The hidden role of cardiac troponin interferents in diagnosis and clinical management of myocarditis: a single center experience

Background Cardiac troponin (cTn) is a key myocardial injury biomarker; however, false-positive cTn results can occur due to heterophil antibodies and troponin macrocomplexes. The role of cTn interferents in diagnosing and clinical management of patients with suspected or biopsy-proven myocarditis remains unexplored. Purpose 1) To retrospectively assess the frequency of cTn interferents in a single-center cohort of patients with a history of myocarditis and abnormal cTn levels (higher than sex and/or age-specific 99th percentile), tested for cTn interferents due to clinical suspicion of cTn false-positive results, including asymptomatic patients with long-standing (weeks to months) low-level cTn with a plateau pattern or those admitted to the hospital from the Emergency Department (ED) for atypical chest pain with unremarkable ECG and echocardiogram. 2) To assess how cTn interferents testing impacted on diagnosis and clinical management. Methods We retrospectively included myocarditis patients that were tested for cTn interferents due to suspicion of false-positive cTn results because of long-standing, low-level plateau cTn and no or atypical symptoms, normal coronary arteries, and unremarkable ECG. Patients’ clinical and laboratory data were collected at diagnosis and follow-up. Cardiac troponin I and T concentrations were measured using fully-automated chemiluminescent two-site immunoassays. Results A total of 29 myocarditis patients (20 male, mean age 42 ± 13 years) were retrospectively included after being tested for cTn interferents due to clinical suspicion of a false-positive cTn result. Of these, 9 (31%) tested positive for interferents (4 for heterophilic antibodies and 5 for troponin macrocomplexes). cTn interferents were more frequently detected in patients evaluated for a suspected relapse than in those undergoing routine follow-up at the outpatient clinic (p<0.01). Among interferent-positive patients, troponin levels at the time of interferent testing were lower than at diagnosis (117 vs. 776 ng/L; p=0.036), and in 8 out of 9 cases, the identification of cTn interferents contributed to exclude a suspected myocarditis relapse. In 5 out of 20 true cTn-positive cases without interferents, testing for troponin interferents alone led to changes in treatment decisions and indications for invasive procedures. At the last follow-up (mean 57 ± 38 months), 60% of interferent-negative patients had persistently elevated troponin levels, with no impact on prognosis. Conclusions In our single-center cohort of selected myocarditis patients with clinical suspicion of false-positive cTn results, cTn interferents were identified in one-third of cases. Upon detection of cTn interferents, the suspicion of myocarditis relapse was reconsidered in nearly all cases. Clinicians should be aware of cTn interferents in myocarditis to prevent misdiagnosis and unnecessary interventions.