Why is drug-eluting stent (DES) percutaneous coronary intervention (PCI) of ostial left circumflex (LCx) lesions at higher risk for in-stent restenosis (ISR)?

Why Ostial LCx Lesions Have Higher ISR Risk After DES PCI

Ostial left circumflex (LCx) lesions treated with drug-eluting stents, particularly when using two-stent techniques for distal left main bifurcation disease, have substantially higher rates of in-stent restenosis primarily due to mechanical stress from cardiac motion-induced cyclic bending and the technical complexity of achieving optimal stent apposition at the branch ostium.

Mechanical Factors: The Primary Culprit

Cyclic Bending and Cardiac Motion

• Large cyclic changes in the left main-LCx bending angle during the cardiac cycle are the most significant predictor of ostial LCx ISR, with pre-procedural cyclic bending angle changes >16.4° associated with an 11-fold increased risk of restenosis (adjusted OR 11.58,95% CI 4.04-33.19) 1

• The mean bending angle changes from 66.8° at end-diastole to 54.1° at end-systole, creating a dynamic range of approximately 13° throughout each cardiac cycle that subjects the stent to repetitive mechanical stress 1

• Post-procedural cyclic bending angle changes >9.8° and stent-induced diastolic bending angle changes >11.6° remain independent predictors of ostial LCx ISR even after stent placement 1

Anatomic and Hemodynamic Considerations

• Bifurcations are inherently prone to lesion development and restenosis due to greater shear stress and more frequent turbulent blood flow at these locations 2

• The ostial location creates challenges for optimal stent deployment, with difficulty achieving complete lesion coverage and proper stent expansion at the vessel origin 3

Two-Stent Technique Complications

Dramatically Higher Restenosis Rates

• Patients treated with two-stent techniques for distal left main bifurcation lesions show target lesion revascularization rates as high as 25%, with restenosis confined mainly to the left circumflex ostium 2

• Complex lesions requiring a two-stent strategy have significantly higher occurrence of LCx ostial ISR (HR 2.51,95% CI 1.59-3.97) and repeat target lesion revascularization for recurrent LCx ISR (HR 4.32,95% CI 0.97-19.20) compared to single-stent approaches 4

• In one series of distal left main bifurcation lesions treated with double-stent techniques, in-lesion restenosis occurred in 42% of patients, with 82% involving the branch ostia 2

Technical Challenges

• Achieving optimal stent apposition at the ostium is technically demanding, with risks of incomplete coverage, stent distortion, and gaps at the carina that promote neointimal hyperplasia 2

• Plaque shift occurs in 4.5% to 26% of bifurcation PCI cases, potentially compromising the side branch ostium 2

Clinical Outcomes and Pattern Recognition

Restenosis Patterns

• Ostial lesions demonstrate focal restenosis patterns in 85% of cases, predominantly at branch ostia 2

• The geographic position of ISR at the ostium represents a particularly high-risk pattern, with target lesion revascularization rates ranging from 10% for focal patterns to 80% for total occlusions 2

Overall Outcomes

• Despite higher restenosis rates, cardiac death rates remain relatively low in patients with LCx ostial ISR, with no cardiac deaths at 2 years in some series, though repeat revascularization remains common 4

• Contemporary data show that ostial lesions have significantly higher 12-month death (8.8% vs 4%) and major adverse cardiac events (24.2% vs 13.8%) compared to proximal non-ostial lesions 3

Mechanism of ISR at Ostial Sites

• The predominant mechanism of ISR is neointimal hyperplasia due to smooth muscle cell proliferation and extracellular matrix production, which is exacerbated by mechanical stress at ostial locations 2

• Repetitive mechanical deformation from cardiac motion creates chronic injury that stimulates excessive neointimal response despite drug-eluting properties of the stent 1

Treatment Implications

Preferred Strategies

• When treating ostial LCx lesions in the context of distal left main disease, single-stent approaches with provisional side branch stenting show superior outcomes with target lesion revascularization rates <5%, nearly equivalent to ostial or mid-left main lesions 2

• For established ISR at the ostial LCx, repeat PCI with DES is superior to plain balloon angioplasty (HR for repeat TLR with balloon: 3.29,95% CI 1.41-7.69) 4

Critical Pitfall to Avoid

• Routine use of two-stent techniques for all distal left main bifurcations should be avoided unless there is a large side branch with high occlusion risk, as this dramatically increases ostial LCx restenosis without improving mortality outcomes 2, 4