Long-term survival of chronic limb-threatening ischemia (CLTI) patients following lower-extremity revascularization (LER) is poor with >50% mortality at 5 years. Coronary artery disease is the primary cause of death and the Coronary Artery Revascularization Prophylaxis (CARP) trial (NEJM 2004) showed that coronary revascularization prior to vascular surgery did not improve long-term survival. Accordingly, optimal medical therapy is the current guideline-directed standard of care following LER, but this has not reduced the high mortality of CLTI patients. We sought to determine whether a new strategy of selective coronary revascularization after recovery from LER, in addition to optimal medical therapy, could reduce adverse coronary events and improve long-term survival. This strategy is based on the noninvasive diagnosis of unsuspected (silent) coronary ischaemia using coronary CT-derived fractional flow reserve (FFRCT) and multidisciplinary Vascular Team patient management.

We compared two groups of symptomatic CLTI patients with no cardiac history or coronary symptoms who underwent elective LER surgery: Group I: 103 patients enrolled in a prospective ethics committee-approved study of pre-operative cardiac evaluation using FFRCT to identify patients with asymptomatic ischaemia-producing coronary stenosis (FFRCT ≤0.80) with selective post-operative coronary revascularization (FFRCT group); and Group II: 120 concurrent matched controls with standard pre-operative cardiac evaluation and no post-operative coronary revascularization (Control). Both groups received optimum post-operative medical therapy. In FFRCT, lesion-specific coronary ischaemia was defined as FFRCT≤0.80 with FFRCT ≤0.75 indicating severe ischaemia. Endpoints included myocardial infarction (MI), cardiovascular (CV) death, and all-cause death during 3-year follow up.

Pre-operative evaluation in the FFRCT group revealed unsuspected (silent) coronary ischaemia in 69% of patients, with severe ischemia in 58% and left main ischaemia in 8%. The status of coronary ischaemia was unknown in Control. LER surgery was performed uneventfully in all patients in both groups. After recovery from surgery, patients in FFRCT with high-risk coronary lesions underwent coronary angiography with elective coronary revascularization in 47 patients (46%); 42 PCI and 5 CABG. During median follow-up of 36 months, compared to Control, the FFRCT group had fewer MIs (3.9% vs 22.5%, p=0.001, HR 0.14, 95% CI 0.05-0.40), fewer CV deaths (2.9% vs 17.5%, p=0.001, HR 0.14, 95% CI 0.04-0.48); and fewer all-cause deaths (10.7% vs. 27.5%, p=0.001, HR 0.32, 95% CI 0.16-0.64.

Pre-operative cardiac evaluation of CLTI patients with no known coronary disease using FFRCT revealed a high prevalence of unsuspected (silent) coronary ischaemia. Selective coronary revascularization of ischaemia-producing coronary lesions following lower-extremity revascularization resulted in fewer MIs, fewer CV deaths and improved three-year survival (89%) compared to patients receiving standard cardiac evaluation and optimum post-operative medical care (73%), p=0.001). These findings highlight the need for prospective, multicenter controlled trials to further define the role of FFRCT in the management of CLTI patients.