左室射血分数正常患者右室心尖起搏后心力衰竭相关基因表达水平变化的研究

Altered expression genes related to contractile function in patients with preserved left ventricular ejection fraction receiving right ventricular apical pacing

目的探讨有室心尖（RVA）起搏是否引起心力衰竭相关基因表达水平的变化。方法选取80例因Ⅲ度房室传导阻滞行永久起搏器植入术的心功能正常患者，随机1：1分为右室心尖起搏组和右室间隔部（RVS）起搏组。术前抽取外周血，测定心肌肌浆网Ca^2＋-ATP酶（SERCA）和视神经萎缩症蛋白（OPA1）的mRNA表达水平，测定NT—proBNP，行超声心动图检查。术后1、6及12个月进行常规起搏器随访，并测定SERCA和OPA1的mRNA表达水平，测定NT—proBNP，行超声心动图检查。结果与术前比较，RVA起搏组术后1、6及12个月SERCA和OPAlmRNA表达水平明显下降（P均〈0．05）。起搏器植入术后12个月，RVA和RVS组间SERCA、OPA1 mRNA表达水平差异有统计学意义（P=0．028，P=0．034）。RVA起搏组术后12个月左室舒张末容积（LVEDV）与术前比较有增加（P=0．038），LVEF值下降差异有统计学意义（P=0．012）。RVA起搏组术后12个月的SERCA和OPA1 mRNA表达水平下降与LVEF值下降呈正相关（r=0．529，95％C10．113-0．287，P=0．017；r=0．495，95％C10．028-0．788，P=0．044）。RVA起搏术后12个月心功能减低组的SERCA、OPA1的mRNA表达水平较无心功能减低组明显下降，差异有统计学意义（P=-0．022，P=0．035）。结论RVA起搏术后外周血SERCA、OPA1的mRNA表达水平下降，这种基因表达水平的变化先于心脏结构及功能改变，而且可能与心功能减低相关。

Objective Long-term right ventricular apex （RVA） pacing may lead to left ventricular （LV） remodeling and heart failure. This study assessed the expression changes of genes regulating LV contractile function and hypertrophy after permanent RVA pacing and investigated whether such changes proceed or even predicted heart failure. Methods We enrolled 80 patients who underwent pacemaker implantation for complete atrioventricu- lar block（AVB）. Patients were randomly assigned to RVA pacing group and right ventrieular septum（RVS） pacing group. Patients underwent mRNA expression level, N-terminal pro-B-type natriuretic peptide （NT-proBNP） level and echocardiographic examination for the evaluation of LV function and structure at the time of implantation and at certain time points during follow-up. Results Peripheral blood mRNA levels of genes sarcoplasmic reticulum calcium ATPase （SERCA） and OPAl （optic atrophy 1 ） decreased in RVA group at 1, 6, and 12 months＇ follow- up, all P〈0,05. There were significant differences in levels of SERCA, OPAl mRNA in between RVA and RVS at 12 months＇ follow-up （P=0.028, P=0.034）. Compared with before implantation, the left ventricular end diastolic volume （LVEDV） and left ventricular ejection fraction （LVEF） decreased in 12 months later in RVA group （P=0.038, P=0.012）. Alterations in SERCA and OPAl gene expression were associated with a deterioration in LVEF that became apparent 12 months later （r=0.529, 95%CI 0.113-0.287, P=0,017, r=0.495, 95%CI 0.028-0.788, P=0.044）. In RVA group, patients with significant LVEF reduction demonstrated more extensive changes of the gene SERCA and OPAl, compared with those not（P=-0.022; P=0.035）. Conclusion Permanent RVA pacing in patients with preserved ejection fraction may have association with alterations in the expression of genes regulating LV contractile fruction and hypertrophy, measured in the peripheral blood. These alterations are traceable at an early stage, before echocardiographic changes are apparent and have a correlation with LVEF decreasing in the long term.