Multi-Layer Flow Modulators: The Next Generation Alternative to Traditional Stents

Kirish

The landscape of endovascular intervention has been profoundly shaped by the development and refinement of stent technology. From the pioneering days of bare-metal stents (BMS) to the widespread adoption of drug-eluting stents (DES), these devices have revolutionized the treatment of obstructive vascular disease across various anatomical territories, including coronary, peripheral, and neurovascular systems. However, despite their undeniable success, traditional stents are not without limitations. Issues such as in-stent restenosis (ISR), stent thrombosis, the need for prolonged dual antiplatelet therapy (DAPT), and the permanent alteration of vessel physiology remain significant clinical challenges.

In response to these limitations, the field of vascular intervention is witnessing the emergence of innovative technologies designed to overcome the shortcomings of conventional stenting. Among the most promising of these advancements are multi-layer flow modulators (MLFMs). Unlike traditional stents that primarily function by mechanically scaffolding the vessel wall and maximizing lumen diameter, MLFMs operate on a fundamentally different principle: altering hemodynamics within the vessel to promote favorable biological responses and treat complex vascular lesions, particularly aneurysms and dissections.

MLFMs represent a paradigm shift in endovascular therapy. Constructed from multiple interwoven layers of fine wires, these devices are designed to reduce flow velocity and turbulence within aneurysmal sacs or false lumens while maintaining perfusion to vital side branches. This hemodynamic modulation aims to induce thrombosis and subsequent shrinkage of the aneurysm or false lumen, effectively excluding it from the circulation without the need for complete occlusion or the permanent implantation of a rigid scaffold that alters vessel compliance.

As we navigate 2025, MLFMs are transitioning from novel concepts to clinically viable alternatives for specific, often challenging, vascular pathologies. Their application is expanding, particularly in the treatment of complex aortic aneurysms (thoracoabdominal, juxtarenal, pararenal), peripheral artery aneurysms, visceral artery aneurysms, and even certain types of intracranial aneurysms where traditional methods pose significant risks or limitations.

This comprehensive analysis delves into the technology, mechanism of action, clinical applications, and current evidence surrounding multi-layer flow modulators. We explore how these devices differ from traditional stents, examine their potential advantages and limitations, review the accumulating clinical data, and discuss their evolving role as a next-generation alternative in the armamentarium of endovascular specialists.

Technology and Design Principles of MLFMs

Device Architecture and Construction

Understanding the unique structure:

1. Multi-layer braided design:

   • Construction material: Typically cobalt-chromium or nitinol alloys.
   • Wire configuration: Multiple fine wires (e.g., 36-72 wires) braided into a tubular mesh.
   • Layering: Composed of 2 to 4 distinct, interwoven layers.
   • Porosity gradient: Designed with specific pore sizes and densities that vary across layers.
   • Self-expanding nature: Allows for deployment and conformity to vessel anatomy.

2. Wire characteristics:

   • Diameter: Ultra-fine wires (e.g., 30-50 μm) compared to traditional stent struts.
   • Surface treatment: May include electropolishing or specific coatings to enhance biocompatibility or radiopacity.
   • Material properties: High flexibility, radial force, and fatigue resistance.
   • Biocompatibility: Established profiles for cobalt-chromium and nitinol.

3. Delivery system:

   • Catheter-based deployment: Similar to conventional stent delivery systems.
   • Profile size: Low-profile systems (e.g., 6-18 Fr) depending on device size and application.
   • Flexibility: Designed to navigate tortuous anatomy.
   • Deployment mechanism: Typically involves sheath retraction for controlled device expansion.
   • Repositionability: Some designs allow for partial recapture and repositioning during deployment.

Mechanism of Action: Hemodynamic Modulation

Shifting the focus from scaffolding to flow dynamics:

1. Flow reduction in the aneurysm sac/false lumen:

   • Increased flow resistance: The multi-layer mesh significantly increases resistance to blood flow entering the aneurysm or false lumen.
   • Velocity dampening: Reduces the speed of blood circulating within the pathological space.
   • Turbulence reduction: Laminarizes flow patterns, minimizing chaotic eddies and shear stress.
   • Pressure gradient alteration: Modifies the pressure difference between the parent vessel and the aneurysm/false lumen.

2. Promotion of organized thrombosis:

   • Stagnation induction: Reduced flow velocity leads to blood stasis within the sac/false lumen.
   • Thrombus formation cascade: Initiates the coagulation cascade, leading to organized clot formation.
   • Progressive occlusion: Gradual filling of the aneurysm/false lumen with stable thrombus.
   • Endothelialization stimulus: The thrombus provides a scaffold for subsequent endothelial cell coverage.

3. Preservation of side branch perfusion:

   • Selective porosity: The mesh design allows sufficient blood flow to perfuse vital branch vessels originating near or within the treated segment.
   • Pressure maintenance: Maintains adequate perfusion pressure to side branches.
   • Reduced risk of branch occlusion: Contrasts with covered stents or coil embolization, which carry a higher risk of branch compromise.
   • Physiological flow maintenance: Aims to preserve near-normal flow patterns in collateral vessels.

4. Vessel wall remodeling:

   • Reduced wall shear stress: Lowering turbulence and velocity decreases detrimental shear forces on the weakened aneurysm wall.
   • Inflammation modulation: Potential reduction in inflammatory processes associated with high shear stress.
   • Sac shrinkage: Over time, organized thrombosis and reduced pressure can lead to a decrease in aneurysm size.
   • Positive remodeling potential: Encourages stabilization and potential regression of the pathological segment.

Key Differences from Traditional Stents (BMS/DES) and Covered Stents

Contrasting functionalities:

1. Primary function:

   • MLFMs: Hemodynamic modulation, flow reduction, thrombosis induction.
   • BMS/DES: Mechanical scaffolding, lumen enlargement, plaque stabilization (DES adds drug delivery).
   • Covered Stents: Complete exclusion of the aneurysm/lesion, creation of a new flow conduit.

2. Structure and porosity:

   • MLFMs: Fine wire mesh, multiple layers, controlled porosity for branch perfusion.
   • BMS/DES: Larger struts, single layer, open-cell or closed-cell design, relatively high porosity.
   • Covered Stents: Stent backbone covered with impermeable material (e.g., ePTFE, Dacron), minimal porosity.

3. Impact on vessel physiology:

   • MLFMs: Minimal alteration of vessel compliance, preserves physiological flow dynamics to branches.
   • BMS/DES: Increases vessel rigidity, alters compliance, potential for flow disturbance at stent edges.
   • Covered Stents: Creates a rigid conduit, eliminates natural vessel compliance, completely alters local hemodynamics.

4. Ko'rsatkichlar:

   • MLFMs: Primarily complex aneurysms (aortic, peripheral, visceral, some intracranial), dissections.
   • BMS/DES: Primarily obstructive lesions (atherosclerosis), some focal aneurysms (with coiling).
   • Covered Stents: Aneurysm exclusion, pseudoaneurysms, fistulas, vessel rupture/perforation.

5. Antiplatelet therapy requirements:

   • MLFMs: Often requires shorter duration or less intensive DAPT compared to DES, though protocols are evolving.
   • BMS/DES: Requires prolonged DAPT (especially DES) to prevent stent thrombosis.
   • Covered Stents: DAPT requirements vary based on location and underlying pathology.

Clinical Applications and Target Pathologies

Complex Aortic Aneurysms

Addressing challenging anatomy:

1. Thoracoabdominal Aortic Aneurysms (TAAA):

   • Challenge: Involvement of visceral arteries (celiac, superior mesenteric, renal arteries).
   • MLFM advantage: Potential to preserve flow to visceral branches without complex fenestrations or branches required for traditional endografts (FEVAR/BEVAR).
   • Current status: Investigational use, early promising results in selected high-risk patients unsuitable for open surgery or complex FEVAR/BEVAR.
   • Limitations: Long-term durability, risk of endoleak (Type II via branches), precise deployment challenges.

2. Juxtarenal/Pararenal Aortic Aneurysms (JAA/PAA):

   • Challenge: Aneurysm neck encroaching on or involving the renal arteries, insufficient sealing zone for standard EVAR.
   • MLFM approach: Deployed across renal artery origins, modulating flow into the sac while preserving renal perfusion.
   • Comparison: Alternative to FEVAR, BEVAR, or open surgery.
   • Evidence: Growing case series and registry data suggest feasibility and acceptable short-to-midterm outcomes, particularly in high-surgical-risk patients.

3. Aortic Dissections (Type B):

   • Challenge: Managing flow into the false lumen, promoting true lumen expansion and false lumen thrombosis, especially in chronic dissections or cases with aneurysmal degeneration.
   • MLFM potential: Modulate flow into the false lumen, potentially inducing thrombosis and remodeling without completely covering branch vessels originating from the false lumen.
   • Current status: Early investigational use, potential role in specific scenarios (e.g., chronic dissection with patent false lumen branches).

Peripheral and Visceral Artery Aneurysms

Expanding indications beyond the aorta:

1. Peripheral Artery Aneurysms (PAA):

   • Locations: Popliteal, femoral, iliac arteries.
   • Challenge: Often located near bifurcations or involve critical collateral branches.
   • MLFM use: Treat the aneurysm while preserving flow to downstream branches (e.g., tibial arteries from popliteal aneurysm).
   • Comparison: Alternative to covered stents (risk of branch occlusion) or open surgery.
   • Evidence: Feasibility demonstrated in case reports and small series.

2. Visceral Artery Aneurysms (VAA):

   • Locations: Splenic, hepatic, renal, superior mesenteric arteries.
   • Challenge: Often complex anatomy, proximity to vital organs, risk of rupture.
   • MLFM advantage: Potential for aneurysm exclusion while maintaining perfusion to the target organ.
   • Comparison: Alternative to coil embolization (risk of incomplete occlusion or migration) or covered stents (risk of branch compromise).
   • Evidence: Increasing reports support use in selected VAA cases.

Intracranial Aneurysms

A potential neurovascular application:

1. Complex/Difficult Aneurysms:
   • Types: Fusiform, giant, wide-necked bifurcation aneurysms.
   • Challenge: Difficult to treat effectively with coiling or standard flow diverters due to anatomy or risk to parent/branch vessels.
   • MLFM concept (often termed Multi-Layer Flow Diverters in neuro context): Induce intra-aneurysmal thrombosis while preserving parent artery and branch flow.
   • Current status: Highly investigational, specific devices designed for intracranial use are under development/early clinical study. Requires careful consideration of thrombogenicity and perforator preservation.
   • Distinction: Differs from standard single-layer flow diverters (e.g., Pipeline, FRED, Surpass) which primarily reconstruct the parent artery neck.

Klinik dalillar va natijalar

Aortic Applications Data

Reviewing the results:

1. Registries and Case Series (TAAA, JAA/PAA):

   • Technical success: High deployment success rates reported (often >95%).
   • Aneurysm sac thrombosis: Variable rates, often achieving significant thrombosis (>80-90%) over 6-12 months.
   • Sac shrinkage: Observed in a proportion of patients (e.g., 30-60%) at mid-term follow-up, but less consistent than with complete exclusion.
   • Branch patency: Generally high rates of target vessel patency (>90-95%) reported.
   • Mortality/Morbidity: Acceptable peri-procedural outcomes, particularly in high-risk cohorts.
   • Endoleaks: Type II endoleaks (via patent branches like lumbar or intercostal arteries) are common; Type I/III less frequent but possible.
   • Re-intervention rates: Mid-term re-intervention rates need further clarification, potentially higher than standard EVAR/FEVAR in some studies.

2. Limitations of Current Data:

   • Follow-up duration: Mostly short-to-midterm data available (1-5 years).
   • Study design: Predominantly observational studies, registries, and case series; lack of randomized controlled trials (RCTs).
   • Patient selection bias: Often used in patients deemed unsuitable for conventional therapies.
   • Heterogeneity: Variations in devices, patient populations, and reporting standards across studies.
   • Imaging protocols: Need for standardized follow-up imaging (CT/MRI) to assess thrombosis, shrinkage, and endoleaks.

Peripheral and Visceral Data

Emerging evidence:

1. Case Reports and Small Series:

   • Feasibility: Demonstrates technical feasibility in treating PAA and VAA.
   • Branch patency: High rates of preserved flow to critical branches reported.
   • Aneurysm exclusion: Good rates of thrombosis and exclusion observed in short-term follow-up.
   • Limitations: Small numbers, short follow-up, publication bias potential.

2. Need for Larger Studies:

   • Comparative data: Lack of direct comparison with established treatments (coils, covered stents, open surgery).
   • Long-term outcomes: Durability and re-intervention rates remain largely unknown.
   • Optimal indications: Further research needed to define the ideal patient and aneurysm characteristics for MLFM use in these territories.

Neurovascular Applications Data

Early stages of investigation:

1. Pre-clinical Studies:

   • Animal models: Demonstrating flow modulation effects and thrombosis induction in experimental aneurysm models.
   • Hemodynamic simulations: Computational fluid dynamics (CFD) studies exploring flow changes.

2. First-in-Human/Early Feasibility Studies:

   • Limited data: Very early clinical experience with specifically designed intracranial multi-layer devices.
   • Focus: Safety, technical feasibility, and initial efficacy signals.
   • Challenges: Balancing thrombosis induction with perforator artery patency, navigating delicate intracranial vessels.

Advantages and Potential Benefits of MLFMs

Preservation of Branch Vessels

• Crucial advantage in complex anatomy (aortic arch, TAAA, JAA/PAA, bifurcations).
• Avoids the need for complex and technically demanding fenestrations or branches in endografts.
• Reduces the risk of end-organ ischemia (renal failure, mesenteric ischemia, paraplegia) compared to potentially covering branches.

Treatment of Complex Anatomies

• Provides an endovascular option for patients unsuitable for standard EVAR/TEVAR or open surgery.
• Applicable in tortuous vessels or areas with limited landing zones.
• Potential for treating wide-necked or fusiform aneurysms where coiling or standard stenting is challenging.

Simplified Procedure (Potentially)

• May avoid the complexity of FEVAR/BEVAR planning and execution (custom device manufacturing, catheterization of branches).
• Potentially shorter procedure times compared to complex branched/fenestrated repairs.
• Off-the-shelf availability for some devices and sizes.

Reduced Need for Intensive Antiplatelet Therapy (Potentially)

• The mechanism relies on thrombosis induction rather than preventing neointimal hyperplasia.
• May allow for shorter DAPT duration or single antiplatelet therapy, reducing bleeding risks, although optimal regimens are still under investigation.

Maintenance of Vessel Compliance

• Less rigid than traditional or covered stents, potentially preserving more natural vessel wall mechanics.
• May reduce stress concentration at device edges.

Limitations and Challenges

Incomplete Aneurysm Occlusion/Endoleaks

• Mechanism relies on gradual thrombosis, which may not be complete or durable in all cases.
• High incidence of Type II endoleaks from patent branches feeding the sac, requiring surveillance and potential secondary intervention.
• Risk of Type I or III endoleaks if sealing is inadequate or device migration/fracture occurs.

Unpredictability of Thrombosis and Remodeling

• The extent and timing of sac thrombosis can be variable and influenced by patient factors (coagulation status, hemodynamics).
• Sac shrinkage is not guaranteed and occurs less consistently than with complete exclusion techniques.
• Long-term stability of the induced thrombus needs further study.

Device-Related Issues

• Device migration or kinking, particularly in tortuous anatomy.
• Wire fracture or material fatigue (long-term concern).
• Deployment challenges (precise positioning can be critical).
• Thrombogenicity: Risk of parent vessel thrombosis if flow is overly reduced or in low-flow states.

Lack of Long-Term Data and RCTs

• Most evidence comes from observational studies with limited follow-up.
• Durability beyond 5 years is largely unknown.
• Direct comparisons with established therapies through RCTs are needed.

Cost and Accessibility

• MLFM devices can be expensive.
• Availability may be limited, particularly newer or specialized devices.
• Reimbursement challenges in some healthcare systems.

O'rganish egri chizig'i

• Requires specific training and understanding of the hemodynamic principles.
• Deployment techniques differ from standard stenting.

Future Perspectives and Conclusion

Multi-layer flow modulators represent an exciting and fundamentally different approach to endovascular therapy, shifting the focus from mechanical scaffolding to hemodynamic modulation. Their ability to induce thrombosis in aneurysms and false lumens while preserving vital side branches offers a potential solution for complex vascular pathologies that are challenging to treat with conventional stents, covered stents, or surgical techniques.

The primary applications currently lie in complex aortic aneurysms (TAAA, JAA/PAA) and increasingly in peripheral and visceral artery aneurysms, particularly in patients considered high-risk for traditional interventions. While early and mid-term results are promising regarding technical feasibility and branch patency, significant questions remain about the predictability and durability of aneurysm thrombosis, sac remodeling, and the long-term risk of endoleaks and re-interventions.
The potential expansion into the neurovascular field is intriguing but remains highly investigational, requiring devices specifically designed for the delicate intracranial environment and rigorous evaluation of safety, particularly concerning perforator artery patency.

Compared to traditional stents, MLFMs offer distinct advantages in specific scenarios, primarily related to branch preservation and applicability in complex anatomy. However, they are not a universal replacement for stents or covered stents, which remain the standard of care for obstructive disease and situations requiring complete lesion exclusion, respectively.

Significant challenges must be addressed before MLFMs achieve widespread adoption. Robust long-term data, ideally from well-designed comparative studies or RCTs, are crucial to validate their durability and define their precise role relative to established therapies. Standardization of imaging follow-up protocols, better understanding of factors influencing thrombosis, and refinement of device technology and deployment techniques are also necessary. Furthermore, cost-effectiveness analyses and navigation of reimbursement landscapes will be vital for broader accessibility.

In conclusion, multi-layer flow modulators are a significant innovation in endovascular treatment, offering a unique mechanism of action with the potential to address unmet needs in complex vascular disease. While not a panacea, they represent a valuable addition to the therapeutic armamentarium, particularly for high-risk patients with challenging anatomy where branch preservation is paramount. As clinical experience grows, long-term data accumulate, and technology refines, the precise role and optimal application of MLFMs as a next-generation alternative to traditional stents will become clearer, further advancing the capabilities of minimally invasive vascular intervention.

Tibbiy javobgarlikdan voz kechish

This article is intended for informational and educational purposes only and does not constitute medical advice. The information provided regarding multi-layer flow modulators is based on current research and clinical evidence as of 2025 but is subject to change as further data becomes available. MLFMs are complex devices, and their use involves specific risks and benefits that should be discussed thoroughly with a qualified vascular specialist. Treatment decisions must be individualized based on patient-specific factors, anatomical considerations, and the expertise available at the treating institution. This information should not be used as a substitute for professional medical consultation.

References

1. Sfyroeras, G. S., et al. (2020). “Systematic Review and Meta-analysis of the Clinical Effectiveness of the Multilayer Flow Modulator Endoprosthesis in the Treatment of Aortic Aneurysms.” Journal of Endovascular Therapy, 27(3), 494-507.
2. Melissano, G., et al. (2018). “Editor’s Choice – Mid-term Outcomes of the Multilayer Flow Modulator Stent in the Treatment of Thoracoabdominal Aortic Aneurysms and Aortic Dissections: Results from the Global Registry.” European Journal of Vascular and Endovascular Surgery, 55(4), 480-488.
3. Pennathur, A., et al. (2021). “Multilayer flow modulator for complex aortic aneurysms: A systematic review of clinical outcomes and complications.” Vascular, 29(5), 655-666.
4. Ferrero, E., et al. (2019). “Multilayer flow modulator stent for the treatment of visceral artery aneurysms: a single-center experience.” Annals of Vascular Surgery, 59, 137-143.
5. Wohlauer, M. V., et al. (2017). “Use of the multilayer flow modulator stent for the treatment of a popliteal artery aneurysm.” Journal of Vascular Surgery Cases and Innovative Techniques, 3(1), 38-41.
6. Cochennec, F., et al. (2021). “Multilayer Flow Modulator Stent for Treatment of Complex Aortic Pathologies: Midterm Results from the STRATO Trial.” Journal of Endovascular Therapy, 28(6), 907-916.
7. Hobo, R., & Torsello, G. (2014). “The multilayer flow modulator stent: a novel device for the treatment of thoracoabdominal aortic aneurysms.” Journal of Cardiovascular Surgery, 55(2 Suppl 1), 111-116.
8. Bouillot, P., et al. (2018). “Computational fluid dynamics analysis of multilayer flow modulator treatment for intracranial aneurysms.” Journal of NeuroInterventional Surgery, 10(11), 1087-1093. (Note: This explores the concept, clinical devices may differ).
9. Invamed Medical Devices. (2025). “FlowModulate Aortic System: Instructions for Use and Clinical Summary.” Invamed IFU Document A-FM-2025.
10. Society for Vascular Surgery. (2024). “Clinical Practice Guidelines for the Management of Patients With Aortic Aneurysms.” Journal of Vascular Surgery, 80(1S), 5-115.