Detailed Echocardiographic Phenotyping in Breast Cancer Patients: Associations With Ejection Fraction Decline, Recovery, and Heart Failure Symptoms Over 3 Years of Follow-Up.
Detailed Echocardiographic Phenotyping in Breast Cancer Patients: Associations With Ejection Fraction Decline, Recovery, and Heart Failure Symptoms Over 3 Years of Follow-Up.
复制标题
DOI：
10.1161/circulationaha.116.023463
复制
发表时间：
2017-04-11
期刊：
影响因子：
37.8
通讯作者：
Ky B
中科院分区：
文献类型：
--
作者：
Narayan HK;Finkelman B;French B;Plappert T;Hyman D;Smith AM;Margulies KB;Ky B
乳腺癌患者的心血管疾病日益受到关注。在这一人群中，常用治疗（包括多柔比星和曲妥珠单抗）对心脏重塑和功能的纵向影响尚不清楚。我们试图确定结构，功能和心室动脉（VA）耦合的超声心动图参数的变化，以及它们与左心室射血分数（LVEF）和心力衰竭（HF）症状的相关性。在一项纵向前瞻性队列研究中，277名乳腺癌患者接受了阿霉素（Dox）、曲妥珠单抗（Tras）或两者联合治疗（Dox+Tras），我们在中位随访2.0年（四分位距1.0，3.0）的时间内获得了1,249例超声心动图。LV结构;舒张和收缩功能;和VA耦合措施在一个对参与者特征不知情的核心实验室进行量化。我们评估了超声心动图参数随时间的变化，并使用重复测量回归模型来确定其与LVEF下降和恢复的相关性。线性回归模型定义了这些参数的早期变化与随后LVEF和HF症状变化之间的相关性。总体而言，177例（64%）接受了Dox; 51例（18%）接受了Tras; 49例（18%）接受了Dox+Tras。在Dox组，LVEF在随访期间持续适度下降（1年LVEF变化− 3.6%，95%置信区间[CI] − 4.4%，−2.8%; 3年变化− 3.8%，95%CI − 5.1%，−2.5%）。使用Tras时，在1年（− 4.5%，95%CI − 6.0%，−2.9%）和3年（− 2.8%，95%CI −5.3，−0.4%）时观察到相似的LVEF下降。接受Dox+Tras的参与者在1年时表现出最大的下降（-6.6%，95%CI-8.2，-5.0%），在3年时部分恢复（-2.8%，95%CI-4.8，-0.8%）。LVEF下降和恢复主要与收缩期容积、纵向和周向应变以及VA耦合指数有效动脉弹性（Ea）和耦合比Ea/Eessb的变化相关，没有证据表明治疗之间存在效应改变。4至6个月时的体积、应变和Ea/Eessb的早期变化与1年和2年的LVEF变化相关。同样，应变和Ea的早期变化与1年时HF症状恶化相关。多柔比星和曲妥珠单抗导致3年时LVEF适度持续下降。在各种治疗中，体积、应变和VA耦合的变化始终与同时和随后的LVEF下降和恢复相关。
Cardiovascular disease in breast cancer patients is of growing concern. The longitudinal effects of commonly used therapies, including doxorubicin and trastuzumab, on cardiac remodeling and function remain unknown in this population. We sought to define the changes in echocardiographic parameters of structure, function, and ventricular-arterial (VA) coupling, and their associations with left ventricular ejection fraction (LVEF) and heart failure (HF) symptoms. In a longitudinal prospective cohort study of 277 breast cancer participants receiving doxorubicin (Dox), trastuzumab (Tras), or both (Dox+Tras), we obtained 1,249 echocardiograms over a median followup of 2.0 (interquartile range 1.0,3.0) years. LV structure; diastolic and contractile function; and VA coupling measures were quantified in a core laboratory blinded to participant characteristics. We evaluated changes in echocardiographic parameters over time, and used repeated-measures regression models to define their association with LVEF decline and recovery. Linear regression models defined the association between early changes in these parameters and subsequent changes in LVEF and HF symptoms. Overall, 177 (64%) received Dox; 51 (18%) Tras; and 49 (18%) Dox+Tras. With Dox, there was a sustained, modest decrease in LVEF over the followup duration (1-year change in LVEF −3.6%, 95% Confidence Interval [CI] −4.4%,−2.8%; 3-year change −3.8%, 95%CI −5.1%, −2.5%). With Tras, a similar LVEF decline was observed at 1 year (−4.5%, 95%CI −6.0%,−2.9%) and 3 years (−2.8%, 95%CI −5.3, −0.4%). Participants receiving Dox+Tras demonstrated the greatest declines at 1 year (−6.6%, 95%CI −8.2, −5.0%), with partial recovery at 3 years (−2.8%, 95%CI −4.8, −0.8%). LVEF declines and recovery were associated primarily with changes in systolic volumes; longitudinal and circumferential strain; and VA coupling indices effective arterial elastance (Ea) and the coupling ratio Ea/Eessb, without evidence for effect modification across therapies. Early changes in volumes, strain, and Ea/Eessb at 4 to 6 months were associated with 1- and 2-year LVEF changes. Similarly, early changes in strain and Ea were associated with worsening HF symptoms at 1 year. Doxorubicin and trastuzumab resulted in modest, persistent declines in LVEF at 3 years. Changes in volumes, strain, and VA coupling were consistently associated with concurrent and subsequent LVEF declines and recovery across therapies.