Department of Physiology and Pharmacology, University of Cantabria School of Medicine, Spain.
Heart. 2011 Jul;97(14):1132-7. doi: 10.1136/hrt.2010.220418. Epub 2011 May 17.
Left ventricular (LV) reverse remodelling after valve replacement in aortic stenosis (AS) has been classically linked to the hydraulic performance of the replacement device, but myocardial status at the time of surgery has received little attention.
To establish predictors of LV mass (LVM) regression 1 year after valve replacement in a surgical cohort of patients with AS based on preoperative clinical and echocardiographic parameters and the myocardial gene expression profile at surgery.
Transcript levels of remodelling-related proteins and regulators were determined in LV intraoperative biopsies from 46 patients with AS by RT-PCR. Using multiple linear regression analysis, an equation was developed (adjusted R²=0.73; p<0.0001) that included positive [preoperative LVM, microRNA-133a, serum response factor (SRF, which is known to be a transactivator of miR-133) and age] and negative [body mass index (BMI), Wolf-Hirschhorn syndrome candidate-2 (WHSC2, which is a target for repression by miR-133a), β-myosin heavy chain, myosin light chain-2, diabetes mellitus, and male gender] independent predictors of LVM reduction.
Aortic valve area gain or the reduction in transvalvular gradient maintained no significant relationships with the dependent variable. Logistic regression analysis identified microRNA-133a as a significant positive predictor of LVM normalisation, whereas β-myosin heavy chain and BMI constituted negative predictors.
Hypertrophy regression 1 year after pressure overload release is related to the preoperative myocardial expression of remodelling-related genes, in conjunction with the patient's clinical background. In this scenario, miR-133 emerges as a key element of the reverse remodelling process. Postoperative improvement of valve haemodynamics does not predict the degree of hypertrophy regression or LVM normalisation. These results led us to reconsider the current reverse remodelling paradigm and (1) to include criteria of hypertrophy reversibility in the decision algorithm used to decide timing for the operation; and (2) to modify other prevailing factors (overweight, diabetes, etc) known to maintain LV hypertrophy.
主动脉瓣狭窄（AS）患者行瓣膜置换术后左心室（LV）逆重构与置换装置的水力性能密切相关，但手术时心肌状态受到的关注较少。
根据术前临床和超声心动图参数以及手术时的心肌基因表达谱，确定 AS 手术患者瓣膜置换术后 1 年 LV 质量（LVM）消退的预测因子。
采用 RT-PCR 检测 46 例 AS 患者 LV 术中活检标本中与重构相关的蛋白和调节剂的转录水平。采用多元线性回归分析，建立了一个包括正相关[术前 LVM、微小 RNA-133a、血清反应因子（SRF，已知是微小 RNA-133 的反式激活因子）和年龄]和负相关[体重指数（BMI）、Wolf-Hirschhorn 综合征候选物-2（WHSC2，是微小 RNA-133 的抑制靶点）、β-肌球蛋白重链、肌球蛋白轻链-2、糖尿病和男性]的独立预测因子的方程（调整 R²=0.73；p<0.0001），用于 LVM 减少。
主动脉瓣口面积增加或跨瓣压差降低与因变量无显著关系。Logistic 回归分析表明微小 RNA-133a 是 LVM 正常化的显著正预测因子，而β-肌球蛋白重链和 BMI 则构成负预测因子。
压力超负荷释放 1 年后的心肌肥厚消退与术前心肌重构相关基因的表达有关，同时与患者的临床背景有关。在这种情况下，微小 RNA-133 成为逆重构过程的关键因素。术后瓣膜血流动力学的改善不能预测心肌肥厚消退的程度或 LVM 正常化。这些结果促使我们重新考虑目前的逆重构模式，并（1）在决定手术时机的决策算法中纳入肥厚逆转的标准；（2）修改已知维持 LV 肥厚的其他流行因素（超重、糖尿病等）。
