Edited by: Sergio Conti, ARNAS Ospedali Civico Di Cristina Benfratelli, Italy
Reviewed by: Deyong Long, Capital Medical University, China; Giovanni Perego, Italian Auxological Institute (IRCCS), Italy
†These authors have contributed equally to this work and share first authorship
‡Senior author
This article was submitted to Cardiac Rhythmology, a section of the journal Frontiers in Cardiovascular Medicine
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The aim of this study was to evaluate the shape of the dose-response relationship between body mass index (BMI) and atrial fibrillation (AF) recurrence in patients who have undergone radiofrequency ablation.
Studies investigating BMI and AF recurrence in patients with AF after ablation were identified through electronic searches in the PubMed, EMBASE, and Cochrane Library databases. The potential non-linear relationship was fitted using robust error meta-regression. Our study was registered with PROSPERO (CRD42019121373).
Twenty-six cohort studies with 7,878 cases/26,450 individuals were included, and a linear dose-response relationship between BMI and AF recurrence (
This study showed that there is a borderline positive linear association between BMI and AF recurrence post ablation. Overweight and obesity are significantly associated with AF recurrence.
Obesity is a rapidly growing global public health concern (
Body mass index, an important predictor of the incidence of AF in the general population, has also been linked to increased AF recurrence after ablation (
The protocol of this study was registered with PROSPERO (International prospective register of systematic reviews) (
We performed this meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (
Two authors (FL and XL) independently systematically searched the Cochrane Library, PubMed, and Embase databases for eligible studies until October 5, 2021. Three groups of keywords (linked to BMI, AF, radiofrequency ablation, respectively) were combined using the Boolean operator “and.” In addition, we searched the reference lists of three previous published meta-analyses (
According to the PICOS (population, intervention, comparison, outcome, and study design), the selection criteria were as follows: (i) population: patients with AF undergoing radiofrequency ablation; (ii) and exposure and comparison: high vs. low BMI level; (iii) outcomes: reported the association between of BMI on AF recurrence. No blank period was pre-defined: (iv) study design: cohort, nested case-control, or clinical trials. For multiple publications/reports created from the same data, the studies with the longest follow-up period or the largest number of AF cases were included. We only included studies with multivariate analysis. Case-control and univariate analysis studies were excluded considering their larger bias. Certain publication types (e.g., reviews, editorials, and animal studies), or studies with insufficient data were excluded from this study. The details reasons of excluded studies were listed in
Basic information of each study, including the authors, publication year, region, study design, participants (sex, age), follow-up time, adjustments for confounders, categories of BMI and adjusted risk ratios (RRs) with its 95% confidence intervals (CIs) for each BMI category were extracted. If multi-adjusted RRs were reported in one study, we extracted the most completely adjusted one.
The quality of all included observational studies were assessed by using Newcastle-Ottawa quality assessment scale (NOS) (
Summary RRs and 95% CIs for a 5-unit increment in BMI were using a random effects model. Study-specific slopes (linear trends) and 95% CIs from the natural logs of the reported RRs and CIs across categories of BMI were calculated by using the method of Greenland and Longnecker (
As shown in
Flow diagram of study selection for the dose-response meta-analysis of body mass index and atrial fibrillation recurrence in patients undergoing radiofrequency ablation.
Basic characteristics of the included studies in the dose-response meta-analysis of BMI and AF recurrence in patients post ablation.
References, country | Source of participants | AF cases, sample size | Mean age (years), male | Follow-up (month), blank period | Study design, AF detection | AF type | BMI data reported (kg/m2) | Adjustment for confounders | Ablation strategy | |
Jongnarangsin et al. ( |
University of Michigan | 127/324 | 57, 76% | 12, 8 weeks | PC, ECG | 72% | 28% | <25 |
Age, gender, type and duration of AF, left atrial size, and LVEF | CPVI |
Chang et al. ( |
National Yang-Ming University School of Medicine | 84/282 | 52, 76% | 12, 2 months | PC, ECG | 76.6% | 23.4% | Continuous | HTN, diabetes, fasting glucose, triglycerides, high-density lipoprotein cholesterol, Mets score | CPVI |
Letsas et al. ( |
NA | 28/72 | 55, 81% | 13, 1 month | PC, ECG | 64% | 36% | Continuous | Use of statins, ACEIs/ARBs, spironolactone, WBC count, C-reactive protein | CPVI |
Tang et al. ( |
Beijing An Zhen Hospital | 242/654 | 57, 71% | 16, 3 months | RC, ECG | 79.8% | 20.2% | <25 |
AF duration, AF type, LAD, left ventricular end-diastolic diameter and ablative strategy | CVPI |
Chilukuri et al. ( |
Johns Hopkins Hospital | 34/109 | 60, 78% | 11, 3 months | PC, ECG | 67% | 33% | <25.0 |
Age, persistent AF, OSA, female, left atrial size, LVEF | SPVI |
Patel et al. ( |
Medical Center, Cleveland | 781/3265 | 56, 84% | 12, 8 weeks | RC, ECG | 53.3% | 46.7% | <30 |
Age, type of AF, echo parameters, type II DM, HTN, CAD | PVAI |
Kang et al. ( |
Korea University Anam Hospital | 32/94 | 59, 81% | 9, 3 months | PC, ECG | NA | NA | Continuous | AF duration, DM, and required cardioversion during ablation | CPVI |
Cai et al. ( |
Hospital of Chongqing Medical University | 47/186 | 55, 66% | 24, 3 months | PC, ECG | 85.6% | 13.4% | <25 |
MetS, AF type, duration of AF history, LAD, DM, ablation strategies, procedural failure, and ERAF. | SPVI or CPVA |
He et al. ( |
Beijing Anzhen Hospital | 106/330 | 59, 68% | 12, 3 months | RC, ECG | 100% | 0% | Continuous | Gender, HTN, Hs-CRP, serum triglyceride, LAD, and eGFR | CPVI |
Sotomi et al. ( |
Sakurabashi-Watanabe Hospital | 40/392 | 62, 76% | 32, 3 months | RC, ECG | 71.2% | 28.8% | <25 |
HTN, persistent AF, high CRP | CVPI |
Baek et al. ( |
Yonsei AF ablation cohort in Japan | 523/1,825 | 58, 74% | 42, 3 months | PC, ECG | NA | NA | <25 |
Age, sex, persistent AF, dyslipidemia, and HTN | CPVI |
Bunch et al. ( |
LDS Hospital or Intermountain Medical Center | 1,067/1,558 | 65, 61% | 36, 3-month | RC, ECG | 56.9% | 43.1% | 21–25 |
Age, sex, HTN, hyperlipidemia, DM, HF, renal failure, OSA, prior cardioversion, CHADS2 | PVI |
Winkle et al. ( |
Sequoia Hospital | 678/2,715 | 64, 70% | 12, 3-month | PC, ECG | 32.7% | 54.9% | <35 |
Age, LAD, sex, AF type, previous cardioversion, number of AADs failed, OSA, previous CVA/TIA, diabetes, CAD, AF duration | CPVI |
Sivasambu et al. ( |
Johns Hopkins Hospital | 354/701 | 59, 72% | 12, 3-month | RC, ECG | 59.1% | 40.9% | 18.5–25 |
HTN, OSA, CHA2DS2-VASC score, and persistent AF | PVI |
Glover et al. ( |
Cardiology of Queen’s University | 636/3,333 | 58, 68% | 20, 3 month | PC, ECG | 67.2% | 27.8% | <25 |
AAD after procedure, achievement of exit and entrance block, first or redo procedure, HTN, CHA2D2S-VAS, OSA, type of AF | CPVI or SPVI |
Providencia et al. ( |
7 European centers | 916/2497 | 61, 72% | 12, 3-month | PC, ECG | 57.6% | 32.8% | Continuous | Age, female, AF duration, AF type, mean of procedures time, CHA2DAS2-VASC, CHF, HTN, DM, stroke, TIA, vascular disease, OSA, eGFR, LAD, LVEF, procedure duration, additional LA line, AAD, fluoroscopy duration, cavotricuspid isthmus ablation | PVI |
Trines et al. ( |
ESC-EHRA-AFA LT registry | 1008/3069 | 59, 68% | 12, 3 months | PC, mixed | 68.3% | 27% | Continuous | HTN | CPVI |
Baek et al. ( |
Inha University College of Medicine and Inha University Hospital | 416/2221 | 55, 79% | 54, 3 months | RC, ECG | 59% | NA | <25 |
Age, sex, non-paroxysmal AF, HF, HTN, DM, LAD, AF duration, and MR LGE ≥ 25% | CPVI |
Bose et al. ( |
NA | 19/103 | 60, 29% | 12, NA | RC, ECG | 100% | 0 | <25 |
Age, sex, CAD, CHD, HTN, DM, dyslipidemia, valvular heart diseases, beta blocker, CCB, AAD | CPVI |
Deng et al. ( |
Guangdong General Hospital | 365/1,410 | 57, 68% | 21, 3 months | PC, ECG | NA | NA | 18.5–25 |
Age, gender, bundle branch block, AF duration, COPD, alcohol consumption, smoking, HTN, DM, stroke/TIA, CAD, LVEF, vascular disease, early recurrence, LAD, and AF type | CPVI |
De Maat et al. ( |
University Medical Center Groningen | 146/414 | 56, 76% | 46, 3-month | RC, ECG | 75% | 25% | Continuous | Age, sex, OSA, AAD, LAD, AF duration, AF type, CHD, total cholesterol, number of PVI procedures HTN, DM, vascular disease, and stroke | CPVI |
Donnellan et al. ( |
Cleveland Clinic | 87/267 | 65, 69% | 12, 3 months | RC, ECG | NA | NA | <31.7 |
OSA, AF type, and LA size, OSA, HF | CPVI |
Kong et al. ( |
University of Chicago | 217 | 64, 68.2% | 12, NA | RC, ECG | Na | Na | <30 |
Age, gender, smoking, HTN, DM, HF, eGFR, and type of AF | PVI |
Calero Nunez et al. ( |
Albacete University Hospital | 34/114 | 54, 70% | 12, NA | RC, ECG | 70.2% | 29.8% | Continuous | Type of AF, OSA, LA size, ejection fraction, and HTN | CPVI |
Abou El Khair ( |
Region Värmland and Örebro | 19/90 | 63, 73% | 12, 3 months | RC, ECG | NA | NA | Continuous | Age, sex, CHA2DS2-VASc score, DM, HF, HTN, LVEDd, and right atrial area. | CPVI |
Mugnai et al. ( |
Electrophysiology centre of Brussels | 89/208 | 59, 66% | 62, 3 months | RC, ECG | 100% | 0 | Continuous | Duration of symptoms, LAD | Index PV isolation |
RC, retrospective cohort; PC, prospective cohort; ECG, electrocardiograph; NA, not available; PVI, pulmonary vein isolation; CPVI, circumferential pulmonary vein isolation; SPVI, segmental pulmonary vein isolation; CPVA, circumferential pulmonary vein ablation; LAD, left atrial diameter; MetS, metabolic syndrome; ERAF, early recurrence of AF after ablation; OSA, obstructive sleep apnea; WBC, white blood cell; CRP, C-reactive protein; CAD, coronary artery disease; AAD, antiarrhythmic drugs; CHRD, centre for heart rhythm disorders; LVEF, left ventricular ejection fraction; eGFR, estimated glomerular filtration rate; ACEIs/ARBs, ACE inhibitors/ARB inhibitors; SHD, structural heart disease; CHF, congestive HF; CVA, cerebrovascular accident; TIA, transient ischemic attack; AF, atrial fibrillation; BMI, body mass index; Par, paroxysmal; HTN, hypertension; COPD, chronic obstructive pulmonary disease; USA, United States of America; MR LGE, late gadolinium enhancement on cardiac magnetic resonance.
The quality of the articles was acceptable, with a majority (
Twenty-six (
Body mass index and atrial fibrillation recurrence in patients undergoing radiofrequency ablation based on a dose-response analysis, per 5 units.
Body mass index and atrial fibrillation recurrence in patients undergoing radiofrequency ablation based on a non-linear dose-response analysis. The solid and dashed lines represent the estimated relative risk and the 95% confidence interval, respectively.
There may be a stronger association between BMI and AF recurrence among groups with larger AF recurrence cases (
Subgroup analysis of BMI and AF recurrence in patients after catheter ablation, dose-response analysis, per 5 unit increase.
Items | Number of studies | RR | 95% CI | ||||
Within subgroup | Between subgroup | ||||||
0.002 | |||||||
Age |
≤60 | 13 | 1.10 | 1.03, 1.17 | 38% | 0.005 | 0.19 |
>60 | 7 | 1.20 | 1.08, 1.33 | 60% | 0.003 | ||
Study design | Retrospective cohort | 10 | 1.11 | 1.02, 1.21 | 39 | 0.001 | 0.12 |
Prospective cohort | 11 | 1.25 | 1.11, 1.39 | 68 | 0.001 | ||
Region | Northern America | 8 | 1.08 | 1.03, 1.12 | 0% | 0.0003 | 0.06 |
Europe | 6 | 1.18 | 1.06, 1.33 | 46% | 0.004 | ||
Asia | 7 | 1.30 | 1.08, 1.56 | 65% | 0.006 | ||
NOS scores | <7 scores | 2 | 1.16 | 1.00, 1.36 | 26% | 0.06 | 0.76 |
7 or high scores | 19 | 1.13 | 1.07, 1.20 | 51% | <0.001 | ||
Publication years | 2008–2013 | 9 | 1.13 | 1.07, 1.19 | 43% | <0.001 | 0.28 |
2014–2021 | 12 | 1.28 | 1.03, 1.60 | 65% | 0.03 | ||
Sample size | ≤1,000 | 14 | 1.24 | 1.08, 1.43 | 57% | 0.003 | 0.11 |
>1,000 | 7 | 1.10 | 1.05, 1.15 | 22% | 0.0001 | ||
Cases | ≤100 | 9 | 1.70 | 1.26, 2.31 | 54% | 0.006 | 0.006 |
>100 | 12 | 1.10 | 1.05, 1.14 | 26% | 0.001 | ||
Adjusted factors | Age (+) | 11 | 1.21 | 1.04, 1.21 | 57% | 0.003 | 0.26 |
Age (−) | 10 | 1.23 | 1.07, 1.42 | 60% | 0.004 | ||
Sex (+) | 13 | 1.19 | 1.09, 1.31 | 59% | <0.001 | 0.90 | |
Sex (−) | 8 | 1.21 | 1.05, 1.40 | 63% | 0.01 | ||
DM (+) | 11 | 1.29 | 1.14, 1.47 | 76% | <0.001 | 0.02 | |
DM (−) | 10 | 1.09 | 1.02, 1.17 | 11% | 0.001 | ||
left atrial size (+) | 9 | 1.16 | 1.04, 1.30 | 64% | 0.004 | 0.86 | |
left atrial size (−) | 12 | 1.15 | 1.06, 1.23 | 45% | 0.04 | ||
Hypertension (+) | 15 | 1.14 | 1.08, 1.20 | 30% | <0.001 | 0.37 | |
Hypertension (−) | 6 | 1.26 | 1.02, 1.57 | 73% | 0.03 | ||
AF categories (+) | 10 | 1.11 | 1.04, 1.18 | 42% | 0.08 | 0.07 | |
AF categories (−) | 11 | 1.29 | 1.11, 1.51 | 62% | 0.001 | ||
Obstructive sleep apnea (+) | 7 | 1.11 | 1.05, 1.17 | 36% | <0.001 | 0.23 | |
Obstructive sleep apnea (−) | 14 | 1.20 | 1.07, 1.36 | 60% | 0.003 |
AF, atrial fibrillation; BMI, body mass index; DM, diabetes mellitus. *The mean age of Khair et al. was not available. Bolded values are meant to be the total results of all studies before subgroup analysis.
In the sensitivity analysis, the pooled results were stable when omitting one study at a time, with an RR range from 1.13 (95% CI: 1.07–1.20,
Based on available cohort studies, we showed a borderline positive linear dose-response relationship between baseline BMI and AF recurrence in patients after ablation. We found a 15% increase in AF recurrence per 5-unit increase in BMI. These results were confirmed in all subgroups stratified by age, sex, study design, region, follow-up duration, sample size, and adjustment. Overall, our results showed that overweigh (BMI > 28 kg/m2) or obesity was independently positively associated with AF recurrence after ablation.
Several well-known risk factors, including age, hypertension, diabetes, and enlarged LAD, have been linked to the recurrence of AF after ablation. Moreover, these comorbidities were common in patients with obesity. Therefore, whether the role of obesity is independent of these comorbidities is still unclear. For example, Jongnarangsin et al. showed that obesity was not associated AF recurrence post AF ablation after adjustments (
Although we found a linear association between BMI and AF (
In the context of AF ablation, obesity was not a new topic. Several reviews have shown that obesity increases the risk of AF relapse after ablation. Three showed that the obese group had a significantly increased risk of AF recurrence (
Several potential mechanisms could explain this association. First, obesity could result in many changes involving various domains, such as hemodynamics, neurohumoral factors, inflammatory factors, metabolic factors, adipokines, and autonomics. For example, obesity leads to a high cardiac output state and the presence of left ventricular hypertrophy (eccentric or concentric) in association with left ventricular diastolic dysfunction (
Some authors proposed that obesity was a phenotypic marker of OSA that is associated with AF recurrence. Obesity is an important risk factor for the incidence of OSA (
The association between underweight and AF relapse is still inconclusive. Based on a retrospective cohort study in China, Deng et al. showed that underweight (BMI < 18.5 kg/m2) significantly increased the risk of AF recurrence (HR 1.85,
In addition, although BMI is widely adopted because it is convenient to apply and inexpensive, BMI is not perfect as a measure of obesity. Because BMI is an indirect measure of obesity, it cannot distinguish between fat and lean tissue and can produce a certain amount of error (
As shown in our results, the likelihood of AF recurrence after ablation increasing with BMI. In patients with grade II obesity (BMI > 35 kg/m2), the risk of AF recurrence increased by 95%. Our findings provide valuable insight for the clinical prevention of AF recurrence after ablation. For patients with severe obesity (BMI > 35 kg/m2), cardiologists should consider that their likelihood of AF relapse is much higher than that of individuals with a normal BMI. Therefore, for those patients strongly considering AF ablation, the risks and benefits should be carefully evaluated.
Weight loss is associated with improvements in risk factors (e.g., hypertension, OSA, and glycemic control), decreased morbidity and mortality, and a decreased risk of AF. Evidence from observational studies, such as the Long-Term Effect of Goal-Directed Weight Management in an Atrial Fibrillation (LEGACY) study, showed that long-term weight loss (bariatric surgery or weight management) could reduce AF risk and burden in people with AF (
The strengths and limitations of this study merit careful consideration. This is the first dose-response meta-analysis that demonstrated a positive linear association between BMI and AF recurrence after ablation with a large sample size and robustness of the findings based on multiple subgroups (e.g., age, sex, duration of follow-up and adjustment for confounding and potential intermediate factors). However, it was limited by the inclusion of observational studies, which cannot definitively prove causation. Although most studies were adjusted for other comorbidities, it is impossible to fully take into account all confounding factors. For example, the dose of antiarrhythmic medication may differ between studies, and studies have shown that LA volume is more accurate than diameter. Second, several studies have shown that underweight and AF patients have worse outcomes (
This study demonstrated a positive independent association between BMI and AF recurrence among patients undergoing ablation, and overweight and obesity were found to be significantly associated with AF recurrence. Further well-designed, prospective studies are required to determine the effect of weight loss on AF recurrence post ablation.
The original contributions presented in this study are included in this article/
JL was responsible for the entire project and revised the draft. FL, TS, and XL performed the systematic literature review and drafted the first version of the manuscript. All authors participated in the interpretation of the results and prepared the final version of the manuscript.
This work was supported by the National Natural Science Foundation of China (Nos. 81760050, 81760048, 82100347, and 8210020907), the Jiangxi Provincial Natural Science Foundation for Youth Scientific Research (No. 20192ACBL21037), and China Postdoctoral Science Foundation (No. 2021M703724).
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
The Supplementary Material for this article can be found online at:
AF, atrial fibrillation; RR, relative risk; BMI, body mass index; ablation, radiofrequency ablation; LAD, left atrial diameter.