Mitral regurgitation severity at left ventricular assist device implantation is associated with distinct myocardial transcriptomic signatures,The Journal of Thoracic and Cardiovascular Surgery

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Mitral regurgitation severity at left ventricular assist device implantation is associated with distinct myocardial transcriptomic signatures
The Journal of Thoracic and Cardiovascular Surgery ( IF 4.9 ) Pub Date : 2021-09-14 , DOI: 10.1016/j.jtcvs.2021.08.061
Neal M Duggal ₁ , Ienglam Lei ₂ , Xiaoting Wu ₂ , Keith D Aaronson ₃ , Francis D Pagani ₂ , Hugo Y-K Lam ₄ , Paul C Tang ₂ ,

Affiliation

Objectives

We examined for differences in pre–left ventricular assist device (LVAD) implantation myocardial transcriptome signatures among patients with different degrees of mitral regurgitation (MR).

Methods

Between January 2018 and October 2019, we collected left ventricular (LV) cores during durable LVAD implantation (n = 72). A retrospective chart review was performed. Total RNA was isolated from LV cores and used to construct cDNA sequence libraries. The libraries were sequenced with the NovaSeq system, and data were quantified using Kallisto. Gene Set Enrichment Analysis (GSEA) and Gene Ontology analyses were performed, with a false discovery rate <0.05 considered significant.

Results

Comparing patients with preoperative mild or less MR (n = 30) and those with moderate-severe MR (n = 42), the moderate-severe MR group weighted less (P = .004) and had more tricuspid valve repairs (P = .043), without differences in demographics or comorbidities. We then compared both groups with a group of human donor hearts without heart failure (n = 8). Compared with the donor hearts, there were 3985 differentially expressed genes (DEGs) for mild or less MR and 4587 DEGs for moderate-severe MR. Specifically altered genes included 448 DEGs for specific for mild or less MR and 1050 DEGs for moderate-severe MR. On GSEA, common regulated genes showed increased immune gene expression and reduced expression of contraction and energetic genes. Of the 1050 genes specific for moderate-severe MR, there were additional up-regulated genes related to inflammation and reduced expression of genes related to cellular proliferation.

Conclusions

Patients undergoing durable LVAD implantation with moderate-severe MR had increased activation of genes related to inflammation and reduction of cellular proliferation genes. This may have important implications for myocardial recovery.

中文翻译：

左心室辅助装置植入时二尖瓣反流的严重程度与不同的心肌转录组特征相关

目标

我们检查了不同程度二尖瓣反流 (MR)患者左心室辅助装置 (LVAD) 植入前心肌转录组特征的差异。

方法

2018 年 1 月至 2019 年 10 月期间，我们在持久 LVAD 植入过程中收集了左心室 (LV) 核心 (n = 72)。进行了回顾性图表审查。从 LV 核心中分离出总 RNA，并用于构建 cDNA 序列文库。使用 NovaSeq 系统对文库进行测序，并使用 Kallisto 对数据进行量化。进行了基因集富集分析 (GSEA) 和基因本体分析，错误发现率 <0.05 被认为是显着的。

结果

比较术前轻度或较少 MR 的患者 (n = 30) 和中度至重度 MR 的患者 (n = 42)，中度至重度 MR 组的体重较轻 ( P = .004)，三尖瓣修复次数较多 ( P = .004)。 043），在人口统计学或合并症方面没有差异。然后，我们将两组与一组无心力衰竭的人类捐赠心脏进行比较 (n = 8)。与供体心脏相比，轻度或轻度MR有3985个差异表达基因（DEG），中重度MR有4587个DEG。具体改变的基因包括针对轻度或更少MR的448个DEG和针对中重度MR的1050个DEG。在 GSEA 上，常见调控基因显示免疫基因表达增加，收缩和能量基因表达减少。在中重度 MR 特异的 1050 个基因中，还有与炎症相关的基因上调，以及与细胞增殖相关的基因表达减少。