Rare incidence of congestive heart failure in gastrointestinal stromal tumor and other sarcoma patients receiving imatinib mesylate.
BACKGROUND
The authors sought to determine the incidence and severity of cardiovascular toxicity caused by imatinib mesylate in gastrointestinal stromal tumor (GIST) and other sarcoma patients, and to explore cardiotoxicity caused by imatinib mesylate using cell culture and in vitro models.


METHODS
To determine the incidence and significance of serious cardiac adverse events in GIST and other sarcoma patients receiving imatinib mesylate, the authors performed a retrospective analysis of 219 consecutive patients treated with imatinib mesylate. In vitro studies of imatinib mesylate on cultured cardiomyocytes and biochemical studies of cardiac lysates from mice treated with imatinib mesylate were performed to define the potential cardiotoxic effects of imatinib mesylate.


RESULTS
Grade 3 or 4 potentially cardiotoxic adverse events (mostly edema or effusions) occurred in 8.2% of patients, were manageable with medical therapy, and infrequently required dose reduction or discontinuation of imatinib mesylate. Arrhythmias, acute coronary syndromes, or heart failure were uncommon, occurring in <1% of treated patients. However, administration of imatinib in a mouse model system resulted in inhibition of activation of protein kinases that are known to be important in the cardiac stress response.


CONCLUSIONS
The authors concluded that imatinib is an uncommon cause of cardiotoxicity, and that the cardiovascular adverse events that occur are manageable when recognized and treated. Nevertheless, our preclinical findings suggest that imatinib remains a potential cardiotoxin. Furthermore, the cardiac consequences of long-term imatinib therapy remain unknown. We therefore recommend treatment of risk factors for cardiovascular disease in imatinib-treated patients in accord with the American Heart Association guidelines for the prevention and treatment of heart failure.
Trent
Jonathan C
JC
Department of Sarcoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Patel
Shalin S
SS
Zhang
Jianhu
J
Araujo
Dejka M
DM
Plana
Juan-Carlos
JC
Lenihan
Daniel J
DJ
Fan
Dominic
D
Patel
Shreyaskumar R
SR
Benjamin
Robert S
RS
Khakoo
Aarif Y
AY
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D002478:Cells, Cultured; D004452:Echocardiography; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy*; D006333:Heart Failure / Q000139:chemically induced*; D006801:Humans; D000068877:Imatinib Mesylate; D015994:Incidence; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000187:drug effects; D010879:Piperazines / Q000009:adverse effects*; D011743:Pyrimidines / Q000009:adverse effects*; D055815:Young Adult
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate