Severe Coronary Calcification Might Delay Healing Following Implantation of Newer-Generation Drug-Eluting Stents

In an autopsy-based, histopathological analysis of stented coronary lesions, severe calcification was an independent risk factor for delayed strut coverage and healing after newer-generation DES. The report of the study led by Torri was recently published in the European Heart Journal.

Newer-generation drug-eluting stents (DES) are known to have faster strut coverage from thinner strut dimensions, compared to first-generation DES. Uncovered struts are the most common cause of stent thrombosis. Therefore, lower rates of stent thrombosis have been shown in newer-generation DES. Having said that, and keeping the high risk of bleeding and mortality associated with long-term dual antiplatelet therapy (DAPT) in mind, utilization of newer-generation DES allows for a shorter duration of DAPT after PCI.

Previous studies have demonstrated that severe calcification of the stented lesion is an independent predictor of adverse clinical outcomes such as stent thrombosis in both bare-metal stents and DES. However, little is known about the histopathological changes of severely calcified lesions after stenting. In the study by Torri et al., the investigators aimed to evaluate the pathologic response of healing in severely calcified lesions after stenting with newer-generation DES.

In the CVPath stent autopsy registry of 1211 stented lesions between 1998 and 2018, 134 newer-generation DES with a duration of implant 30 days or more were analyzed. Based on the extent of calcification in radiographic evaluation, the lesions were divided into severely (SC, n = 46) and non-severely (NS, n = 88) calcified. The lesions were histologically evaluated. Uncovered struts were identified by the presence of platelet and/or fibrin thrombus or bare struts with the absence of neointima. The ratio of uncovered-to-total stent struts per section was calculated and expressed as a percent. The surface calcified area was defined as luminal calcification with the stent strut located directly over the calcified area without any intervening fibrous tissue between the abluminal side of stent strut and calcium.

Diabetes mellitus and chronic kidney disease were more prevalent in the severely calcified group. The prevalence of stent thrombosis was significantly higher in severely-calcified compared with non-severely-calcified [4 (9%) vs. 0 (0%), P = 0.01]. The percentage of uncovered strut per lesion was higher in SC [median 2.4 (IQR 0.0 – 19.0) %] as compared to NC [0.0 (IQR 0.0–4.6) %, P = 0.02]. The presence of severe medial tears was greater in severely calcified lesions (59% vs. 44%, P = 0.03). In addition, the severely calcified lesion had a higher prevalence of ≥ 3 consecutive struts lying directly in contact with the surface calcified area (3SC) (52% vs. 8%, respectively, P < 0.0001). Multivariate analysis revealed that sections with duration of implantation ≤ 6 months [odds ratio (OR): 7.7, P < 0.0001], ≥ 3 consecutive struts on surface calcified area (OR: 6.5, P < 0.0001), strut malapposition (OR: 5.0, P< 0.0001), and lack of severe medial tears (OR: 2.5, P= 0.0005) were independent predictors of delayed strut coverage. The overall prevalence of neoatherosclerosis was significantly lower in severely calcified group (24% vs. 44%, P = 0.02). Neoatherosclerosis in the severely calcified group was most commonly manifested as calcification of the neointima (42%), whereas the presence of foamy macrophage in the neointima was the most common in NC (61%).

The result of the study might have clinical implications. The investigators believe that a longer duration of DAPT may be required in patients with severely calcified lesions detected either angiographically or by intravascular imaging prior to the stent implantation. This is true for patients with chronic kidney disease who oftentimes have extensive cardiovascular calcifications.