troponin levels are often associated with cardiac conditions, but they can also be caused by non-cardiac factors. Some of the non-cardiac causes of elevated troponin levels include:
- Renal failure: Studies have shown that patients with end-stage renal failure often have elevated troponin levels, even in the absence of cardiac disease 2.
- Sepsis: Sepsis, a systemic inflammatory response, can cause elevated troponin levels due to the release of cardiac biomarkers from damaged cardiomyocytes 3.
- Pulmonary embolism: Pulmonary embolism can cause elevated troponin levels due to the strain on the right ventricle and the resulting cardiomyocyte damage 3.
- Inflammatory heart disease: Inflammatory heart disease, such as myocarditis, can cause elevated troponin levels due to the inflammation and damage to the cardiac tissue 3.
- Physical exertion: Intensive physical exertion can cause elevated troponin levels due to the stress and strain on the cardiac muscle 3.
Clinical Implications
Elevated troponin levels in non-cardiac conditions can have significant clinical implications. For example:
- Patients with non-cardiac causes of elevated troponin levels may be misdiagnosed with acute coronary syndrome (ACS) and undergo unnecessary invasive tests 4, 5.
- Elevated troponin levels in non-cardiac conditions can be associated with poor outcomes, including increased mortality 6, 5.
- The use of cardiac diagnostic tests, such as coronary angiography, may not be helpful in excluding non-cardiac causes of elevated troponin levels 5.
Diagnostic Considerations
When evaluating patients with elevated troponin levels, it is essential to consider non-cardiac causes, especially in patients with underlying medical conditions. A thorough clinical evaluation, including a detailed medical history and physical examination, can help identify alternative explanations for elevated troponin levels 4, 3.