Bortezomib-induced Severe Congestive Heart Failure

The clinical manifestations of anti-cancer drug associated cardiac side effects are diverse and can range from acutely induced cardiac arrhythmias to severe contractile dysfunction, and potentially fatal heart failure. Anthracyclines and trastuzumab cardiac toxicity have been well described and left ventricular ejection fraction (LVEF) evaluation is commonly performed before their use. Bortezomib (Velcade), a potent, specific and reversible proteasome inhibitor is approved for treatment of multiple myeloma (MM). The incidence of cardiac failure associated with bortezomib therapy in clinical trials remains incidental. Acute exacerbation of pre-existing congestive cardiac failure has been associated with this therapy but de novo cardiomyopathy has been reported in only one patient receiving bortezomib for small cell lung cancer. As a result, cardiac evaluation is not normally ordered before its use. We describe a 50-year-old female with newly diagnosed MM and no risk factors for cardiac disease that unexpectedly developed florid heart failure after 2 cycles of bortezomib and low-dose dexamethasone. 2-D echocardiogram showed dilated cardiomyopathy with severely decreased LVEF; no changes consistent with amyloid deposits or myocardial scarring were described. Coronary angiogram ruled out coronary artery disease. The mechanism of bortezomib-induced cardiomyopathy has been postulated to be through fluid retention. Based on literature review we hypothesize that the disruption of the ubiquitin-proteasome system by bortezomib may cause cardiomyopathy and severe cardiac failure. As Bortezomib is a new and promising therapy for MM patients, we recommend routinely monitoring cardiac parameters in patients undergoing this treatment.