The patient’s story began with a persistent dry cough. A positron emission tomography–computed tomography scan revealed a central malignant tumor in the upper lobe of his right lung, with metastases already spread to the right hilar, mediastinal, right supraclavicular, cervical root, and axillary lymph nodes. A thoracic surgeon judged the disease inoperable, and bronchoscopy with pathological and immunohistochemical examination of biopsy specimens confirmed small cell neuroendocrine carcinoma, an aggressive subtype notorious for early metastasis and high recurrence rates. His treatment plan reflected current standards for advanced disease: serplulimab, a monoclonal antibody targeting the programmed cell death ligand-1, combined with the chemotherapy agents etoposide and carboplatin.

Even before the second week of treatment, the first warning signs appeared in his blood. Tests revealed elevated cardiac troponin T, measured at 0.058 nanograms per milliliter, and elevated N-terminal proB-type natriuretic peptide at 480.0 picograms per milliliter—two biomarkers that signal injury and strain in heart muscle. Strikingly, the patient felt nothing. He reported no chest tightness or pain, yet the clinical team suspected immune checkpoint inhibitor-related myocardial injury and temporarily suspended both the immunotherapy and chemotherapy. A month later, the biomarkers remained mildly elevated, with troponin T at 0.026 nanograms per milliliter and the natriuretic peptide at 497.0 picograms per milliliter. Because of this persistent signal, the team administered only chemotherapy for the next cycle. Another month on, a follow-up evaluation showed a partial tumor response and, encouragingly, normal troponin concentrations. The patient then completed cycles three through six of the full combination regimen over the following two months.

About one week after finishing the sixth cycle, disaster struck. The man experienced sudden chest pain, and an electrocardiogram showed ST-segment elevation across leads V1 through V6—the classic electrical signature of a hyperacute anterior myocardial infarction, a heart attack affecting the large front wall of the left ventricle. His troponin T concentration exceeded 10 nanograms per milliliter, an enormous value indicating extensive muscle death. Echocardiography revealed a left ventricular ejection fraction of 50 percent, segmental wall motion abnormalities, and an apical mural thrombus measuring approximately 25 by 15 millimeters, a dangerous blood clot clinging to the damaged inner wall of the heart’s main pumping chamber.

Coronary angiography, the gold-standard X-ray imaging of the heart’s arteries, told the rest of the story. The proximal segment of the left anterior descending artery—the vessel commonly called the widow-maker for its role in fatal anterior heart attacks—was 100 percent occluded by diffuse stenosis and thrombus. The intermediate branch showed 40 percent diffuse stenosis, and the mid-segment of the right coronary artery showed 20 percent focal stenosis, while the left circumflex artery and its branches were free of significant narrowing. The interventional team performed thrombus aspiration, retrieving several red clots from the proximal-to-mid segment of the artery. A residual 60 percent stenosis remained, along with distal thrombi in both the left anterior descending and left circumflex arteries, so the operators performed balloon dilation and implanted a stent to hold the vessel open. The patient stabilized without further chest pain and was prescribed twelve months of dual antiplatelet therapy with aspirin and clopidogrel, followed by lifelong aspirin.

Why would a man with no traditional cardiovascular risk factors suffer such a severe arterial occlusion? The report’s authors point to a mechanism that has captivated cardiovascular researchers in recent years. Immune checkpoint inhibitors work by blocking co-inhibitory molecules—cytotoxic T lymphocyte associated protein-4, programmed cell death protein-1, and programmed cell death ligand-1—that normally act as brakes on T cells. By releasing these brakes, the drugs reactivate the immune system and enable T cells to kill tumor cells. But those same checkpoint pathways also restrain inflammation inside atherosclerotic plaques. When the brakes come off, T cells infiltrate plaques in the coronary arteries, promoting the initiation, progression, and exacerbation of atherosclerosis. Animal and human studies have now elucidated this dual role, and imaging studies have visualized checkpoint inhibitor–driven inflammation within arterial walls.

The epidemiological signal is substantial. A study by Drobni and colleagues cited in the report demonstrated that patients treated with immune checkpoint inhibitors had an approximately fourfold higher risk of cardiovascular disease and a sevenfold higher risk of myocardial infarction compared with individuals not receiving these drugs. Cardiovascular adverse events associated with checkpoint inhibitors remain relatively rare overall, but the report notes their mortality can reach approximately 40 percent, a figure that demands attention from every oncology service. Severe immune-related adverse events of all kinds occur in 20 to 50 percent of patients receiving these agents, most commonly affecting the colon, skin, thyroid, lungs, and liver, with multi-organ involvement frequently occurring. The heart, however, presents uniquely high stakes.

Diagnosis follows the same principles applied to patients without cancer. According to the 2022 European Society of Cardiology Guidelines on cardio-oncology, criteria for checkpoint inhibitor-associated myocardial infarction rest on symptoms, an early 12-lead electrocardiogram, and serial measurements of cardiac troponin. In this case, the pattern was textbook: sudden chest pain, ST-segment elevation, soaring troponin, and an occluded artery confirmed on angiography. What happened next is equally instructive for clinicians managing cancer patients with heart disease. Four months after the heart attack, imaging showed progression of the right upper lobe tumor with obstructive changes and increased nodular lesions, and troponin T remained slightly elevated at 0.026 nanograms per milliliter. The patient underwent thirty sessions of thoracic radiotherapy over the following month. Three months after completing radiotherapy, his cough worsened and computed tomography revealed new metastases in the right lung, right pleura, and pericardium, prompting initiation of second-line chemotherapy with etoposide and carboplatin.

Crucially, the heart held up. Before the second cycle of second-line chemotherapy, an electrocardiogram showed left axis deviation of the QRS complex, low voltage in the limb leads, and poor R-wave progression in leads V2 and V3—residual traces of the anterior infarction. But coronary computed tomography angiography performed one year after stent implantation confirmed patent stents with no evidence of in-stent restenosis or occlusion, showing only mild plaque-induced stenosis at both ends of the right coronary artery and left anterior descending stents. The patient’s course demonstrates that cancer treatment can safely resume after an immune-related cardiovascular event when the coronary circulation is stabilized and monitored, a message with immediate practical value for the growing population of patients facing this dilemma.

The authors argue that their case carries a broader mandate. Approximately 40 percent or more of patients with cancer now meet the indications for checkpoint inhibitor therapy, and an increasing number of lung cancer patients receive combination chemotherapy and immunotherapy as first-line treatment. Given the definite association between these drugs and increased atherosclerotic risk, the team contends that patients undergoing long-term immunotherapy—especially those with pre-existing cardiovascular risk factors—should be monitored for immune-related atherosclerosis, with regular assessment before each treatment cycle. No consensus yet exists on the optimal monitoring frequency, a gap the report explicitly highlights. The authors also stress the importance of educating patients receiving checkpoint inhibitors about cardiac symptoms, so that warning signs are recognized and immune-associated atherosclerosis is identified and managed in a timely manner. As immunotherapy continues to extend survival across cancer types, this case stands as a vivid illustration that the immune system, once unleashed, must be watched in every organ it touches—including the arteries that keep the heart alive.

Subject of Research: Immune checkpoint inhibitor-associated myocardial infarction and accelerated atherosclerosis in lung cancer immunotherapy

Article Title: Immune checkpoint inhibitor-associated myocardial infarction in a patient with lung cancer undergoing six cycles of immunotherapy: a case report

Article References: Zhang, Y., He, X., Wang, Y., Chen, H., Liu, Y., & Cheng, L. (2025). Immune checkpoint inhibitor-associated myocardial infarction in a patient with lung cancer undergoing six cycles of immunotherapy: a case report. Clinical Cancer Bulletin, 4(1), Article 11. https://doi.org/10.1007/s44272-025-00038-y

Image Credits: AI Generated

DOI: 10.1007/s44272-025-00038-y

Keywords: immune checkpoint inhibitors, myocardial infarction, small cell lung cancer, atherosclerosis, cardiotoxicity, immunotherapy, serplulimab, percutaneous coronary intervention, cardio-oncology, troponin, PD-L1, coronary stent