Morbidly Obese Patients With Symptomatic Atrial Fibrillation

Why Are We Holding Back on Bariatric Surgery?

有癥狀性心房顫動(dòng)的病態(tài)肥胖患者

為什么要推遲減肥手術(shù)？

翻譯 苗 貓 排版 丹妮

歡 迎 關(guān) 注         Luffy麻醉頻道

In the last decade, hospitalizations for atrial fibrillation (AF) 房顫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房顫發(fā)病率 is projected to 預(yù)計(jì)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代謝綜合征, risk factors such as elevated waist circumference腰圍, 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 肥胖相關(guān)合并癥such as obstructive sleep apnea阻塞性呼吸睡眠暫停 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身心功能領(lǐng)域, indicating a greater symptom burden in obese individuals.

01

在過(guò)去的十年里，美國(guó)因房顫住院的人數(shù)增加了23%，這甚至超出了人類(lèi)的死亡人數(shù)，給我們的醫(yī)療保健系統(tǒng)成本帶來(lái)了巨大的負(fù)擔(dān)。這一趨勢(shì)預(yù)計(jì)將不斷惡化，到2050年，美國(guó)房顫的患病率預(yù)計(jì)將增加到1590萬(wàn)人。患病率這一驚人的上升部分是歸因于促進(jìn)房顫發(fā)展的風(fēng)險(xiǎn)因素的同步上升。在患有代謝綜合征的受試者中，腰圍增大、血壓升高、甘油三酯升高、高密度脂蛋白膽固醇含量降低和空腹血糖受損等風(fēng)險(xiǎn)因素逐步增加了房顫風(fēng)險(xiǎn)。特別是肥胖，會(huì)使房顫發(fā)展風(fēng)險(xiǎn)增加50%。阻塞性睡眠呼吸暫停等肥胖相關(guān)合并癥與房顫發(fā)病率、負(fù)擔(dān)和治療效果之間也存在劑量依賴(lài)性關(guān)系。此外,（BMI）較高的房顫患者在36項(xiàng)簡(jiǎn)表健康調(diào)查中的精神和身體功能得分較低，表明肥胖個(gè)體的癥狀更嚴(yán)重。

Catheter ablation導(dǎo)管消融 is a class I indication適應(yīng)癥 for patients with drug-refractory藥物難治性 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病態(tài)肥胖 compared with normal weight controls.Fortunately, with aggressive risk factor modification including dramatic weight loss, the substrate for AF 房顫發(fā)病基礎(chǔ)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

（導(dǎo)管）射頻消融是藥物難治性房顫患者的一級(jí)適應(yīng)癥。然而，房顫癥狀最嚴(yán)重的患者，特別是體重指數(shù)≥40千克/平方米的患者，從該手術(shù)中獲益較少，因?yàn)槎囗?xiàng)隊(duì)列研究表明，與正常體重對(duì)照組相比，病態(tài)肥胖患者導(dǎo)管消融后房顫復(fù)發(fā)率較高。幸運(yùn)的是，通過(guò)積極控制風(fēng)險(xiǎn)因素，包括顯著的體重減輕，可能會(huì)控制房顫基礎(chǔ)。因此，為了改善患者的結(jié)局，臨床醫(yī)生在管理AFs時(shí)應(yīng)強(qiáng)調(diào)控制風(fēng)險(xiǎn)因素，尤其是體重減輕，并為患者提供合適的方法去達(dá)成目標(biāo)。

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

兩項(xiàng)大型前瞻性隊(duì)列研究，DARK-AF(積極的風(fēng)險(xiǎn)因素降低研究：對(duì)心房顫動(dòng)底物的影響)和LEGISE(心房顫動(dòng)隊(duì)列中目標(biāo)導(dǎo)向體重管理的長(zhǎng)期效應(yīng))顯示，在接受導(dǎo)管消融前體重下降大于10%的房顫和肥胖患者中，導(dǎo)管消融結(jié)果有顯著改善。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，通過(guò)減去足夠的體重來(lái)改善房顫結(jié)局的方式，穩(wěn)定性更低。在對(duì)病態(tài)肥胖(平均體重指數(shù)，38±4 kg/m2)和長(zhǎng)期持續(xù)性房顫患者(中位數(shù)，-24.9 kg[四分位數(shù)范圍，-19.1至-56.7]；P<0.001)的單獨(dú)研究中，兩項(xiàng)隊(duì)列研究的結(jié)果沒(méi)有重復(fù)。這表明，心房重塑晚期的病態(tài)肥胖患者通過(guò)改變生活方式和單靠藥物來(lái)實(shí)現(xiàn)的減重量難以充分改變房顫發(fā)病基礎(chǔ)。也有可能，長(zhǎng)期房顫患者不太可能受到體重減輕的影響; 因此，在房顫的發(fā)展史早期進(jìn)行干預(yù)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 減肥手術(shù)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復(fù)發(fā)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 內(nèi)科合并癥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心血管并發(fā)癥. 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

在一項(xiàng)單中心回顧性隊(duì)列研究中，Donnellan等人公布了239名病態(tài)肥胖并接受房顫消融(定義為體重指數(shù)≥40或≥35 kg/m2伴肥胖相關(guān)合并癥)的患者的數(shù)據(jù)。這些患者中，51人在消融前接受過(guò)減肥手術(shù)。在消融后平均36個(gè)月的隨訪中，接受過(guò)減肥手術(shù)的患者中有20%的人發(fā)生了復(fù)發(fā)性心律失常(P<0.0001)，而沒(méi)有接受過(guò)減肥手術(shù)的患者中有61%的人出現(xiàn)了反復(fù)心律失常(P<0.0001)。在減肥手術(shù)組中，消融前體重指數(shù)從47.6±9.3kg/m2降至36.7±7kg/m2。此外，從迄今為止最大的減肥手術(shù)隊(duì)列研究發(fā)現(xiàn)，瑞典肥胖受試者登記中，接受減肥手術(shù)的患者相對(duì)于對(duì)照組 (風(fēng)險(xiǎn)比, 0.71 [95% CI, 0.60–0.83]; P<0.001)房顫發(fā)展風(fēng)險(xiǎn)降低了29%.4兩組間的術(shù)前體重指數(shù)(47.1vs47.7 kg/m2；P=0.76)及合并內(nèi)科并發(fā)癥差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。參加SOS（瑞典肥胖受試者）的受試者主要是中年人，在研究開(kāi)始時(shí)只有3%的人患有心血管疾病。2年后，手術(shù)組的體重變化明顯大于對(duì)照組(23.4%的體重下降，0.1%的體重增加)。關(guān)于手術(shù)風(fēng)險(xiǎn)的擔(dān)憂(yōu)，一項(xiàng)隊(duì)列研究觀察了既往心肌梗死患者減肥手術(shù)后的結(jié)果，發(fā)現(xiàn)心血管并發(fā)癥的風(fēng)險(xiǎn)沒(méi)有增加。與沒(méi)有接受減肥手術(shù)的匹配隊(duì)列相比，接受過(guò)減肥手術(shù)的冠心病史肥胖患者死亡、心肌梗死或中風(fēng)的長(zhǎng)期死亡風(fēng)險(xiǎn)是匹配隊(duì)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控制風(fēng)險(xiǎn)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

總之，肥胖和房顫的患病率持續(xù)上升，并且一種疾病往往會(huì)促進(jìn)另一種疾病的發(fā)生發(fā)展。控制風(fēng)險(xiǎn)因素是房顫治療中必不可少的部分，但適度的減重往往不足以提高房顫導(dǎo)管消融效果的持續(xù)性。與非肥胖房顫患者相比，若沒(méi)有減少足夠的體重，病態(tài)肥胖患者在導(dǎo)管消融效果可能不理想，且更有可能發(fā)展為持續(xù)性房顫，這將更難治療。

We recommend a 2-pronged approach雙管齊下, 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 轉(zhuǎn)診bariatric surgery may be the only way. Further research studies, including randomized control trials that compare bariatric surgery as first-line therapy一線治療 in this population, would certainly be of great benefit.

06

我們建議采取雙管齊下的方法，首先將病態(tài)肥胖和有癥狀的房顫患者接收進(jìn)入減肥診所，提供嚴(yán)格的飲食和運(yùn)動(dòng)咨詢(xún)，對(duì)于改變生活方式仍不能使總體重減少至少20%的患者，應(yīng)盡早進(jìn)行減肥手術(shù)(圖)。病態(tài)肥胖患者減重，尤難實(shí)現(xiàn)。接受藥物治療的患者體重只會(huì)略有增加，而預(yù)計(jì)通過(guò)減肥手術(shù)可以顯著減輕體重(多達(dá)110磅)。僅僅承認(rèn)肥胖與房顫導(dǎo)管消融的不良結(jié)果之間的聯(lián)系難以令人滿(mǎn)意。我們必須提出一種現(xiàn)實(shí)的方法來(lái)改變最常見(jiàn)心律失常的自然進(jìn)程。對(duì)于有嚴(yán)重臨床癥狀的房顫和病態(tài)肥胖的患者，早期轉(zhuǎn)診進(jìn)行減肥手術(shù)可能是唯一的方法。若進(jìn)一步研究，包括將減肥手術(shù)作為這類(lèi)人群的一線治療方法的隨機(jī)對(duì)照試驗(yàn)，肯定會(huì)大有裨益。

Figure. 提出了治療流程

AF：房顫

ARREST：積極危險(xiǎn)因素減少研究對(duì)房顫發(fā)病基礎(chǔ)的影響

BMI：體重指數(shù)

LEGACY：目標(biāo)導(dǎo)向體重管理在房顫隊(duì)列中的長(zhǎng)期效果

【學(xué)習(xí)筆記】

atrial fibrillation (AF) 房顫

 the prevalence of AF房顫發(fā)病率 

is projected to 預(yù)計(jì)

metabolic syndrome代謝綜合征

 waist circumference腰圍

triglycerides甘油三酯

lipoprotein cholesterol

脂蛋白膽固醇

fasting glucose空腹血糖 

obesity-associated comorbidities 

肥胖相關(guān)合并癥 

obstructive sleep apnea

阻塞性呼吸睡眠暫停

Catheter ablation導(dǎo)管消融 

indication適應(yīng)癥 

drug-refractory藥物難治性

morbid obesity病態(tài)肥胖 

 the substrate for AF

 房顫發(fā)病基礎(chǔ)

advanced atrial remodeling

晚期心房重塑

bariatric surgery 減肥手術(shù)

 recurrent arrhythmia

復(fù)發(fā)性心律失常 

 medical comorbidities 

內(nèi)科合并癥

 cardiovascular disease 

心血管疾病

 previous myocardial infarction

心梗史 

cardiovascular complications

心血管并發(fā)癥

previous coronary artery disease冠心病史

 risk factor modification

控制風(fēng)險(xiǎn)因素

referral to 轉(zhuǎn)診

 first-line therapy一線治療 

END

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