INTRODUCTION
Obstructive sleep apnea (OSA) is a chronic and multifactorial disease characterized by increased pharyngeal airway resistance during sleep with subsequent repetitive collapse of the upper airway [1]. OSA is associated with decreased quality of life [2] and is a risk factor for cardiovascular disease [3], diabetes [4], stroke [5], premature death [6], and reduced cognitive function [7].
Obesity is the most prevalent risk factor for OSA, with a prevalence of more than 40% in patients with a body mass index (BMI) ≥30 kg/m2 [1]. Therefore, weight loss is the cornerstone of treatment for patients with obesity-associated OSA [8]. There is evidence that bariatric surgery is effective for improvement of OSA with a reported 65% reduction in apnea-hypopnea index (AHI) in patients with a BMI >40 kg/m2 [9]. However, evidence related to the effects of weight loss on OSA in less obese patients, but in whom the prevalence of OSA could be as high as 70%, is limited [8].
Recently, endoscopic endoluminal approaches to address Class I and II obese patients (BMI ranging from 30 to 39.9 kg/m2) have become a topic of interest. Endoscopic sleeve gastroplasty (ESG) is a novel, safe, and less invasive restrictive endoluminal approach for patients with a BMI of 28 to 34.9 kg/m2 [10]. ESG is an incisionless procedure done by endoscopy (instead of coelioscopy) where a suturing device is inserted through the mouth to reduce the size of the stomach. Sutures are placed in the gastric body (anterior to posterior wall) to reduce the size of the stomach and induce a gastroparesis. As sleeve gastrectomy, the reduction of the size of the stomach induces early satiety limiting oral intakes and metabolic changes that induce weight loss [11]. The advantages of this technique are short time procedure (around 1 hour) with fast recovery (day clinic) and patients can go back to work after a few days (one to five) [11]. Efficiency of ESG is less than sleeve gastrectomy (16% total body weight loss [TBWL] in meta-analysis vs. 25% TBWL for sleeve gastrectomy) but morbidity is also less (around 2% for ESG vs. 5% for sleeve gastrectomy) [12]. Moreover, adverse events related to ESG are anecdotal (gastrointestinal discomfort) [10] while those related to bariatric surgery can be lifethreatening [13]. Based on a risk/benefit approach (balance between acceptability of complications and efficiency of treatment), recent guidelines proposed that the more invasive techniques (bariatric surgery) were reserved for patients with a high risk of obesity related comorbidities (BMI >40 kg/m2 or ≥35 kg/m2 with comorbidities) [14] while patients with a BMI ranging from 28 to 34.9 kg/m2 with comorbidities or 35 to 39.9 kg/m2 without comorbidities are candidate for endoscopic bariatric and metabolic therapies as first line of treatment [11].
A meta-analysis that evaluated the effects of ESG on obesity-related comorbidities reported an overall reduction of 50% in AHI after ESG [15]. However, the included studies were performed in patients with a BMI >35 kg/m2 and without any sleep analyses [16-19].
This study aimed to evaluate the efficacy of ESG via endoluminal gastric plication using an endoluminal-suturing device to improve severe OSA in patients with BMI values ranging from 28 to 34.9 kg/m2.
METHODS
This prospective, monocentric study was performed between November 2021 and February 2023. The protocol was approved by the Research Ethics Committee of Erasme Hospital in Brussels, Belgium (SRB2020/274). All enrolled patients provided written informed consent before the procedure. This study is registered in ClinicalTrials.gov (NCT04979234).
Study Group
Patients were recruited through a multidisciplinary platform with all physicians involved in the treatment of obesity including gastroenterologists, abdominal surgeons, endocrinologist, pneumologists, dieticians, physiotherapists, and psychologists. In this multidisciplinary platform, every patient who had a complete bariatric workup are discussed in a multidisciplinary meeting to select the best therapy according to published guidelines and patient’s will. In our study, every class I obese patient with a BMI between 28 and 34.9 kg/m2 underwent a complete multidisciplinary bariatric workup with a baseline polysomnography (PSG). In cases of severe OSA (AHI ≥30/h), patients were assigned to undergo ESG with endomina® (EndoTools Therapeutics S.A., Gosselies, Belgium) plus lifestyle management for 6 months. Complete eligibility criteria for ESG are described in Supplementary Materials (in the online-only Data Supplement).
Patients with a BMI ranging from 28 and 34.9 kg/m2 were selected in our study as it is the recommendations of the recently published guidelines [11] and only few data are available concerning the evolution of OSA after weight loss in this particular population. Moreover, we selected patients with severe OSA as we think that they were more likely to present an improvement of their AHI.
Demographic data, TBWL and percentage excess weight loss (EWL), which is the difference between initial BMI and final BMI divided by the difference between initial BMI and a BMI of 25 kg/m2, were collected at 1, 3, and 6 months after the endoscopic procedure.
Endoluminal Procedure and Postoperative Course
The endomina® is a triangulation platform used with any flexible endoscope and a dedicated needle (TAPES, EndoTools Therapeutics S.A., Gosselies, Belgium) to create gastrointestinal tissue approximations. Sutures were placed in the gastric body, starting from the incisura and going up to the fundo-gastric junction, according to a previously described technique (Fig. 1) [10]. Sutures were placed anterior to posterior (double plications) in a single pattern (i.e., single-layer suturing) to tubulize and reduce the stomach volume (Fig. 1). All procedures were done under general anesthesia with oro-tracheal intubation. Patients were kept overnight per protocol. Patients received antispasmodic and antiemetic drugs for 10 days and a proton pump inhibitor for 3 months. They were on a liquid diet for 3 days after the procedure and then returned to solid food within 10 days. EndoTools Therapeutics provided a research grant including the endomina® platforms, TAPES suturing devices, and technical support upon request.
Dietetic Support
Face-to-face dietetic consultations with a trained dietician were performed throughout the study. A dietary evaluation was performed before the procedure, at 2 weeks and at 1, 3, and 6 months post-procedure. Dietary consultations were free of charge for all patients. Patients were prescribed a low-calorie, high-protein diet and lifestyle counselling [14]. Physical activity was promoted.
Sleep Evaluation
Patients underwent an in-hospital overnight PSG at the sleep center conducted by experienced technicians before and 6 months after the endoscopic procedure. In the case of patients who were already undergoing continuous positive airway pressure (CPAP) treatment, 1 week of CPAP washout was performed before PSG [20]. The patients did not nap on the monitoring day and did not drink tea, coffee, alcohol, or other beverages that would have interfered with their sleep. An experienced technician applied the scalp electrode per international standards [21]. The polysomnographic recordings performed in our unit meet the recommendations of the American Academy of Sleep Medicine [21] and are carried out with a B3IP system with a TC09 headbox (Medatec, Braine-le-chateau, Belgium). The applied PSG montage was as follows: two electro-oculogram channels, three electroencephalogram channels (F4-M1, C4-M1, and O2-M1, where M1 is A1 mastoid reference), one submental electromyogram channel, electrocardiogram, pressure cannula to detect oro-nasal airflow, finger pulse-oximetry, a microphone to record breathing sounds and snoring, plethysmographic inductive belts to measure thoracic and abdominal breathing, and anterior tibialis electrodes. Polysomnographic recordings were scored visually by physicians trained in sleep medicine following the American Academy of Sleep Medicine standards on the Interpretation of Sleep and Related Events [22]. Apnea was defined as a ≥90% drop in nasal and oral airflow from baseline and a continuous event of ≥10 seconds, with or without thoracic and abdominal respiratory movements. Hypopnea was defined as a decline in nasal and oral airflow of ≥30% from the baseline with a continuous event of ≥10 seconds, accompanied by a decrease in oxygen saturation of ≥3% or an event with arousal. The AHI is the combined average number of apneas and hypopneas per hour of sleep. The oxygen desaturation index (ODI) obtained from the PSG was defined as the number of times oxygen saturation decreases by ≥3%/h during sleep. Sleep duration with an oxygen saturation of less than 90% (T90) and arousal index were recorded. The patients filled out the Epworth sleepiness scale (ESS) the day before each PSG.
Objectives
The primary endpoint of the study was the percentage of AHI reduction 6 months after the endoscopic procedure.
Secondary endpoints were as follows: 1) effectiveness on OSA defined as the proportion of patients with AHI reduction of 50% at 6 months after the endoscopic procedure; 2) improvements in respiratory sleep parameters (ODI, T90, snoring, and the arousal index) evaluated by an overnight PSG at 6 months; 3) improvements in sleepiness evaluated by the ESS; and 4) effectiveness on weight loss, defined as the reduction of EWL and TBWL 6 months after the endoscopic procedure, and its correlation with a decrease in AHI.
Statistical Analysis
Data were analyzed using IBM SPSS Statistics for Windows v27 (IBM Corp., Armonk, NY, USA). Descriptive statistics were computed for all study variables. Discrete variables were expressed as count (percentage), and continuous variables as mean ± standard deviation (SD) or median (interquartile range). Paired t-test or Wilcoxon rank test was used for comparisons with baseline data, as appropriate. For EWL and TBWL, the treatment effect was assessed using linear mixed models with time as a repeated factor. The fixed effects estimates are reported as means with 95% confidence intervals (CI). The association between variables was set by estimating their correlation with a Pearson correlation test. All statistical tests were two-tailed, and a p-value <0.05 was considered statistically significant.
RESULTS
The study enrolled ten patients (mean age: 51 ± 11 years). The baseline characteristics and clinical data for these ten patients are summarized in Table 1. Eight out of ten were female. Three patients were active smokers (10 pack-year). Six patients reported drinking alcohol more than two units per day. All patients underwent ESG with endomina® with a technical success rate of 100%. Two of ten patients complained of transient mild epigastric pain and/or dyspeptic symptoms (early satiety, belching) post-procedure that did not require medication and resolved within 4 weeks.
Overall, patients experienced a 54% (±11%) reduction in AHI 6 months after the endoscopic procedure. Seven patients (70%) experienced an AHI reduction ≥50%, and five (50%) had AHI values of <15 events/h at 6 months after ESG. The evolution of respiratory sleep parameters and sleepiness 6 months after ESG are summarized in Table 2. The evolution of the ESS at baseline, 1, 3, and 6 months after ESG is shown in Fig. 2.
There was a significant reduction in BMI at 6 months after ESG (32.3 ± 1.6 kg/m2 vs. 29.1 ± 1.9 kg/m2, p < 0.001). Six months after ESG, TBWL was 10.1% ± 3.4% and EWL was 45.4% ± 14.0%. There was no evidence of a significant correlation between AHI and TBWL or between AHI and EWL 6 months after the endoscopic procedure.
DISCUSSION
This pilot study suggests that weight loss after endoscopic sleeve gastroplasty by endomina®, in combination with routine dietary and lifestyle counseling, induces 1) a reduction in AHI, 2) an improvement in respiratory sleep parameters, and 3) a reduction in daytime sleepiness, 6 months after the endoscopic procedure in patients with BMI values ranging from 28 to 34.9 kg/m2. These results warrant further discussion regarding weight loss, respiratory sleep parameters, and daytime sleepiness.
In terms of weight loss, all indicators were improved after ESG by endomina®, confirming that this treatment is clinically safe and effective. These improvements were in line with those in previously reported studies [10]. Considering the clinical outcome of each patient, one patient (patient 1) did not improve after ESG as she had no substantial decrease in EWL (-23%) or in AHI (+13 events/h). Interestingly, this particular patient did not change her dietary habits after ESG and, therefore, did not reach the goal in terms of weight [23]. This patient must be considered a treatment failure. However, the treatment non-responder rate observed in this study aligns with previously reported data (10% vs. 15%) [10].
With 70% of patients experiencing a reduction in AHI of more than 50%, ESG-induced weight loss is effective for treating OSA in patients with BMI values ranging from 28 to 34.9 kg/m2. These results align with data published following bariatric surgery [24]. Moreover, half of the patients had a post-ESG AHI of less than 15 events, allowing them to stop CPAP treatment. These results are more significant than previously reported studies of the effects of ESG on OSA (50% vs. 18%) [25]. As our patients presented with several predictive factors for persistent OSA after weight loss (preoperative AHI ≥30 events/h and EWL <60%), these results are lower than the evolution of AHI after bariatric surgery (50% vs. 74%) [26]. There was no significant correlation between the change in AHI and weight loss. These findings have already been described after bariatric surgery [27] and could be explained, at least partly, by the presence of metabolic and weight-independent factors that influence sleep [28,29].
There was an overall improvement in respiratory sleep parameters after ESG in our patients, except for snoring. This is probably due to high variability in snoring in our population. These results confirm the impact of ESG on OSA severity. This has already been reported in a study on bariatric surgery [9,30].
Regarding symptoms of daytime sleepiness, there was a progressive improvement from the first month after ESG to 6 months in patients with BMI values ranging from 28 to 34.9 kg/m2. As the ESS score was reduced from 10 to 6 points, our patients significantly improved their sleep quality. Similar results have already been reported in a study on bariatric surgery [9,30].
In this study, we selected less obese patients (BMI ranging from 28 to 34.9 kg/m2) because nearly no data was available concerning the evolution of OSA after weight loss in this particular population. However, these patients remain at high risk of OSA as the prevalence of OSA in patients with a BMI ranging from 28 to 34.9 kg/m2 could be as high as 70% [8]. Moreover, ESG could be efficient, even with a low weight reduction, as a part of the improvement following weight loss depends on metabolic and weight-independent factors [29]. Therefore, the recent guidelines recommend endoscopic bariatric and metabolic therapies as first line of treatment for patients with a BMI ranging from 28 to 34.9 kg/m2 with comorbidities [11]. These recommendations are based on a risk/benefit approach: as these patients are less obese, a loss of 16% of TBWL after ESG should be enough to reduce obesity-related comorbidities with a decreased risk of adverse events [12].
The limitations of this study are inherent to a pilot study without randomization, with a small number of patients included, and with the COVID-19 pandemic occurring during recruitment. However, even with a small population, the results are promising. Larger randomized controlled trials are needed to confirm these preliminary results. Nonetheless, this pilot study provides data that support the further investigation of ESG as an alternative to bariatric surgery to treat obesity-related comorbidities in less obese patients.
The strength of this study is its prospective design, which included two in-hospital overnight PSGs with a CPAP washout and high patient compliance.
In conclusion, weight loss induced by ESG with endomina®, in addition to lifestyle modification in patients with BMI values ranging from 28 to 34.9 kg/m2, achieves a significant reduction in OSA with improved respiratory sleep parameters and daytime sleepiness. As this was a pilot study, further randomized controlled trials should be performed to confirm these results.
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