Background: Anthracycline-containing chemotherapy (Anth-C) is associated with long-term cardiovascular mortality. Although cardiovascular risk assessment has traditionally focused on the heart, evidence has demonstrated that vascular dysfunction also occurs during and up to 1 year following Anth-C. Whether vascular dysfunction persists long-term or negatively influences cardiac function remains unknown. Hence, the present study evaluated ventricular-arterial coupling, in concert with measures of vascular structure and function, in the years following Anth-C.
Methods: Arterial elastance (Ea), end-systolic elastance (Ees), and ventricular-arterial coupling (Ea/Ees) were measured during rest and exercise using echocardiography. Resting vascular function (flow-mediated dilation) and structure (carotid intima-media thickness, arterial stiffness) were also measured.
Results: Thirty breast cancer survivors (6.5 ± 3.6 years after Anth-C) with normal left ventricular ejection fraction (LVEF) (60% ± 6%) and 30 matched controls were studied. At rest, no differences were found in Ea, Ees, Ea/Ees, or LVEF between groups. The normal exercise-induced increase in Ees was attenuated in survivors at 50% and 75% of maximal workload (p < .01). Ea/Ees was also higher at all workloads in the survivors compared with the controls (p < .01). No differences in vascular structure and function were observed between the two groups (p > .05).
Conclusion: In the years after Anth-C, ventricular-arterial coupling was significantly attenuated during exercise, primarily owing to decreased LV contractility (indicated by a reduced Ees). This subclinical dysfunction appears to be isolated to the heart, as no differences in Ea were observed. The previously reported adverse effects of Anth-C on the vasculature appear to not persist in the years after treatment, as vascular structure and function were comparable to controls.
Implications for practice: Anthracycline-induced cardiotoxicity results in significantly impaired ventricular-arterial coupling in the years following chemotherapy, owing specifically to decreased left ventricular contractility. This subclinical dysfunction was identified only under exercise stress. A comprehensive evaluation of vascular structure and function yielded no differences between those treated with anthracyclines and controls. Combined with a stress stimulus, ventricular-arterial coupling might hold significant value beyond characterization of integrative cardiovascular function, in particular as a part of a risk-stratification strategy after anthracycline-containing chemotherapy. Although vascular function and structure were not different in this cohort, this does not undermine the importance of identifying vascular (dys)function in this population, because increases in net arterial load during exercise might amplify the effect of reductions in contractility on cardiovascular function after anthracycline-containing chemotherapy.
摘要
背景. 含蒽环类的化疗方案 (Anth-C) 与远期心血管死亡率相关。尽管心血管风险的评估一般关注的是心脏, 但已有证据证实 Anth-C 治疗期间和治疗后至多 1 年内也会发生血管功能障碍。血管功能障碍是否会持续存在, 或者是否对心脏功能有不利影响, 都尚属未知。因此, 本研究对 Anth-C 治疗后数年中的心室-动脉偶联进行了评价, 同时测量了血管结构及功能。
方法. 在静息和活动状态下使用超声心动图对动脉弹性 (Ea)、收缩末期动脉弹性 (Ees) 和心室-动脉偶联 (Ea/Ees) 进行测量。还测量了静息状态下的血管功能 (血流介导性舒张) 与结构 (颈动脉内膜中层厚度、动脉硬度)。
结果. 我们对 30 例左心室射血分数 (LVEF) 正常 (60%±6%) 的乳腺癌存活患者 (Anth-C 治疗后 6.5±3.6 年) 及 30 例匹配对照进行了研究。静息状态下组间 Ea、Ees、Ea/Ees 和 LVEF 均无差异。正常人活动引起 Ees 增加, 而在乳腺癌存活者的 Ees 在最大工作负荷的 50%和 75%出现下降 (P < 0.01)。存活者在所有工作负荷下的 Ea/Ees 均高于对照 (P < 0.01)。两组的血管结构和功能之间未见差异 (P > 0.05)。
结论. Anth-C 治疗后数年, 运动期间的心室-动脉偶联显著变差, 主要是由左心室收缩力下降 (Ees 降低提示) 所致。由于未观察到 Ea 的区别, 这一亚临床功能障碍看似与心脏无关。既往研究报告 Anth-C 对血管的不良作用似乎不会持续至治疗后数年, 因为数年后患者的血管结构与功能与对照相似。The Oncologist 2016;21:141–149
对临床实践的提示: 蒽环类引起的心脏毒性导致了化疗数年后患者显著的心室-血管偶联受损, 这是由于左心室收缩性下降所致。这一亚临床功能障碍仅见于活动应激下。对血管结构和功能进行综合评价未发现曾接受蒽环类治疗的受试者与对照之间存在差异。结合应激刺激, 心室-动脉偶联可能在综合心血管功能以外具有明显的价值, 尤其是作为含蒽环类方案化疗后进行风险分层策略的一部分。尽管这一队列中血管功能和结构未发生变化, 但并未削弱识别血管功能 (障碍) 对于该人群的重要性, 因为在接受含蒽环类药物化疗后, 活动期间的净动脉负荷增加可能会放大心血管功能中收缩性降低的效应。
Keywords: Cardiotoxicity; Contractility; Echocardiography; Exercise; Vascular.
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