Expect the unexpected: Fulminant myocardial cytotoxic injury from Trabectedin Journal Article


Authors: Tsay, A. J.; Satish, M.; Corley, E.; Ezema, A.; DeJesus, N.; Wisely, S.; McAleer, E.; Zhang, C.; Yuan, S.; Homan, E.; Liu, J. E.; Weinsaft, J. W.; D’Angelo, S.; Feldman, S. A.; Chan, A. T.
Article Title: Expect the unexpected: Fulminant myocardial cytotoxic injury from Trabectedin
Abstract: Background: Trabectedin (Tbt) is an alkylating agent prescribed for soft tissue sarcomas after treatment failure of first line agents. While cardiomyopathy can occur with Tbt treatment after anthracycline exposure, Tbt-induced fulminant myocardial cytotoxic injury in the setting of other systemic cytotoxicity associated with Tbt has not been reported. Case presentation: 51-year-old female with hypertension, hyperlipidemia, metastatic leiomyosarcoma with progression of disease despite several lines of chemotherapy including doxorubicin-based therapy was started on Trabectedin (Tbt) 5 days prior to presentation with symptoms of fever, myalgias, arthralgias, and palpitations. She was admitted for management of rhabdomyolysis, acute kidney and liver injuries which were reportedly known to be associated with Tbt treatment. A baseline electrocardiogram (ECG) revealed sinus tachycardia with non-specific T-wave changes, and a transthoracic echocardiogram (TTE) was unremarkable. However, on day 3 of hospitalization, an episode of asymptomatic sustained monomorphic ventricular tachycardia with a heart rate of 150 beats per minute was captured on telemetry. A 12-lead ECG revealed new septal T-wave inversions. Labs revealed rising hs-TnI levels (peak at 37,933ng/L) and serum markers suggested multi-organ failure. Steroids were initiated given its role in treating multi-organ Tbt-induced toxicity. A cardiac MRI to rule out myocarditis and left heart catheterization to rule out obstructive coronary artery disease were forgone due to acute renal failure. A right heart catheterization with an endomyocardial biopsy was performed revealing normal cardiac filling pressures and indices. Pathology showed cytoplasmic vacuoles indicating drug-induced myocardial cytotoxicity. Serial echocardiograms revealed preserved biventricular function. The patient’s clinical condition deteriorated with multi-organ failure despite maximal supportive care in the intensive care unit. She ultimately passed away, and an autopsy was declined. Conclusion: This is the first reported case of fulminant myocardial injury after initiation of Tbt with histologic evidence of drug-induced myocardial cytotoxicity. While it is unclear if anthracyclines potentiate Tbt cytotoxic injury as in this case, it is plausible; and that Tbt-induced cardiotoxicity ranges from subclinical to fulminant. Given increasing use of Tbt in refractory high-grade sarcomas, raising awareness of its toxicity profile will improve early detection and outcomes. © The Author(s) 2024.
Keywords: adult; cancer chemotherapy; clinical article; middle aged; prednisone; case report; hypertension; chemotherapy; myalgia; creatinine; sarcoma; aspartate aminotransferase; acute kidney failure; heart palpitation; intensive care unit; cardiotoxicity; soft tissue sarcoma; methylprednisolone; hyperbilirubinemia; trabectedin; leiomyosarcoma; echocardiography; electrocardiogram; hyperlipidemia; liver injury; cardiomyopathy; multiple organ failure; sinus tachycardia; rhabdomyolysis; heart catheterization; myocarditis; cancer; human; female; article; heart muscle biopsy; cardio-oncology; continuous hemodialysis; monomorphic ventricular tachycardia; obstructive coronary artery disease
Journal Title: Cardio-Oncology
Volume: 10
ISSN: 2057-3804
Publisher: Biomed Central Ltd  
Date Published: 2024-10-15
Start Page: 70
Language: English
DOI: 10.1186/s40959-024-00257-7
PROVIDER: scopus
PMCID: PMC11476495
PUBMED: 39407287
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Jennifer Liu
    118 Liu
  2. Sandra Pierina D'Angelo
    252 D'Angelo
  3. Angel T Chan
    22 Chan
  4. Stephen Charles Wisely
    4 Wisely
  5. Annie Tsay
    3 Tsay