Case Presentation: Here we present a 75-year-old African American female with hypertension, hyperlipidemia, and CML on dasatinib with recurrent resting chest pain. Upon initial presentation, she described the pain which woke her from sleep as left-sided pressure, radiating down her left arm, and not relieved by nitroglycerin. Her exam was as follows: BP 166/78 mmHg, HR 82 bpm, SpO2 98% on room air, afebrile, with regular rate and rhythm, normal heart sounds, lungs clear to auscultation, and without peripheral edema. EKG showed sinus rhythm with first degree AV block. Her HS-troponin level peaked approximately 3.5 hours later at 898 ng/L, concerning for Non-ST elevation MI. She had a transthoracic echocardiogram (TTE) and left heart catheterization (LHC) showing normal biventricular systolic function, Grade II left ventricular diastolic dysfunction, moderately elevated left ventricular filling pressure, and mild non-obstructive coronary disease. The patient was discharged home with her hypertension regimen. Over the next 5 months, she presented several times with similar chest pain and intermittently elevated HS-troponin. On her fifth presentation, she underwent a cardiac MRI which demonstrated patchy intramyocardial and epicardial late gadolinium enhancement suggesting fibrosis in a myocarditis pattern. One month later, the patient presented with chest pain and her HS-troponin level was ≥25,000 ng/L. EKG showed sinus rhythm with new T-wave inversions in V2 and V3 and new inferior Q waves. She underwent urgent TTE and LHC which were unchanged. Due to concern for possible TKI-induced myocarditis and after discussing with Oncology, the patient’s dasatinib was held and she was started on daily prednisone. Unfortunately, the patient was unable to tolerate a repeat cardiac MRI and was discharged home with follow-up arranged. Since stopping her dasatinib, the patient has been chest pain free.
Discussion: According to the American Cancer Society, chronic myeloid leukemia (CML), a myeloproliferative neoplasm, will affect roughly 1 in 500 people in their lifetime, amounting to approximately 15% of all new cases of leukemia in the United States annually (1). Tyrosine kinase inhibitors (TKIs) are used in the treatment of BCR-ABL1 positive CML. There are only four FDA approved first line treatments for chronic phase CML. These include first generation TKI imatinib, and second generation TKIs dasatinib, nilotinib, and bosutinib. Ponatinib, a third generation TKI, is used in treatment resistant CML (2). While uncommon, vascular and cardiac side effects are most associated with TKIs nilotinib and ponatinib. Dasatinib has been associated with peripheral edema and pulmonary hypertension (3). Interestingly, while few, there are sparse case reports describing a possible association between TKIs and myocarditis (4). Ultimately, given the complexity of CML, its diagnosis, and management, adaptation of medical therapy due to the presence of side effects requires a multidisciplinary approach.
Conclusions: Consequently, this case describes an unusual side effect of the tyrosine-kinase inhibitor dasatinib and raises the question of how commonly myocarditis occurs with use of TKIs. Further research is required to fully investigate the potential side effects of tyrosine-kinase inhibitors.