Coronary in-stent restenosis

Last revised by Joachim Feger on 16 Dec 2021

Coronary in-stent restenosis (ISR) is referred to as an increasing loss of the stented arterial lumen after a percutaneous coronary intervention (PCI) and coronary stent placement which requires revascularization.

However, there are different clinical and angiographic definitions:

Angiographic evidence of in-stent restenosis is defined as re-narrowing of the previously stented arterial lumen >50% compared to the diameter of the respective vessel.

Clinical evidence of in-stent restenosis is defined by a new lesion within the stent associated with symptoms and signs of myocardial ischemia.

Coronary in-stent restenosis is the most common complication after percutaneous coronary intervention but has been reduced step-by-step with the introduction of coronary stents and subsequent improvements in stent technology.  Clinical restenosis is less common than angiographic restenosis with rates of ≤5% and 10% after 12 months for newer generation drug-eluting stents 1,2.

Factors that increase the likelihood of developing coronary in-stent restenosis include 1,3:

  • procedure-related
    • small vessel lumen
    • residual stenosis after stent placement
    • longer stent length
    • complex or bifurcated lesion
  • stent-related 
  • patient-related
    • premature discontinuation of dual antiplatelet therapy
    • diabetes mellitus
    • chronic renal insufficiency

Clinical symptoms of restenosis include angina, ischemic changes on electrocardiogram and/or positive cardiac biomarkers e.g. troponins. About 18% of patients with in-stent restenosis present with acute coronary syndrome 3.

If left untreated in-stent restenosis can develop the following complications 1-5:

Coronary in-stent restenosis usually occurs as a result of a reaction to arterial wall injury and can be focal or diffuse. It is considered as a distinct pathophysiological process with the following contributing factors 1-4:

  • prolapse of the disrupted plaque
  • elastic recoil of the arterial wall
  • constrictive negative remodeling
  • neointimal hyperplasia 
  • neoatherosclerosis

Demonstration of a luminal diameter reduction >50% within the stent or the adjacent 5 mm proximal and distal to it are referred to as angiographic in-stent restenosis 1,3. Imaging modalities with the capacity to demonstrate myocardial ischemia such as stress echo, nuclear stress imaging or a cardiac stress MRI can be used to objectify clinical restenosis in the stent-related vascular territory.

Stress echocardiography might reveal stress-induced wall motion abnormalities in the respective coronary vascular territory of the stented coronary artery.

CT imaging of coronary stents is considered challenging 7. Still, it is a non-invasive option for the evaluation regarding coronary in-stent stenosis in some patients (e.g. who decline ICA for the time being) and depending on the type and size (≥3 mm) of the coronary stent might reveal good results. A high-end CT scanner will be highly beneficial for this task 6,7.

Invasive coronary angiography (ICA) will depict angiographic evidence of in-stent restenosis as a reduction in luminal diameter of >50% within the stent lumen or a re-narrowing of >75% of the cross-sectional vessel area acquired by imaging modalities using a 3D data set 1,2

A classification system also exists for the length of in-stent restenosis on coronary angiography 8

  • type I - focal restenosis: ≤10 mm in length
  • type II - diffuse intrastent restenosis: >10 mm in length, confined to the stent
  • type III - diffuse proliferative restenosis:  >10 mm in length, exceeds the stent
  • type IV - total occlusion: coronary stent thrombosis

A cardiac MRI stress test might show a perfusion defect or stress-related wall motion abnormalities corresponding to the respective coronary vascular territory and can also detect complications as myocardial infarction 4.

The radiological report should include a description of the following features based on the coronary artery segment and cardiac segmentation models:

  • cardiac CT
    • stent stenosis
    • location of the stent
    • other coronary artery stenoses
  • cardiac stress test

Coronary in-stent restenosis requires repeat revascularization and most patients can be treated again with percutaneous coronary intervention and repeat stenting with a newer generation drug-eluting stent or drug-coated balloon angioplasty 2-4 alternatively they can be treated with bypass surgery 4.

Coronary in-stent restenosis can mimic the appearance or presentation of the following clinical conditions 1:

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