Although model organisms have provided insight into the earliest stages of cardiac and hepatic vascularization, we know very little about this process in humans because of ethical restrictions and the technical difficulty of obtaining embryos during very early development. In this study, we demonstrate that micropatterned human pluripotent stem cell-derived gastruloids enable in vitro modeling of the earliest stages of vascularization. We identify a combination of vascular-inducing factors that give rise to cardiac vascularized organoids with a spatially organized and branched vascular network. To show the broader utility of our vascularization strategy, we use the same vascular-inducing factors to produce hepatic vascularized organoids. Our results suggest that a conserved developmental program generates the vasculature within different types of organs.

OBJECTIVES:Long-term survival after carotid endarterectomy (CEA) is limited by adverse cardiac events with 5% annual mortality. We sought to determine whether diagnosis of silent coronary ischemia together with elective ischemia-targeted coronary revascularization can reduce death and myocardial infarction (MI) and improve long-term survival of patients after CEA. METHODS:Observational cohort study of patients with no cardiac history or coronary symptoms undergoing elective CEA. Patients enrolled in a prospective study of preoperative cardiac evaluation using coronary computed tomography-derived fractional flow reserve (FFRCT) to detect silent (asymptomatic) coronary ischemia together with elective postoperative ischemia-targeted coronary revascularization were compared with matched controls with standard preoperative cardiac evaluation and no elective coronary revascularization. Lesion-specific coronary ischemia was defined as an FFRCT of ≤0.80 distal to >30% stenosis with severe ischemia defined as an FFRCT of ≤0.75. End points included all-cause death, cardiac death, MI, stroke, and major adverse cardiovascular events (MACE) (defined as cardiovascular death, MI, or stroke) during 5 years of follow-up. RESULTS:FFRCT (n = 100) and control (n = 100) cohorts were well-matched with no significant differences in age, gender, comorbidities, or indications for CEA. Asymptomatic lesion-specific coronary ischemia (FFRCT of ≤0.80) was present in 57% of FFRCT patients, with severe ischemia in 44% and left main ischemia in 7%; 43% had no coronary ischemia (FFRCT of >0.80). The status of coronary ischemia was unknown in the controls. CEA was performed successfully in both cohorts with no deaths or neurological events, and all patients received optimal postoperative medical therapy. Elective ischemia-targeted coronary revascularization was performed in 33% of FFRCT patients within 3 months of CEA. Controls had no elective coronary revascularization. During 5 years of follow-up, compared with controls, the FFRCT group had fewer all-cause deaths (11% vs 24%; hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.17-0.77; P = .016); fewer cardiac deaths (3% vs 13%; HR, 0.15; 95% CI, 0.03-0.69; P = .009); fewer MIs (3% vs 21%; HR, 0.07; 95% CI, 0.02-0.31; P < .001), and fewer MACEs (10% vs 33%; HR, 0.21; 95% CI, 0.10-0.44; P < .001) with no differences in stroke. There were no cardiac deaths or MIs among patients with no coronary ischemia (FFRCT of >0.80). Annual mortality in FFRCT was 2.2% per year compared with 4.8% per year in controls. CONCLUSIONS:Diagnosis of silent coronary ischemia together with elective ischemia-targeted coronary revascularization after CEA decrease the 5-year risk of all-cause death, cardiac death, MI, and MACE by >50% and improved survival (89%) compared with patients receiving standard cardiac evaluation and care (76%).

Background and Objectives: Lower extremity arterial disease is one of the most prevalent manifestations of atherosclerosis. The results from numerous studies regarding the best revascularization method of an occluded superficial femoral artery have been conflicting. The aim of this study was to compare the patency of transvenous endovascular with open femoropopliteal bypass, both with vein and prosthetic grafts. To our knowledge, a direct patency comparison between transvenous endovascular and open femoropopliteal bypass has not been published. This could help elucidate which method is preferable and in which cases. Materials and Methods: Patients with complex TASC-C and D SFA lesions were offered endovascular transvenous or open bypass. A total of 384 consecutive patients with PAD requiring surgical treatment were evaluated for inclusion in this study. Three-year follow-up data were collected for 52 endovascular procedures, 80 prosthetic grafts, and 44 venous bypass surgeries. Bypass patency was investigated by Duplex US every 6 months. Kaplan–Meier plots were used to analyze primary, primary-assisted, and secondary patency for endovascular transvenous, autovenous, and prosthetic bypasses. Results: Primary, primary-assisted, and secondary patency in venous group at 3 years was 70.5%, 77.3%, and 77.3%, respectively. In the endovascular transvenous group, primary, primary-assisted, and secondary patency at 3 years was 46.2%, 69.2%, and 76.9%, respectively. The lowest patency rates at 3 years were noted in the prosthetic graft group with 22.5% primary, 26.6% primary-assisted, and 28.2% secondary patency. Conclusions: The saphenous vein is the best graft to perform in above-the-knee femoropopliteal bypass. Transvenous endovascular bypass is a viable option with comparable primary-assisted and secondary patency. Primary patency is substantially lower for endovascular transvenous compared to venous bypass. Patients treated with endovascular transvenous bypass will require a significant number of secondary procedures to provide optimal patency. Prosthetic grafts should only be used if no other option for bypass is available.

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.

It is well-known that patients undergoing coronary artery bypass grafting (CABG) with coexisting carotid artery disease are at increased risk for perioperative stroke and death. The prevalence of carotid disease among patients undergoing CABG is 6% to 14%, 1 Feldman D.N. Swaminathan R.V. Geleris J.D. et al. Comparison of trends and in-hospital outcomes of concurrent carotid artery revascularization and coronary artery bypass graft surgery: the United States experience 2004-2012. J Am Coll Cardiol Interv. 2017; 10: 286-298 Crossref PubMed Scopus (48) Google Scholar and the risk of stroke following CABG increases from 3% for unilateral 50% to 99% stenosis to 5% for bilateral 50% to 99% stenoses and 10% for carotid occlusion. 2 Naylor A.R. Mehta Z. Rothwell P.M. Bell P.R.F. Carotid artery disease and stroke during coronary artery bypass: a critical review of the literature. Eur J Vasc Endovasc Surg. 2002; 23: 283-294 Abstract Full Text PDF PubMed Scopus (370) Google Scholar The risk of stroke and death are notably higher in patients with a history of transient ischemic attack (TIA)/stroke. In an effort to reduce the risk of stroke, a variety of strategies have been proposed for carotid treatment with carotid endarterectomy (CEA) or carotid artery stenting (CAS) in conjunction with CABG. These strategies have been compared in numerous studies over the past four decades with conflicting results. But they are not often compared with the strategy of no treatment of coexisting carotid disease and treatment with CABG alone. Thus, the optimal approach to managing carotid artery disease in patients undergoing CABG remains unsettled. The key unresolved clinical questions are: (1) does any carotid intervention in addition to CABG improve outcome, and if so, (2) what is the optimal method (CEA or CAS), timing (combined or staged), and sequence (before or after) of carotid intervention? Systematic review and meta-analysis of the treatment strategies for coronary artery bypass graft patients with concomitant carotid artery atherosclerotic diseaseJournal of Vascular SurgeryVol. 78Issue 4PreviewStroke is one of the devastating complications after coronary artery bypass graft (CABG). Underlying carotid artery atherosclerotic disease is reported to be an independent risk factor. The optimal treatment strategy for these patients remains under debate. Full-Text PDF

Myocardial injury, as evidenced by postoperative troponin (TnT) elevation, is a common complication after noncardiac surgery. In this issue of the Journal, Farazdaghi et al 1 Farazdaghi A. Manunga J.M. Bhatti U.H. Nuttall G.A. Bower T.C. Heins C. et al. Asymptomatic myocardial injury identified on postoperative troponin testing after open or endovascular surgical procedures is a predictor of mortality. J Vasc Surg. 2023; 77: 1216-1223 Abstract Full Text Full Text PDF Scopus (1) Google Scholar reported that routine TnT testing after vascular surgical procedures revealed that 25% of patients had experienced a myocardial injury that was associated with increased early and late mortality, irrespective of cardiac symptoms. 1 Farazdaghi A. Manunga J.M. Bhatti U.H. Nuttall G.A. Bower T.C. Heins C. et al. Asymptomatic myocardial injury identified on postoperative troponin testing after open or endovascular surgical procedures is a predictor of mortality. J Vasc Surg. 2023; 77: 1216-1223 Abstract Full Text Full Text PDF Scopus (1) Google Scholar This is consistent with numerous studies showing that myocardial injury after noncardiac surgery (MINS) is associated with high postoperative mortality. In a meta-analysis of 195 studies reporting the outcomes of 530,867 noncardiac surgeries, 19% of the patients had experienced a MINS (93% asymptomatic) with 1-year mortality of 21% compared with 5% for patients without a MINS. 2 Smilowitz N.R. Redel-Traub G. Hausvater A. Armanious A. Nicholson J. Puelacher C. et al. Myocardial injury after noncardiac surgery: a systematic review and meta-analysis. Cardiol Rev. 2019; 27: 267-273 Crossref PubMed Scopus (77) Google Scholar The study by Farazdaghi et al 1 Farazdaghi A. Manunga J.M. Bhatti U.H. Nuttall G.A. Bower T.C. Heins C. et al. Asymptomatic myocardial injury identified on postoperative troponin testing after open or endovascular surgical procedures is a predictor of mortality. J Vasc Surg. 2023; 77: 1216-1223 Abstract Full Text Full Text PDF Scopus (1) Google Scholar has provided valuable long-term mortality data showing that vascular patients with TnT elevation had had an alarmingly high 81% mortality at 8 years compared with 49% for patients without TnT elevation (P < .0001). However, TnT testing was not linked to a specific management plan for patients with TnT elevation, and only 29% had had documented cardiology follow-up. 1 Farazdaghi A. Manunga J.M. Bhatti U.H. Nuttall G.A. Bower T.C. Heins C. et al. Asymptomatic myocardial injury identified on postoperative troponin testing after open or endovascular surgical procedures is a predictor of mortality. J Vasc Surg. 2023; 77: 1216-1223 Abstract Full Text Full Text PDF Scopus (1) Google Scholar Thus, one might question the value of routine postoperative TnT testing if not accompanied by an algorithm to guide further cardiac evaluation and/or treatment of those with a positive test. Medical therapy alone has not been shown to effectively reduce the high mortality. Asymptomatic myocardial injury identified on postoperative troponin testing after open or endovascular surgical procedures is a predictor of mortalityJournal of Vascular SurgeryVol. 77Issue 4PreviewElevated troponin (TnT) levels after open or endovascular surgical procedures have been previously shown to correlate with significantly higher postoperative and short-term mortality. The incidence of asymptomatic myocardial injury after vascular surgical procedures has also been shown to be high. The aim of the present study was to evaluate the utility of routine postoperative TnT screening and long-term outcomes for patients with postoperative TnT elevation. Full-Text PDF

Abstract Background The clinical importance of physiological distribution of coronary atherosclerosis is emerging. However, this concept has limited clinical application because of complex formulas and technical difficulties in measurement. Purpose We aimed to evaluate the utility of a simple physiological metric using pressure drop across the lesion, through the analysis of association with hemodynamic and plaque characteristics. Methods The analysis was conducted on a total 246 lesions in 136 vessels from DISCOVER-FLOW study, which was the first-in-human, prospective, international, multi-center study demonstrating the diagnostic accuracy of coronary computational tomographic angiography (CCTA)-derived fractional flow reserve (FFRCT) for invasive FFR. All vessel- and lesion-level hemodynamic as well as plaque parameters were analyzed by independent core laboratories using CCTA and computational fluid dynamic techniques. Functional significance (FS) was defined as CTA-derived FFR (FFRCT) ≤ 0.80, and physiological focal disease (PFD) was defined as change in FFRCT across the lesion (ΔFFRCT) ≥ 0.06 and FFR drop across the lesion ≥ 0.0015/mm. The lesions were categorized into four groups based on the existence of FS and/or PFD and denoted as follows: FS(-) PFD(-) for group A, FS(-) PFD(+) for group B, FS(+) PFD(-) for group C, FS(+) PFD(+) for group D; Statistics of hemodynamic and plaque characteristics among the four groups were compared. Results 48.8% and 54.5% of total lesions were designated as FS and PFD, respectively. Vessel-level characteristics such as total plaque volume (TPV) of vessel and percent atheroma volume (PAV) of vessel were positively associated with FS (all p<0.001 for A vs C and B vs D). In the lesion level, wall shear stress (WSS) was higher when PFD was present, regardless of FS (136.5 vs 260.8, p<0.001 with A vs B; 125.6 vs 299.9, p<0.001 with C vs D, Figure panel a). Plaque burden at minimal lumen area (PB) was significantly greater with PFD in both negative FS and positive FS (52.3 vs 68.5, p<0.001 with A vs B; 49.5 vs 81.1, p<0.001 with C vs D, Figure panel b). Other volumetric plaque factors such as plaque volume (PV) and PAV, were also significantly greater with PFD in both negative FS and positive FS (all p<0.01 for A vs B and C vs D, Figure panel c and d). Adverse plaque characteristics (APC) were found to be frequently present in conjunction with PFD, regardless of FS (30.0% vs 53.6%, p=0.013 with A vs B; 26.2% vs 68.0%, p<0.001 with C vs D, Figure panel e). PFD without FS showed significantly higher in all hemodynamic and plaque characteristics compared to FS without PFD (B vs C - p<0.001 for WSS, PV, PAV; p=0.002 for PB; p=0.012 for APC, Figure). Conclusions Hemodynamic and morphological characteristics related to plaque vulnerability were associated with a pressure drop-derived index, PFD, independent of functional significance of the vessel.

Background and aims: Hemodynamic and plaque characteristics can be analyzed using coronary CT angiography (CTA). We aimed to explore long-term prognostic implications of hemodynamic and plaque characteristics using coronary CT angiography (CTA). Methods: Invasive fractional flow reserve (FFR) and CTA-derived FFR (FFRCT) were undertaken for 136 lesions in 78 vessels and followed-up to 10 years until December 2020. FFRCT, wall shear stress (WSS), change in FFRCT across the lesion (Delta FFRCT), total plaque volume (TPV), percent atheroma volume (PAV), and low-attenuation plaque volume (LAPV) for target lesions [L] and vessels [V] were obtained by independent core laboratories. Their collective influence was evaluated for the clinical endpoints of target vessel failure (TVF) and target lesion failure (TLF).Results: During a median follow-up of 10.1 years, PAV[V] (per 10% increase, HR 2.32 [95% CI 1.11-4.86], p = 0.025), and FFRCT[V] (per 0.1 increase, HR 0.56 [95% CI 0.37-0.84], p = 0.006) were independent predictors of TVF for the per-vessel analysis, and WSS[L] (per 100 dyne/cm2 increase, HR 1.43 [1.09-1.88], p = 0.010), LAPV [L] (per 10 mm3 increase, HR 3.81 [1.16-12.5], p = 0.028), and Delta FFRCT[L] (per 0.1 increase, HR 1.39 [1.02-1.90], p = 0.040) were independent predictors of TLF for the per-lesion analysis after adjustment for clinical and lesion characteristics. The addition of both plaque and hemodynamic predictors improved the predictability for 10-year TVF and TLF of clinical and lesion characteristics (all p < 0.05). Conclusions: Vessel-and lesion-level hemodynamic characteristics, and vessel-level plaque quantity, and lesion -level plaque compositional characteristics assessed by CTA offer independent and additive long-term prognostic value.

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.

Background: Patients with Peripheral Artery Disease (PAD) undergoing lower-extremity revascularization are at increased risk of death and Myocardial Infarction (MI) due to co-existing Coronary Artery Disease (CAD) which is often unrecognized due to absence of chest pain symptoms. A new cardiac diagnostic test, coronary CT-derived Fractional Flow Reserve (FFRCT), can identify patients with unsuspected (silent) coronary ischemia. We sought to determine whether pre-operative diagnosis of silent coronary ischemia using FFRCT can facilitate multidisciplinary care to reduce post-operative death and MI and improve survival of PAD patients. Methods: Symptomatic PAD patients with no cardiac history or symptoms were enrolled in a prospective, open-label study of coronary CTA and FFRCT testing before lower-extremity revascularization and were compared to historic control patients with standard pre-operative cardiac evaluation and care. Lesion-specific coronary ischemia was defined as FFRCT ≤ 0.80 distal to a coronary stenosis. Endpoints included Cardiovascular (CV) death, MI and allcause death through 1 year follow up. Results: Baseline characteristics of the CTA-FFRCT (n=135) and Control (n=135) groups were similar with regard to age (66 ± 8 years), gender, co-morbidities and indication for surgery (>80% for CLTI). CTA-FFRCT evaluation revealed unsuspected (silent) coronary ischemia in 68% of patients and 40% of patients had elective post-operative coronary revascularization (PCI in 47, CABG in 7). The status of coronary ischemia was unknown in Control patients and none had elective coronary revascularization. At one year, CTA-FFRCT had fewer CV deaths (0.7% vs. 5.9%, p=0.04) and MIs (2.2% vs. 8.1%, p=0.03) and improved survival (99.3% vs. 94.1%, p=0.02) compared to Control. Conclusion: Pre-operative diagnosis of silent coronary ischemia in patients undergoing lower-extremity revascularization surgery can identify high-risk patients and facilitate multi-disciplinary patient care with selective post-operative coronary revascularization. This strategy reduced post-operative death and MI and improved one-year survival compared to standard care.

Objectives: The aim of this study was to determine whether selective coronary revascularization of Peripheral Artery Disease (PAD) patients with silent coronary ischemia can improve survival following lower-extremity revascularization compared to patients with no cardiac symptoms receiving best medical therapy alone. Methods: Matched cohort analysis of PAD patients with no cardiac history or symptoms with (a) pre-operative CT-derived fractional flow reserve (FFRCT) evaluation to detect silent coronary ischemia and selective post-operative coronary revascularization (FFRCT-Guided) or (b) standard pre-operative cardiac evaluation with monitored post-operative medical therapy in the VOYAGER PAD trial (Medical Therapy). The status of silent ischemia in Medical Therapy was unknown. Study endpoints included death, Myocardial Infarction (MI) and death or MI. Results: Among 78 FFRCT-Guided patients, 53 (68%) had silent coronary ischemia (FFRCT ≤ 0.80) of which 29 (55%) had post-operative coronary revascularization. Among 79 Medical Therapy patients none had elective coronary revascularization. During a median follow-up of 30 months, compared to Medical Therapy, FFRCT-Guided patients had fewer deaths (5.1% vs. 22.8%; adjusted Hazard Ratio (HR): 0.292; 95% Confidence Interval (CI) 0.086-0.997; p=0.049), fewer MIs (3.8% vs. 15.2%; HR: 0.233; 95% CI 0.058-0.936; p=0.040) and fewer deaths or MI (7.7% vs. 26.6%, HR 0.323, 95% CI 0.115-0.909, p=0.032). Conclusion: Coronary revascularization of PAD patients with silent ischemia in addition to medical therapy was associated with fewer deaths and MIs following lower-extremity revascularization compared to PAD patients with no coronary symptoms receiving best medical therapy alone.

Background: Patients with critical limb-threatening ischemia (CLTI) have had poor long-term survival after lower extremity revascularization owing to coexistent coronary artery disease. A new cardiac diagnostic test, coronary computed tomography-derived fractional flow reserve (FFRCT), can identify patients with ischemia-producing coronary stenosis who might benefit from coronary revascularization. We sought to determine whether the diagnosis of silent coronary ischemia before limb salvage surgery with selective postoperative coronary revascularization can reduce the incidence of adverse cardiac events and improve the survival of patients with CLTI compared with standard care. Methods: Patients with CLTI and no cardiac history or symptoms who had undergone preoperative testing to detect silent coronary ischemia with selective postoperative coronary revascularization (group I) were compared with patients with standard preoperative cardiac clearance and no elective postoperative coronary revascularization (group II). Both groups received guideline-directed medical care. Lesion-specific coronary ischemia in group I was defined as FFRCT of <= 0.80 distal to a stenosis, with severe ischemia defined as FFRCT of <= 0.75. The endpoints included all-cause death, cardiovascular (CV) death, myocardial infarction (MI), major adverse CV events (i.MACE; CV death, MI, unplanned coronary revascularization, stroke) through 2 years of follow-up. Results: Groups I (n = 111) and II (n = 120) were similar in age (66 +/- 9 vs 66 +/- 7 years), gender (78% vs 83% men), comorbidities, and surgery performed. In group I, unsuspected, silent coronary ischemia was found in 71 of 103 patients (69%), with severe ischemia in 58% and left main coronary ischemia in 8%. Elective postoperative coronary revascularization was performed in 47 of 71 patients with silent ischemia (66%). In group II, the status of silent coronary ischemia was unknown. The median follow-up was >2 years for both groups. The 2-year outcomes for groups I and II were as follows: all-cause death, 8.1% and 20.0% (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.18-0.84; P=.016); CV death, 4.5% and 13.3% (HR, 0.32; 95% CI, 0.11-0.88; P=.028); MI, 6.3% and 17.5% (HR, 0.33; 95% CI, 0.14-0.79; P=.012); and major adverse CV events, 10.8% and 23.3% (HR, 0.44; 95% CI, 0.22-0.88; P=.021), respectively. Conclusions: The preoperative evaluation of patients with CLTI and no known coronary artery disease using coronary FFRCT revealed silent coronary ischemia in two of every three patients. Selective coronary revascularization of patients with silent coronary ischemia after recovery from limb salvage surgery resulted in fewer CV deaths and MIs and improved 2-year survival compared with patients with CLTI who had received standard cardiac evaluation and care. Prospective controlled studies are required to further define the role of FFRCT in the evaluation and treatment of patients with CLTI.

A 63-year-old man with a ruptured abdominal aortic aneurysm (AAA) into the inferior vena cava (IVC) underwent aortobifemoral bypass and closure of the aortocaval fistula (ACF). An additional bypass graft from the right iliac limb to the right internal iliac artery was placed to avoid colonic and pelvic ischemia. Preoperative computed tomography angiography (CTA) revealed an 8.6 cm AAA with rupture into the IVC through an 8.5 mm ACF (A). In addition, there was a 5.8 cm right common iliac and a 5.3 cm left common iliac artery aneurysm (B). The patient became hemodynamically unstable during CTA, and suffered a cardiac arrest with prompt cardiac resuscitation, intubation, and immediate transfer to the operating room. Ten hours after successful surgery the patient was awake and stable. He had no cardiac history, no symptoms suggestive of coronary artery disease (CAD) and had no electrocardiographic changes. However, the troponin level increased to 217,479.7 ng/L and the creatine kinase MB level increased to 504.6 ng/mL. Coronary angiography revealed left main coronary stenosis and subocclusion of the right coronary artery (C). Percutaneous coronary revascularization was performed with implantation of drug-eluting stents in the left main and right coronary artery. The patient recovered uneventfully. The 6-month follow-up CTA demonstrated patent aortobifemoral and right internal iliac bypass grafts and the IVC without signs of stenosis (D). Written informed consent was obtained from the patient for his anonymized information to be published in this article. AAA rupture into the IVC is rare and is associated with high mortality.1Davidovic L. Dragas M. Cvetkovic S. Kostic D. Cinara I. Banzic I. Twenty years of experience in the treatment of spontaneous aorto-venous fistulas in a developing country.World J Surg. 2011; 35: 1829-1834Crossref PubMed Scopus (19) Google Scholar, 2Simons J. Baril D. Goodney P. Bertges D. Robinson W. Cronewett J. et al.The effect of postoperative myocardial ischemia on long -term survival after vascular surgery.J Vasc Surg. 2013; 58: 1600-1608Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, 3Krievins D. Zellans E. Erglis A. Zvaigzne L. Lacis A. Jegere S. et al.High prevalence of asymptomatic ischemia-producing coronary stenosis in patients with critical limb ischemia: anatomic and functional assessment with coronary CT-derived fractional flow reserve (FFRCT).Vasc Dis Manag. 2018; 15: E96-E101Google Scholar, 4Aboyans V. Ricco J.B. Bartelink M.E.L. Björck M. Brodmann M. Cohnert T. et al.2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European Society for Vascular Surgery (ESVS).Eur Heart J. 2018; 39: 763-816Crossref PubMed Scopus (1389) Google Scholar Preoperative diagnosis of ACF with CTA facilitated expeditious surgical treatment in this patient. Patients who survive surgery but have biomarker evidence of myocardial injury have reduced long-term survival.2Simons J. Baril D. Goodney P. Bertges D. Robinson W. Cronewett J. et al.The effect of postoperative myocardial ischemia on long -term survival after vascular surgery.J Vasc Surg. 2013; 58: 1600-1608Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar Patients with AAA commonly have coexistent CAD. Pre-operative diagnosis of silent coronary ischemia with coronary CTA and fractional flow reserve derived from CT (FFRCT) can identify high risk patients who may benefit from coronary revascularisation.3Krievins D. Zellans E. Erglis A. Zvaigzne L. Lacis A. Jegere S. et al.High prevalence of asymptomatic ischemia-producing coronary stenosis in patients with critical limb ischemia: anatomic and functional assessment with coronary CT-derived fractional flow reserve (FFRCT).Vasc Dis Manag. 2018; 15: E96-E101Google Scholar Ruptured AAA into IVC with unsuspected CAD can be successfully treated with prompt image-based diagnosis and involvement of a multidisciplinary vascular team.4Aboyans V. Ricco J.B. Bartelink M.E.L. Björck M. Brodmann M. Cohnert T. et al.2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European Society for Vascular Surgery (ESVS).Eur Heart J. 2018; 39: 763-816Crossref PubMed Scopus (1389) Google Scholar

Vascular surgery patients have increased risk of postoperative death/myocardial infarction (MI), but randomized trials show no survival benefit from preoperative coronary revascularization. A new noninvasive test, coronary computed tomography angiography (CTA)-derived fractional flow reserve (FFRCT), can identify patients with coronary ischemia and guide coronary revascularization. We sought to determine whether FFRCT-guided coronary revascularization can reduce preoperative cardiac events and improve survival compared with best medical management. We compared 2-year outcomes of patients undergoing lower extremity revascularization in two consecutive Institutional Review Board-approved trials at our institution: group I, patients with no cardiac symptoms having preoperative FFRCT to detect silent ischemia with selective postoperative coronary revascularization; and group II, patients enrolled in the randomized, double-blind study of postoperative medical care ± rivaroxaban (VOYAGER trial) with exclusion of patients with history of MI or prior coronary revascularization. In group I, lesion-specific coronary ischemia was defined as FFRCT ≤0.80, with FFRCT ≤0.75 indicating severe ischemia. The primary end point was major adverse cardiovascular events (cardiac death, MI, or unplanned coronary revascularization); secondary end points were MI, cardiovascular death, stroke, and survival at 1 year and 2 years. Group I (n = 77) and group II (n = 76) were similar with regard to age (66 ± 9 years vs 66 ± 8 years), sex (79/78% male), comorbidities, medications, preoperative ankle-brachial index, and indications for surgery (critical limb-threatening ischemia in >80%). Coronary CTA in group I showed extensive calcification (Agatston score, 1229 ± 1096) with ≥50% stenosis in 52 patients (68%). FFRCT revealed silent coronary ischemia in 69%, with severe ischemia in 56%, multivessel ischemia in 43%, and left main in 8%. Vascular surgery was performed in all patients with no cardiovascular events. After recovery from surgery, coronary angiography was performed in 43 patients (56%) with coronary revascularization in 29 patients (38%). Group II had no coronary revascularization. Postoperatively, both groups had guideline-directed medical care ± rivaroxaban in group II. At 1 year, compared with group II, cardiac deaths were reduced in group I (0% vs 7.9%; P = .014), as were MIs (2.6% vs 11.8%; P = .03). During 2 years of follow-up, group I showed a reduction in major adverse cardiovascular events (2.6% vs 11.8%; P = .03; Fig 1) and improved survival (98.7% vs 86.8%; P = .007, Kaplan-Meier, log-rank test; Fig 2). Preoperative diagnosis of silent coronary ischemia using CTA-FFRCT with selective postoperative coronary revascularization reduced postoperative cardiac death and MI and improved 2-year survival compared with standard coronary care with best medical therapy. Prospective controlled studies are needed to further define the role of coronary revascularization in patients undergoing peripheral vascular surgery.Fig 2Two-year survival, group I (98.7%) vs group II (86.8%; P = .007).View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Objective: Patients undergoing peripheral vascular surgery have increased risk of death and myocardial infarction (MI), which may be due to unsuspected (silent) coronary ischaemia. The aim was to determine whether pre-operative diagnosis of silent ischaemia using coronary computed tomography (CT) derived fractional flow reserve (FFRCT) can facilitate multidisciplinary care to reduce post-operative death and MI, and improve survival. Methods: This was a single centre prospective study with historic controls. Patients with no cardiac symptoms undergoing lower extremity surgical revascularisation with pre-operative coronary CTA-FFRCT testing were compared with historic controls with standard pre-operative testing. Silent coronary ischaemia was defined as FFRCT <= 0.80 distal to coronary stenosis with FFRCT <= 0.75 indicating severe ischaemia. End points included cardiovascular (CV) death, MI, and all cause death through one year follow up. Results: There were no statistically significant differences between CT angiography (CTA-FFRCT) (n = 135) and control (n = 135) patients with regard to age (66 +/- 8 years), sex, comorbidities, or surgery performed. Coronary CTA showed >= 50% stenosis in 70% of patients with left main stenosis in 7%. FFRCT revealed silent coronary ischaemia in 68% of patients with severe ischaemia in 53%. The status of coronary ischaemia was unknown in the controls. At 30 days, CV death and MI in the CTA-FFRCT- group were not statistically significantly different from controls (0% vs. 3.7% [p = .060] and 0.7% vs. 5.2% [p = .066], respectively). Post-operative coronary revascularisation was performed in 54 patients to relieve silent ischaemia (percutaneous coronary intervention in 47, coronary artery bypass graft in seven). At one year, CTA-FFR a patients had fewer CV deaths (0.7% vs. 5.9%; p = .036) and MIs (2.2% vs. 8.1%; p = .028) and improved survival (p = .018) compared with controls. Conclusion: Pre-operative diagnosis of silent coronary ischaemia in patients undergoing lower extremity revascularisation surgery can facilitate multidisciplinary patient care with selective post-operative coronary revascularisation. This strategy reduced post-operative death and MI and improved one year survival compared with standard care.