Abstract Background Up to 30% of coronary artery lesions continue to induce myocardial ischemia (FFR ≤ 0.8) despite angiographically successful PCI. This proportion is even larger after PCI to the left anterior descending (LAD) artery as it supplies blood to the largest myocardial territory and often has diffuse disease. Post PCI FFR is an important tool to risk stratify patients, as lower values are associated with a worse prognosis. Therefore, achieving a good functional PCI result after LAD treatment is crucial. PCI optimization tools such as intravascular ultrasound (IVUS) and FFR were both proven to be superior to angiography-guided PCI, however, there is a lack of studies comparing these two modalities head-to-head, especially in the long LAD lesions. Purpose To compare functional PCI result assessed with FFR measured immediately post PCI and at 9-12 months follow-up between IVUS optimization and FFR optimization strategies after percutaneous treatment of long LAD lesions. Methods This was a single center observational study, which enrolled 127 patients. 61 patients underwent PCI optimized with FFR (historical FFR optimization group) and for 66 patients PCI was optimized with IVUS. FFR measurement was performed using intravenous adenosine with a pullback before and after PCI for all patients. Post PCI FFR was recorded in both groups when the PCI result was considered to be final and no more optimization was performed afterwards. Patients also underwent invasive follow-up at 9-12 months post PCI with FFR measurement at the same location (Figure 1). A case example of IVUS optimization strategy is demonstrated in Figure 2. Results The average patients age (66.5 ± 9.5) and baseline clinical characteristics (males 70.1%, diabetes 20.5%, hypertension 92.1%, dyslipidemia 91.3%, smoking 23.0%, chronic kidney disease 21.3%) did not differ between IVUS and FFR optimization groups. IVUS strategy resulted in the longer stented segment compared to FFR group (62 [48-75] mm vs 52 [36-63] mm, p=0.03). The proportion of patients with optimal functional PCI result (FFR > 0.9) did not differ significantly between two groups (16.7% in IVUS group vs 15% in FFR group), however, there was a lower incidence of residual myocardial ischemia in the IVUS optimization group: 0% of patients with post-PCI FFR ≤ 0.8 in the IVUS group vs 13.3% in the FFR group (p=0.002). The trend for smaller ischemia prevalence in IVUS optimization strategy continued during follow-up: there were 4.5% of patients with target vessel related myocardial ischemia in IVUS group and 18.0% in FFR group (p=0.015). Conclusion(s) In the treatment of long LAD lesions IVUS PCI optimization strategy was associated with lower incidence of poor functional PCI result and smaller ischemia burden at follow-up compared to FFR optimization strategy. The implementation of intravascular imaging should be mandatory in the treatment of long diffuse coronary disease.Figure 1Figure 2