Biomarkers and Personalized Medicine in Cardiovascular Disease Symposium

Beyond Acute Coronary Syndrome: Troponin Kinetics and Assay Concordance Reveal ICI-Associated Myocarditis

Haley Kempf¹, Nilesh Vora²

University of California Irvine, CA, USA

Long Beach Memorial Hospital, CA, USA

Background: High-sensitivity cardiac troponin has evolved from a diagnostic marker for acute coronary syndrome (ACS) to a central tool in cardio-oncology for detecting subclinical myocardial injury, risk stratification, and treatment-related toxicity. However, interpretation remains challenging in cancer patients, where elevations may reflect overlapping processes including immune-mediated inflammation, microvascular dysfunction, and extracardiac sources. Emerging evidence highlights the importance of troponin kinetics, assay-specific differences (hs-cTnI vs hs-cTnT), and integration with multimodal imaging, yet clinical frameworks remain limited—particularly in patients with persistently rising troponin despite non-obstructive coronary arteries.

Case Presentation: A 73-year-old female with metastatic renal cell carcinoma on lenvatinib and pembrolizumab presented with acute chest pain. Electrocardiogram showed lateral ST-segment elevations and T-wave inversions. High-sensitivity (hs) troponin I was elevated at 13,600 ng/L, rising to >125,000 ng/L within 12 hours. Hs-troponin T was 2430 ng/L. Creatine phosphokinase was 354 U/L. She was treated for suspected ACS and underwent emergent coronary angiography, which revealed non-obstructive disease. Recurrent chest pain prompted repeat angiography with unchanged findings. Persistent biomarker elevation prompted evaluation for non-ischemic etiologies. Cardiac MRI demonstrated mildly reduced left ventricular systolic function (LVEF 44%) with extensive non-ischemic late gadolinium enhancement and elevated T2 signal, consistent with immune checkpoint inhibitor (ICI)–associated myocarditis. Inflammatory markers were elevated, and BNP rose from 53 to 645 pg/mL. High-dose intravenous corticosteroids were initiated; however, troponin continued to rise, prompting escalation to abatacept therapy, after which biomarkers stabilized. Subsequent testing demonstrated normalization of troponin I. Following resolution of heart failure, imaging revealed profound tumor response to ICI, allowing the patient to become a surgical candidate.

Discussion: This case highlights the diagnostic value of troponin kinetics, as a persistent rise despite two negative angiograms raised suspicion for a non-ischemic process. Cardiac MRI confirmed myocarditis, emphasizing biomarker–imaging concordance. Concordance between hs-cTnT and hs-cTnI, with elevated creatine phosphokinase, underscores the complexity of biomarker interpretation in cardio-oncology. In immune checkpoint inhibitor therapy, re-expression of fetal troponin T in skeletal muscle may occur; when myocarditis coexists with myositis, elevated troponin T may originate from skeletal muscle while cardiac-specific troponin I remains normal.

Conclusion: Persistent troponin elevation in oncology patients without obstructive coronary disease represents a high-risk, under-defined entity. Early integration of advanced imaging and nuanced biomarker interpretation may reduce unnecessary invasive procedures and improve diagnostic accuracy.

Key words: High-sensitivity troponin, Immune Checkpoint Inhibitor, Myocarditis

Disclosure: We do not have any financial or non-financial interest that has arisen directly from application of this research. There is no competing interest to declare.