Timing and safety of angioplasty during carotid artery stenting

Today, carotid endarterectomy (CEA) remains the gold standard treatment of carotid artery stenosis. Over six decades, CEA evolved to effectively eliminate one of the major sources of embolization to the brain and prevent stroke. In comparison, carotid artery stenting (CAS) is a relatively recent procedure that is yet to realize its full potential and purpose. Despite a number of large clinical trials, controversy still exists with regards to the efficacy of CAS in comparison to CEA.[1–3] Interdisciplinary debate with differing emphasis on specific adverse outcomes after each procedure precludes a national consensus. However, in the grand scheme of things, CAS is far from being optimal.

Only a handful of studies showed no efficacy to distal embolic protection device (EPD) use. Those where either underpowered [4,5] or lacked homogeneity in the case of a systematic review by Elderle et al. [6]. Conversely, the evidence to the benefit of EPD use is overwhelming.[7–12] Two systematic reviews in 2003 [7] and 2008 [8] demonstrated that distal protection devices reduce the stroke and death rate by 67% as well as ipsilateral Diffusion Weighted – MRI (DW-MRI) lesions by 27%, respectively. DW-MRI lesions are being increasingly used as a surrogate for stroke and clinically silent brain lesions are a cause for concern. Moreover, the CREST trial protocol specifically required the use of EPD unless otherwise contra-indicated.[1]

More recently, the proximal embolic protection approach (reversal flow) is showing very promising results. In the ROADSTER trial, only 4 out of the 141 (2.8%) patients enrolled in the pivotal arm experienced death or stroke within 30 days of CAS.[13] However, more data on such approach remains to be seen in a larger and more heterogeneous patient population.

Compared with CAS, CEA consistently has higher perioperative cardiac complications and lower stroke rates.[1] This is perhaps best explained by the surgery’s ability to completely remove the source of embolization – which represents the highest risk to stroke. When carotid stenting was first introduced, it was modeled after the very successful cardiac percutaneous coronary intervention. The latter included liberal use of balloon angioplasty to achieve the best blood flow and angiographic picture after the intervention.[14] As recent as 2006 [15] and 2010,[1] CAS technique recommendations included both predilation prior to stent deployment and postdilation. However, it is perhaps this rigid emulation of other stenting procedures that may be CAS’s detriment.

Instead of attempting to alleviate the arterial stenosis with CAS, we should aim for plaque stabilization as the top priority – even if at the expense of a higher residual stenosis. Carotid stenting is the only stenting procedure where the very sensitive brain tissue is at the affected end downstream. In coronary or peripheral artery stenting, muscle can arguably endure more emboli than nerves. Therefore, the best counter measure to the high perioperative stroke/death rate after CAS is perhaps to achieve the best possible plaque stabilization with the least number of manipulations across the carotid lesion. Vos et al. showed with transcranial duplex (TCD) during CAS that microembolization increases with each exchange of the wire or catheter across the stenosis.[16] In descending order, the phases that yielded the most isolated microemboli were: stent deployment, wiring, postdilation and predilation. In a similar study, the Antonius et al. [17] found that isolated microemboli and the number of heartbeats with showers were highest during stent placement and postdilation and lowest during predilation. These findings are probably explained by the fact that postdilation forces the metal struts into the atheromatous plaque, resulting in embolic fractures that are carried downstream.

In theory, it may be argued that forgoing any angioplasty during stenting could result in the lowest embolic showers and therefore reduced neurologic sequelae. However, forcing the stent catheter delivery system through a significantly stenotic lesion has a high risk of dislodging large atheromatous emboli. Careful and slow predilation with a small coronary balloon at low atmospheric pressure is our recommended technique to allow safe passage of the stent catheter. Primary stenting might work best in asymptomatic moderate carotid stenosis patients (<60% stenosis). However, medical management is probably the better treatment approach for these lesions.

Moreover, a lower intra-procedural embolic load does not always lead to lower perioperative stroke/death.[18] This is partly because of the fact that any combination or complete forgoing of balloon angioplasty in CAS has consequences that extend far beyond the intra-procedural period. Stents used today in the carotid artery are self-expanding and continue to expand days after the procedure. Significant microembolization continues up to 24 h after CAS.[19] Recent advancements in stent design, such as the micro-mesh double layer stents (Terumo, InspireMD and Gore) may prove beneficial in terms of post-stent deployment embolization. However, this is yet to be proven and become widely accepted.

More importantly, some CAS techniques, namely post-stent deployment ballooning, have been shown to increase the incidence of post-procedural hemodynamic depression which in turn leads to higher death/stroke rate.[20–22] Aggressive post-stent ballooning entails increased carotid body manipulation and could result in profound hypotension and bradycardia. A sustained decrease in blood pressure can lead to increased stroke and death rate by means of decreased cerebral blood flow affecting watershed areas that are most vulnerable because of concomitant intracerebral arterial disease.

In several trials, predilation has been left to the discretion of the operator depending on the degree of carotid stenosis,[1,2] whereas postdilation was recommended for routine use by the operator guidelines of the CREST trial. In ex vivo experiments Ohki et al. demonstrated that when predilation was performed, the number of plaque debris released upon stent deployment was lower.[23] Others have confirmed those findings clinically by showing that predilation lowered the stroke/death by 50% compared with primary/direct stent implantation.[24] We theorize that the performance of predilation under embolic protection prepares the vessel better to receive the stent and prevents aggressive lesion manipulation during self-expansion of the stent. This therefore serves to reduce heavy microembolic showering in the immediate post-procedural period.

Our recent work on more than 3500 CAS patients in the Vascular Quality Initiative database showed that the dual use of predilation and postdilation resulted in more than twice the perioperative stroke/death rate compared with using predilation alone.[20] In addition to resulting in a large embolic load during the procedure,[17] postdilation can dramatically increase the rate or hemodynamic depression.[20,21] These two additive effects of postdilation have a significant adverse impact on perioperative outcomes of CAS.

In conclusion, carotid artery stenting must not be modeled after other stenting procedures. Once we recognize that plaque stabilization is the most significant objective of CAS, postdilation and its angiographic benefits are outweighed by its adverse effect on outcomes.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.