关键词： ACE, angiotensin-converting enzyme ACS, acute coronary syndrome AE, adverse event AF, atrial fibrillation ARB, angiotensin receptor blocker ASCT, autologous stem cell transplantation BP, blood pressure CVAE, cardiovascular adverse event ESC, European Society of Cardiology FMD, flow-mediated dilatation GLS, global longitudinal strain HF, heart failure HFpEF, heart failure with preserved ejection fraction IHD, ischemic heart disease IMiD, immunomodulatory drug Kd, carfilzomib and dexamethasone LA, left atrial LV, left ventricular LVEF, left ventricular ejection fraction MM, multiple myeloma NO, nitric oxide NP, natriuretic peptide OS, overall survival PBMC, peripheral blood mononuclear cell PFS, progression-free survival PH, pulmonary hypertension PI, proteasome inhibitor PWV, pulse wave velocity PrA, proteasome activity RRMM, relapse or refractory multiple myeloma SBP, systolic blood pressure TMA, thrombotic microangiopathy UPP, ubiquitin proteasome pathway VTE, venous thromboembolism Vd, bortezomib and dexamethasone WM, Waldenström’s macroglobulinemia bortezomib cardiovascular toxicity carfilzomib eNOS, endothelial nitric oxide synthase ixazomib proteasome inhibition

来  源：   DOI：10.1016/j.jaccao.2022.12.005   PDF(Pubmed)

Abstract：
Proteasome inhibitors (PIs) are the backbone of combination treatments for patients with multiple myeloma and AL amyloidosis, while also indicated in Waldenström\'s macroglobulinemia and other malignancies. PIs act on proteasome peptidases, causing proteome instability due to accumulating aggregated, unfolded, and/or damaged polypeptides; sustained proteome instability then induces cell cycle arrest and/or apoptosis. Carfilzomib, an intravenous irreversible PI, exhibits a more severe cardiovascular toxicity profile as compared with the orally administered ixazomib or intravenous reversible PI such as bortezomib. Cardiovascular toxicity includes heart failure, hypertension, arrhythmias, and acute coronary syndromes. Because PIs are critical components of the treatment of hematological malignancies and amyloidosis, managing their cardiovascular toxicity involves identifying patients at risk, diagnosing toxicity early at the preclinical level, and offering cardioprotection if needed. Future research is required to elucidate underlying mechanisms, improve risk stratification, define the optimal management strategy, and develop new PIs with safe cardiovascular profiles.
摘要：
蛋白酶体抑制剂（PIs）是多发性骨髓瘤和AL淀粉样变性患者联合治疗的骨干，同时也出现在Waldenström巨球蛋白血症和其他恶性肿瘤中。PIs作用于蛋白酶体肽酶，由于积累聚集而导致蛋白质组不稳定，展开,和/或受损的多肽;持续的蛋白质组不稳定性然后诱导细胞周期停滞和/或细胞凋亡。卡菲佐米,静脉内不可逆PI,与口服给药的Ixazomib或静脉内可逆性PI如硼替佐米相比,表现出更严重的心血管毒性特征。心血管毒性包括心力衰竭，高血压,心律失常,和急性冠脉综合征。因为PI是血液系统恶性肿瘤和淀粉样变性治疗的关键组成部分，管理他们的心血管毒性包括识别有风险的患者，在临床前水平早期诊断毒性，并在需要时提供心脏保护。未来的研究需要阐明潜在的机制，改善风险分层，定义最优管理策略，并开发具有安全心血管特征的新PI。
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