Five years after being implanted with a bioresorbable scaffold (BRS), treated vessels show signs of substantial recovery, according to a small imaging substudy of the ABSORB A trial published in the December 9, 2014, issue of the Journal of the American College of Cardiology. 

“Overall, our long-term OCT observations suggest a favorable vascular healing response with late lumen enlargement, increased luminal symmetry, [side branch] patency, complete strut resorption, and formation of a potentially protective tissue layer,” the authors say.

In the 2006 pilot trial, 30 patients with stable or unstable angina or silent ischemia received an early version of the Absorb BVS (1.0; Abbott Vascular)—a balloon-expandable bioresorbable scaffold with a poly-L-lactic acid backbone and a poly-D,L-lactide coating that releases everolimus. 

For the substudy, investigators led by Evelyn Regar, MD, PhD, of Erasmus University Medical Center (Rotterdam, the Netherlands), used qualitative and quantitative OCT imaging to evaluate the vascular response in 8 patients at 5 years.

The Scaffold Has Disappeared

No binary stenosis was seen on angiography. Scaffold struts were no longer discernible due to complete resorption, and the mean lumen area increased from 5.03 mm² at year 2 to 6.39 mm² at year 5 (P = .02)—close to baseline level (6.91 mm²). Moreover, lumen eccentricity decreased from 0.24 at baseline to 0.15 at 5 years (P < .05).

A signal-rich layer, which consists of the neointimal layer, resorbed struts, and preexisting fibrous tissue, was seen between the lumen border and internal elastic lamina in all patients, providing evidence that the lumen was being protected from underlying plaque components. Median values for the mean, minimum, and maximum thickness of this layer were 330 µm, 150 µm, and 570 µm, respectively, while median symmetry (ratio of minimal to maximal thickness) was 0.26.

OCT analysis also provided insight into the morphology of the “neoplaque”—a consolidation of underlying plaque, biodegraded struts, and neointima that resembles native atherosclerosis. The mean minimum cap thickness was 310 µm. Based on neoplaque mapping, necrotic core or mixed plaque in more than 1 quadrant was seen in 7 patients. Comparison with previous imaging revealed no evidence of de novo necrotic core accumulation of adluminal origin.

In 1 patient, however, a thin-cap fibroatheroma was observed at the distal scaffold segment with cap disruption and a small thrombus. A second look at previous OCT imaging revealed possible scaffold discontinuity at 4 months.

OCT Traits Suggest Plaque Stabilization

Attenuation analysis was used to characterize quantitatively the signal-rich area and neoplaque. High-attenuation regions have been associated with high-risk necrotic core or macrophages, while low attenuation areas have been linked to a healthy vessel, intimal thickening, or calcified plaque. The mean per-patient attenuation within the signal-rich layer was 1.77 mm^-1. The surface layers (first 200 µm) had low attenuation, with high-attenuation areas located deeper in the plaque.

All side branches were patent, having TIMI flow grade 3. At 5 years, neointimal bridges were identified in 13 side branches. Mean thickness of neointimal bridges was reduced from 341 µm at 2 years to 227 µm at 5 years (P < .001).

OCT analysis of conventional DES implanted at the same time as the Absorb BVS showed more than 95% neointimal coverage, with no malapposed struts. However, neoatherosclerosis was seen in all metallic devices.

According to the investigators, late luminal enlargement has been attributed to outward remodeling in animal studies and plaque burden reduction in clinical trials. Their finding is also consistent with IVUS findings in a larger ABSORB cohort between 6 months and 2 years as well as CT follow-up at 5 years, they add.

To test the idea that neointimal growth after BRS resorption may act as a barrier against exposure of thrombogenic plaque components to the bloodstream—the “plaque sealing” hypothesis—the investigators focused on the signal-rich layer of plaque nearest the lumen. The minimum thickness of 150 µm is well above the 65-µm threshold accepted as the beginning of high risk for plaque rupture, they observe, suggesting that “[t]his signal-rich layer could be protective against very late scaffold thrombosis or de novo thrombosis by plaque progression and rupture.” 

Findings Favorable but Require Caution

In an accompanying editorial, Nieves Gonzalo, MD, PhD, of Hospital Clínico San Carlos (Madrid, Spain), George D. Dangas, MD, PhD, of Mount Sinai Medical Center (New York, NY), and Borja Ibanez, MD, PhD, of Centro Nacional de Investigaciones Cardiovasculares, Carlos III (Madrid, Spain), say the “most exciting data” are those related to the pattern of vessel healing, which “suggests that a BVS implant can produce a favorable tissue response.” The putative advantage over metallic stents, they add, is that “the healing process appears to incorporate initial generation of a new fibrous cap and subsequent scaffold dissolution, leaving an uncaged coronary segment. 

However, the editorial sounds a note of caution. Although the signal-rich layer of tissue separating the plaque from the lumen is claimed as an imaging surrogate for vascular healing, “[we] have no evidence that this type of tissue response exerts a clinically relevant protective role,” they write.

The study is limited by its very small sample size and highly selected patient population. Dr. Regar and colleagues note. Also, with no information about plaque characteristics before scaffold implantation, any extrapolation of the device’s performance to confirmed vulnerable plaques remains speculative, they add. 

Another unknown is the impact of BRS on bifurcation lesions, which were excluded from ABSORB A, the editorialists observe. Although the patency of small side branches initially “jailed” by the scaffolds is encouraging, these cannot be considered true bifurcations from an interventional perspective, they say.

Finally, they note that the scaffold implanted in ABSORB A patients differs from the current iteration, which has markedly higher initial mechanical stability and a longer resorption time. 

Clinical Confirmation Needed

In an email with TCTMD, Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY), said the various long-term OCT, IVUS, and vasomotion studies of Absorb showing progressive lumen enlargement, vessel circularity, plaque regression, and normalized vasomotor responses are “highly encouraging.

“We are hopeful that [these] will translate to improved 5-year outcomes with the Absorb BVS compared to metallic DES,” he added, a prospect that is being tested in the large-scale randomized ABSORB IV trial. 

Dr. Stone said the concept of plaque sealing is “intriguing but needs clinical correlation,” which may be provided by the PROSPECT Absorb study.

“This is all very promising,” he concluded, “and the next 5 to 10 years will tell us if bioresorbable scaffolds are truly the next major breakthrough in interventional cardiology.”

Sources:

1. Karanasos A, Simsek C, Gnanadesigan M, et al. OCT assessment of the long-term vascular healing response 5 years after everolimus-eluting bioresorbable vascular scaffold. J Am Coll Cardiol. 2014;64:2343-2356.

2. Gonzalo N, Dangas G, Ibanez B. Long-term favorable coronary healing after bioresorbable scaffold implantation: insights from OCT [editorial]. J Am Coll Cardiol. 2014;64:2357-2359. 

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