Biomarkers and Personalized Medicine in Cardiovascular Disease Symposium

Comparison of Gen5 and Gen6 high-sensitivity cardiac troponin T in a real-world setting

Nolan R. Martin, Megan Woelkers, Megan Palacio, Raymond T. Suhandynata, Robert L. Fitzgerald, Lori B. Daniels

Background: Accuracy and precision are crucial characteristics of cardiac troponin T (cTnT) assays, since results are instrumental in managing patients in acute care settings. We examined discrepancies between the Gen5 and Gen6 cTnT assays in paired analyses of real-world cases.

Methods: This retrospective analysis compared same-specimen Gen5 and Gen6 assay results from 1,847 encounters at a single center. Cases were classified by peak cTnT (based on sex-specific 99^th percentile upper reference limit [URL]) and time-to-peak cTnT. Cases with discordance in peak or time-to-peak cTnT were categorized into four groups: Gen5 normal/Gen6 positive (+), Gen5+/Gen6 normal, concordant but Gen5+ sooner, and concordant but Gen6+ sooner. Up to 10 cases with the greatest relative difference between Gen5 and Gen6 results in each category were independently adjudicated for myocardial infarction and final diagnosis by two physicians with access to complete medical records.

Results: Gen5 and Gen6 assays were concordant in 1,703 of 1,847 cases (92%). Gen6 was elevated alone in 100 cases (5%) versus 24 cases (1%) for Gen5. Gen6 elevated sooner in 19 cases (1%) versus one case (<1%) for Gen5. Four of reviewed cases were excluded due to lack of documentation, leaving this distribution: Gen6+ alone (9 cases); Gen6+ sooner (8); Gen5+ alone (10); and Gen5+ sooner (1). Most discordant cases exhibited a shorter time-to-positive Gen6 (n=8, 29%) or Gen5-/Gen6+ (n=9, 32%). Four of the nine Gen5-/Gen6+ cases had a parallel (but Gen 6 higher) rise/fall in cTnT for both assays, suggesting higher sensitivity for injury with Gen6. The remaining five cases included single cTnT values; in 3, Gen6 tracked with abnormal CKMB, NT-proBNP, and symptoms, suggesting greater Gen6 sensitivity for injury, while 2 cases were clinically ambiguous. Of the 10 Gen5+/Gen6- cases, nine lacked signs or symptoms of ischemia and appeared to be Gen5 “fliers”. One case exhibited a negative Gen6 result preceded by a positive Gen6 result, while Gen5 remained elevated, suggesting an isolated false negative Gen6. The case in which Gen5 rose sooner than Gen6 included similar trends, but Gen5 had a faster time-to-positive.

Conclusion: In this single-center, real-world cohort of patients with cTnT measured for routine care, Gen5 and Gen6 assays were concordant in most cases. When assays diverged, Gen6 tended to show greater sensitivity for myocardial injury and fewer fliers.

Keywords: Acute coronary syndrome, high-sensitivity cardiac troponin T