Ischemia-Guided Coronary Revascularization Following Lower-Extremity Revascularization Improves 5-Year Survival of Patients With Chronic Limb-Threatening Ischemia.

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.

Diagnosis and treatment of ischemia-producing coronary stenoses improves 5-year survival of patients undergoing major vascular surgery.

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.

First-in-human feasibility study of the aXess graft (aXess-FIH): 6-Month results.

OBJECTIVE: The creation of an arteriovenous fistula (AVF) is considered the most effective hemodialysis (HD) vascular access. For patients who are not suitable for AVF, arteriovenous grafts (AVGs) are the best access option for chronic HD. However, conventional AVGs are prone to intimal hyperplasia, stenosis, thrombosis, and infection. Xeltis has developed an AVG as a potential alternative to currently available AVGs based on the concept of endogenous tissue restoration. The results of the first 6-month follow-up are presented here. METHODS: The aXess first-in-human (FIH) study [NCT04898153] is a prospective, single-arm, multicenter feasibility study that evaluates the early safety and performance of the aXess Hemodialysis Graft. A total of 20 patients with end-stage renal disease were enrolled across six European investigational sites. RESULTS: At 6-months follow-up, all grafts were patent with primary and secondary patency rates were 80% and 100%, respectively. Three patients required a re-intervention to maintain graft patency, while one re-intervention was required to restore patency. One graft thrombosis and zero infections were reported. CONCLUSION: The expected advantages of the novel aXess Hemodialysis Graft over conventional AVGs would be evaluated by the analysis on long-term safety and effectiveness during the 5-year follow-up of the currently ongoing trial.

Successful Mechanical Thrombectomy for Basilar Artery Occlusion in a Pediatric Patient: A Case Report.

Studies have shown the benefits of endovascular treatment (EVT) in adult stroke cases, but its application in pediatric stroke remains controversial. Despite evidence of improved outcomes in adults, there are no established recommendations for EVT in children. Conducting individual case reports and case series is vital to understanding its potential advantages and disadvantages in this context. In this case report, a 9-year-old male initially diagnosed with gastroenteritis developed sudden left-sided weakness 1 day after admission. Comprehensive imaging revealed acute ischemia in the cerebellum, indicating a basilar artery thrombus. Urgent endovascular treatment (EVT) was performed 8.5 h after the onset of neurological symptoms, achieving successful revascularization. The patient underwent rehabilitation and was later discharged with improved neurological status. Despite extensive investigations, the stroke's origin remained unknown. After six months, the patient exhibited complete neurological recovery, highlighting the patient's remarkable resilience.

A pilot study to evaluate a novel localized treatment to stabilize small- to medium-sized infrarenal abdominal aortic aneurysms.

OBJECTIVE: There is no proven therapy to reduce growth rates of small- to medium-sized abdominal aortic aneurysms (AAAs). Ex vivo and animal studies have demonstrated that a novel stabilizing agent, 1,2,3,4,6-pentagalloyl glucose (PGG), delivered locally to the aneurysm sac, can bind to elastin and collagen to re-establish strength and resist enzymatic degradation. We aimed to demonstrate that a one-time administration of PGG solution to the aneurysm wall is safe and potentially effective to slow the growth of small- to medium-sized AAAs. METHODS: Patients with small- to medium-sized infrarenal AAAs (maximum diameter <5.5 cm) were recruited. Via transfemoral access, a 14F or 16F dual-balloon delivery catheter was introduced into the aneurysm sac. A single, 3-minute, localized endoluminal infusion of PGG was delivered via a 'weeping' balloon to the aneurysm wall. Independent core laboratory measurements of maximum aneurysm sac diameter and sac volume measurements based on computed tomography angiography (CTA) were used for assessments at 1, 6, 12, 24, and 36 months. The primary endpoints were technical success and safety (major adverse events at 30 days). The secondary endpoint was growth stabilization, defined as freedom from aneurysm sac enlargement (diameter increase >5 mm per year or volume increase of >10% per year). RESULTS: Twenty patients (19 male) were enrolled at five centers from May 2019 to June 2022 (mean age, 67.8 years; range, 50-87 years). All procedures were technically successful. The safety profile was consistent with standard interventional procedures. Four patients demonstrated transient elevations of liver enzymes levels that returned to normal by 30 days with no clinical symptoms. Through November 2022, follow-up CTA data is available on the first 11 patients. The average changes in maximum aneurysm diameter from baseline to 6, 12, 24, and 36 months were 0.2 mm, 1.1 mm, 1.2 mm, and 0.8 mm, respectively, and the average changes in volume were 2.0%, 9.6%, 18.1%, and 11.6%, respectively. At 12 months, none of the aneurysms showed growth >5.0 mm, and three had volume growth >10%. CONCLUSIONS: The early results of this first-in-human, small cohort study demonstrated that a single, localized PGG administration to patients with small- to medium-sized infrarenal AAAs is safe. Longer term follow-up on all 20 treated patients is needed to better assess the potential impact on aneurysm growth.

Study protocol of a prospective single-arm multicenter clinical study to assess the safety and performance of the aXess hemodialysis graft: The pivotal study.

BACKGROUND: Arteriovenous grafts (AVGs) are used for patients deemed unsuitable for the creation of an autogenous arteriovenous fistula (AVF) or unable to await maturation of the AVF before starting hemodialysis. However, AVGs are prone to infection and thrombosis resulting in low long-term patency rates. The novel aXess Hemodialysis Graft consists of porous polymeric biomaterial allowing the infiltration by cells and the growth of neotissue, while the graft itself is gradually absorbed, ultimately resulting in a fully functional natural blood vessel. The Pivotal Study will examine the long-term effectiveness and safety of the aXess Hemodialysis Graft. METHODS: The Pivotal Study is a prospective, single-arm, multicenter study that will be conducted in 110 subjects with end-stage renal disease who are not deemed suitable for the creation of an autogenous vascular access. The primary efficacy endpoint will be the primary patency rate at 6 months. The primary safety endpoint will be the freedom from device-related serious adverse events at 6 months. The secondary endpoints will include the procedural success rate, time to first cannulation, patency rates, the rate of access-related interventions to maintain patency, the freedom from device-related serious adverse events and the rate of access site infections. Patients will be followed for 60 months. An exploratory Health Economic and Outcomes Research sub-study will determine potential additional benefits of the aXess graft to patients, health care institutions, and reimbursement programs. DISCUSSION: The Pivotal study will examine the long-term performance and safety of the aXess Hemodialysis Graft and compare the outcome measures with historical data obtained with other graft types and autogenous AVFs. Potential advantages may include superior long-term patency rates and lower infection rates versus currently available AVGs and a shorter time to first cannulation compared to an autologous AVF. As such, the aXess Hemodialysis Graft may fulfill an unmet clinical need in the field of hemodialysis access.

Three-Year Patency Results following Endovascular Transvenous Femoropopliteal Bypass.

Background and Objectives: Peripheral artery disease is one of the most common vascular pathologies. There is an ongoing debate among specialists on whether open or endovascular revascularization is preferred in cases of complex superficial femoral artery (SFA) lesions. The purpose of this study was to assess patency results of a relatively new transvenous endovascular bypass device. This could add to existing evidence and aid in comparison between open and endovascular bypass. Materials and Methods: Patients with complex TASC-C and D SFA lesions who had indications for revascularization were identified. Prospective analysis of stent graft patency from 54 transvenous femoropopliteal bypass procedures was performed. Patency was assessed by Duplex ultrasound every six months. Kaplan-Meier analysis was performed to assess primary, primary-assisted, and secondary patency of transvenous bypass. Results: Following endovascular transvenous femoropopliteal bypass, 3-year graft primary, primary-assisted, and secondary patency was 43.8%, 66.3%, and 73.9%, respectively. Conclusions: Transvenous endovascular femoropopliteal bypass is a viable option for selected patients who lack adequate saphenous vein or have comorbidities that increase the risk of open femoropopliteal bypass. Strict post-operative follow-up is necessary to improve patency rates.

Rivaroxaban in patients with symptomatic peripheral artery disease after lower extremity bypass surgery with venous and prosthetic conduits.

BACKGROUND: Patients with peripheral artery disease (PAD) requiring lower extremity revascularization (LER) have a high risk of adverse limb and cardiovascular events. The results from the VOYAGER PAD (efficacy and safety of rivaroxaban in reducing the risk of major thrombotic vascular events in subjects with symptomatic peripheral artery disease undergoing peripheral revascularization procedures of the lower extremities) trial have demonstrated that rivaroxaban significantly reduced this risk with an overall favorable net benefit for patients undergoing surgical revascularization. However, the efficacy and safety for those treated by surgical bypass, including stratification by bypass conduit (venous or prosthetic), has not yet been described. METHODS: In the VOYAGER PAD trial, patients who had undergone surgical and endovascular infrainguinal LER to treat PAD were randomized to rivaroxaban 2.5 mg twice daily or placebo on top of background antiplatelet therapy (aspirin 100 mg to be used in all and clopidogrel in some at the treating physician's discretion) and followed up for a median of 28 months. The primary end point was a composite of acute limb ischemia, major amputation of vascular etiology, myocardial infarction, ischemic stroke, and cardiovascular death. The principal safety outcome was major bleeding using the TIMI (thrombolysis in myocardial infarction) scale. The index procedure details, including conduit type (venous vs prosthetic), were collected at baseline. RESULTS: Among 6564 randomized patients, 2185 (33%) had undergone surgical LER. Of these 2185 patients, surgical bypass had been performed for 1448 (66%), using a prosthetic conduit for 773 patients (53%) and venous conduit for 646 patients (45%). Adjusting for the baseline differences and anatomic factors, the risk of unplanned limb revascularization in the placebo arm was 2.5-fold higher for those receiving a prosthetic conduit vs a venous conduit (adjusted hazard ratio [HR], 2.53; 95% confidence interval [CI], 1.65-3.90; P < .001), and the risk of acute limb ischemia was three times greater (adjusted HR, 3.07; 95% CI, 1.84-5.11; P < .001). The use of rivaroxaban reduced the primary outcome for the patients treated with bypass surgery (HR, 0.78; 95% CI, 0.62-0.98), with consistent benefits for those receiving venous (HR, 0.66; 95% CI, 0.49-0.96) and prosthetic (HR, 0.87; 95% CI, 0.66-1.15) conduits (Pinteraction = .254). In the overall trial, major bleeding using the TIMI scale was increased with rivaroxaban. However, the numbers for those treated with bypass surgery were low (five with rivaroxaban vs nine with placebo; HR, 0.55; 95% CI, 0.18-1.65) and not powered to show statistical significance. CONCLUSIONS: Surgical bypass with a prosthetic conduit was associated with significantly higher rates of major adverse limb events relative to venous conduits even after adjustment for patient and anatomic characteristics. Adding rivaroxaban 2.5 mg twice daily to aspirin or dual antiplatelet therapy significantly reduced this risk, with an increase in the bleeding risk, but had a favorable benefit risk for patients treated with bypass surgery, regardless of conduit type. Rivaroxaban should be considered after lower extremity bypass for symptomatic PAD to reduce ischemic complications of the heart, limb, and brain.

Long term clinical and functional venous outcomes after endovascular transvenous femoro-popliteal bypass.

BACKGROUND: Peripheral artery disease is widespread in Western societies affecting around 13% of the population above 50 years of age. Despite recent improvements of endovascular treatment, open surgical bypass is still recommended as the treatment of choice for long segment TASC D lesions. The DETOUR procedure was introduced as an endovascular alternative in cases of long-segment superficial femoral artery occlusion. This unconventional technique raises several questions regarding the effect of the bypass graft on femoral venous physiology. METHODS: We conducted a 3-year follow-up study of subjects enrolled and treated in the prospective, multicenter DETOUR study at the Pauls Stradins clinical university hospital, Riga, Latvia. In total, 52 consecutive patients (54 procedures) were enrolled in this study from 2015 until 2019. We performed Venous Clinical Severity Score (VCSS) and Villalta (VS) Score assessments, Duplex ultrasound measuring femoral and popliteal vein diameters, venous occlusion plethysmography and digital photoplethysmography to assess and compare venous physiology at baseline and at follow-up visits every 6 months. RESULTS: At baseline mean femoral vein diameter was 11.1 mm (SD=1.5). At 36-months following intraluminal stent-graft placement, mean femoral vein diameter was 11.1 mm (SD=1.7) with no evidence of enlargement of the femoral vein (P=0.2). Popliteal vein diameter was not significantly changed during 24-months of follow-up (P=0.12) but showed a small (0.02 mm) statistically significant decrease in diameter at 36-months compared to baseline. During the study period, only one patient (1.9%) developed clinically significant ipsilateral DVT 1-month after surgery. Clinically silent femoral venous thrombosis was documented in 8 legs during 36-month follow-up. In one case the thrombus was occlusive and in 7 cases the thrombus was non-occlusive. At baseline, 48 of 52 patients (92%) had no or minor venous symptoms ([VCSS 0-2] with clinically significant venous symptoms in only 4 patients [VCSS≥3]). At one-month follow-up, the venous clinical severity score increased in all patients compared to baseline. At 6-month follow-up, the VCSS had returned to baseline in the majority of patients with no significant changes during the 3-year follow-up period. At baseline, all patients had a VS of 0-2 indicating minor or no venous symptoms (mean 0.4 [SD 0.7]). At the 1-month follow-up visit 3 patients (5.8%) had a VS≥3 (two patients had a score of 3 and one patient a score of 4), indicating significant venous symptoms. At the 6-month visit and thereafter, all the VS in all patients had returned to baseline. Transvenous endovascular procedure did not significantly alter venous physiology in treated leg. CONCLUSIONS: Percutaneous transvenous femoropopliteal bypass provided safe and effective lower-extremity revascularization with minimal effect on long-term venous function. The femoral and popliteal vein remained patent with no compensatory enlargement in response to the presence of the bypass graft within the femoral vein. During 3-year follow-up there were no significant changes in venous symptom scores or physiologic function.

Coronary revascularization of patients with silent coronary ischemia may reduce the risk of myocardial infarction and cardiovascular death after carotid endarterectomy.

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.

Percutaneous Femoropopliteal Bypass: 2-Year Results of the DETOUR System.

PURPOSE: This study investigated the 2-year safety and effectiveness of the PQ Bypass DETOUR system as a percutaneous femoropopliteal bypass. MATERIALS AND METHODS: Seventy-eight patients with 82 long-segment femoropopliteal lesions were enrolled in this prospective, single-arm, multicenter study. The DETOUR system deployed Torus stent grafts directed through a transvenous route. Eligible patients included those with lesions of >10 cm and average of 371±55 mm. Key safety endpoints included major adverse events (MAEs) and symptomatic deep venous thrombosis in the target limb. Effectiveness endpoints included primary patency defined as freedom from ≥50% stenosis, occlusion, or clinically-driven target vessel revascularization (CD-TVR), primary assisted, and secondary patency. RESULTS: Chronic total occlusions and severe calcium occurred in 96% and 67% of lesions, respectively. Core laboratory-assessed total lesion length averaged 371±51 mm with a mean occlusion length of 159±88 mm. The rates of technical and procedural success were 96%, with satisfactory delivery and deployment of the device without in-hospital MAEs in 79/82 limbs. The MAE rate was 22.0%, with 3 unrelated deaths (4%), 12 CD-TVRs (16%), and 1 major amputation (1%). Deep venous thrombosis developed in 2.8% of target limbs, and there were no reported pulmonary emboli. Primary, assisted primary, and secondary patency rates by the Kaplan-Meier analysis were 79±5%, 79±5%, and 86±4%, respectively. CONCLUSIONS: The PQ Bypass DETOUR system is a safe and effective percutaneous alternative to femoropopliteal open bypass with favorable results through 2 years. The DETOUR system provides a durable alternative to conventional endovascular modalities and open surgery for patients with long, severely calcified, or occluded femoropopliteal lesions.

Effect of Rivaroxaban and Aspirin in Patients With Peripheral Artery Disease Undergoing Surgical Revascularization: Insights From the VOYAGER PAD Trial.

BACKGROUND: Patients with peripheral artery disease requiring lower extremity revascularization (LER) are at high risk of adverse limb and cardiovascular events. The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) demonstrated that rivaroxaban significantly reduced this risk. The efficacy and safety of rivaroxaban has not been described in patients who underwent surgical LER. METHODS: The VOYAGER PAD trial randomized patients with peripheral artery disease after surgical and endovascular LER to rivaroxaban 2.5 mg twice daily plus aspirin or matching placebo plus aspirin and followed for a median of 28 months. The primary end point was a composite of acute limb ischemia, major vascular amputation, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was Thrombolysis in Myocardial Infarction major bleeding. International Society on Thrombosis and Haemostasis bleeding was a secondary safety outcome. All efficacy and safety outcomes were adjudicated by a blinded independent committee. RESULTS: Of the 6564 randomized, 2185 (33%) underwent surgical LER and 4379 (67%) endovascular. Compared with placebo, rivaroxaban reduced the primary end point consistently regardless of LER method (P-interaction, 0.43). After surgical LER, the primary efficacy outcome occurred in 199 (18.4%) patients in the rivaroxaban group and 242 (22.0%) patients in the placebo group with a cumulative incidence at 3 years of 19.7% and 23.9%, respectively (hazard ratio, 0.81 [95% CI, 0.67-0.98]; P=0.026). In the overall trial, Thrombolysis in Myocardial Infarction major bleeding and International Society on Thrombosis and Haemostasis major bleeding were increased with rivaroxaban. There was no heterogeneity for Thrombolysis in Myocardial Infarction major bleeding (P-interaction, 0.17) or International Society on Thrombosis and Haemostasis major bleeding (P-interaction, 0.73) on the basis of the LER approach. After surgical LER, the principal safety outcome occurred in 11 (1.0%) patients in the rivaroxaban group and 13 (1.2%) patients in the placebo group; 3-year cumulative incidence was 1.3% and 1.4%, respectively (hazard ratio, 0.88 [95% CI, 0.39-1.95]; P=0.75) Among surgical patients, the composite of fatal bleeding or intracranial hemorrhage (P=0.95) and postprocedural bleeding requiring intervention (P=0.93) was not significantly increased. CONCLUSIONS: The efficacy of rivaroxaban is associated with a benefit in patients who underwent surgical LER. Although bleeding was increased with rivaroxaban plus aspirin, the incidence was low, with no significant increase in fatal bleeding, intracranial hemorrhage, or postprocedural bleeds requiring intervention. Registration: URL: http://www.clinicaltrials.gov; Unique Identifier: NCT02504216.

Low-dose rivaroxaban plus aspirin in older patients with peripheral artery disease undergoing acute limb revascularization: insights from the VOYAGER PAD trial.

AIMS: In this secondary analysis of the VOYAGER trial, rivaroxaban 2.5 mg twice/day plus aspirin 100 mg/day was assessed in older adults. Advanced age is associated with elevated bleeding risk and unfavourable net benefit for dual antiplatelet therapy in chronic coronary artery disease. The risk-benefit of low-dose rivaroxaban in patients ≥75 years with peripheral artery disease (PAD) after lower extremity revascularization (LER) has not been described. METHODS AND RESULTS: The primary endpoint was a composite of acute limb ischaemia, major amputation, myocardial infarction, ischaemic stroke, or cardiovascular death. The principal safety outcome was thrombolysis in myocardial infarction (TIMI) major bleeding analysed by the pre-specified age cut-off of 75 years. Of 6564 patients randomized, 1330 (20%) were >75 years. Absolute 3-year Kaplan-Meier cumulative incidence rates for primary efficacy (23.4% vs. 19.0%) and safety (3.5% vs. 1.5%) endpoints were higher in elderly vs. non-elderly patients. Efficacy of rivaroxaban (P-interaction 0.83) and safety (P-interaction 0.38) was consistent irrespective of age. The combination of intracranial and fatal bleeding was not increased in patients >75 years (2 rivaroxaban vs. 8 placebo). Overall, benefits (absolute risk reduction 3.8%, number needed to treat 26 for the primary endpoint) exceeded risks (absolute risk increase 0.81%, number needed to harm 123 for TIMI major bleeding). CONCLUSION: Patients ≥75 years with PAD are at both heightened ischaemic and bleeding risk after LER. No excess harm with respect to major, intracranial or fatal bleeding was seen in older patients yet numerically greater absolute benefits were observed. This suggests that low-dose rivaroxaban combined with aspirin should be considered in PAD after LER regardless of age.

Diagnosis of silent coronary ischemia with selective coronary revascularization might improve 2-year survival of patients with critical limb-threatening ischemia.

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.

Venous outcomes at 1 year after using the femoral vein as a conduit for passage of percutaneous femoropopliteal bypass.

OBJECTIVE: The DETOUR 1 study was performed to assess the safety of the femoral vein as a "pass through" conduit for covered stent placement during fully percutaneous femoropopliteal bypass, also known as the DETOUR procedure. METHODS: At eight participating centers in this prospective, single-arm, international trial, 78 patients (82 femoropopliteal lesions) were enrolled. All patients had patent femoral veins measuring ≥10 mm in diameter at baseline. The DETOUR procedure involved delivery of a series of TORUS stent grafts, deployed from contralateral common femoral artery access, to the ipsilateral proximal superficial femoral artery, with entry into the femoral vein and re-entry into the arterial vasculature at the above-the-knee popliteal artery. The TORUS stent grafts are deployed in an overlapping configuration as an arterial-arterial conduit. Due to this novel transvenous approach, we assessed specific considerations related to the venous system to analyze the risk of risk of venous thromboembolic complications. Symptomatic deep vein thrombosis, nonocclusive material associated with the graft such as benign endovenous graft-associated material, pulmonary embolism, Venous Clinical Severity Score (VCSS) and Villalta scores, and luminal occupancy by the stent graft were assessed as the ratio of cross-sectional areas of the stent graft to the native vein at baseline and 1 year after the procedure. RESULTS: A duplicate femoral vein was present in 20.7% of cases. The majority of patients (86.8%) had a femoral vein luminal area preservation of ≥55%. Thirty-two patients experienced an increase in the vein diameter over time after the procedure, but this pattern of venous remodeling was not uniform. The patients who had a compensatory increase in the vein diameter had a smaller average baseline vein diameter compared with the patients who did not have a compensatory increase in vein diameter (P = .0414). Only two patients (2.4%) developed ipsilateral symptomatic deep vein thrombosis) through 1 year of follow-up. There were no pulmonary embolism in any patient in the series. The overall VCSS and Villata scores did not change during follow-up. Mean VCSS and Villata were 0.8 ± 1.4 and 0.5 ± 1.1 at 1 year, compared with 0.6 ± 1.0 and 0.4 ± 0.9 at baseline, respectively. CONCLUSIONS: As a percutaneous alternative to open surgical bypass for complex femoropopliteal peripheral arterial disease, the transvenous bypass has a low rate of deep venous thrombotic and obstructive complications. Cross-sectional vein area is preserved, and in some patients, the compensatory vein diameter increases with time, supporting the feasibility and safety of using the lower extremity deep venous system as a pass-through conduit for the DETOUR percutaneous femoropopliteal bypass. TRIAL REGISTRATION: NCT02471638.

Diagnosis and management of silent coronary ischemia in patients undergoing carotid endarterectomy.

BACKGROUND: Coronary artery disease is the primary cause of death in patients with carotid artery disease and silent ischemia is a marker for adverse coronary events. A new noninvasive cardiac diagnostic test, coronary computed tomography-derived fractional flow reserve (FFRCT) can reliably identify ischemia-producing coronary stenosis in patients with coronary artery disease and help to select patients for coronary revascularization. The purpose of this study is to determine the prevalence of silent coronary ischemia in patients undergoing carotid endarterectomy (CEA) and to evaluate the usefulness of FFRCT in selecting patients for coronary revascularization to decrease cardiac events and improve survival. METHODS: Patients with no cardiac history or symptoms admitted for elective CEA were enrolled in a prospective, open-label, institutional review board-approved study and underwent preoperative coronary computed tomography angiography (CTA) and FFRCT with results available to physicians for patient management. Lesion-specific coronary ischemia was defined as FFRCT of 0.80 or less distal to a focal coronary stenosis with an FFRCT of 0.75 or less, indicating severe ischemia. Primary end point was incidence of major adverse cardiovascular events (MACE; defined as cardiovascular death, myocardial infarction, or stroke) at 30 days and 1 year. RESULTS: Coronary CTA and FFRCT was performed in 90 CEA patients (age 67 ± 8 years; male 66%). Lesion-specific coronary ischemia was found in 51 patients (57%) with a mean FFRCT of 0.71 ± 0.14. Severe coronary ischemia was present in 39 patients (43%), 26 patients had multivessel ischemia, and 5 had left main disease. CEA was performed as scheduled in all patients with no postoperative deaths or myocardial infarctions. There were no MACE events at 30 days. After recovery from surgery, 36 patients with significant lesion-specific ischemia underwent coronary angiography with coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) in 30 patients (33%). Survival at 1 year was 100% and freedom from MACE was 98%. CONCLUSIONS: Patients undergoing CEA have a high prevalence of unsuspected (silent) coronary ischemia, which may place them at risk for coronary events. Preoperative diagnosis of silent ischemia using CTA and FFRCT can identify high-risk patients and help to guide patient management. Selective postoperative coronary revascularization of patients with significant ischemia may decrease the risk of cardiac events and improve survival, but longer follow-up is needed and prospective, controlled trials are indicated.

Pre-operative Diagnosis of Silent Coronary Ischaemia May Reduce Post-operative Death and Myocardial Infarction and Improve Survival of Patients Undergoing Lower Extremity Surgical Revascularisation.

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-FFRCT 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.