P146 A CASE OF TYROSINE–KINASE INHIBITOR INDUCED CARDIOTOXICITY

Abstract

Abstract This case is about a 69 years–old woman with no prior cardiovascular disease and a history of rheumatoid arthritis;in 2017 underwent right nephrectomy for renal cancer. A few weeks before admission, due to evidence of secondary bone lesions at a follow–up CT–scan, a single dose of the tyrosine kinase inhibitor (TKI) Nivolumab was administered. On the same evening she suffered from a severe reacutization of arthritic symptoms, that led her Oncologist to suspend treatment with nivolumab, and oral corticosteroid therapy was initiated. The following weeks remained though characterized by intense persistent asthenia, severe arthralgias, profuse diarrhea and a syncopal episode; no chest pain was reported. Given the persistence of symptoms, she went to the Emergency Room. Initial work–up revealed a complete heart block, with a previously unknown right bundle branch block (see Figure 1). At blood tests there was a significant increase of troponin I to 7616 ng/L (Normal<12ng/L), BNP 1113 pg/mL (NR < 100 pg/mL), creatinine 2.34 mg/dL (NR 0.55–1.02mg/dL), CPK 1681 U/L (NR 10–145 U/L) and D–dimer 17780 mcg/L (NR < 600). She was immediately transferred to our Cardiologic Intensive Care Unit, where an echocardiogram showed normally functioning ventricular chambers and no valvulopathies. Due to the ongoing acute kidney injury and the history of right nephrectomy, a coronary angiography was not immediately performed, considering the low probability of ACS (no typical symptoms, no regional wall motion abnormalities).Suspecting nivolumab–induced myocarditis, high–dose glucocorticoids were initiated. After a few days we observed persistence of bradycardia and complete AV block despite isoprenaline infusion, and due to signs of peripheral malperfusion (acute kidney injury, hypotension) a definitive leadless pace–maker Micra was implanted (this choice given the need of immunosuppressive therapy that could predispose her to device infections). After normalization of renal function, we performed a coronary angiography that showed normal coronary arteries. Despite the initial improvement of the clinical conditions, the patient suffered a fatal cardiac arrest due to electromechanical dissociation 3 weeks after admission. This case report is an important example showing the significant mortality of cardiotoxicity induced by tyrosine–kinase inhibitors, a side effect that every Cardiologist must be aware of in order to recognize it and immediately intervene with the appropriate therapy.