心房颤动患者心房肌组织醛固酮水平和CYP11B2基因与心房结构重构研究

目的探讨心房颤动（房颤）患者心房肌组织醛固酮水平和醛固酮合成酶基因CYP11B2mRNA表达与房颤时心房结构重构的关系。方法入选进行人工心脏瓣膜置换术的风湿性心脏瓣膜病患者25例，其中窦性心律者12例，慢性房颤（≥6个月）者13例。上述患者均于术前行经胸超声心动图检查并留取相关资料，于手术时同时取左右心房侧壁组织。用放射免疫法测定心房组织醛固酮水平；用VG染色法对胶原容量分数（CVF）半定量分析；实时荧光定量PCR测定CYP11B2mRNA在心房肌组织中的表达情况。结果与窦性心律组比较，房颤组左心房内径显著扩大（P〈0．01）；心房肌组织醛固酮水平和CVF均明显增加（P均〈0．001）；心房肌组织CYP11B2mRNA表达也明显增加（P〈0．001）；上述指标无论是在窦性心律时还是在房颤时其在左右心房之间差异无统计学意义（P均〉0．05）。CVF和左心房内径显著正相关（r=0．845，P〈0．001）；心房组织醛固酮水平与左心房内径（r=0．814，P〈0．001）和CVF（r=0．885，P〈0．001）均呈明显正相关；CYP11B2mRNA表达量和CVF亦呈明显正相关（r=0．757，P〈0．001）。结论心房颤动时心房结构重构与其组织醛固酮水平增加和CYPI1B2mRNA表达增加有关，醛固酮受体拮抗剂可能在阻止房颤的心房结构重构进程上发挥治疗作用。     

心房颤动患者循环血浆肾素、血管紧张素Ⅱ和醛固酮的变化及临床意义

目的 分析心房颤动患者循环血浆肾素、血管紧张素Ⅱ(AngⅡ)、醛固酮(Ald)的水平变化,并探讨其临床意义。方法入选42例患者,男19例,女23例,年龄37-80(63.02±10.66)岁。按有无心房颤动病史分为三组:窦性心律组(SR组)14例,阵发性心房颤动组(pAF组)15例,慢性心房颤动组(cAF组)13例。应用放射免疫方法测定循环血浆肾素、AngⅡ、Ald浓度。结果cAF组患者平均左心房直径与SR组和pAF、组相比明显增大(分别增大45.3％和31.8％,P<.01),而且cAF组患者循环血浆肾素、AngⅡ、Ald浓度与SR组相比明显升高(分别升高83.3％、61.7％、34.2％,P<0.01-0.02)。三组患者左心房直径与其循环血浆肾素、AngⅡ、Ald浓度变化具有明显的正相关关系(P<0.05-0.01)。结论心房颤动时存在肾素-血管紧张素系统(RAS)和Ald的激活。RAS和Ald可能参与了心房结构重构的发生。Ald的作用靶点可能主要是心房间质。     

心房颤动患者左、右心房肌组织AT_1-R、AT_2-R、CYP11B2的mRNA表达

目的：观察心房颤动患者左、右心房肌组织中的血管紧张素Ⅱ受体1型(AT_1-R)、2型(AT_2-R)、醛固酮合成酶(CYP11B2)的mRNA表达情况。方法：取23例因心脏病住院接受开胸手术的心房颤动患者的左、右心耳组织,用半定量聚合酶链式反应技术测定AT_1-R、AT_2-R和CYP11B2 mRNA在左、右心房肌组织中的表达情况。结果：与右心房相比,AT_1-R mRNA在左心房肌组织中的表达有增高的趋势,但无统计学差异；AT_2-R mRNA在左心房肌组织中的表达明显上调了21．3%(P＜0．05)。CYP11B2 mRNA在左、右心房肌组织中的表达没有差异。结论：AT_1-R可能主要介导了左心房结构重构,AT_2-R mRNA表达升高可能是对左心房结构重构的一种适应和代偿机制。     

心房颤动患者左、右心房肌组织AT1-R、AT2-R、CYP11B2的mRNA表达

目的：观察心房颤动患者左、右心房肌组织中的血管紧张素Ⅱ受体1型（AT1-R）、2型（AT2-R）、醛固酮合成酶（CYP11B2）的mRNA表达情况。方法：取23例因心脏痛住院接受开胸手术的心房颤动患者的左、右心耳组织,用半定量聚合酶链式反应技术测定AT1-R、AT2-R和CYP11B2 mRNA在左、右心房肌组织中的表达情况。结果：与右心房相比,AT1,-R mRNA在左心房肌组织中的表达有增高的趋势,但无统计学差异;AT2-R mRNA在左心房肌组织中的表达明显上调了21．3％（P〈0．05）。CYP11B2 mRNA在左、右心房肌组织中的表达没有差异。结论：AT1-R可能主要介导了左心房结构重构,AT2-R mRNA表达升高可能是对左心房结构重构的一种适应和代偿机制。     

心房颤动患者心房组织醛固酮和心房基质重构研究

目的 探讨心房颤动患者心房组织醛固酮水平和心房基质重构的相关关系。方法 入选行人工瓣膜置换术的风湿性心脏病患者25例,其中窦性心律者12例,慢性心房颤动者（房颤时程≥6月）13例。术前进行经胸超声心动图检查并留取有关资料,于手术时取左右心房侧壁组织,用放射免疫法测定心房组织醛固酮水平;用VG染色法对总胶原容量分数（CVF）半定量分析;RT-PCR检测Ⅰ型和Ⅲ型胶原mRNA表达改变。结果 与窦性心律者比较心房颤动组左房内径显著扩大（均P<0.01）;心房肌组织醛固酮［右房:(310.3±69.6) vs (154.5±35.8)pg/g,左房:(334.2±76.6) vs (166.5±38.6)pg/g,均P<0.01］、Ⅰ型胶原mRNA表达［右房:(1.95±0.22) vs (0.71±0.11),左房:(2.05±0.28) vs (0.74±0.16),均P<0.01］和CVF［右房:(13.0±1.9)％ vs (6.5±1.1)％,左房:(14.1±1.7)％ vs (6.7±1.2)％,均P<0.01］均明显增加;Ⅲ型胶原mRNA表达在房颤组和窦性心律组间无差异;上述指标在左、右心房之间无差异。Ⅰ型胶原mRNA与左心房直径（r＝0.885,P<0.01）、CVF和左心房直径（r＝0.845,P<0.01）均显著正相关;心房组织醛固酮水平与左心房内径（r＝0.814,P<0.01）和CVF（r＝0.885,P<0.01）均呈明显正相关。结论 心房组织醛固酮水平可能在心房颤动心房基质重构中起重要作用,并可能参与了心房颤动的发生和维持。     

丹参对自发性高血压大鼠心肌醛固酮合成的抑制作用及其机制

目的研究丹参对自发性高血压大鼠(SHRs)心肌醛固酮合成的作用及可能机制.方法 12周龄雄性SHRs 30只和WKY大鼠15只,分为3组对照组、高血压组、丹参组.丹参组经腹腔给予丹参注射液 1.5 mg/(kg*d)共12周.采用放射免疫法、荧光分光光度法和逆转录聚合酶链反应(RT-PCR)技术测定各组心肌组织醛固酮含量、醛固酮合成酶活性及醛固酮合成酶基因CYP11B2的mRNA表达水平.结果经丹参治疗后SHRs心肌醛固酮含量及醛固酮合成酶活性明显降低(P<0.01, P<0.05),分别下降51.3%、39.7%,CYP11B2基因的mRNA表达水平显著下调(P<0.01).结论丹参可能通过下调醛固酮合成酶基因CYP11B2的表达,降低醛固酮合成酶的活性,从而抑制心肌醛固酮的合成.     

糖尿病大鼠血管醛固酮及其合成酶CYP11B2 mRNA的变化

目的　探讨糖尿病大鼠血管醛固酮及其合成酶CYP11B2mRNA的变化。方法　建立STZ糖尿病大鼠肠系膜血管体外灌流模型 ,以高效液相 (HPLC)分离、纯化血管生成的醛固酮后作放免检测 ,采用逆转录聚合酶链反应 (RT PCR)法检测醛固酮合成酶CYP11B2mRNA。结果　 (1)肾上腺切除大鼠肠系膜血管醛固酮生成量与正常对照组比较无显著差异〔(0 .82± 0 .19)ng/ 2 0min(n =8)vs (0 .88± 0 .19)ng/ 2 0min (n =8) ,P >0 .0 5〕。 (2 )糖尿病大鼠肠系膜血管醛固酮生成量较正常对照组显著减少〔(0 .5 3± 0 .2 2 )ng/ 2 0min (n =8)vs (0 .88± 0 .19)ng/ 2 0min (n =8) ,P <0 .0 1〕。 (3)肾上腺切除大鼠和其他各组肠系膜血管均可检测到醛固酮合成关键酶—CYP11B2mRNA ,糖尿病组肠系膜血管CYP11B2表达则较正常对照组减弱。结论　SD大鼠肠系膜血管能分泌醛固酮 ,糖尿病大鼠CYP11B2受抑制 ,血管醛固酮生成量减少     

醛固酮合酶基因多态性与原发性高血压及血浆醛固酮水平的关系

目的　探索武汉地区汉族人群中醛固酮合酶 (CYP11B2 )基因 3 44C/T多态性与原发性高血压 (EH)的相关性 ,及高血压人群醛固酮合酶CYP11B2基因 3 44C/T多态性与血浆醛固酮(pAldo)水平的相关性。方法　应用PCR RELP技术对 2 0 4例CYP11B2基因 3 44C/T多态性进行分析 ,应用放射免疫法测定 10 6例EH组的血浆醛固酮水平。结果　CYP11B2基因 3 44C/T多态性以TT和CT为主要基因型 ,与EH无明显相关性 (P >0 .0 5 )。高血压患者血浆醛固酮水平在CYP11B2基因 3 44C/T的 3个不同基因型组比较差异有显著性 (P <0 .0 1)。结论　武汉地区汉族人群CYP11B2基因 3 44C/T多态性频率与EH没有明显相关性。高血压人群的血浆醛固酮水平与CYP11B2基因 3 44C/T多态性相关     

丹参对自发性高血压大鼠心肌醛固酮合成的抑制作用及其机制

目的　研究丹参对自发性高血压大鼠 (SHRs)心肌醛固酮合成的作用及可能机制。方法　 12周龄雄性SHRs 30只和WKY大鼠 15只 ,分为 3组 :对照组、高血压组、丹参组。丹参组经腹腔给予丹参注射液 1 5mg/ (kg·d)共 12周。采用放射免疫法、荧光分光光度法和逆转录聚合酶链反应 (RT PCR)技术测定各组心肌组织醛固酮含量、醛固酮合成酶活性及醛固酮合成酶基因CYP11B2的mRNA表达水平。结果经丹参治疗后SHRs心肌醛固酮含量及醛固酮合成酶活性明显降低 (P <0 0 1,P <0 0 5 ) ,分别下降 5 1 3%、39 7% ,CYP11B2基因的mRNA表达水平显著下调(P <0 0 1)。结论丹参可能通过下调醛固酮合成酶基因CYP11B2的表达 ,降低醛固酮合成酶的活性 ,从而抑制心肌醛固酮的合成     

培哚普利抑制充血性心力衰竭大鼠心脏合成醛固酮及其合成酶基因的表达

目的　评价血管紧张素转换酶抑制剂培哚普利长期应用对充血性心力衰竭大鼠心脏合成醛固酮的影响。方法　雄性Wistar大鼠结扎左冠状动脉前降支 ,制成充血性心力衰竭模型 ,用培哚普利处理 2 0周 ,以假手术大鼠和未处理的心肌梗死后充血性心力衰竭大鼠作对照 ,离体灌注大鼠心脏 ,灌注液经反向高效液相色谱法纯化 ,放射免疫法检测醛固酮 ,用逆转录聚合酶链式反应检测非梗死心肌醛固酮合成酶基因CYP11B2mRNA的表达情况。结果　心力衰竭组离体心脏灌注液中醛固酮 (10 77.7± 39.9)mg h水平明显高于假手术组 (5 0 0 .3± 2 0 .6 )mg h ,心肌CYP11B2mRNA表达增加 ;培哚普利治疗组不能使血浆AngⅡ (16 0 .5± 12 .1)mg ml、醛固酮 (2 6 2 .0± 18.9)mg ml水平明显降低 ,但是可以明显降低离体心脏灌注液中AngⅡ (112 .1± 16 .5 )mg h和醛固酮 (799.9± 6 3.4 )mg h水平 ,抑制非梗死心肌CYP11B2mRNA的表达增加。结论　充血性心力衰竭时 ,大鼠心脏局部合成醛固酮增加 ,长期应用培哚普利可以抑制心力衰竭大鼠心脏局部醛固酮的合成和CYP11B2表达     

Association between transforming growth factor β1 and atrial fibrillation in essential hypertensive patients

Abstract

Background: Transforming growth factor β₁ (TGFβ₁) was one of the main factors for accelerating atrial fibrosis and has been reported with significantly higher level in plasma of the patients with essential hypertension (EH), especially in those with target organ damage. The contribution of TGFβ₁ in the pathogenesis of atrial fibrillation (AF) in EH patients remains unknown. Methods: 75 EH patients with documented AF were divided into the paroxysmal AF group (EH+pAF, n?=?44) or the chronic AF group (EH+cAF, n?=?31), and 37 EH patients with sinus rhythm (SR) were assigned into the EH+SR group. All data including EH duration, blood pressure, lipids, glucose and left atrial diameter (LAD) measured by ultrasonic cardiogram were recorded. The serum levels of TGFβ₁ and connective tissue growth factor (CTGF) were detected, and compared with normal controls (NC group, n?=?36). Results: The serum levels of TGFβ₁ and CTGF in all EH groups were significantly higher than those in the NC group (p?<?0.001, respectively). Among the EH groups, TGFβ₁ and CTGF levels were highest in the cAF group, followed by the pAF and the SR groups (p?<?0.005). However, no significant difference was observed in TGFβ₁ and CTGF levels between the cAF group and the pAF group. The serum TGFβ₁ in AF patients was independently correlated with LAD, the presence of AF, aldosterone, CTGF and age. Conclusion: The serum TGFβ₁ promotes CTGF synthesis and causes left atrial enlargement and remodeling, which is possibly involved in the pathogenesis of AF in EH patients.     

氯通道ClC-1、ClC-2在人心房肌的表达及与心房颤动的关系

目的研究氯通道ClC-1和ClC-2基因在人心房组织的表达及与心房颤动(AF)的关系。方法将71例风湿性心瓣膜病接受换瓣手术患者分为三组,窦性心律(SR)组31例,阵发性房颤(PAF)组7例,慢性房颤(CAF)组33例,于术中获取右心耳组织,应用半定量逆转录-聚合酶链反应(RT-PCR)检测心房组织ClC-1和ClC-2的mR-NA相对含量。结果①ClC-1、ClC-2基因在人心房组织有表达。②与SR组比较,PAF组ClC-1的mRNA表达增加但无统计学意义(1.05±0.22vs1.01±0.13,P>0.05),CAF组的表达明显增加(1.25±0.18vs1.01±0.13,P<0.001),CAF组较PAF组亦明显增加(P<0.01)。ClC-1的mRNA表达水平与左房内径、AF持续时间呈正相关[(r=0.344,P=0.003)(r=0.405,P<0.001)]。③与SR组比较,PAF组ClC-2的mRNA表达无增加(1.03±0.14vs1.04±0.15,P>0.05),CAF组的表达明显增加(1.26±0.13vs1.04±0.15,P<0.001),CAF组较PAF组亦明显增加(P<0.01)。ClC-2的mRNA表达与左房内径、AF持续时间呈正相关[(r=0.441,P<0.001)(r=0.331,P=0.005)]。结论AF患者ClC-1、ClC-2的mRNA表达水平的增加可能是心房肌电重构的分子基础。     

心房颤动患者血清尿酸水平的变化及临床意义

目的分析心房颤动(AF)患者血清尿酸(UA)水平的变化,并探讨这一变化的临床意义。方法顺序入选共159例AF患者和健康体检者,分为3组:健康对照组,52例,年龄32～66岁,平均(54±1)岁;阵发性AF组(pAF组,AF持续时间<6个月),60例,年龄47～71岁,平均(52±1)岁;慢性AF组(cAF组,AF持续时间>6个月),47例,年龄51～77岁,平均(59±1)岁。样本入选后,详细记录入选者的一般临床资料特征,生物化学技术测定3组入选者的血清UA、高敏C反应蛋白(hs-CRP)水平,经胸多普勒心脏超声测定3组入选者的左心房前后径、左心室舒张末期内径和左心室射血分数,并对入选样本的基本资料和所测临床数据与AF的发生进行单因素和多因素分析。结果 cAF组血清UA水平(476.45±140.87)μmol/L与对照组(293.12±76.77)μmol/L和pAF组(302.38±78.19)μmol/L比较,明显升高(P<0.001)。单因素分析中,年龄(OR:1.116,P<0.001)、hs-CRP(OR:7.603,P<0.001)、UA(OR:1.008,P<0.001)、左心室射血分数(OR:0.864,P<0.001)、左心房前后径(OR:1.365,P=0.001)、高血压(OR:11.407,P<0.001)、服用B受体阻滞剂(OR:8.109,P<0.001)和血管紧张素转换酶抑制剂/血管紧张素Ⅱ受体拮抗剂(OR:4.569,P=0.003)与AF发生有显著性关系。多因素Logistic回归分析显示,仅有hs-CRP与AF的发生独立相关(OR:3.267,P=0.001)。但亚组分析中,左心室射血分数(OR:0.907,P=0.007)和hs-CRP(OR:2.338,P=0.025)是与pAF发生显著相关的独立变量;UA(OR:1.005,P=0.04)和hs-CRP(OR:3.535,P=0.002)是与cAF发生显著相关的独立变量。结论 cAF的发生与患者血清UA水平升高有关,可能是高尿酸血症介导了炎症激活和氧化应激。此结论尚需更大样本的相关性研究来验证。     

心房颤动患者心房组织囊性纤维化跨膜转运调节体氯通道基因表达

目的探讨心房颤动(简称房颤)患者心房组织囊性纤维化跨膜转运调节体(CFTR)氯通道基因的表达。方法应用半定量逆转录多聚酶链反应(RT-PCR)比较窦性心律(SR)组(n=31)、阵发性房颤(PAF)组(n=7)和慢性房颤(CAF)组(n=33)患者心房组织CFTR氯通道基因的表达。结果与SR组相比,PAF组CFTR的mRNA表达有增加但未达到统计学意义(P>0.05),CAF组的表达明显增加,CAF组较PAF组亦明显增加(1.20±0.12 vs1.08±0.18,P<0.05)。CFTR的mRNA表达与左房内径呈正相关(r=0.312,P=0.008)。结论慢性房颤患者心房组织CFTR氯通道基因表达上调,可能在房颤心房电重构中起作用。     

Differential phosphorylation-dependent regulation of constitutively active and muscarinic receptor-activated IK,ACh channels in patients with chronic atrial fibrillation

OBJECTIVE: In chronic atrial fibrillation (cAF) the potassium current IK,ACh develops agonist-independent constitutive activity. We hypothesized that abnormal phosphorylation-dependent regulation underlies the constitutive IK,ACh activity. METHODS: We used voltage-clamp technique and biochemical assays to study IK,ACh regulation in atrial appendages from 61 sinus rhythm (SR), 11 paroxysmal AF (pAF), and 33 cAF patients. RESULTS: Compared to SR basal current was higher in cAF only, whereas the muscarinic receptor (2 micromol/L carbachol)-activated IK,ACh was smaller in pAF and cAF. In pAF the selective IK,ACh blocker tertiapin abolished the muscarinic receptor-activated IK,ACh but excluded agonist-independent constitutive IK,ACh activity. Blockade of type-2A phosphatase and the subsequent shift to increased muscarinic receptor phosphorylation (and inactivation) reduced muscarinic receptor-activated IK,ACh in SR but not in cAF, pointing to an impaired function of G-protein-coupled receptor kinase. Using subtype-selective kinase inhibitors we found that in SR the muscarinic receptor-activated IK,ACh requires phosphorylation by protein kinase G (PKG), protein kinase C (PKC), and calmodulin-dependent protein kinase II (CaMKII), but not by protein kinase A (PKA). In cAF, constitutive IK,ACh activity results from abnormal channel phosphorylation by PKC but not by PKG or CaMKII, whereas the additional muscarinic receptor-mediated IK,ACh activation occurs apparently without involvement of these kinases. In cAF, the higher protein level of PKCepsilon but not PKCalpha, PKCbeta1 or PKCdelta is likely to contribute to the constitutive IK,ACh activity. CONCLUSIONS: The occurrence of constitutive IK,ACh activity in cAF results from abnormal PKC function, whereas the muscarinic receptor-mediated IK,ACh activation does not require the contribution of PKG, PKC or CaMKII. Selective drug targeting of constitutively active IK,ACh channels may be suitable to reduce the ability of AF to become sustained.     

心房颤动患者心房组织肿瘤坏死因子-α的表达

目的观察肿瘤坏死因子-α(TNF-α)在心房颤动(简称房颤)患者心房组织中基因转录和蛋白表达的改变,探讨房颤患者心房结构重构的分子机制。方法75例风湿性心脏瓣膜病接受换瓣手术者分为三组,其中窦性心律组34例、阵发性房颤组11例、持续性房颤组30例,于术中取右心耳组织,采用苦味酸天狼猩红染色法对心房组织胶原沉积量及分布情况进行分析,分别采用半定量逆转录-聚合酶链反应技术和免疫印迹法测定TNF-α的mRNA含量和蛋白含量。结果①房颤组心房组织存在明显纤维化,纤维化程度与左房内径、房颤持续时间呈正相关(r=0.390,0.320,P均<0.05);②持续性房颤组心房组织中TNF-α的mRNA及蛋白水平较窦性心律组、阵发性房颤组明显增加(P<0.01)。TNF-α的mRNA水平与房颤持续时间呈正相关(r=0.298,P=0.01);蛋白表达水平与左房内径、房颤持续时间、胶原容积分数呈正相关(r分别为0.280,0.334,0.383,P均<0.05)。结论房颤患者心房组织中TNF-α的表达增加可能是引起房颤患者心房结构重构的分子机制之一。     

心房颤动复律后维持窦性心律影响因素的临床分析

目的探讨心房颤动（Af）复律后维持窦性心律的影响因素。方法选择2006年～2008年首次诊断Af（发病时间〈3个月）经药物或直流电成功转复窦性心律的住院患者98例。随访6个月后Af未复发者为维持窦性心律组（A组）52例,Af复发者（B组）46例。回顾性对比分析两组的临床特征、心电图指标、超声心动图（UCG）参数及相互关系,探讨A组的独立预测因子及诊断价值。结果 6个月随访后,52例（占53%）仍维持窦性心律,46例Af复发,半数以上复发在复律后2周内。两组间在性别、年龄、基础心脏病、β受体阻断剂使用、复律方式、左心室射血分数（LVEF）等差异无统计学意义。B组与A组相比,复律前Af持续时间（28.7±26.3d对1.3±1.4d,P〈0.01）、P波最大时间（Pmax）（P〈0.01）和P波离散度（Pd）（52±12ms对40±10ms,P〈0.01）、左心房直径（LAD）（47±4mm对41±3mm,P〈0.01）和左房自发性声学显影（P〈0.01）差异有统计学意义;但是两组间P波最小时间（Pmin）差异无显著性。多元回归分析显示：Af持续时间〈7d（OR=2.61）、LAD〈45mm（OR=2.10）和Pd〈47ms（OR=3.72）是复律后维持窦性心律的独立预测因子,准确性分别为82%、83%和86%。Pmax和左房无自发性声学显影仅是单因素影响因子。结论复律前Af持续时间、左房大小和Pd是预测Af复律后维持窦性心律的重要因素。     

Short-term sinus rhythm predicts long-term sinus rhythm and clinical improvement after intraoperative ablation of atrial fibrillation

Aims: Our aim was to compare the long-term effects on rhythm and qualityof life (QoL) after left atrial epicardial radiofrequency (RF)ablation vs. no ablation in patients undergoing cardiac surgery. Methods and results: Thirty-nine patients with ECG documented atrial fibrillation(AF) scheduled for coronary artery bypass grafting (CABG) withor without concomitant valve surgery were consecutively electedfor epicardial RF ablation. Thirty-nine age- and gender-matchedpatients scheduled for CABG with or without concomitant valvesurgery only and with documented AF served as controls. Thefollow-up after ablation was 32 ± 11 months. The percentageof patients in sinus rhythm (SR) at long-term follow-up was62 vs. 33% (P = 0.03) after ablation and no ablation, respectively.SR at 3 months was highly predictive of that at 32 months (sensitivity95%, positive predictive value 86%). Long-term SR was associatedwith better QoL, fewer symptoms, higher ejection fraction, andsmaller left and right atria than AF. Conclusion: SR at 3 months was highly predictive of long-term SR that wasassociated with clinical improvement when compared with patientsstill in AF. AF at 3 months did not preclude a later stabilizationto SR.     

Aldosterone synthase gene polymorphism as a determinant of atrial fibrillation in patients with heart failure

We analyzed the possible association between aldosterone synthase (CYP11B2) T-344C polymorphism, which is associated with increased aldosterone activity, and the prevalence of atrial fibrillation (AF) in 196 consecutive patients who had symptomatic systolic heart failure (HF; left ventricular ejection fraction <40%) for > or =3 months before recruitment. Genomic DNA was extracted from peripheral blood leukocytes using a standard protocol. Subjects were genotyped for the CYP11B2 polymorphism using the polymerase chain reaction/restriction fragment length polymorphism approach. AF was present in 63 patients (33%) with HF. We found the -344 CC genotype to be a strong independent marker for AF. Almost 1/2 (45%) of patients with this genotype had AF compared with 1/4 (27%) with -344 TT and TC genotypes (p = 0.01). A multivariate stepwise logistic regression model that included age, gender, New York Heart Association class, CYP11B2 -344CC genotype, and echocardiographic measurements of left ventricular ejection fraction, left atrial dimension, left ventricular end-diastolic diameter, and mitral regurgitation severity showed that the CYP11B2 CC genotype (adjusted for age and left atrial size) was an independent predictor of AF (adjusted odds ratio 2.35, 95% confidence interval 1.57 to 3.51, p = 0.03). In conclusion, CYP11B2 T-344C promoter polymorphism predisposes to clinical AF in patients with HF.