Frances1 b9b1cf

High-sensitivity cardiac troponin: scope for improvement?

Acute chest pain remains the most common reason for emergency hospital admissions in the West, accounting for around 10% of visits. The majority of these patients do not have a life-threatening condition, but around 17% will be diagnosed with acute myocardial infarction (AMI). A physical examination and an ECG or serial ECGs remain essential. Diagnosis is straightforward in patients with typical cardiac symptoms and notable ST-segment deviation, but biomarker testing is necessary in patients with atypical symptoms and non-diagnostic ECGs. Despite huge and sustained efforts by the scientific community during the last six decades, a perfect cardiac biomarker to detect which of these patients have AMI has not yet been found. The cardiac troponin immunoassay, first developed in 1989, has now given rise to a fifth generation hs-cTn immunoassay that is currently used to facilitate the triage of chest pain patients, but is there any scope for improvement in either cardiac biomarker tests or their role in patient management?
The perfect cardiac biomarker would be present in significant concentration in the myocardium but not in any other tissues, and be released rapidly into the blood when MI occurs. It would persist for sufficient duration to allow diagnosis via a rapid and relatively inexpensive assay. Current hs-cTn assays can detect cardiac troponin release within 3 hours and MI can be ruled out in the approximately 60% of chest pain patients who have undetectable levels, or levels below the 99th percentile upper reference limit of a healthy population; the negative predictive value is nearly 100%. Tests are cost-effective and fairly rapid: central labs are able to provide results within an hour, and POC test results can be available within 10 to 20 minutes. However, predictably, the increased sensitivity of hs-cTn assays lowers specificity, resulting in values above normal in patients with conditions other than MI, including atrial fibrillation, hypertension, hepatic and renal disorders, acute and chronic pulmonary disease and even some allergic reactions. Using the currently set diagnostic cut-off for MI, the low positive predictive value results in approximately 22% of chest pain patients without MI remaining in hospital under observation.
Is cTn the best cardiac biomarker that will ever be available, or is it possible that an ever-increasing knowledge of the pathophysiology of acute cardiac disease together with current technological advances may eventually discover the perfect biomarker? Until this happens hs-cTn assays, with probable refinements in their use, will remain an integral part of suspected MI patient management.