Longitudinal Assessment of Vascular Function With Sunitinib in Patients With Metastatic Renal Cell Carcinoma.
Longitudinal Assessment of Vascular Function With Sunitinib in Patients With Metastatic Renal Cell Carcinoma.
复制标题
DOI：
10.1161/circheartfailure.117.004408
复制
发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Ky B
中科院分区：
文献类型：
--
作者：
Catino AB;Hubbard RA;Chirinos JA;Townsend R;Keefe S;Haas NB;Puzanov I;Fang JC;Agarwal N;Hyman D;Smith AM;Gordon M;Plappert T;Englefield V;Narayan V;Ewer S;ElAmm C;Lenihan D;Ky B
舒尼替尼广泛用于转移性肾细胞癌（mRCC），可导致高血压、左心室功能障碍和心力衰竭。然而，舒尼替尼与血管功能和心功能障碍之间的关系尚不清楚。在84例mRCC患者的多中心前瞻性研究中，超声心动图、动脉血压计和b型利钠肽（BNP）测量在舒尼替尼开始后的基线、3.5、15和33周进行，与舒尼替尼周期1、3和6相关。计算血管功能参数的平均变化和95%置信区间。使用线性回归模型估计血管功能与左室射血分数（LVEF）、纵向应变、舒张功能（E/ E’）和BNP之间的关系。舒尼替尼治疗3.5周后，所有受试者的平均收缩压（BP）升高9.5 mmHg (95% CI 2.0, 17.1, p=0.02)，舒张压升高7.2 mmHg （95% CI 4.3, 10.0, p<0.001）。舒尼替尼导致大动脉刚度（颈-股脉波速度）和阻力负荷（总外周阻力（TPR）、动脉弹性（EA））增加（均p<0.05），以及脉动负荷（总动脉顺应性、波反射）的变化。血管功能与收缩功能障碍（LVEF，纵向应变）之间无统计学意义的关联。然而，随着时间的推移，基线TPR、EA和主动脉阻抗与舒张功能和充盈压力恶化有关。在mRCC患者中，舒尼替尼在治疗3.5周内导致血压、动脉硬度、阻力和脉搏负荷的早期显著升高。基线血管功能参数与舒张功能恶化有关，但与收缩功能无关。
Sunitinib, used widely in metastatic renal cell carcinoma (mRCC), can result in hypertension, left ventricular (LV) dysfunction, and heart failure. However, the relationships between vascular function and cardiac dysfunction with sunitinib are poorly understood. In a multi-center prospective study of 84 mRCC patients, echocardiography, arterial tonometry, and b-type natriuretic peptide (BNP) measures were performed at baseline, 3.5, 15, and 33 weeks following sunitinib initiation, correlating with sunitinib cycles 1, 3, and 6. Mean change in vascular function parameters and 95% confidence intervals were calculated. Linear regression models were used to estimate associations between vascular function and LV ejection fraction (LVEF), longitudinal strain, diastolic function (E/e’), and BNP. Following 3.5 weeks of sunitinib, mean systolic blood pressure (BP) increased by 9.5 mmHg (95% CI 2.0, 17.1, p=0.02) and diastolic BP by 7.2 mmHg (95% CI 4.3, 10.0, p<0.001) across all participants. Sunitinib resulted in increases in large artery stiffness (carotid-femoral pulse wave velocity) and resistive load (total peripheral resistance (TPR), arterial elastance (EA)) (all p<0.05) as well as changes in pulsatile load (total arterial compliance, wave reflection). There were no statistically significant associations between vascular function and systolic dysfunction (LVEF, longitudinal strain). However, baseline TPR, EA, and aortic impedance were associated with worsening diastolic function and filling pressures over time. In patients with mRCC, sunitinib resulted in early, significant increases in BP, arterial stiffness, resistive and pulsatile load within 3.5 weeks of treatment. Baseline vascular function parameters were associated with worsening diastolic, but not systolic function.