接受心脏再同步化治疗的心力衰竭患者的心肌基因表达

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Myocardial Gene Expression in Heart Failure Patients Treated With Cardiac Resynchronization Therapy
接受心脏再同步化治疗的心力衰竭患者的心肌基因表达
Responders Versus Nonresponders
有效者与无效者比较
Objectives: We studied whether functional improvement after cardiac resynchronization therapy (CRT) is associated with reversal of the heart failure (HF) gene program. -
目的：我们探讨了心脏再同步化治疗（CRT）的功能改善是否与心力衰竭相关基因的逆转有关。
Background: Cardiac resynchronization therapy improves exercise tolerance and survival in patients with advanced congestive HF and dyssynchrony.
背景：心脏再同步化治疗改善晚期充血性心力衰竭合并失同步化患者的运动耐量和生存。
Methods: Twenty-four patients referred for CRT underwent left ventricular (LV) endomyocardial biopsies immediately before CRT implantation (baseline). In addition, 17 of them underwent LV endomyocardial biopsy procurement 4 months later (follow-up). In 6 control patients with normal LV function, LV biopsies were obtained at the time of coronary artery bypass grafting. The LV messenger ribonucleic acid (mRNA) levels of contractile and calcium regulatory genes were measured by quantitative real time polymerase chain reaction and normalized for glyceraldehyde 3-phosphate dehydrogenase (GAPDH). The HF patients showing an improvement in New York Heart Association (NYHA) functional class by >1 score and a relative increase in LV ejection fraction 25% at 4 months after CRT were considered as responders.
方法：24例接受CRT的患者在植入CRT 前（baseline）接受了左心室（LV）内膜下心肌活检。其中17例患者在4月后（随访）再次接受了左心室内膜下心肌活检。6例左心室功能正常的对照者在接受冠脉搭桥时接受了左心室心肌活检。采用定量实时聚合酶链反应测定心室收缩蛋白和钙调蛋白基因信使RNA水平，采用3-磷酸甘油醛脱氢酶标准化。治疗4个月后纽约心功能分级改善大于1级或左室射血分数增加25％以上的心力衰竭患者被定义为有效者。
Results: The HF patients were characterized by lower LV mRNA levels of -myosin heavy chain (-MHC), β-myosin heavy chain (β-MHC), sarcoplasmic reticulum calcium ATPase 2 (SERCA), phospholamban (PLN), and higher brain natriuretic peptide (BNP) mRNA levels as compared with control subjects. Responders to CRT (n = 11) showed an increase in LVEF (p < 0.001), a decrease in left ventricular end-diastolic diameter (p = 0.003), and NYHA functional class (p = 0.002), and a reduction in N-terminal proBNP levels (p = 0.032) as compared with baseline. This was associated with an increase in mRNA levels of -MHC (p = 0.035), SERCA (p = 0.032), a decrease in BNP mRNA levels (p = 0.002), and an increase in the ratio of -/β-MHC (p = 0.018) and SERCA/PLN (p = 0.012). No significant changes in molecular profile were observed in nonresponders.
结果：心力衰竭患者与对照组患者相比左室肌球蛋白重链、β肌球蛋白重链、肌质网钙ATP酶2、受磷蛋白的信使RNA水平较低，而脑钠肽信使RNA水平高于对照组。CRT有效者（n＝11）与基线值相比，左室射血分数升高（P<0.001），左室舒张末期内径降低（P＝0.002），前脑钠肽N末端水平降低（P＝0.032）。这与肌球蛋白重链（P＝0.035）和肌质网钙ATP酶（P＝0.032）的信使RNA升高相关，而与脑钠肽信使RNA水平降低有关（P＝0.002），同时与肌球蛋白重链/β肌球蛋白重链（P＝0.018）、肌质网钙ATP酶2/受磷蛋白（P＝0.012）的比值增加相关。无效者分子表型没有显著变化。
Conclusions: In HF patients with electromechanical cardiac dyssynchrony, functional improvement related to CRT is associated with favorable changes in established molecular markers of HF, including genes that regulate contractile function and pathologic hypertrophy.
结论：在有电机械失同步化的心力衰竭患者中，CRT治疗后功能改善与已经明确的心力衰竭分子标志物改变相关，包括调节收缩功能和病理性肥大的基因。