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PURPOSE: To determine whether diagnosis of asymptomatic (silent) coronary ischemia using coronary computed tomography (CT)-derived fractional flow reserve (FFRCT) together with targeted coronary revascularization of ischemia-producing coronary lesions following lower-extremity revascularization can reduce adverse cardiac events and improve long-term survival of patients with chronic limb-threatening ischemia (CLTI). MATERIALS AND METHODS: Prospective cohort study of CLTI patients with no cardiac history or symptoms undergoing elective lower-extremity revascularization. Patients with pre-operative coronary computed tomography angiography (CTA) and FFRCT evaluation with selective post-operative coronary revascularization (FFRCT group) were compared with patients with standard pre-operative evaluation and no post-operative coronary revascularization (control group). Lesion-specific coronary ischemia was defined as FFRCT≤0.80 distal to a coronary stenosis with FFRCT≤0.75 indicating severe ischemia. Endpoints included all-cause death, cardiac death, myocardial infarction (MI) and major adverse cardiovascular (CV) events (MACE=CV death, MI, stroke, or unplanned coronary revascularization) during 5 year follow-up. RESULTS: In the FFRCT group (n=111), FFRCT analysis revealed asymptomatic (silent) coronary ischemia (FFRCT≤0.80) in 69% of patients, with severe ischemia (FFRCT≤0.75) in 58%, left main ischemia in 8%, and multivessel ischemia in 40% of patients. The status of coronary ischemia in the control group (n=120) was unknown. Following lower-extremity revascularization, 42% of patients in FFRCT had elective coronary revascularization with no elective revascularization in controls. Both groups received guideline-directed medical therapy. During 5 year follow-up, compared with control, the FFRCT group had fewer all-cause deaths (24% vs 47%, hazard ratio [HR]=0.43 [95% confidence interval [CI]=0.27-0.69], p<0.001), fewer cardiac deaths (5% vs 26%, HR=0.18 [95% CI=0.07-0.45], p<0.001), fewer MIs (7% vs 28%, HR=0.21 [95% CI=0.10-0.47], p<0.001), and fewer MACE events (14% vs 39%, HR=0.28 [95% CI=0.15-0.51], p<0.001). CONCLUSIONS: Ischemia-guided coronary revascularization of CLTI patients with asymptomatic (silent) coronary ischemia following lower-extremity revascularization resulted in more than 2-fold reduction in all-cause death, cardiac death, MI, and MACE with improved 5 year survival compared with patients with standard cardiac evaluation and care (76% vs 53%, p<0.001). CLINICAL IMPACT: Silent coronary ischemia in patients with chronic limb-threatening ischemia (CLTI) is common even in the absence of cardiac history or symptoms. FFRCT is a convenient tool to diagnose silent coronary ischemia perioperatively. Our data suggest that post-surgery elective FFRCT-guided coronary revascularization reduces adverse cardiac events and improves long-term survival in this very-high risk patient group. Randomized study is warranted to finally test this concept.
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OBJECTIVE: Patients undergoing vascular surgery procedures have poor long-term survival due to coexisting coronary artery disease (CAD), which is often asymptomatic, undiagnosed, and undertreated. We sought to determine whether preoperative diagnosis of asymptomatic (silent) coronary ischemia using coronary computed tomography (CT)-derived fractional flow reserve (FFRCT) together with postoperative ischemia-targeted coronary revascularization can reduce adverse cardiac events and improve long-term survival following major vascular surgery METHODS: In this observational cohort study of 522 patients with no known CAD undergoing elective carotid, peripheral, or aneurysm surgery we compared two groups of patients. Group I included 288 patients enrolled in a prospective Institutional Review Board-approved study of preoperative coronary CT angiography (CTA) and FFRCT testing to detect silent coronary ischemia with selective postoperative coronary revascularization in addition to best medical therapy (BMT) (FFRCT guided), and Group II included 234 matched controls with standard preoperative cardiac evaluation and postoperative BMT alone with no elective coronary revascularization (Usual Care). In the FFRCT group, lesion-specific coronary ischemia was defined as FFRCT ≤0.80 distal to a coronary stenosis, with severe ischemia defined as FFRCT ≤0.75. Results were available for patient management decisions. Endpoints included all-cause death, cardiovascular death, myocardial infarction (MI), and major adverse cardiovascular events (MACE [death, MI, or stroke]) during 5-year follow-up. RESULTS: The two groups were similar in age, gender, and comorbidities. In FFRCT, 65% of patients had asymptomatic lesion-specific coronary ischemia, with severe ischemia in 52%, multivessel ischemia in 36% and left main ischemia in 8%. The status of coronary ischemia was unknown in Usual Care. Vascular surgery was performed as planned in both cohorts with no difference in 30-day mortality. In FFRCT, elective ischemia-targeted coronary revascularization was performed in 103 patients 1 to 3 months following surgery. Usual Care had no elective postoperative coronary revascularizations. At 5 years, compared with Usual Care, FFRCT guided had fewer all-cause deaths (16% vs 36%; hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.22-0.60; P < .001), fewer cardiovascular deaths (4% vs 21%; HR, 0.11; 95% CI, 0.04-0.33; P < .001), fewer MIs (4% vs 24%; HR, 0.13; 95% CI, 0.05-0.33; P < .001), and fewer MACE (20% vs 47%; HR, 0.36; 95% CI, 0.23-0.56; P < .001). Five-year survival was 84% in FFRCT compared with 64% in Usual Care (P < .001). CONCLUSIONS: Diagnosis of silent coronary ischemia with ischemia-targeted coronary revascularization in addition to BMT following major vascular surgery was associated with fewer adverse cardiovascular events and improved 5-year survival compared with patients treated with BMT alone as per current guidelines.
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BACKGROUND: Major adverse cardiac events (MACEs) are the primary cause of death after carotid endarterectomy (CEA). We sought to determine whether selective coronary revascularization of CEA patients with asymptomatic coronary ischemia can reduce the risk of MACEs, myocardial infarction (MI), and cardiac death after endarterectomy compared with CEA patients receiving standard cardiac evaluation and care. METHODS: Two groups of patients with no cardiac history or symptoms undergoing elective CEA were compared. Group I: patients enrolled in a prospective study of noninvasive preoperative cardiac evaluation using coronary computed tomography (CT)-derived fractional flow reserve (FFRCT) to detect asymptomatic (silent) coronary ischemia with selective postoperative coronary revascularization. Group II: matched Control patients with standard preoperative cardiac evaluation and no postoperative coronary revascularization. Lesion-specific coronary ischemia in group I was defined as FFRCT ≤ 0.80 distal to coronary stenosis with severe ischemia defined as FFRCT ≤ 0.75. End points included MACEs, cardiac death, MI, cardiovascular (CV) death, stroke, and all-cause death through 3-year follow-up. RESULTS: Group I (n = 100) and group II (n = 100) patients were similar in age (68 vs 67 years), gender (65% vs 62% male), comorbidities, and indications for CEA (53% vs 48% symptomatic carotid stenosis). In group I, FFRCT analysis revealed lesion-specific coronary ischemia in 57% of patients, severe coronary ischemia in 44%, left main ischemia in 7%, and multivessel ischemia in 28%. The status of coronary ischemia in group II was unknown. CEA was performed without complications in both groups, and all patients received optimal postoperative medical therapy. In group I, elective coronary revascularization was performed in 33 patients (27 percutaneous coronary intervention; 6 coronary artery bypass grafting) 1 to 3 months after CEA. Group II patients had no elective coronary revascularization. During 3-year follow-up, compared with group II, group I patients had fewer MACEs (4% vs 17%, hazard ratio [HR]: 0.21 [95% confidence interval (CI): 0.07-0.63], P = .004), fewer cardiac deaths (2% vs 9%, HR: 0.20 [95% CI: 0.04-0.95], P = .030), fewer MIs (3% vs 17%, HR: 0.16 [95% CI: 0.05-0.54], P = .001), and fewer CV deaths (2% vs 12%, HR: 0.16 [95% CI: 0.004-0.07], P = .009). There were no significant differences in the rates of stroke or all-cause death. CONCLUSIONS: Preoperative diagnosis of silent coronary ischemia with selective coronary revascularization after CEA may reduce the risk of MACEs, cardiac death, MI, and CV death during 3-year follow-up compared with CEA patients receiving standard cardiac evaluation and care.