Coronary in-stent restenosis

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.

Terminology

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.

Epidemiology

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.

Risk factors

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 
  • bare-metal stent
  • 1st generation drug-eluting stents
  • thick struts
• patient-related
  • premature discontinuation of dual antiplatelet therapy
  • diabetes mellitus
  • chronic renal insufficiency

Clinical presentation

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.

Complications

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

• myocardial infarction (type 4c)
• coronary stent thrombosis
• sudden cardiac death

Pathology

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

Radiographic features

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.

Echocardiography

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

CT 

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.

Coronary angiography

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

MRI

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.

Radiological report

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
  • signs of myocardial ischemia

Treatment and prognosis

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.

Differential diagnosis

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

• coronary stent thrombosis
• coronary artery dissection
• myocarditis
• aortic dissection