Jerkins James H, Suciu Anca, Mazimba Sula, Calvo Alejandro
Department of Graduate Medical Education, Kettering Medical Center, USA; Medical Oncology and Hematology, Kettering Medical Center, USA.
Cardiol Res. 2010 Dec;1(1):20-23. doi: 10.4021/cr105e. Epub 2010 Nov 20.
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 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.
抗癌药物相关心脏副作用的临床表现多种多样，范围从急性诱发的心律失常到严重的收缩功能障碍，甚至可能发展为致命的心力衰竭。蒽环类药物和曲妥珠单抗的心脏毒性已有详细描述，在使用前通常会进行左心室射血分数（LVEF）评估。硼替佐米（万珂）是一种强效、特异性且可逆的蛋白酶体抑制剂，已被批准用于治疗多发性骨髓瘤（MM）。在临床试验中，与硼替佐米治疗相关的心力衰竭发生率仍然较低。已有报道称，这种治疗与既往存在的充血性心力衰竭急性加重有关，但仅有一名接受硼替佐米治疗小细胞肺癌的患者被报告出现心肌病。因此，在使用前通常不会常规进行心脏评估。我们报告了一名50岁新诊断为MM且无心脏病危险因素的女性，在接受2个周期的硼替佐米和低剂量地塞米松治疗后意外出现了严重的心力衰竭。二维超声心动图显示扩张型心肌病，LVEF严重降低；未发现与淀粉样沉积物或心肌瘢痕形成一致的变化。冠状动脉造影排除了冠状动脉疾病。硼替佐米诱发心肌病的机制被推测为通过液体潴留。基于文献综述，我们假设硼替佐米对泛素 - 蛋白酶体系统的破坏可能导致心肌病和严重心力衰竭。由于硼替佐米是一种对MM患者有前景的新疗法，我们建议对接受该治疗的患者常规监测心脏参数。
