【作者】 王云帆；

【导师】 陈鹏；

【作者基本信息】 浙江大学 ， 内科学， 2011， 博士

【摘要】 研究背景：心房颤动是临床常见的心律失常之一。近年来随着心血管系统疾病罹患率的增加,其发病率逐年上升。而房颤也相应地增加心血管系统疾病的发病率及死亡率。房颤的治疗方案包括转复窦律、控制室率及抗凝治疗等,但临床治疗策略的制定较复杂,不但取决于房颤类型,还与伴发的其他合并症密切相关。基于肺静脉隔离的经导管射频消融术是目前治疗房颤的主要方法之一,特别是症状性、复发性及药物难治性房颤的首选治疗方案。随着消融技术的完善,新材料及器械的发明和应用,射频消融术在房颤治疗方面的应用日益广泛。尽管射频消融术已在房颤治疗领域取得一定的进展,但术后房颤、房扑及房速等房性心律失常复发的现象仍较常见。消融线不完整、消融线两侧的组织恢复传导等是肺静脉隔离术失败的主要原因。而持续性房颤发作及心房增大等引起的心房电重构、结构重构等因素是则是复发的重要病理生理机制。针对房颤射频消融术后复发相关的各种危险因素、预测因子的研究方兴未艾。本文结合当前的热点及争议,拟用Meta分析的方法对房颤射频消融术后早期复发与晚期复发的联系加以研究,并对炎症因子CRP与射频消融术后房颤复发率的关系进行探讨。第一部分房颤射频消融术后早期复发与晚期复发的关系：Meta分析目的：研究房颤射频消融术后早期复发与晚期复发之间的关系,并探索房颤射频消融术后各种复发模式,如早期复发、晚期复发及“延迟治愈”等人群的危险因素及临床特征。方法：计算机检索Pubmed、Embase、Cochrane library和Web of Science等数据库的相关文献。检索词为"atrial fibrillation"、"catheter ablation"、"pulmonary vein isolation"和"recurrence"等。手工检索Circulation、JACC、European Heart Journal和Heart Rhythm等杂志并对检索结果的参考文献进行扩展检索。制定文献纳入、排除标准对检索文献进行筛选。设计质量评价清单对纳入文献进行质量评价并提取相关数据。对房颤射频消融术后早期复发人群及无早期复发人群的晚期复发率进行比较,并对早期复发、晚期复发及延迟治愈人群的临床特征进行分析。同时对纳入文献进行异质性检验,若存在显著异质性则进一步行亚组分析及敏感性分析。结果：初检获得260篇相关文献,严格筛选后共14篇文献(总样本量4021人)纳入本研究。Meta分析结果表明,房颤射频消融术后早期复发人群的晚期房颤复发率是无早期复发人群的4.59倍(95% CI 2.94-7.18,P<0.00001)。亚组分析显示各文献对早期复发的时间定义不同是异质性的主要来源。早期复发人群与无早期复发人群相比,年龄更大(P=0.0009),房颤病史更长(P<0.0001),左房内径更大(P=0.004),结构性心脏病和高血压病的患病率更高(分别为P=0.0004和P=0.003)。而无晚期复发的人群中阵发性房颤所占比例显著高于晚期复发人群(P=0.0004)。延迟治愈人群与早期复发但无延迟治愈人群相比平均年龄更低(-3.58；95%CI-5.92--1.24,P=0.003),左房内径更小(-2.38；95%CI-3.80—0.95,P=0.001),而与无复发人群的临床特征相比则无显著差异。结论：房颤射频消融术后,个体的早期复发并不决定是否出现晚期复发,但早期复发群体的晚期复发率显著高于无早期复发群体。相比于早期复发但无延迟治愈的人群,延迟治愈人群的临床特征更接近无复发人群。第二部分C反应蛋白与房颤射频消融术后复发的关系：Meta分析目的：研究房颤射频消融术前基础CRP水平与术后房颤复发率之间的关系。方法：计算机检索Pubmed、Embase、Cochrane library和Web of Science等数据库。检索关键词包括"atrial fibrillation"、"C-reactive protein"、"catheter ablation"、"pulmonary vein isolation"、"inflammation"和"recurrence"等。手工检索Circulation、JACC、European Heart Journal和Heart Rhythm等杂志及其增刊并对参考文献进行扩展检索。制定纳入、排除标准并筛选文献。对纳入文献进行质量评价并提取数据。比较房颤复发人群与无复发人群的术前基础CRP水平,并比较术前高CRP水平人群与低CRP水平人群的消融术后房颤复发率。根据异质性检验的结果行亚组分析及敏感性分析。同时对上述各组人群的临床特征进行比较。结果：初检获得111篇文献,按纳入、排除标准筛选后共10篇文献(总样本量2021人)纳入本研究。Meta分析表明射频消融术后房颤复发人群的基础CRP水平较无复发人群高0.96mg/L(95% CI0.44-1.47,P=0.0003)。而基础CRP较高人群的术后房颤复发率是低CRP人群的1.93倍(95% CI 1.37-2.73,P=0.0002)。纳入研究之间异质性较显著(P<0.0001,I2=77%),亚组分析及敏感性分析表明二次消融术和是否纳入结构性心脏病患者可能是异质性的来源。术后房颤复发人群的体重指数(P<0.00001)及左房内径(P<0.0001)明显大于无复发人群。结论：房颤射频消融术前基础CRP水平与术后的房颤复发率相关,且增高的基础CRP水平与术后的房颤复发率增加相关。更多还原

【Abstract】 Background:Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice, and its prevalence has increased during the past few decades. AF is also contributing substantially to cardiac morbidity and mortality. Management of patients with AF requires knowledge of its pattern of presentation, underlying conditions, and decisions about restoration and maintenance of sinus rhythm, control of the ventricular rate, and anti-thrombotic therapy.Catheter ablation such as pulmonary vein isolation (PVI) has become the first line of therapy in patients with symptomatic, recurrent, drug-refractory AF. With continuing advances in techniques and devices of PVI, more patients will be offered this treatment option.However, despite these advances in ablation technique, recurrence of AF following PVI is still frequent during the follow-up. The mechanisms that account for the recurrence are still under research. Uncompleted ablation lines and reconnection with the isolated pulmonary vein activities may contribute to parts of the reasons. Atrial remodeling induced by the "AF begets AF" effect may also play an important role.In order to study these mechanisms mentioned above, we performed two independent Meta-analyses mainly about the two topics below:(1)the association between early recurrent atrial fibrillation (ERAF) and late recurrent atrial fibrillation (LRAF) after catheter ablation; and (2)the association between C-reactive protein (CRP) and recurrence rate of atrial fibrillation following ablation.Part 1:The association between early recurrent atrial fibrillation and late recurrent atrial fibrillation after catheter ablation: a Meta-analysisAims:The main purpose of this part is to explore the association between early recurrent atrial fibrillation and late recurrent atrial fibrillation after catheter ablation. Meanwhile, the clinical characteristics of the patients with early recurrence, late recurrence and "delayed cure" would also be studied.Methods:We searched the online databases of PubMed, Embase, the Cochrane library, and Web of Science for relative literatures published January 2011 or earlier. In addition, manual search with Circulation, JACC, European Heart Journal and Heart Rhythm was also performed. Then, these studies were selected by an including and excluding criteria. The included studies were evaluated according to a quality scoring checklist and the statistical data were extracted. We compared the LRAF rate between the patients with and without ERAF. The clinical characteristics of the patients with ERAF. LRAF and "delayed cure’" would also be analyzed. Heterogeneity test was performed using the Cochrane Q statistic. Subgroup and sensitivity analyses would be performed if significant heterogeneity was found.Results:Of the 260 initially identified studies,14 studies with 4021 patients were finally included. A Meta-analysis of 14 observational studies documented that the risk ratio of LRAF rate between the patients with and without ERAF was 4.59(5%CI 2.94-7.18, P<0.00001). Subgroup analysis revealed that the different definitions of ERAF of the included studies may be a source of heterogeneity. Compared with patients without ERAF, those with ERAF were associated with older age (P=0.0009), longer AF duration (P＜.0001), increased left atrium (LA) diameter (P=0.004), and higher prevalence of structure heart disease (SHD) and hypertension (P=0.0004 and P=0.003, respectively). The ratio of paroxysmal atrial fibrillation patients was lower in LRAF group than those without LRAF (P=0.0004). The "delayed cure" patients were associated with younger age (-3.58; 95%CI-5.92--1.24, P=0.003) and smaller LA diameter (-2.38; 95%CI-3.80--0.95, P=0.001) than those with ERAF but absent of "delayed cure". There were no significant differences between the "delayed cure" patients and those without any recurrent AF.Conclusion:The ERAF did not predict LRAF in individual patient. However, the LRAF rate was significantly higher in patients with ERAF than those without. As compared with the patients with ERAF but absent of "delayed cure", the clinical characteristics of patients with "delayed cure" were more similar as those without recurrent AF.Part 2:The association between C-reactive protein and recurrent atrial fibrillation after catheter ablation: a Meta-analysisAims:The objective of this part is to study the association between CRP and AF recurrence after catheter ablationMethods:We searched the online databases of PubMed, Embase, the Cochrane library, and Web of Science for relative literatures published January 2011 or earlier. In addition, manual search with Circulation. JACC. European Heart Journal and Heart Rhythm was also performed. Then, these studies were selected by an including and excluding criteria. The included studies were evaluated according to a quality scoring checklist and the statistical data were extracted. We compared the baseline CRP levels between the patients with AF recurrence and those without. The AF recurrence rates of the patients with high or low CRP levels were also compared. The clinical characteristics of these patients would also be studied. Heterogeneity test was performed using the Cochrane Q statistic. Subgroup and sensitivity analyses would be performed if significant heterogeneity was found.Results:Of the 111 initially identified studies,10 studies with 2021 patients were finally included. A Meta-analysis of 9 included studies documented that the weighted mean difference of baseline CRP levels between the patients with, and those without AF relapse was 0.96 mg/1 (95% CI 0.44 to 1.47; P= 0.0003). Significant heterogeneity was found between these 9 studies (P< 0.0001; 12=77%). Subgroup analysis and sensitivity analysis revealed that repeat ablation procedures and whether excluding patients with SHD might be the sources of heterogeneities. The other meta-analysis with 2 included studies showed that the risk ratio of AF recurrence rates between the patients with high baseline CRP levels and those with low CRP levels was 1.93 (95%CI 1.37 to 2.73; P= 0.0002). The patients with AF recurrence were associated with higher Body Mass Index (P< 0.00001) and increased LA diameter (P< 0.0001) as compared with those without AF recurrence.Conclusion:The baseline CRP levels were associated with AF recurrence rates after successful catheter ablation and increased baseline CRP levels were correlated with higher risk for AF recurrence following ablation.更多还原