经典高分文献阅读·有症状性心房颤动的病态肥胖患者 为什么要推迟减肥手术？

Morbidly Obese Patients With Symptomatic Atrial Fibrillation

Why Are We Holding Back on Bariatric Surgery?

有症状性心房颤动的病态肥胖患者

为什么要推迟减肥手术？

翻译 苗 猫 排版 丹妮

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In the last decade, hospitalizations for atrial fibrillation (AF) 房颤have increased by 23% in the United States, which—beyond the human toll—is associated with a significant cost burden to our health care system.This trend is expected to worsen, and by the year 2050, the prevalence of AF房颤发病率 is projected to 预计increase to 15.9 million people in the United States.This alarming rise in prevalence is in part attributable to the parallel rise of risk factors that facilitate the development of AF.In subjects with metabolic syndrome代谢综合征, risk factors such as elevated waist circumference腰围, elevated blood pressure, elevated triglycerides甘油三酯, low high-density lipoprotein cholesterol高密度脂蛋白, and impaired fasting glucose空腹血糖 are associated with a stepwise increase in AF risk.1 Obesity肥胖 specifically is associated with a 50% increase in the risk of AF development.There has also been a dose-dependent relationship between obesity-associated comorbidities 肥胖相关合并症such as obstructive sleep apnea阻塞性呼吸睡眠暂停 and AF incidence, burden, and response to treatment.Furthermore, AF patients with a higher body mass index (BMI) report lower scores on the 36-Item Short Form Health Survey in both mental and physical function domains身心功能领域, indicating a greater symptom burden in obese individuals.

01

在过去的十年里，美国因房颤住院的人数增加了23%，这甚至超出了人类的死亡人数，给我们的医疗保健系统成本带来了巨大的负担。这一趋势预计将不断恶化，到2050年，美国房颤的患病率预计将增加到1590万人。患病率这一惊人的上升部分是归因于促进房颤发展的风险因素的同步上升。在患有代谢综合征的受试者中，腰围增大、血压升高、甘油三酯升高、高密度脂蛋白胆固醇含量降低和空腹血糖受损等风险因素逐步增加了房颤风险。特别是肥胖，会使房颤发展风险增加50%。阻塞性睡眠呼吸暂停等肥胖相关合并症与房颤发病率、负担和治疗效果之间也存在剂量依赖性关系。此外,（BMI）较高的房颤患者在36项简表健康调查中的精神和身体功能得分较低，表明肥胖个体的症状更严重。

Catheter ablation导管消融 is a class I indication适应症 for patients with drug-refractory药物难治性 symptomatic AF However, patients who are most symptomatic from AF, specifically patients with a BMI ≥40 kg/m2, derive fewer benefits from this procedure, as multiple cohort studies have demonstrated higher rates of AF recurrence after catheter ablation in patients with morbid obesity病态肥胖 compared with normal weight controls.Fortunately, with aggressive risk factor modification including dramatic weight loss, the substrate for AF 房颤发病基础appears to be modifiable. Therefore, to enhance patient outcomes, clinicians managing AFs should emphasize risk factor modification, especially weight loss, and provide patients with the appropriate tools to succeed.

02

（导管）射频消融是药物难治性房颤患者的一级适应症。然而，房颤症状最严重的患者，特别是体重指数≥40千克/平方米的患者，从该手术中获益较少，因为多项队列研究表明，与正常体重对照组相比，病态肥胖患者导管消融后房颤复发率较高。幸运的是，通过积极控制风险因素，包括显著的体重减轻，可能会控制房颤基础。因此，为了改善患者的结局，临床医生在管理AFs时应强调控制风险因素，尤其是体重减轻，并为患者提供合适的方法去达成目标。

Two large prospective cohort studies, ARREST -AF (Aggressive Risk factor Reduction Study: Implications for the Substrate for Atrial Fibrillation) and LEGACY (Long-Term Effect of Goal Directed Weight Management in an Atrial Fibrillation Cohort), showed significant improvement in catheter ablation outcomes in patients with AF and obesity who lost at least 10% of body weight before undergoing catheter ablation. However, in ARREST and LEGACY , the average BMI was <35 kg/m2; whether those with BMI >35 kg/m2, and especially those with BMI >40 kg/m2, are capable of achieving sufficient weight loss to influence AF outcomes is less certain. The results of ARREST and LEGACY were not replicated in a separate study of patients with morbid obesity (mean BMI, 38±4 kg/m2) and long-standing, persistent AF where significant weight loss (median, –24.9 kg [interquartile range, –19.1 to –56.7]; P<0.001) did not influence the outcome of AF ablation.2 This suggests that in very obese individuals with advanced atrial remodeling晚期心房重塑, the amount of weight loss that patients are generally capable of achieving through lifestyle change and medication alone is insufficient to adequately modify the underlying substrate. It is also possible that long-term AF is less likely to be affected by weight loss; therefore, intervening early in the natural history of AF may be best.

03

两项大型前瞻性队列研究，DARK-AF(积极的风险因素降低研究：对心房颤动底物的影响)和LEGISE(心房颤动队列中目标导向体重管理的长期效应)显示，在接受导管消融前体重下降大于10%的房颤和肥胖患者中，导管消融结果有显著改善。然而，在CARARK和REGISTION中，平均BMI<35 kg/m2；BMI>35 kg/m2的患者，尤其是BMI>40的患者，通过减去足够的体重来改善房颤结局的方式，稳定性更低。在对病态肥胖(平均体重指数，38±4 kg/m2)和长期持续性房颤患者(中位数，-24.9 kg[四分位数范围，-19.1至-56.7]；P<0.001)的单独研究中，两项队列研究的结果没有重复。这表明，心房重塑晚期的病态肥胖患者通过改变生活方式和单靠药物来实现的减重量难以充分改变房颤发病基础。也有可能，长期房颤患者不太可能受到体重减轻的影响; 因此，在房颤的发展史早期进行干预可能是最好的。  

In a single-center retrospective cohort, Donnellan et al presented data on 239 patients who were morbidly obese and underwent AF ablation (defined as BMI ≥40or≥35 kg/m2 with obesity-related complications).Of these patients, 51 had undergone bariatric surgery 减肥手术before ablation. At a mean followup of 36 months after ablation, 20% of those who had undergone bariatric surgery, compared to 61% without bariatric surgery, had recurrent arrhythmia复发性心律失常 (P<0.0001).3 In the bariatric surgery group, BMI decreased from 47.6±9.3 kg/m2 to 36.7±7 kg/m2 before ablation. Furthermore, in the SOS (Swedish Obese Subjects) registry, the largest bariatric surgery cohort study to date, patients who underwent bariatric surgery had a 29% lower risk for development of AF than patients in the control group (hazard ratio, 0.71 [95% CI, 0.60–0.83]; P<0.001). There were no differences in preoperative BMI (47.1 vs 47.7 kg/m2; P=0.76) or medical comorbidities 内科合并症between groups. Subjects enrolled in SOS were primarily middle-aged, with only 3% having cardiovascular disease 心血管疾病at the beginning of the study period. Weight changes were significantly greater in the surgical group than in the control group (23.4% of body weight lost vs 0.1% gained) at 2 years. Regarding concerns about surgical risk, a cohort study looking at outcomes after bariatric surgery in patients with previous myocardial infarction心梗史 found no increased risk of cardiovascular complications心血管并发症. Obese patients with previous coronary artery disease冠心病史 who underwent bariatric surgery had half the long-term risk of death, MI, or stroke compared to matched cohorts who did not undergo bariatric surgery

04

在一项单中心回顾性队列研究中，Donnellan等人公布了239名病态肥胖并接受房颤消融(定义为体重指数≥40或≥35 kg/m2伴肥胖相关合并症)的患者的数据。这些患者中，51人在消融前接受过减肥手术。在消融后平均36个月的随访中，接受过减肥手术的患者中有20%的人发生了复发性心律失常(P<0.0001)，而没有接受过减肥手术的患者中有61%的人出现了反复心律失常(P<0.0001)。在减肥手术组中，消融前体重指数从47.6±9.3kg/m2降至36.7±7kg/m2。此外，从迄今为止最大的减肥手术队列研究发现，瑞典肥胖受试者登记中，接受减肥手术的患者相对于对照组 (风险比, 0.71 [95% CI, 0.60–0.83]; P<0.001)房颤发展风险降低了29%.4两组间的术前体重指数(47.1vs47.7 kg/m2；P=0.76)及合并内科并发症差异无统计学意义(P>0.05)。参加SOS（瑞典肥胖受试者）的受试者主要是中年人，在研究开始时只有3%的人患有心血管疾病。2年后，手术组的体重变化明显大于对照组(23.4%的体重下降，0.1%的体重增加)。关于手术风险的担忧，一项队列研究观察了既往心肌梗死患者减肥手术后的结果，发现心血管并发症的风险没有增加。与没有接受减肥手术的匹配队列相比，接受过减肥手术的冠心病史肥胖患者死亡、心肌梗死或中风的长期死亡风险是匹配队列的一半。

In conclusion, the prevalence of both obesity and AF continues to rise and the presence of one often facilitates the presence of the other. Risk factor modification控制风险因素 is an integral part of AF management, yet modest weight loss often appears to be insufficient to improve durability of the catheter ablation procedure for AF . Without sufficient weight loss, extremely obese patients can expect suboptimal results after catheter ablation compared to nonobese patients with AF , and they are more likely to experience a progression to persistent AF , which is ultimately harder to treat.

05

总之，肥胖和房颤的患病率持续上升，并且一种疾病往往会促进另一种疾病的发生发展。控制风险因素是房颤治疗中必不可少的部分，但适度的减重往往不足以提高房颤导管消融效果的持续性。与非肥胖房颤患者相比，若没有减少足够的体重，病态肥胖患者在导管消融效果可能不理想，且更有可能发展为持续性房颤，这将更难治疗。

We recommend a 2-pronged approach双管齐下, beginning with the enrollment of patients with morbid obesity and symptomatic AF in weight loss clinics that provide rigorous counseling on diet and exercise, followed by early referral to bariatric surgery for patients in whom lifestyle modifications do not achieve at least a 20% loss of total body weight (Figure). Weight loss, especially in patients with morbid obesity, is difficult to achieve, whereas significant weight loss can be expected (up to 110 lbs) with bariatric surgery, compared with a modest weight gain in medically treated patients. Simply acknowledging the link between obesity and worse outcomes for catheter ablation of AF is unacceptable. We have to come up with a realistic way to modify the natural progression of the most common arrythmia, and in patients with highly symptomatic AF and morbid obesity, early referral to 转诊bariatric surgery may be the only way. Further research studies, including randomized control trials that compare bariatric surgery as first-line therapy一线治疗 in this population, would certainly be of great benefit.

06

我们建议采取双管齐下的方法，首先将病态肥胖和有症状的房颤患者接收进入减肥诊所，提供严格的饮食和运动咨询，对于改变生活方式仍不能使总体重减少至少20%的患者，应尽早进行减肥手术(图)。病态肥胖患者减重，尤难实现。接受药物治疗的患者体重只会略有增加，而预计通过减肥手术可以显著减轻体重(多达110磅)。仅仅承认肥胖与房颤导管消融的不良结果之间的联系难以令人满意。我们必须提出一种现实的方法来改变最常见心律失常的自然进程。对于有严重临床症状的房颤和病态肥胖的患者，早期转诊进行减肥手术可能是唯一的方法。若进一步研究，包括将减肥手术作为这类人群的一线治疗方法的随机对照试验，肯定会大有裨益。

Figure. 提出了治疗流程

AF：房颤

ARREST：积极危险因素减少研究对房颤发病基础的影响

BMI：体重指数

LEGACY：目标导向体重管理在房颤队列中的长期效果

【学习笔记】

atrial fibrillation (AF) 房颤

 the prevalence of AF房颤发病率 

is projected to 预计

metabolic syndrome代谢综合征

 waist circumference腰围

triglycerides甘油三酯

lipoprotein cholesterol

脂蛋白胆固醇

fasting glucose空腹血糖 

obesity-associated comorbidities 

肥胖相关合并症 

obstructive sleep apnea

阻塞性呼吸睡眠暂停

Catheter ablation导管消融 

indication适应症 

drug-refractory药物难治性

morbid obesity病态肥胖 

 the substrate for AF

 房颤发病基础

advanced atrial remodeling

晚期心房重塑

bariatric surgery 减肥手术

 recurrent arrhythmia

复发性心律失常 

 medical comorbidities 

内科合并症

 cardiovascular disease 

心血管疾病

 previous myocardial infarction

心梗史 

cardiovascular complications

心血管并发症

previous coronary artery disease冠心病史

 risk factor modification

控制风险因素

referral to 转诊

 first-line therapy一线治疗 

END

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