High-Sensitivity Cardiac Troponin T and Acute MI Diagnosis

Approximately 10% of all emergency department (ED) consultations concern patients with symptoms suggestive of acute myocardial infarction (AMI). The primary method of diagnosis of AMI involves utilization of electrocardiography (ECG) and cardiac troponin (cTn) assay.

Former-generation cTn assays were limited by a delayed increase of circulating levels for 3 or 4 hours, often requiring serial sampling for 6 to 12 hours. Resulting delays in accurate diagnosis (rule-in) slows prompt use of evidence-based therapies. Likewise, delays in excluding disease (rule-out) interfere with evaluation of alternative diagnoses and create overcrowding in the ED.

Sensitive and high-sensitivity cardiac troponin (hs-cTn) assays have recently been developed, enabling measurement of cTn concentrations unreliably detected with previous generations of the tests. The new tests have improved the accuracy of early diagnosis of AMI; researchers have suggested that more rapid rule-in and rule-out of AMI might be possible with the new tests.

It is currently uncertain how best to take advantage of the novel hs-cTn tests in clinical practice; opinions vary whether and to what extent a shortening of the time interval to the second sample is feasible and safe. Researchers recently conducted a prospective multicenter study aimed at developing and validating an algorithm for rapid rule-out and rule-in of AMI using high-sensitivity cardiac troponin T (hs-cTnT) baseline levels and changes within 1 hour. Study results were reported online in Archives of Internal Medicine [doi:10.1001/archinternmed.2012.3698].

The study enrolled 872 unselected patients with acute chest pain presenting to the ED. At presentation and after 1 hour, hs-cTnT was measured in a blinded fashion. Two independent cardiologists adjudicated the final diagnosis. The researchers derived an hs-cTnT algorithm incorporating baseline values and absolute changes within 1 hour from 436 randomly selected patients; the algorithm was validated in the remaining 436 patients.

The primary prognostic end point was death during 30 days of follow-up.

In 17% of patients (n=147), AMI was the adjudicated final diagnosis; unstable angina was diagnosed in 12% of patients (n=104), cardiac symptoms of origin other than coronary artery disease in 15% (n=128), noncardiac symptoms in 48% (n=416), and symptoms of unknown origin in 9% (n=77). Compared with other final diagnoses, baseline levels of hs-cTnT were significantly higher in patients with AMI.

After applying the hs-cTnT algorithm developed in the deprivation cohort to the validation cohort, 60% of patients (n=259) could be classified as rule-out, 17% (n=76) as rule-in, and 23% (n=101) in the observational zone within 1 hour. No patient with AMI was missed.

Overall, the algorithm resulted in a sensitivity and negative predictive value of 100% for rule-out, a specificity of 97% and positive predictive value of 84% for rule-in, and a prevalence of AMI of 8% in the observational zone group.

Cumulative 30-day survival was 99.89% in patients classified as rule-out, 98.6% in patients classified as observational zone, and 95.3% in patients classified as rule-in (P<.001).

In summary, the researchers said, “Using a simple algorithm incorporating hs-cTnT baseline values and absolute changes within the first hour allowed a safe rule-out as well as an accurate rule-in of AMI within 1 hour in 77% of unselected patients with acute chest pain. This novel strategy may obviate the need for prolonged monitoring and serial blood sampling in 3 of 4 patients.”