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Drug-eluting stents (DES) are more likely to exhibit delayed strut coverage and malapposition when implanted in chronic total occlusions (CTOs) than in other lesion types, according to a registry study published online October 7, 2014, ahead of print in EuroIntervention.

Because such deficits in DES healing, revealed by optical coherence tomography (OCT), may be linked to increased stent thrombosis risk, the authors suggest regular OCT monitoring to help determine the optimal duration of dual antiplatelet therapy (DAPT).

Delayed Coverage Patterns Observed

In total, 2,257 cross-sections with 19,943 struts were analyzed. Each strut was categorized as:

• Covered
• Uncovered apposed
• Uncovered malapposed 

At about 6 months, higher rates of uncovered struts, including malapposed struts, were seen in DES-treated CTOs compared with controls as was reduced endothelialization (table 1).

Table 1. OCT Analysis: Strut Level

In addition, in a cross-sectional analysis, DES-treated CTOs were more likely to show a significant proportion of uncovered or malapposed struts than controls (table 2).

Table 2. OCT Analysis: Cross-Section Level

Analysis at the lesion level yielded similar patterns of delayed coverage in the CTO group.

OCT imaging of 4 CTO patients approximately 6 months later demonstrated that the proportions of uncovered struts had declined, whether apposed (to 8.3%) or malapposed (to 4.3%), while neointimal thickness had increased (to 115.0 ± 49.3 µm).

In total, 7 lesions were treated with an antegrade wiring technique, 7 required high-penetration wires, and 6 were approached with retrograde dissection and reentry. No differences were seen in the number of uncovered or malapposed struts or neointimal thickness according to PCI strategy.

At 12 months, more CTO than non-CTO patients (78.9% vs 64.3%) remained on DAPT, although the difference was not significant (P = .34). Two patients in the CTO group were readmitted to the hospital with unstable angina and both underwent successful repeat revascularization. Five patients from the control group were also readmitted due to unstable angina. There were no instances of acute MI, stent thrombosis, major bleeding, or death in either arm.

Initial Insights Into Differential Healing in CTOs

“This is the first [in vivo] study that shows that there is a difference in the way stents heal after being implanted in CTOs compared with non-CTO vessels despite equally long lengths,” Dimitrios Karmpaliotis, MD, PhD, of Columbia University Medical Center, told TCTMD in a telephone interview.

But a link between CTO and increased stent thrombosis or late MACE—though intuitive and suggested in some registries before multivariable adjustment—remains unproven, he said.

Since basic science and animal studies suggest that disruption of the vessel wall may impair healing, Dr. Karmpaliotis added, it is reassuring that the study found no correlation between disruptive CTO stenting techniques such as antegrade and retrograde subintimal tracking and increased healing delay or malapposition. However, the numbers in the subanalysis were quite small, he cautioned.

The authors suggest that delayed stent healing may be explained by the hypoxic environment within CTOs and the absorption of mural thrombus accompanied by suppression of neointimal tissue.

Emmanouil S. Brilakis, MD, PhD, of the VA North Texas Health Care System (Dallas, TX), suggested a similar mechanism. In a telephone interview with TCTMD, he said the most plausible explanation for late acquired malapposition is that when the chronically underperfused area behind a CTO grows larger following revascularization, the stent effectively becomes undersized. In fact, in some cases the stent can be seen floating in the vessel, he said, adding, “If the stent were apposed to the wall, it probably would have been covered.”

OCT Monitoring ‘Not Ready for Prime Time’

Dr. Karmpaliotis said serial OCT monitoring of stents over time, as advocated by the study authors to assess the duration of DAPT, is “an interesting potential recommendation, but it’s far from ready for prime time.”

Dr. Brilakis was also wary of the authors’ proposal. Noting that at 12 months most of the DES struts in CTOs were covered, he said it is unclear whether covered but malapposed stents carry an added risk of stent thrombosis. Part of his reluctance to endorse ongoing OCT, he explained, stems from the fact that such follow-up exposes patients not only to additional invasive procedures but also to the oculostenotic reflex—clinicians’ instinct to treat an observed stenosis regardless of its clinical significance.

Except in cases where the stent is “floating” in an aneurysm, “the risk [of OCT] may outweigh the benefit,” Dr. Brilakis concluded. Nonetheless, he endorsed an “empiric” policy of extending DAPT for CTO patients.

He added that further research into the healing process after DES implantation in CTOs is needed, especially when novel PCI techniques involving intentional dissection are used.

Meanwhile, Dr. Brilakis said, regardless of the clinical impact of delayed stent coverage, achievement of optimal acute results after PCI, using IVUS guidance and adequate postdilation, remains key to improved outcomes.

Source:
Heeger C-H, Busjahn A, Hildebrand L, et al. Delayed coverage of drug-eluting stents after interventional revascularization of chronic total occlusions assessed by optical coherence tomography: the ALSTER-OCT-CTO registry. Eurointervention. 2014;Epub ahead of print.

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