Cracking (The Code of) Coronary Artery Calcification Towin the Last Battle of Percutaneous Coronary Intervention

Still in the Middle of a Rocky Road

Norihiro Kogame; Patrick W. Serruys; Yoshinobu Onuma


Eur Heart J. 2020;41(6):797-800. 

In This Article

Abstract and Introduction


Vascular calcification is classified into two categories according to its location. Calcification in the medial layer is called Monckeberg's atherosclerosis and is seen mainly in the peripheral arteries. Intimal calcification is the dominant type of calcification seen in the coronary arteries. Coronary artery calcification (CAC) pathologically begins as microcalcification (0.5–15 μm) resulting from apoptosis of foam cells and/or smooth muscle cells.[1] Microcalcification may become calcified sheets or plates,[1] which 'may fracture, leading to the formation of nodular calcification'.[1]

Nodular calcification is considered in 2–7% as an underlying cause of acute coronary thrombotic events due to discontinued endothelial lining,[1] although the relationship of CAC and plaque vulnerability is much more complex and not completely elucidated. Early CAC is associated with a risk of acute coronary syndrome, whereas advanced CAC is a passive, degenerative, and stable phenomenon, characteristic of the ageing process. In the 5-year serial assessment with fusion of intravascular ultrasound (IVUS, greyscale and virtual histology) and optical coherence tomography (OCT), calcification volume increased from baseline to 5 years by 2.3 mm3 whereas the most frequent precursor of calcification was necrotic core.[2] Clinically and non-invasively, detection and quantitative assessment of CAC is most often performed by the Agatston Scoring method using computed tomography without enhancement by contrast agent.[3] CAC implies the presence of (a)symptomatic coronary artery disease irrespective of other risk factors, and is an independent predictor of future adverse events.[1]

During percutaneous coronary intervention (PCI), CACs are an impediment to crossing the lesion with standard devices and to dilation with a standard balloon, which often results in stent underexpansion, and procedural complications such as slow flow/no reflow, dissection, and perforation.[4] Therefore, calcified lesions often require the use of dedicated techniques such as a rotablator, cutting/scoring balloon, or intravascular lithotripsy. 'Calcified plaque, the ultimate remnant after cell death, have to be removed mechanically or by some kind of osteoclastic biological process, currently inexistent in our vascular pharmacological armamentarium[5]'.

Angiographically identified severe coronary calcification is a known predictor of adverse clinical outcomes after revascularization with either PCI or coronary artery bypass graft (CABG).[4,6–8] In a large patient-level pooled analysis of acute coronary syndrome patients treated with stent, moderate or severe calcification was associated with a 62% higher risk of stent thrombosis and a 44% higher risk of target lesion failure than in non- or mildly calcified lesions.[4] Adverse clinical outcomes with presence of CAC may be related to a number of comorbidities (age, male sex, diabetes mellitus, and chronic kidney disease), larger plaque burden, increased technical complexity of PCI, post-procedural stent fracture, and stent underexpansion.[4,9] However, the pathophysiological mechanism for this elevated risk is poorly understood.

In this issue of the European Heart Journal, Torii et al. report the pathological response of a severely calcified lesion to the implantation of newer generation drug-eluting stents (DES) from a large pathological registry with 1211 stents.[10] A total of 134 lesions treated with newer generation DES with a duration of implant of ≥30 days were histologically analysed, and classified into two groups according to the presence or absence of severe calcification defined by radiographs [severely calcified lesion (SC, n = 46) and non-severely calcified lesion (NC, n = 88)]. Median duration of stent implant was 360 (158–720) days and 365 (150–720) days in SC and NC, respectively. SC was associated with higher prevalence of uncovered strut per lesion {2.4 [interquartile range (IQR) 0.0–19.0] % in SC vs. 0.0 [IQR 0.0–4.6] % in NC, P = 0.02} and severe medial tear (59% in SC vs. 44% in NC, P = 0.03) compared with NC. Severe medial tear was associated with exuberant neointima. Of note, ≥3 consecutive struts lying directly in contact with the superficial calcification was one of the independent predictors of uncovered struts and delayed healing (odds ratio 6.5, P < 0.0001). Paradoxically, lack of severe medial tear was also an independent predictor of uncovered struts and delayed healing (odds ratio 2.5, P = 0.0005).

The study clearly demonstrated that severely calcified lesions detected by radiographs are associated with delayed healing (e.g. higher prevalence of uncovered struts) after implantation of newer generation DES. This study explains the underlying mechanism for an increased risk when treating calcified lesions; some caveats exist, however, in the interpretation of these results in clinical and/or procedural contexts.