What ongoing studies are evaluating coronary imaging‑guided revascularization of unstable lesions in patients with multivessel coronary artery disease?

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Last updated: September 18, 2026 • View editorial policy

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Ongoing Studies on Coronary Imaging-Guided Revascularization in Multivessel Disease

The DEFINE GPS trial (NCT04451044) is currently investigating whether pre-procedural coronary pressure mapping with iFR pullback combined with 'virtual PCI' planning improves post-PCI clinical outcomes in patients with multivessel coronary artery disease. 1

Key Active Investigation

The DEFINE GPS trial represents the most significant ongoing study specifically addressing imaging-guided revascularization of unstable lesions in multivessel disease. This trial is evaluating:

  • Pre-procedural coronary pressure mapping using instantaneous wave-free ratio (iFR) pullback
  • Virtual PCI technology that combines invasive coronary pressure mapping superimposed on anatomical information from invasive coronary angiography
  • Prediction of post-PCI coronary pressure for any combination of stent location and length
  • Modification of procedural planning, which preliminary data suggests occurs in approximately 30% of cases 1

Context and Rationale

The rationale for DEFINE GPS stems from compelling preliminary evidence:

Post-PCI residual ischemia occurs in approximately 25% of patients after angiographically successful PCI, with roughly 80% of these cases attributable to focal lesions not identified by angiography alone 1. This represents a critical gap in current practice that imaging guidance aims to address.

Virtual PCI technology has demonstrated the ability to accurately predict post-PCI coronary pressure, allowing operators to optimize stent placement before actual deployment. The AQVA trial (n=300) already demonstrated that QFR/ICA-based virtual PCI achieved higher rates of optimal post-PCI QFR compared to conventional angiography-guided PCI (93.4% vs 84.9%, P=0.009) 1.

Recent Completed Evidence Supporting This Direction

While DEFINE GPS is ongoing, several recently completed trials have established the foundation for imaging-guided approaches in multivessel disease:

RENOVATE-COMPLEX PCI showed that intravascular imaging-guided PCI reduced the composite of cardiac death, target vessel-related MI, or clinically driven target-vessel revascularization compared to angiography-guided PCI by 2 years (7.7% vs 12.3%; HR 0.64; 95% CI 0.45-0.89; P=0.008) 1.

OCTOBER trial demonstrated that OCT-guided PCI reduced cardiac death, target-lesion MI, or ischemia-driven target-lesion revascularization compared to angiography-guided PCI at 2 years (10.1% vs 14.1%; HR 0.70; 95% CI 0.50-0.98; P=0.035) 1.

OCCUPI trial post-hoc analysis (2026) specifically examined patients with multivessel disease and complex lesions, showing OCT-guided PCI reduced 1-year MACE compared to angiography-guided PCI (4.7% vs 8.9%; HR 0.51; 95% CI 0.31-0.85; P=0.008) 2.

Clinical Implications

The DEFINE GPS trial addresses a critical question: whether advanced imaging guidance with virtual PCI planning can further optimize outcomes beyond what has already been demonstrated with conventional intravascular imaging. This is particularly relevant given that:

  • Post-PCI iFR/FFR optimization can be improved with additional intervention in some cases, but residual ischemia (≤0.80) persists in 18% of cases even after optimization attempts 1
  • Pre-procedural planning using virtual PCI may prevent suboptimal stent placement rather than attempting to correct it after deployment

Important Caveats

The focus on "unstable lesions" in multivessel disease requires clarification. Current evidence and ongoing trials primarily address:

  1. Anatomically complex lesions rather than specifically "unstable" plaque morphology
  2. Functionally significant stenoses identified by physiology (FFR/iFR) or imaging
  3. Optimization of stent deployment to reduce residual ischemia

The concept of targeting specifically "unstable" or vulnerable plaques in non-culprit vessels remains investigational, with intracoronary imaging offering unique information on plaque vulnerability, though dedicated outcome trials in this specific context remain limited 3.

References

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