Despite recent advances in percutaneous techniques, device designs, delivery system profiles, and operator skills, the management of symptomatic infrainguinal arterial occlusive disease remains a challenge. 

Though peripheral arterial disease is a systemic process that typically affects multiple arterial beds, approximately half of all infrainguinal atherosclerotic lesions localize to the femoropopliteal (FP) segment. The FP arteries are muscular distributing conduits that lie relatively superficial in the thigh, connect to highly mobile articulation sites, and are surrounded by the dynamic thigh muscles. These features render the arterial wall subject to unique biomechanic, anatomic, and hemodynamic forces that cause changes to the artery’s geometry during locomotion. Ambulation causes axial elongation and shortening, while musculoskeletal activities (such as turning, twisting, walking, and bending) are associated with radial compression and other (nonradial) cyclic deformities while the rhythmic pulsatile blood flow produces repetitive radial extension. This distinctive biomechanical environment has not been observed in other vascular beds and appears to explain the artery’s predilection to atherosclerotic lesions that are typically diffuse and complex in nature, respond poorly to revascularization techniques (particularly plain old balloon angioplasty, POBA) and tend to recur and require future reintervention.^1,2

The disappointing performance of POBA (50% acute failure rate necessitating bailout stenting and <40% 12-month patency) and stainless steel stents (rigid, susceptible to crush and restenosis) in the femoropopliteal arteries fueled the search for prostheses that provide sufficient radial force while flexibly conform to the artery to accommodate the biomechanical demands of this segment.^3-7 Consequently, an era of utilizing nitinol, an alloy with unique superelastic and thermal memory properties suitable for the infrainguinal bed, began and led to the development of nitinol self-expanded stents. The superiority of primary and provisional nitinol stenting over POBA was evident by they significantly improved patency rates, particularly in intermediate to long lesions.^8,9 Nonetheless, in-stent restensosis (ISR) was soon recognized as a major limitation to the durability of nitinol stents. In-stent restenosis is caused by intimal hyperplasia, which is an exaggerated healing process to arterial wall barotrauma during angioplasty mediated by inflammatory mechanisms and fueled by ongoing interaction between stent struts and the arterial wall.^10,11

Stent fracture (SF) as a clinical phenomenon came to light in 2004 when Allie and Walker published a landmark report documenting high prevalence of SF (65%) and associated ISR.¹² Soon thereafter, additional observations linked SF to adverse outcomes including ISR, stent thrombosis, pseudoaneurysm formation, and distal embolization.^13-16 The SIROCCO trial was the first to prospectively evaluate the rate of stent fractures in first generation nitinol stents. In this trial, stent fractures were common (20%), most appeared within the first year in subjects who received 3 or more stents, and many were adjacent to stent overlap zones. Importantly, the SIROCCO failed to document strong association between SF and ISR.¹⁷ Nonetheless, the SF issue took center stage and had an enormous impact on femoropopliteal stenting trials. In fact, in June 2006 the FDA mandated monitoring for SF as a safety endpoint in all subsequent stent trials. 

While data on the prevalence of SF and their clinical sequel were being collected, newer nitinol stents were being designed. Several modifications were made to the stent architecture (such as struts length, shape and angles, the density and geometry of the microconnectors and markers), stent material composition, and stent finishing (intensive surface polishing to avoid imperfections). The newer generation stents are stronger, yet more adaptable, and produced in lengths of up to 25 cm to avoid overlap. Moreover, revised stent implantation instructions, particularly avoiding stent elongation during deployment, were widely disseminated. These structural and technical improvements paid off and translated into greater primary patency and remarkably fewer stent fractures. Subsequently, the FDA approved several nitinol stents for femoropopliteal indications. Table 1 summarizes the data on FDA-approved nitinol stents, including patency and SF rates. Collecting data on SF continues to be mandatory because SF remains commonly encountered in practice and its clinical impact is often evident. 

In this issue of Vascular Disease Management, Babaev et al report on a real-life series of 97 consecutive patients who underwent implantation of 205 nitinol stents to 105 of their limbs; and presented with symptomatic ISR approximately 15 months after the index procedure. Based on their in-a-limb analysis, the authors report SF in 30% (31/105 limbs). Despite this relatively high prevalence, SF-related ISR (defined as the presence of a SF within 1 cm from the stenotic lesion) was noted in only 3 limbs. Hence, 10% (3/31) of the limbs with fractured stents had ISR within 1 cm from a fracture, and 2.9% (3/105) of all limbs with ISR had a SF within 1 cm from the stenotic lesion. The authors concluded that while stent fractures are common, their relationship to ISR is rather modest. 

Other notable findings of the study include the absence of a strong relationship between the presence of multiple overlapping stents (28% of limbs had 3 or more overlapping stents) and advanced fractures (56% of fractures were type 3, 4, or 5) and the incidence of fracture-associated ISR. Similarly, the presence of multiple fractures (35% of the limbs had ≥2 SF) did not predict ISR in the affected limb. On the other hand, when multivariate analysis was carried out, ongoing smoking was the only factor associated with stent fractures. 

I would like to congratulate Dr. Babaev for his contribution to Vascular Disease Management and for reigniting the discussion about the important topic of SF and their clinical impact on stent patency and reintervention. Our attempts to study this phenomenon as a clinical event have been hindered by the lack of a standardized reporting system for SF diagnosis and their mechanistic contribution to ISR. Published studies used different formulas to calculate SF prevalence. Some divided the total number of fractures seen on radiographs by the total number of patients reviewed (in-a-patient analysis); while others used the total number of limbs (in-a-limb analysis) or the total number of stents as the denominator. If we apply each of these different definitions, the prevalence of SF in this study will be 45% (total 44 SF/97 patients), 30% (31 limbs with SF/105 total limbs) or 21% (44 SF/205 total number of stents). Similarly, the burden of SF on overall ISR can also differ depending on the denominator used: 3% (3/97), 30% (3/30) or 1.5% (3/205). This highlights the need for standardized reporting. 

The issue of defining the association between SF and ISR based solely on the presence of the two pathologies within 1 cm of each other warrants further discussion. Stent fracture can cause stent instability and compromise stent performance against the biomechanical forces affecting the entire femoropopliteal arterial wall. For example, the presence of a complex (type 3, 4, or 5) fracture can significantly change the interaction between the stent struts (on both sides of the fracture) and the arterial wall; eventually promoting intimal hyperplasia and ISR at regions farther than the predefined 1-cm radius. Therefore, the presence of ISR in fractured stents cannot be attributed exclusively to non-fracture-related factors. Likewise, until other conclusive evidence is available, the presence of SF may be counted as a potential contributor to the development of ISR within the contiguous stented segment.

Another challenge with reporting on SF is related to the diagnostic methodology employed. All operators and technologists should be trained to recognize them. In addition to high resolution digital x-ray imaging in 2 different projections separated by at least 45°, at least 50% magnification should be applied when scrutinizing the integrity of peripheral stents. Moreover, adjudication of the radiographic images should be performed by at least 2 blinded interpreters with reasonable experience and interobserver variability. 

In conclusion, newer stent designs, improved operator skill, revised deployment techniques, production of longer stents, and adherence to best medical therapy and intensive risk factor management have all contributed to superior stent patency and lower restenosis rates. We should also remind ourselves that stents will continue to have their indications in the FP system and we, as a community, need to continue our effort to perfect their engineering and minimize their complications, including SF and ISR.  

References

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