加国头条 i4cc.ca ｜乳腺癌治疗后心脏功能变化新分类

　　某些乳腺癌治疗药物与心脏功能障碍风险相关，其中左心室射血分数变化最为常见。乳腺癌患者接受具有心脏毒性的癌症治疗后，左心室射血分数轻度下降，伴有生化指标和功能异常的发生率增加，表明尚未达到诊断心脏毒性常规临界值的左心室射血分数下降，其临床意义可能大于以往认知。

　　2019年5月1日，美国癌症学会《癌症》在线发表宾夕法尼亚大学、芝加哥西北大学、圣迭戈加利福尼亚大学、塔夫茨大学、希望之城国家医学中心、加拿大渥太华大学的研究报告，通过隐匿类型变化模型，仔细分析了与左心室射血分数变化类型相关的临床特征、生化特征、功能特征，确定了接触蒽环类和（或）曲妥珠单抗后的三类左心室射血分数变化。

　　该纵向队列研究对314例接受蒽环类和（或）曲妥珠单抗治疗的乳腺癌患者进行定期胸部超声心动图检查、生化指标测定、问卷调查。通过单因素和多因素多项式回归模型，分析了基线因素和左心室射血分数变化类型之间的相关性。通过广义推算方程，定义各个类型心血管测量值随时间的平均变化。

　　结果，确定左心室射血分数变化的三个不同类型：

一型：稳定
二型：轻度、持续下降
三型：早期显著下降，随后部分恢复

　　其中，与二型或三型相关的因素包括：基线左心室射血分数较高、放疗、蒽环类和（或）曲妥珠单抗序贯治疗。

　　对于二型患者，可见超声心动图纵向应变持续异常、脑型利尿钠肽前体氨基末端持续异常、心力衰竭症状。

　　对于三型患者，可见类似二型患者的异常，但是存在恢复趋势，尤其超声心动图纵向应变。

　　因此，该研究结果表明，对于左心室射血分数轻度、持续下降的乳腺癌治疗后患者，存在超声心动图持续异常、心脏功能生化指标持续异常、心力衰竭症状，故有必要开展进一步研究确定心力衰竭的长期风险，尤其对于左心室射血分数轻度下降的乳腺癌治疗后患者。

Cancer. 2019 May 1. [Epub ahead of print]

Detailed phenotyping reveals distinct trajectories of cardiovascular function and symptoms with exposure to modern breast cancer therapy.

Demissei BG, Finkelman BS, Hubbard RA, Zhang L, Smith AM, Sheline K, McDonald C, Narayan HK, Narayan V, Waxman AJ, Domchek SM, DeMichele A, Shah P, Clark AS, Bradbury AR, Carver JR, Upshaw J, Armenian SH, Liu P, Ky B.Demissei BG, Finkelman BS, Hubbard RA, Zhang L, Smith AM, Sheline K, McDonald C, Narayan HK, Narayan V, Waxman AJ, Domchek SM, DeMichele A, Shah P, Clark AS, Bradbury AR, Carver JR, Upshaw J, Armenian SH, Liu P, Ky B.

University of Pennsylvania, Philadelphia, Pennsylvania; Northwestern University, Chicago, Illinois; University of Ottawa Heart Institute, Ottawa, Ontario, Canada; The University of California at San Diego, San Diego, California; Tufts University School of Medicine, Boston, Massachusetts; City of Hope, Duarte, California.

Modest declines in left ventricular ejection fraction (LVEF) in patients with breast cancer who are treated with cardiotoxic cancer therapy are accompanied by an increased incidence of biochemical and functional abnormalities. This suggests that declines in LVEF that do not reach the conventional thresholds used for the diagnosis of cardiotoxicity could be more clinically important than previously understood.

BACKGROUND: Breast cancer therapies are associated with a risk of cardiac dysfunction, most commonly defined by changes in left ventricular ejection fraction (LVEF). Recently, the authors identified 3 classes of LVEF change after exposure to anthracyclines and/or trastuzumab using latent class growth modeling. The objective of the current study was to characterize the clinical, biochemical, and functional profiles associated with LVEF trajectory class membership.

METHODS: Transthoracic echocardiography and biomarker assessments were performed and questionnaires were administered at standardized intervals in a longitudinal cohort of 314 patients with breast cancer who were treated with anthracyclines and/or trastuzumab. Univariable and multivariable multinomial regression analyses evaluated associations between baseline variables and LVEF trajectory class membership. Generalized estimating equations were used to define mean changes in cardiovascular measures over time within each class.

RESULTS: Among the 3 distinct subgroups of LVEF changes identified (stable [class 1]; modest, persistent decline [class 2]; and significant early decline followed by partial recovery [class 3]), higher baseline LVEF, radiotherapy, and sequential therapy with anthracyclines and/or trastuzumab were associated with class 2 or 3 membership. Sustained abnormalities in longitudinal strain and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were observed in patients in class 2, as were heart failure symptoms. Similar abnormalities were observed in patients in class 3, but there was a trend toward recovery, particularly for longitudinal strain.

CONCLUSIONS: Patients with modest, persistent LVEF declines experienced sustained abnormalities in imaging and biochemical markers of cardiac function and heart failure symptoms. Further investigation is needed to characterize the long-term risk of heart failure, particularly in those with modest LVEF declines.

KEYWORDS: anthracyclines breast cancer cardiotoxicity chemotherapy trastuzumab

PMID: 31042319

DOI: 10.1002/cncr.32149