Author + information
- Nickolas Kipshidze, MD, PhD∗ ( )(, )
- Akaki Archvadze, MD,
- Stefan Bertog, MD,
- Martin B. Leon, MD and
- Horst Sievert, MD
- ↵∗New York Cardiovascular Research, 1726 2nd Avenue, #4S, New York, New York 10128
Obesity is associated with adverse cardiovascular and metabolic conditions. Dietary, medical, or surgical weight loss strategies are frequently unsuccessful and accompanied by risks. Although many appetite-limiting hormones have been discovered, only 1 hormone, ghrelin, has been shown to be orexigenic (appetite stimulating) (1). Ghrelin-producing cells are located in the fundus of the stomach; through ghrelin secretion, these cells stimulate appetite, resulting in weight gain (1). Several animal studies have shown that embolization of arteries supplying the gastric fundus reduces serum ghrelin levels and food intake (2–4). In addition, significant weight loss has been demonstrated in humans after left gastric artery embolization to treat active upper gastrointestinal bleeding (5). The aim of this prospective, single-arm study was an initial evaluation of the safety and efficacy of left gastric artery embolization with the intent to reduce plasma ghrelin levels and body weight. The study was approved by the local ethics committee.
On August 2, 2012, the first procedure was conducted at the Cardiovascular Department of N. Kipshidze Central University Hospital (Tbilisi, Georgia) (N.K., A.A). After 6-F femoral arterial access, a 6-F Heartrail II JR-4.0 guide catheter (Terumo Europe N.V., Leuven, Belgium) was used to engage the celiac trunk, and angiography was performed to identify the origin and anatomy of the left gastric artery. In some cases, a 0.35-inch guidewire was advanced into the common hepatic or splenic artery to stabilize the guide catheter position. The left gastric artery, a branch of the celiac trunk, was wired with a 0.014-inch Runthrough NS PTCA Guide Wire (Terumo Europe N.V.), and an Excelsior 1018 Microcatheter (Boston Scientific Corp., Cork, Ireland) was advanced over the guidewire into the mid-segment of the left gastric artery. Subsequently, the guidewire was removed while maintaining the microcatheter position in the mid-left gastric artery, and selective angiography was performed to ensure proper catheter position and allow definition of the anatomy and course of the left gastric artery (Figures 1A and 1B). Repeat injections of small amounts of BeadBlock Embolic Bead, 300- to 500-μm compressible microspheres (Biocompatibles UK Limited, Surrey, United Kingdom) mixed with contrast (1:1 ratio) into the left gastric artery were then performed with angiography between injections to assess flow characteristics. Injections were continued until the distal branches of the left gastric artery were no longer visible during contrast injection (Figure 1C). The guidewire and microcatheter were then withdrawn, and the patients were transferred to a monitored unit where the introducer sheath was removed and manual pressure was applied to obtain hemostasis. All subsequent embolizations were performed in a similar fashion. All patients remained in the hospital until the first follow-up gastroscopy 1 day after the intervention. A second follow-up gastroscopy was performed 1 week after the procedure. Patients’ weights were measured and body mass index calculated. For the duration of the study, no specific instructions were given to improve dietary habits and/or the level of physical activity.
Statistical analysis was performed using SPSS version 12.0 for Windows (Lead Technologies Inc., Chicago, Illinois). All values were presented as mean ± SD. Comparison of weight, body mass index, and plasma ghrelin level between different time points was done with the paired t test. In addition, a Wilcoxon signed rank test was performed.
Baseline characteristics are outlined in Table 1. There were no procedural complications, and all patients were discharged after completion of the first follow-up gastroscopy on the day after the intervention. Three of the 5 patients described mild transient epigastric discomfort after the procedure. However, follow-up gastroscopies were unremarkable. All patients reported a reduction in their appetite. Mean weight was reduced by 10%, 13%, 16%, 17%, and 17% at 1-, 3-, 6-, 12-, and 20- to 24-month follow-up, respectively (p < 0.05, regardless of whether the paired t test or Wilcoxon signed rank test was used for calculation) (Table 2, Figure 2A). Blood ghrelin levels were significantly lower at 1- and 3-month follow-up (by 29% and 36% from baseline, respectively, p < 0.05) and increased at 6-month follow-up compared with 3-month follow-up while remaining 19% lower than the baseline (p < 0.05, regardless of whether the paired t test or Wilcoxon signed rank test was used for calculation) (Table 3, Figure 2B). For 4 of the 5 patients, blood ghrelin levels were available at 12 months. These remained (21%) lower than baseline levels (p < 0.05 with paired t test and 0.068 with Wilcoxon signed rank test) (Table 3, Figure 2B).
Our results suggest that a weight reduction may be achieved in obese patients by left gastric artery embolization. The observed weight loss may be a result of a reduction in ghrelin levels.
There are several limitations. First, the absence of a control group does not allow definitive conclusions regarding efficacy. Although for the duration of the study, participants were not supplied with any specific instructions to improve their dietary or exercise habits, it is possible that the procedure and study participation led to a higher motivation for diet control and exercise. However, in this case, an increase rather than the observed decrease in plasma ghrelin levels would be expected. Second, the intermediate-term follow-up is too short to allow conclusions regarding weight loss durability. A rebound phenomenon mediated by a ghrelin level increase to baseline levels causing recurrent weight gain is conceivable. Third, using microparticles of intermediate size may limit reflux and collateral damage and limit the degree of mucosal injury. However, although there was no evidence by endoscopy for gastritis or ulcer formation in the short term and no symptoms to suggest gastritis throughout follow-up, given the limited number of patients, the risk of gastric ulcer formation may be significant but too small to have been observed in our study.
In conclusion, percutaneous left gastric artery embolization with embolic beads as described in our study appears safe. It leads to a reduction in plasma ghrelin levels and is accompanied by a significant weight loss at intermediate-term follow-up. Further studies with larger patient numbers and the use of a dedicated device are needed to examine the utility of this procedure and to determine the best procedural technique that allows ghrelin level reductions while minimizing the risk of ulcer formation.
Please note: Drs. Kipshidze and Leon are major shareholders of Endobar Solutions LLC. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2015 American College of Cardiology Foundation