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常染色体显性多囊肾病中左心室功能障碍和奥曲肽长效释放剂的作用:ALADIN 试验的横断面和纵向亚研究。

Left ventricular dysfunction in ADPKD and effects of octreotide-LAR: A cross-sectional and longitudinal substudy of the ALADIN trial.

机构信息

Department of Advanced Medical Sciences, Federico II University, Naples, Italy.

Department of Public Health, Nephrology Unit, Federico II University, Naples, Italy.

出版信息

Int J Cardiol. 2019 Jan 15;275:145-151. doi: 10.1016/j.ijcard.2018.10.063. Epub 2018 Oct 22.

Abstract

BACKGROUND AND AIM

In autosomal dominant polycystic kidney disease (ADPKD) cardiac abnormalities have been observed before the onset of hypertension or renal dysfunction. We sought to characterize, in ADPKD patients, left ventricular (LV) function and its changes after somatostatin-analogue octreotide-LAR treatment.

METHODS

In a 1:1:1 cross-sectional study, we evaluated LV function by speckle-tracking echocardiography in 34 ADPKD patients from one ALADIN-trial center and in 34 age- and gender-matched healthy controls and 34 equally-matched renal controls with non-cystic chronic kidney disease. Changes in LV function were compared in the 16 and 18 ADPKD patients originally randomized to 3 year-treatment with octreotide-LAR or placebo, respectively.

RESULTS

LV twist and untwisting rates were lower in ADPKD patients that in healthy or renal controls (6.1 ± 2.6° vs. 11.1 ± 2.1° and 10.2 ± 3.7°; -49.5 ± 18.1°/s vs. -79.8 ± 12.2°/s and -84.3 ± 25.9°/s, respectively, all p < 0.001). The correlation between LV mass or diastolic BP and untwisting rate was positive in ADPKD patients (r = 0.38, p = 0.025 and r = 0.44, p = 0.011, respectively), not significant in healthy controls and negative in renal controls (r = -0.38; p = 0.023 and r = -0.40, p = 0.012, respectively. LV untwisting rate improved from -49.9 ± 18.6°/s to -70.3 ± 27.5°/s with octreotide-LAR, but did not change with placebo (p = 0.027 for treatment effect). At adjusted linear regression analysis, octreotide-LAR therapy emerged as the only independent predictor of untwisting rate improvement at final visit [beta coefficient -0.504 (95% CI -46.905--6.367), p = 0.014].

CONCLUSIONS

In ADPKD patients LV function is early impaired. Somatostatin-analogue therapy might help in preventing or ameliorating LV dysfunction in this population. Clinical Trial Registration http://www.clinicaltrials.gov, NCT0030928.

摘要

背景与目的

在常染色体显性多囊肾病(ADPKD)中,心脏异常在高血压或肾功能障碍发生之前就已经出现。我们旨在研究生长抑素类似物奥曲肽 LAR 治疗后,ADPKD 患者的左心室(LV)功能及其变化。

方法

在一项 1:1:1 的横断面研究中,我们使用斑点追踪超声心动图评估了来自一个 ALADIN 试验中心的 34 名 ADPKD 患者、34 名年龄和性别匹配的健康对照者以及 34 名患有非囊性慢性肾病的肾脏对照者的 LV 功能。最初随机分配至奥曲肽 LAR 或安慰剂治疗 3 年的 16 名和 18 名 ADPKD 患者之间的 LV 功能变化进行了比较。

结果

ADPKD 患者的 LV 扭转和解旋率低于健康或肾脏对照者(6.1±2.6° vs. 11.1±2.1°和 10.2±3.7°;-49.5±18.1°/s vs. -79.8±12.2°/s 和-84.3±25.9°/s,均 P<0.001)。ADPKD 患者的 LV 质量或舒张压与解旋率呈正相关(r=0.38,P=0.025 和 r=0.44,P=0.011),在健康对照者中无显著相关性,在肾脏对照者中呈负相关(r=-0.38;P=0.023 和 r=-0.40,P=0.012)。奥曲肽 LAR 治疗后,LV 解旋率从-49.9±18.6°/s 改善至-70.3±27.5°/s,但安慰剂治疗后无变化(治疗效果 P=0.027)。经调整后的线性回归分析显示,奥曲肽 LAR 治疗是最终访视时解旋率改善的唯一独立预测因素[β系数-0.504(95%CI-46.905-6.367),P=0.014]。

结论

ADPKD 患者的 LV 功能早期受损。生长抑素类似物治疗可能有助于预防或改善该人群的 LV 功能障碍。

临床试验注册

http://www.clinicaltrials.gov,NCT0030928。

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