Early Diagnosis and Longitudinal Monitoring of Myocardial Infarction in Tuberculosis Patients with High-Throughput...

Patients with Tuberculosis (TB) face a significantly increased risk of myocardial infarction (MI). Diagnosis is challenging, however, due to overlapping clinical symptoms between MI and TB. To address this clinical problem, we developed an integrated diagnostic strategy combining a biomarker panel with a high-throughput suspension array platform. Using a training cohort of 1389 TB patients, a four-biomarker model comprising high-sensitivity cardiac troponin I (hs-cTnI), myoglobin (Myo), creatine kinase isoenzyme MB (CK-MB), and interleukin-6 (IL-6) was established, demonstrating superior diagnostic performance (area under the curve, 0.98) compared to single-marker hs-cTnI. To detect the four-biomarker panel simultaneously, a suspension array was constructed using dual fluorescent protein (DsRed-Clover)-encoding microbeads, yielding 60 resolvable clusters. The assay exhibited excellent analytical sensitivity across broad dynamic ranges for IL-6 (1.0 fg/mL-5.0 ng/mL; limit of detection (LOD), 0.7 fg/mL), hs-cTnI (3.3 fg/mL-10 ng/mL; LOD 3.3 fg/mL), Myo (10.0 pg/mL-100.0 ng/mL; LOD 5.0 pg/mL), and CK-MB (10.0 pg/mL-2.0 μg/mL; LOD 1.4 pg/mL). The results from serum and whole blood samples correlated strongly with a commercial electrochemiluminescence immunoassay. An independent validation cohort of 224 patients confirmed exquisite diagnostic performance, with 97.7% sensitivity, 93.3% specificity, and 94.2% accuracy, and longitudinal monitoring further confirmed the utility for tracking MI progression. This sensitive, cost-effective, and rapid platform completes detection within approximately 30 min with a 200 μL sample and offers a promising solution for early, precise MI diagnosis in TB patients.