Impact of body mass index on procedural complications, procedure duration, and radiation dose in patients with atrial fibrillation undergoing radiofrequency ablation: A systematic review and meta‐analysis

Abstract Background The association of body mass index (BMI) and procedure‐related factors in patients with atrial fibrillation (AF) after radiofrequency ablation (RFA) is still unclear. Hypothesis BMI is associated with increased the radiation dose, procedure duration, and procedural complications. Methods Prospective studies assessing BMI and procedure duration, radiation dose, and procedural complications in patients with AF after RFA were identified through electronic searches of PubMed, Embase, and the Cochrane Library database. Results Ten studies with 14 735 participants undergoing RFA were included. Procedure duration was significantly longer in patients with overweight or obesity than in patients with normal BMI, with a mean difference (MD) of 0.95. Patients with overweight and obesity were exposed to a larger radiation dose, with standard MD of 1.71 and 1.98, respectively. There was no significant association between overweight or obesity and the risk of procedural complications (RR of 0.91 for overweight, 1.01 for obesity, 0.89 for stage I obesity, 1.00 for stage II obesity, and 0.94 for stage III obesity). Further analysis showed there was no significant difference regarding stroke or transient ischemic attack (overweight, RR: 0.92; obesity, RR: 1.02); cardiac tamponade (overweight, RR: 0.92; obesity, RR: 1.02); groin hematoma (overweight, RR: 0.62; obesity, RR: 0.40); or pulmonary vein stenosis (overweight, RR: 0.49; obesity, RR: 0.40) among BMI groups. Conclusion Based on available evidence, we first showed that patients with overweight/obesity undergoing RFA experienced a significantly increased procedure duration and received a larger radiation dose than patients with normal BMI; however, there was no significant difference in procedural complications between patients with overweight/obesity and patients with normal BMI.

however, there was no significant difference in procedural complications between patients with overweight/obesity and patients with normal BMI.

K E Y W O R D S
atrial fibrillation, body mass index, complications, meta-analysis, obesity, radiofrequency Overweight/obesity is considered a risk factor for hypertension, stroke, coronary artery disease, and diabetes mellitus and poses a major challenge to the prevention of chronic diseases throughout the world. [1][2][3] Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice and is associated with an increased risk of stroke and all-cause mortality. Obesity has been reported as an independent risk factor for new-onset AF, being associated with a 20% higher risk of AF than normal weight. 4 However, a number of clinical studies and meta-analyses found that compared with patients with normal weight, patients with overweight or obesity did not have worse or even better outcomes among patients with AF, known as the "obesity paradox." [5][6][7] This phenomenon was also found in patients with obesity and other diseases; for example, in studies examining the rate of complications in patients undergoing percutaneous coronary intervention, the rate of complications was paradoxically found to decrease in patients with mild/moderate obesity. 8,9 In recent decades, radiofrequency ablation (RFA) of AF has emerged as an effective therapy and now has a Class I indication in symptomatic patients with drug-refractory AF. 10 However, the impact of obesity on procedural complications in patients undergoing RFA is inconsistent. [11][12][13] Previous evidence demonstrated that the amount of radiation exposure for obese patients was more than twice that for patients with a normal BMI, 14 which might result in a higher rate of complications for patients with obesity. Subsequently, a prospective study reported that the odds ratio of complications increased 3.1-fold in those with morbid obesity. 12 This association was confirmed by another observational cohort study of 3265 females. 11 However, several cohort studies found no clear association. 11,15,16  BMI, AF, and catheter ablation) were combined using the Boolean operator "AND." The first group of key words was linked to body mass ("body mass index" (BMI) OR "body weight" OR "obesity" OR "overweight" OR "central obesity"). The second group was linked to the type of diagnosis ("AF" OR "atrial flutter" OR "atrial tachycardia" OR "supraventricular tachycardia"). The third group of key words was linked to outcomes ("procedure time" OR "radiation" OR "complication" OR "pericardial effusion/tamponade" OR "stroke or transient ischemic attack" OR "groin hematoma" OR "pulmonary vein stenosis." The last group of key words was linked to the intervention ("catheter ablation" OR "RFAs"). No language restrictions were applied to the literature search. The detailed search strategy is provided in Table S2 in Supplemental Material S1. In addition, this study has been registered with PROSPERO (International prospective register of systematic reviews)registration number-CRD42019121373.

| Outcome definitions and study selection
The primary endpoints were the procedure duration, the amount of radiation and procedure complications in patients with AF undergoing RFA. Secondary endpoints were major complications, including stroke or transient ischemic attack, pulmonary vein stenosis, cardiac tamponade, and groin hematoma. Studies were considered eligible if they (a) were designed as prospective epidemiological studies (cohort, nested case-control, or clinical trial); (b) provided data on the assessment of at least one of the primary endpoints; and (c) for multiple publications/reports created from the same data, contained the longest follow-up period or the largest number of cases. Certain publication types (eg, reviews, editorials, letters, conference abstracts, and animal studies) or studies with insufficient data were excluded from this study.

| Data extraction and quality assessment
Two researchers independently assessed the eligibility of the literature according to the aforementioned inclusion criteria. All discrepancies were resolved through discussion or by a third researcher, as necessary. Two authors independently extracted the basic characteristics from each study, mainly including the first author, publication year, geographical location, study type, participants (sex, age, and sample size), duration of follow-up, adjustments for confounders, categories of BMI and the number of cases and sample size for each BMI category.
The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of all included studies. 18 The validated NOS items with a total of nine stars involved three aspects, including the selection of cohorts, the comparability of cohorts, and the assessment of the outcome. In this meta-analysis, an NOS score of ≥6 stars indicated a moderate-to high-quality study; otherwise, the scores indicated a low-quality study. 19,20

| Statistical analyses
We expressed dichotomous outcome data as risk ratios (RRs) with 95% confidence intervals (CIs) and continuous outcome data as weighted mean differences (MDs) or standardized MDs with 95%

CIs. BMI was a categorical variable according to the standard World
Health Organization definition, in which "normal weight" was defined as a BMI of 18.5 to <25, underweight was defined as a BMI of <18.5, overweight was defined as a BMI of 25 to <30, obese was defined as a BMI of ≥30, grade 1 obesity was defined as a BMI of 30 to <35, grade 2 obesity was defined as a BMI of 35 to <40, and grade 3 obesity was defined as a BMI of ≥40. Count data for complications were used to generate unadjusted RRs and 95% CIs for different BMI groups. Given the heterogeneity in study designs and populations, the meta-analysis was performed using a randomeffects model. To examine the influence of individual studies on the pooled results, a sensitivity analysis was performed by removing each study. To assess the heterogeneity across studies, the I 2 (95% CI) statistic was calculated with the following interpretation: low heterogeneity, defined as I 2 < 50%; moderate heterogeneity, defined as I 2 = 50% to 75%; and high heterogeneity, defined as I 2 > 75%. 21 Possible publication bias was assessed using Egger's test. 22     The reporting quality of the included articles was high. All included studies obtained an NOS of ≥6 points (Table S4 in Supplemental Material S1).

| Relationship between BMI and the duration of the procedure and amount of radiation
Six studies 13,15,23-26 that were included in this analysis reported the procedure duration. The procedure duration was significantly longer in patients with overweight or obesity, with an MD of 0.95 (95% CI: 1.69-0.21) (Figure 1). There was no evidence of heterogeneity in the overweight (I 2 = 0, P = .69) groups and moderate heterogeneity in the obese (I 2 = 68%, P = .004) groups. However, the heterogeneity was not significant when Sivasambu et al was excluded (I 2 = 43%, P = .15), with a significant difference persisting between the obese and normal groups.
Four studies 14,15,23,25 reported the radiation dose, with two studies using the unit of G and another two using the unit of uG × m 2 .
Because a different unit was used across trials, the effect of the MD was used to summarize the results. 28 We found that patients with overweight and obesity had a larger radiation dose than patients with normal BMI, with an SMD of 1.71 (95% CI: 0.71-2.71) and 1.98 (95% CI: 0.88-3.29), respectively ( Figure 2). There was significant heterogeneity in the overnight (I 2 = 98%, P < .05) and obese (I 2 = 97%, P < .05) groups.
Overall, neither overweight nor obesity increased the risk of procedural complications (RR of 0.91 for overweight, 1.01 for obesity, 0.89 for stage I obesity, 1.00 for stage II obesity, and 0.94 for stage III obesity), with no evidence of heterogeneity (I 2 = 0) ( Figure 3). In addition, compared with the nonobese group, the obesity group also did not experience an increased rate of procedural complications (Figure 3).

| Sensitivity analysis and publication bias
In the sensitivity analysis, the pooled results were not significantly changed when omitting one study at a time. Publication bias was not  It is known that morbid obesity significantly increases mortality in the general population. 33 In addition, morbid obesity also significantly increased the rate of complications in patients undergoing PCI. 8 Although we did not observe an increased rate of procedural compli-

| Study limitations
Our meta-analysis has some limitations that need to be mentioned.
First, all of the included studies were observational. The inability to access individual patient data necessitated the use of a univariate meta-analysis. A causal relationship between BMI and procedural complications could not be established due to confounding by other risk factors that may have influenced the results. 34 For example, a previous study showed that in females, obesity increased the risk of procedural complications by 13%. 11 Moreover, in another prospective cohort, Shoemaker et al 12 found that female sex was a significant predictor of complications after adjusting for age and coronary artery disease. Second, there is significant heterogeneity between studies, which might be derived from the difference in baseline (eg, follow-up duration, ablation strategy) characteristics of the patients. Third, we included only 10 studies that met our inclusion criteria. A small number of included studies may affect the reliability of the conclusions.
Fourth, the experience of surgeon across the centers was varied and that is very important for the study outcomes, which also might influence our results.

T A B L E 2
The association between BMI and the risk of major complications Abbreviations: BMI, body mass index; CI, confidence interval; RR, risk ratio.

| CONCLUSION
Based on available evidence, we first showed that patients with overweight/obesity undergoing RFA experienced a significantly increased procedure duration and radiation dose; however, there was no significant difference in procedural complications between patients with overweight/obesity and patients with normal BMI. Further studies are required to determine the effect of morbidity obesity or weight reduction on the outcomes in patients with AF after RFA.