The vascular biology behind endovascular therapies

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Peripheral arterial disease (PAD) produces a global health burden and remains a leading cause of disability, limb loss and reduced quality of life. PAD is also a proxy for cardiovascular and cerebrovascular death. Endovascular therapies have become widely used among symptomatic patients refractory to medical and exercise therapy alone, including stents, drug-eluting balloons, atherectomy, and vessel modification devices.

Our current understanding of the biologic mechanisms of these devices remains incomplete. Endovascular practitioners need a deep understanding of the vascular biology and biomechanics of endovascular therapies to enable critical appraisal, identify gaps in existing knowledge and define unmet needs for their current and future patients.

Chronically occluded lower extremity arteries, particularly long-segment TASC-C and -D lesions, were long considered untreatable with percutaneous approaches and amenable only to surgical bypass. Endovascular techniques which intentionally create an intramural channel within the arterial media, followed by angioplasty with or without stent placement, were first described by Bolia but have since evolved to encompass a wide array of dedicated technologies. This approach, known as subintimal recanalisation, has now become routine for many interventionalists. What is remarkable is that the vascular remodeling following subintimal recanalisation almost completely replicates the histologic elements of a native artery.

Understanding the remodelling changes after this approach can guide selection of subsequent use of other endovascular techniques to maintain vessel patency and limb preservation.
Angioplasty balloons and stents as delivery platforms for anti-proliferative drugs to the therapeutic targets of fibroblasts and smooth muscle cells within the media and adventitia have become widely utilised in endovascular therapy. Interventionalists need to distinguish cytostatic from cytotoxic drugs, understand their pharmacokinetics and mechanisms within the cell cycle. Perhaps as importantly, various coating and polymeric delivery systems (excipients) differ greatly in efficiency and efficacy and are significant determinants of clinical benefits of these therapies.

tim clark
Timothy Clark

Bioabsorbable scaffolds offer enormous potential to provide a stent-like scaffold to optimise arterial remodelling, while resorbing over time to leave no permanent implant behind. These devices gained rapid, nearly global adoption in the coronary vessels until the risks of late thrombosis were recognised and led to their near-abandonment. In the peripheral vascular applications, bioabsorbable scaffolds face a demanding list of attributes: high radial force, predictable resorption without particulate embolization or thrombosis, and sufficient radio-opacity to enable precise deployment within heavily calcified vessels. Despite these challenges, several promising technologies may soon yield these devices for the periphery with favourable effects on vascular remodelling.

Atherectomy is a widely utilised technique in endovascular therapy, but randomised trials dating back to first-generation plaque excisional devices have consistently struggled to show a compelling, cost-effective clinical benefit of this therapy. A wide array of atherectomy systems have since evolved, however the extent to which these devices remove significant quantities of plaque, thrombus, or cellular/fibrotic deposits remains insufficiently understood. Vascular remodelling after atherectomy is variable and often unpredictable, and intraprocedural risks of embolic debris worsening underlying limb ischaemia remain an ongoing concern. A broader understanding of the vascular biology behind the purported mechanisms of various atherectomy systems is needed.

Vessel preparation techniques employ devices to score, cut, sonicate, or create microfenestrations in a vessel wall prior to subsequent angioplasty or stent placement. These techniques are considered beneficial when peripheral arteries are highly calcified or extremely stenotic. It is key to understand the vessel wall modifications that occur with these ‘vessel prep’ devices and to what extent these modifications confer a benefit in sustaining vessel patency.

Lastly, self-expanding nitinol stents, including bare-metal, drug-eluting and polytetrafluoroethylene-covered, are widely used in the femoropopliteal artery. The femoropopliteal artery experiences among the highest levels of torsion and compression within the body. These stents are typically laser-cut, electropolished nitinol tubes which are shape-set to undergo prescribed expansion upon delivery within a vessel. Specific stent design features may be less prone to strut fractures and thereby, intimal hyperplasia and thrombosis. Certain stent designs
can create spiral laminar flow, which may reduce wall shear stress and platelet activation.

Each of these topics were explored within a Categorical Course at the Society of Interventional Radiology Annual Scientific Meeting (11–16 June, Boston, USA). By understanding the biology of vascular remodelling, which occurs following endovascular interventions including angioplasty, subintimal recanalisation of chronic total occlusions, stent placement and atherectomy, we hoped to provide further insight to vascular interventionists to distinguish existing endovascular devices based on design, mechanism and performance.

Timothy Clark is director of interventional radiology at Penn Presbyterian Medical Center, University of Pennsylvania, Philadelphia, USA, and professor of clinical radiology in the Department of Radiology at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.

Disclosures: Clark is a consultant for BD, Boston Scientific, Teleflex, B. Braun and Baylis Medical, and receives royalties from Teleflex and Merit Medical. He is founder of Forge Medical and NeuRx Medical.


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