Acute cholecystitis (AC) in patients unfit for surgery requires prompt minimally invasive management. Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) using lumen-apposing metal stents (LAMS) has emerged as an effective alternative to percutaneous drainage, but success and safety depend on accurate assessment of gallbladder wall integrity and vascularity before stent deployment. Contrast-enhanced harmonic EUS (CH-EUS) with Sonovue® allows real-time visualization of perfusion and microvascular changes, potentially improving detection of complicated AC such as gangrene or wall discontinuity. The aim of this study was to evaluate the pre-procedural utility of CH-EUS in characterizing gallbladder wall alterations in high surgical-risk patients with AC and to assess its concordance with CT imaging, diagnostic impact on procedural planning, and association with outcomes following EUS-GBD.

We retrospectively analyzed a prospectively maintained database of eighteen consecutive patients with moderate-to-severe AC according to Tokyo Guidelines 2018, all considered unfit for cholecystectomy after multidisciplinary review. Prior transabdominal ultrasound and/or contrast-enhanced CT were available in all cases, and findings were compared with endosonography. CH-EUS with Sonovue® was used to assess wall thickness, layer structure, perfusion behavior, intramural necrosis, and suspected wall interruption. When feasible, EUS-GBD was performed during the same session using a cautery-enhanced LAMS. Primary outcomes included characterization of enhancement patterns and their complementary value vs radiology. Secondary outcomes included technical/clinical success and adverse events of EUS-GBD.

Eighteen patients (67% male, median age 78 years [range 44–91]) were included. Cardiovascular comorbidities were frequent (Charlson Comorbidity Index mean 5.5 ± 1.6), and 44.4% were receiving anticoagulation. All cases were classified as moderate-to-severe AC. Transabdominal ultrasound was performed in 83.3% and CT in 38.8%, revealing gallbladder wall thickening in 77.7% and suspected necrosis in three cases

On EUS, 100% exhibited wall thickening >3 mm, loss of normal stratification in 61.1%, and a hypoechoic inflammatory pattern in 66.6%. Gallstones or sludge were detected in 83.3%, and common bile duct stones in 16.6%, confirming higher sensitivity than CT for intraluminal pathology. 

At CH-EUS, 7/18 patients (38.8%) showed hypo-enhancement, consistent with ischemia/gangrenous evolution, while 11/18 (61.2%) presented iso-/hyper-enhancement. Perfusion defects indicating necrosis or focal wall disruption were visualized in 22.2%. CH-EUS confirmed or clarified radiological suspicion in cases with ambiguous CT findings, demonstrating that TC and CH-EUS provide complementary structural and perfusion-based information crucial for selecting the safest entry site for LAMS deployment. 

Fourteen patients (77.7%) underwent same-session EUS-GBD with 100% technical and clinical success and only one self-limiting bleeding episode (5.5%). No adverse reactions to Sonovue® occurred.

In high-risk AC patients, CH-EUS with Sonovue® provides actionable characterization of gallbladder wall viability by detecting perfusion defects associated with ischemia or perforation. This information complements CT rather than replacing it, refining eligibility and guiding a safe stent trajectory for EUS-GBD. The excellent clinical success and low complication rate support routine pre-procedural contrast enhancement during EUS in fragile patients. Larger studies are needed to confirm these findings and validate perfusion-based criteria for risk stratification before gallbladder drainage.