Yes, there are significant differences between native coronary artery stenosis and in-stent restenosis (ISR) in terms of pathophysiology, risk factors, treatment approaches, and outcomes. Here’s a detailed comparison:

1. Pathophysiology

• Native Coronary Artery Stenosis: Caused by the progression of atherosclerosis, which involves the buildup of plaque (lipid deposits, inflammatory cells, and fibrous tissue) within the arterial wall. The process is gradual and involves endothelial dysfunction, inflammation, and smooth muscle cell proliferation. Plaque rupture or erosion can lead to acute coronary syndromes (e.g., myocardial infarction).
• In-Stent Restenosis (ISR): Occurs after percutaneous coronary intervention (PCI) with stent placement. Primarily caused by neointimal hyperplasia, an exaggerated healing response characterized by the proliferation and migration of smooth muscle cells into the stent lumen. Other mechanisms include chronic inflammation (due to the presence of the stent), incomplete stent apposition, and stent under expansion. ISR is less likely to involve plaque rupture compared to native stenosis.

2. Risk Factors

• Native Coronary Artery Stenosis: Traditional cardiovascular risk factors: hypertension, hyperlipidemia, diabetes, smoking, obesity, and family history. Age and male gender are also significant risk factors.
• In-Stent Restenosis (ISR): Stent-related factors: Drug-eluting stents (DES) have a lower risk of ISR compared to bare-metal stents (BMS), but DES can still cause ISR, especially if stent deployment is suboptimal. Patient-related factors: Diabetes, chronic kidney disease, and genetic predisposition. Lesion-related factors: Small vessel diameter, long lesions, and bifurcation lesions. Procedural factors: Inadequate stent expansion, malposition, or geographic miss (failure to cover the entire lesion).

3. Clinical Presentation

• Native Coronary Artery Stenosis: Symptoms depend on the degree of stenosis and may include stable angina (chest pain on exertion) or acute coronary syndromes (unstable angina, myocardial infarction).
• In-Stent Restenosis (ISR): Often presents as recurrent angina, typically within 6–12 months after stent placement. ISR can also present as acute coronary syndromes, though this is less common than with native stenosis.

4. Diagnostic Evaluation

• Native Coronary Artery Stenosis: Diagnosed using non-invasive tests (e.g., stress testing, CT angiography) or invasive coronary angiography.
• In-Stent Restenosis (ISR): Coronary angiography remains the gold standard, but intravascular imaging (e.g., intravascular ultrasound [IVUS] or optical coherence tomography [OCT]) is often used to assess stent-related issues (e.g., malposition, under expansion).

5. Treatment Approaches

• Native Coronary Artery Stenosis: Medical therapy (e.g., antiplatelets, statins, beta-blockers, ACE inhibitors) is the first-line treatment. Revascularization (PCI or coronary artery bypass grafting [CABG]) is considered for significant stenosis with symptoms or evidence of ischemia.
• In-Stent Restenosis (ISR): Repeat PCI: Often involves the use of drug-eluting balloons (DEBs) or additional stents (preferably DES). Atherectomy or laser therapy: Used in cases of severe neointimal hyperplasia or calcified lesions. Intravascular imaging: Helps guide treatment by identifying underlying causes (e.g., stent under expansion). CABG: Considered in complex or recurrent ISR cases.

6. Prognosis

• Native Coronary Artery Stenosis: Prognosis depends on the extent of atherosclerosis, response to medical therapy, and success of revascularization.
• In-Stent Restenosis (ISR): ISR carries a higher risk of recurrent restenosis compared to native stenosis, particularly if the underlying cause (e.g., stent under expansion) is not addressed. Patients with ISR often require closer follow-up and more aggressive risk factor management.

Conclusion

While both native coronary artery stenosis and in-stent restenosis involve narrowing of the coronary arteries, their underlying mechanisms, risk factors, and treatment strategies differ significantly. ISR is a unique entity that requires specialized approaches, particularly the use of intravascular imaging and advanced interventional techniques, to address stent-related issues and prevent recurrence.

and what would be the consequences for the patients undergoing CABG, with native or ISR?

The surgeon may face more incomplete revascularization in the ISR patient, when you now consider the coronary proximal to the stent may not benefit from a bypass distal to the ISR lesion. Also, the "jailed" perforating vessels originating from where the stent is expanded, may be less likely to benefit from flow from the bypass, either from being occluded when the stent was inflated or by the intimal hyperplasia limiting retrograde inflow into the stent.

Thanks.

Several times after the end of protamine . we observed sudden ST elevation while after the completion of the CABG procedure and before protamine administration everything was OK; even when the graft seemed being morphologically and functionally perfect ; the latter phenomena was observed just in the patients with previous stenting.

We concluded that in competition with graft flow and prothrombotic effect of protamine , the stent was abruptly occluded by in-situ thrombose formation , a key difference compared with native stenosis.

Of course all branches subtended via the stent mesh structure (such as septal and diagonal) are compromised; a potential reason for perioperative MI and why the patients with previous stenting are at higher risk by the time of CABG.

We deemed such phenomena as "Stenting hegemonies".