Left Atrial Appendage Amputation Using a Modified Appendage Clip: An Experimental Canine Study
Atrial fibrillation (AF) remains one of the most prevalent cardiac arrhythmias worldwide, significantly contributing to stroke risk due to thrombus formation in the left atrial appendage (LAA). The LAA’s complex, sac-like morphology promotes blood stasis, leading to over 90% of cardiogenic thrombi. Current strategies for LAA exclusion include surgical amputation, percutaneous endovascular occlusion, and epicardial ligation. However, these approaches face limitations such as incomplete closure, device-related complications, or procedural complexity. This study evaluated a modified left atrial appendage clip (LAAC) system for minimally invasive thoracotomy implantation in a canine model, assessing its feasibility, safety, and long-term efficacy through multimodal analyses.
Experimental Design and Methodology
The study utilized 24 healthy Labrador Retrievers (mean weight 34.5 ± 3.1 kg), divided into four groups for terminal evaluations at 7, 60, 90, and 180 days post-implantation. The modified LAAC system, consisting of a clamp and delivery apparatus, was deployed via a 2–3 cm left parasternal incision in the fourth intercostal space under general anesthesia. Intraoperative transesophageal echocardiography (TEE) using a PHILIPS EPIQ 7C system with 2.0–7.0 MHz probes guided clip placement. Two-dimensional (2D), three-dimensional (3D), and Doppler TEE measurements assessed LAA anatomy, clip positioning, and blood flow dynamics before and after deployment. Immediate procedural success was verified by incising the distal LAA in one randomly selected dog per group to confirm complete exclusion, followed by layered suturing.
Procedural Outcomes and Immediate Postoperative Results
The LAAC implantation was technically successful in all animals, with an average procedural duration of 4.17 ± 2.90 minutes. Intraoperative 2D TEE demonstrated preserved left atrial dimensions (anteroposterior diameter: 2.53 ± 0.42 cm vs. 2.55 ± 0.35 cm post-implantation) and cardiac function parameters, including ejection fraction (64.8 ± 5.1% vs. 63.9 ± 5.5%) and stroke volume (32.5 ± 4.7 mL vs. 31.8 ± 5.2 mL). 3D TEE confirmed complete LAA exclusion in all cases, with no residual flow between the left atrium and LAA. Doppler evaluations revealed unimpaired blood flow through adjacent structures, particularly the left pulmonary vein, with no stenosis or velocity changes (peak flow velocity: 0.61 ± 0.12 m/s pre- vs. 0.59 ± 0.15 m/s post-implantation). Hemodynamic stability was maintained throughout the procedure, with systolic and diastolic blood pressures showing no statistically significant variation (123.5 ± 10.2/78.4 ± 6.8 mmHg pre- vs. 120.7 ± 9.5/75.9 ± 7.1 mmHg post-implantation).
Histopathological and Morphological Evolution
Gross examination at sacrifice intervals demonstrated progressive LAA remodeling. The 7-day group exhibited LAA hyperemia and swelling, transitioning to marked atrophy in the 60-, 90-, and 180-day cohorts. Fibrosis between the clip arms increased chronologically, progressing from minimal collagen deposition at 7 days to dense connective tissue formation by 180 days. Histological analysis revealed:
- 7 days: Acute inflammatory infiltration (predominantly neutrophils) at clip-tissue interfaces, with early endothelial hyperplasia at the atrial orifice.
- 60 days: Mature endothelialization across the clipped orifice, reduced inflammation (lymphocytes/macrophages), and initial fibrotic encapsulation.
- 90 days: Thickened endothelial lining (23.4 ± 4.1 μm vs. 8.9 ± 1.7 μm baseline), resolving inflammation, and advancing fibrosis.
- 180 days: Complete endothelial continuity (35.6 ± 5.3 μm thickness), negligible inflammation, and mature fibrosis isolating the LAA remnant.
Notably, hematoxylin-eosin staining confirmed absent thrombus formation in all groups and no pathological changes in adjacent cardiac structures.
Comparative Advantages Over Existing Techniques
Traditional surgical LAA ligation carries risks of incomplete exclusion (15–38% incidence) and suture-line thrombogenesis. Percutaneous occlusion devices depend on precise anatomical matching and carry 3–5% risks of pericardial effusion or device embolism. The modified LAAC addressed these limitations through:
- Mechanical Exclusion Precision: The clip’s parallel deployment along the LAA base avoided circumflex artery or pulmonary vein compression, confirmed by intraoperative TEE.
- Endothelialization Capacity: Progressive endothelial coverage at the clipped orifice prevented thrombogenic substrate exposure, contrasting with persistent bare metal surfaces in endovascular devices.
- Tissue Remodeling: Induced fibrosis between clip arms created a biological barrier against recanalization, a critical failure mode in suture-based ligation.
Long-Term Safety and Functional Preservation
No procedural or delayed complications occurred, including hemorrhage, clip migration, atrial rupture, or pericardial tamponade. Cardiac functional preservation was evidenced by stable ventricular dimensions (left ventricular end-diastolic diameter: 3.82 ± 0.31 cm vs. 3.79 ± 0.28 cm at 180 days) and valvular hemodynamics. Systemic inflammatory markers (C-reactive protein, leukocyte counts) remained within normal ranges across all intervals.
Clinical Implications and Future Directions
This study establishes the LAAC system as a rapid, reproducible method for anatomical LAA exclusion, with advantages over existing techniques in simplicity, safety, and biological integration. The observed endothelialization timeline supports clinical transitions, as complete orifice coverage occurred within 60 days—comparable to endothelial healing after surgical closure. Future investigations should:
- Evaluate device performance in diseased models with AF-induced atrial dilatation
- Optimize clip sizing algorithms using 3D echocardiographic measurements
- Assess thromboprophylaxis requirements during endothelialization phases
- Conduct large-scale trials to validate long-term exclusion durability beyond 6 months
Conclusion
The modified LAAC system demonstrated consistent efficacy in achieving complete, stable LAA exclusion in canines, supported by serial imaging and histopathological validation. By combining mechanical occlusion with physiological endothelial repair mechanisms, this approach offers a promising alternative to conventional LAA management strategies, particularly for patients ineligible for anticoagulation or percutaneous interventions.
DOI: https://doi.org/10.1097/CM9.0000000000001122
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