Cardiotoxicity is not always the only explanation - a case report

Abstract Cisplatin is a platinum-based chemotherapeutic agent; in fact, it is known as a vasculotoxic agent, but there are some case reports describing mild myocardial dysfunction related to cisplatin-based chemotherapy. Truncating variants in the titin (TTN) gene are rare in cardiomyopathy genes, but they are known to occur more frequently among cancer patients with cancer therapy-induced cardiomyopathy. We present the case of a 54-year-old female who was brought to the emergency room with shortness of breath at mild exertion. Biologically, we noted elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) at 5453 pg/mL. Her medical history includes six series of cisplatin-based chemotherapy for invasive cervical carcinoma at 47 years old with subsequent remission. The electrocardiography (ECG) noted sinus rhythm and T-wave inversion in inferior and lateral leads. The transthoracic echocardiography (TTE) revealed a dilated left ventricle with severe diffuse hypokinesia of the walls, an estimated ejection fraction of 15%, systolic dysfunction of the right ventricle, and severe mitral functional regurgitation. Her family history includes her mother being diagnosed with cardiomyopathy and sudden cardiac death (SCD) at 54 years old and a brother with SCD at 34 years old. Furthermore, the systolic dysfunction seems to be caused by more than just the cardiotoxic effects of platinum-based chemotherapy. This, corroborated with the family history, rather advocates for a possible genetic etiology, so we performed genetic testing, which detected a likely pathogenic mutation in the TTN gene (c.64915C>T, p (Arg21639Ter). Additionally, a unicameral implantable cardioverter-defibrillator was considered for primary prevention of SCD. The present case illustrates the importance of baseline cardiac evaluation of the patients receiving cardiotoxic chemotherapy. The identification of genetic risk factors helps us to identify patients at high risk for developing cardiomyopathies secondary to chemotherapy and associated adverse outcomes.