Association between PET-derived ischemic burden and cardiopulmonary functional gain after CTO revascularization

Introduction Revascularization of chronic total occlusions (CTO) aims to reduce myocardial ischemia and improve functional capacity. However, it remains unclear which CTO patients derive the greatest objective functional benefit from percutaneous coronary intervention (PCI). Purpose To evaluate whether baseline ischemic burden measured by [13N]NH3 PET-CT predicts functional benefit after CTO-PCI and whether ischemia reduction correlates with changes in cardiopulmonary exercise testing (CPET). Methods Thirty-two CTO patients were prospectively evaluated with [13N]NH3 PET-CT and treadmill CPET before and after PCI. Ischemia was quantified using summed difference score (SDS), both globally and within the CTO territory. CPET parameters included peak VO2, % predicted peak VO2, O2 pulse, VE/VCO2 slope, and exercise duration. A maximal effort (RER >1.10) was achieved in 59% at both evaluations; however the full cohort was analyzed to reflect real-world response. Pearson correlations and multivariable linear regression adjusted for age and baseline CPET values were performed. Results CTO-PCI reduced global SDS (−5.6±5.9; p<0.001) and regional SDS (−4.4±4.0; p<0.001), indicating marked ischemia reduction. This was accompanied by improvements in peak VO2 (Δ1.6±2.7mL/kg/min; p=0.001), % predicted peak VO2 (Δ9.7±11.4%; p<0.001), O2 pulse (Δ1.2±1.8mL/beat; p<0.001), and exercise duration (Δ70.1±151.4s; p=0.016), with a trend toward lower VE/VCO2 slope (p=0.070). Reduction in global ischemia (Δ global SDS) correlated with improvement in peak VO2 (r=−0.454; p=0.009) and % predicted peak VO2 (r=−0.509; p=0.003), remaining independently associated after multivariable adjustment (peak VO2: β=−0.24, 95% CI −0.37 to −0.10; p=0.002; % predicted peak VO2: β=−1.09, 95% CI −1.63 to −0.54; p=0.001). Baseline global SDS showed a modest, non-significant correlation with Δ peak VO2 (r=0.342; p=0.055), which was not retained after adjustment (p=0.342). In contrast, baseline global SDS independently predicted change in VE/VCO2 slope (β=−0.32, 95% CI −0.59 to −0.04; p=0.036). Regional ischemia (baseline or Δ SDS) was not independently associated with peak VO2 gain. Conclusion In CTO patients, PCI resulted in marked global ischemia reduction and objective improvement in exercise capacity. Importantly, functional gain in peak oxygen consumption was independently linked to the magnitude of global - rather than territorial - ischemia relief. These findings suggest that the benefit of CTO revascularization extends beyond simple reperfusion of the occluded vessel and may reflect restoration of balanced global myocardial perfusion, potentially through attenuation of coronary steal phenomenon. By linking global ischemia reduction to improvements in exercise capacity, our results provide mechanistic insight into how ischemia relief translates into functional recovery and support an ischemia-guided approach to CTO revascularization.