Illness Trajectories After Revascularization in Patients With Peripheral Artery Disease: A Unified Approach to Understanding the Risk of Major Amputation and Death.

BACKGROUND: The aim of this study was to investigate the illness trajectories of patients with peripheral artery disease (PAD) after revascularization and estimate the independent risks of major amputation and death (from any cause) and their interaction. METHODS: Data from Hospital Episode Statistics Admitted Patient Care were used to identify patients (≥50 years of age) who underwent lower limb revascularization for PAD in England from April 2013 to March 2020. A Markov illness-death model was developed to describe patterns of survival after the initial lower limb revascularization, if and when patients experienced major amputation, and survival after amputation. The model was also used to investigate the association between patient characteristics and these illness trajectories. We also analyzed the relative contribution of deaths after amputation to overall mortality and how the risk of mortality after amputation was related to the time from the index revascularization to amputation. RESULTS: The study analyzed 94 690 patients undergoing lower limb revascularization for PAD from 2013 to 2020. The majority were men (65.6%), and the median age was 72 years (interquartile range, 64-79). One-third (34.8%) of patients had nonelective revascularization, whereas others had elective procedures. For nonelective patients, the amputation rate was 15.2% (95% CI, 14.4-16.0) and 19.9% (19.0-20.8) at 1 and 5 years after revascularization, respectively. For elective patients, the corresponding amputation rate was 2.7% (95% CI, 2.4-3.1) and 5.3% (4.9-5.8). Overall, the risk of major amputation was higher among patients who were younger, had tissue loss, diabetes, greater frailty, nonelective revascularization, and more distal procedures. The mortality rate at 5 years after revascularization was 64.3% (95% CI, 63.2-65.5) for nonelective patients and 33.0% (32.0-34.1) for elective patients. After major amputation, patients were at an increased risk of mortality if they underwent major amputation within 6 months after the index revascularization. CONCLUSIONS: The illness-death model provides an integrated framework to understand patient outcomes after lower limb revascularization for PAD. Although mortality increased with age, the study highlights patients <60 years of age were at increased risk of major amputation, particularly after nonelective revascularization.

Preoperative coronary interventions for preventing acute myocardial infarction in the perioperative period of major open vascular or endovascular surgery.

BACKGROUND: Postoperative myocardial infarction (POMI) is associated with major surgeries and remains the leading cause of mortality and morbidity in people undergoing vascular surgery, with an incidence rate ranging from 5% to 20%. Preoperative coronary interventions, such as coronary artery bypass grafting (CABG) or percutaneous coronary interventions (PCI), may help prevent acute myocardial infarction in the perioperative period of major vascular surgery when used in addition to routine perioperative drugs (e.g. statins, angiotensin-converting enzyme inhibitors, and antiplatelet agents), CABG by creating new blood circulation routes that bypass the blockages in the coronary vessels, and PCI by opening up blocked blood vessels. There is currently uncertainty around the benefits and harms of preoperative coronary interventions. OBJECTIVES: To assess the effects of preoperative coronary interventions for preventing acute myocardial infarction in the perioperative period of major open vascular or endovascular surgery. SEARCH METHODS: We searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS, and CINAHL EBSCO on 13 March 2023. We also searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) or quasi-RCTs that compared the use of preoperative coronary interventions plus usual care versus usual care for preventing acute myocardial infarction during major open vascular or endovascular surgery. We included participants of any sex or any age undergoing major open vascular surgery, major endovascular surgery, or hybrid vascular surgery. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes of interest were acute myocardial infarction, all-cause mortality, and adverse events resulting from preoperative coronary interventions. Our secondary outcomes were cardiovascular mortality, quality of life, vessel or graft secondary patency, and length of hospital stay. We reported perioperative and long-term outcomes (more than 30 days after intervention). We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included three RCTs (1144 participants). Participants were randomised to receive either preoperative coronary revascularisation with PCI or CABG plus usual care or only usual care before major vascular surgery. One trial enrolled participants if they had no apparent evidence of coronary artery disease. Another trial selected participants classified as high risk for coronary disease through preoperative clinical and laboratorial testing. We excluded one trial from the meta-analysis because participants from both the control and the intervention groups were eligible to undergo preoperative coronary revascularisation. We identified a high risk of performance bias in all included trials, with one trial displaying a high risk of other bias. However, the risk of bias was either low or unclear in other domains. We observed no difference between groups for perioperative acute myocardial infarction, but the evidence is very uncertain (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.02 to 4.57; 2 trials, 888 participants; very low-certainty evidence). One trial showed a reduction in incidence of long-term (> 30 days) acute myocardial infarction in participants allocated to the preoperative coronary interventions plus usual care group, but the evidence was very uncertain (RR 0.09, 95% CI 0.03 to 0.28; 1 trial, 426 participants; very low-certainty evidence). There was little to no effect on all-cause mortality in the perioperative period when comparing the preoperative coronary intervention plus usual care group to usual care alone, but the evidence is very uncertain (RR 0.79, 95% CI 0.31 to 2.04; 2 trials, 888 participants; very low-certainty evidence). The evidence is very uncertain about the effect of preoperative coronary interventions on long-term (follow up: 2.7 to 6.2 years) all-cause mortality (RR 0.74, 95% CI 0.30 to 1.80; 2 trials, 888 participants; very low-certainty evidence). One study reported no adverse effects related to coronary angiography, whereas the other two studies reported five deaths due to revascularisations. There may be no effect on cardiovascular mortality when comparing preoperative coronary revascularisation plus usual care to usual care in the short term (RR 0.07, 95% CI 0.00 to 1.32; 1 trial, 426 participants; low-certainty evidence). Preoperative coronary interventions plus usual care in the short term may reduce length of hospital stay slightly when compared to usual care alone (mean difference -1.17 days, 95% CI -2.05 to -0.28; 1 trial, 462 participants; low-certainty evidence). We downgraded the certainty of the evidence due to concerns about risk of bias, imprecision, and inconsistency. None of the included trials reported on quality of life or vessel graft patency at either time point, and no study reported on adverse effects, cardiovascular mortality, or length of hospital stay at long-term follow-up. AUTHORS' CONCLUSIONS: Preoperative coronary interventions plus usual care may have little or no effect on preventing perioperative acute myocardial infarction and reducing perioperative all-cause mortality compared to usual care, but the evidence is very uncertain. Similarly, limited, very low-certainty evidence shows that preoperative coronary interventions may have little or no effect on reducing long-term all-cause mortality. There is very low-certainty evidence that preoperative coronary interventions plus usual care may prevent long-term myocardial infarction, and low-certainty evidence that they may reduce length of hospital stay slightly, but not cardiovascular mortality in the short term, when compared to usual care alone. Adverse effects of preoperative coronary interventions were poorly reported in trials. Quality of life and vessel or graft patency were not reported. We downgraded the certainty of the evidence most frequently for high risk of bias, inconsistency, or imprecision. None of the analysed trials provided significant data on subgroups of patients who could potentially experience more substantial benefits from preoperative coronary intervention (e.g. altered ventricular ejection fraction). There is a need for evidence from larger and homogeneous RCTs to provide adequate statistical power to assess the role of preoperative coronary interventions for preventing acute myocardial infarction in the perioperative period of major open vascular or endovascular surgery.

Neoadjuvant chemotherapy is associated with improved disease-free survival in pancreatic cancer patients undergoing pancreaticoduodenectomy with vascular resection.

BACKGROUND AND OBJECTIVES: Neoadjuvant chemotherapy (NAC) is becoming favored for all pancreatic adenocarcinoma (PDAC). Patients with seemingly resectable disease infrequently still display vascular involvement intraoperatively. Outcomes following NAC versus upfront surgery in patients undergoing pancreaticoduodenectomy (PD) with vascular resection are unknown. METHODS: We performed a retrospective cohort study of PDAC patients who underwent PD with vascular resection between January 1, 2013, to December 31, 2020, within a single academic center. Clinicopathologic characteristics and disease-free survival (DFS) were compared between NAC versus upfront surgery cohorts using the Kaplan-Meier estimate and Cox proportional-hazards regression model. RESULTS: Eighty-one patients who underwent PD with vascular resection for PDAC were included. Forty-six patients (56%) received NAC. The NAC cohort more often had pathologic N0 status (47.8% vs. 8.6%, p < 0.001), had decreased vascular invasion (11% vs. 40%, p = 0.002), and completed chemotherapy (80% vs. 40%, p < 0.01). The NAC cohort demonstrated improved DFS (40.5 vs. 14.3 months, p = 0.007). In multivariable analysis, NAC remained independently associated with increased DFS (HR = 0.48, p = 0.02). CONCLUSIONS: NAC was associated with improved clinicopathologic outcomes and DFS in PD with vascular resection. These findings demonstrate the advantage of NAC in PDAC patients undergoing PD with vascular resection.

Anticoagulation in Patients with Premature Peripheral Artery Disease Undergoing Lower Extremity Revascularization.

BACKGROUND: Premature peripheral artery disease (PAD), defined by lower extremity revascularization (LER) at age ≤ 50 years, is associated with poor major adverse limb events. The early onset of disease is thought to be influenced by genetic factors that regulate homeostasis of the vascular wall and coagulation. The aim of this study is to investigate the effect of anticoagulation as an adjunct to antiplatelet therapy on the outcomes of LER in patients with premature PAD. METHODS: There were 8,804 patients with premature PAD on preoperative and postoperative antiplatelet therapy only and 1,236 patients on preoperative and postoperative anticoagulation plus antiplatelet therapy in the Vascular Quality Initiative peripheral vascular intervention, infrainguinal, and suprainguinal files. Propensity score matching (2:1) was performed between patients with premature PAD who were on antiplatelet therapy and those on anticoagulation plus antiplatelet therapy. Perioperative and 1-year outcomes were analyzed including reintervention, major amputation, and mortality. RESULTS: Patients on anticoagulation were more likely to have coronary artery disease (48.7% vs. 41.2%, P < 0.001), congestive heart failure (20.2% vs. 13.1%, P < 0.001), and have undergone prior LER (73.9% vs. 49.2%, P < 0.001) compared to patients on antiplatelet therapy only. They were also less likely to be independently ambulatory (74.2% vs. 81.8%, P < 0.001) and be on a statin medication (66.8% vs. 74.3%, P < 0.001) compared to patients on antiplatelet therapy only. Patients on anticoagulation were also less likely to be treated for claudication (38.1% vs. 48.6%, P < 0.001), and less likely to be treated with an endovascular procedure (64.8% vs. 73.8%, P < 0.001). After matching for baseline characteristics, there were 1,256 patients on antiplatelet therapy only and 628 patients on anticoagulation. Patients on anticoagulation were more likely to require a return to the operating room (3.7% vs. 1.6%, P < 0.001) and had higher perioperative mortality (1.1% vs. 0.3%, P = 0.032), but major amputation was not significantly different (1.8% vs. 1.6%, P = 0.798) compared to patients on antiplatelet therapy alone. At 1 year, amputation-free survival was higher in patients on antiplatelets only compared to patients on anticoagulation and antiplatelet medications (87.5% vs. 80.9%, log-rank P = 0.001). CONCLUSIONS: Anticoagulation in addition to antiplatelet therapy in patients with premature PAD undergoing LER is associated with increased reintervention and mortality at 1 year.

Comparison of mortality and amputation after lower extremity bypass versus peripheral vascular intervention in patients with chronic limb-threatening ischemia and comorbid chronic kidney disease.

OBJECTIVE: Comorbid chronic kidney disease (CKD) is associated with worse outcomes for patients with chronic limb-threatening ischemia (CLTI). However, comparative effectiveness data are limited for lower extremity bypass (LEB) vs peripheral vascular intervention (PVI) in patients with CLTI and CKD. We aimed to evaluate (1) 30-day all-cause mortality and amputation and (2) 5-year all-cause mortality and amputation for LEB vs PVI in patients with comorbid CKD. METHODS: Individuals who underwent LEB and PVI were queried from the Vascular Quality Initiative with Medicare claims-linked outcomes data. Propensity scores were calculated using 13 variables, and a 1:1 matching method was used. The mortality risk at 30 days and 5 years in LEB vs PVI by CKD was assessed using Kaplan-Meier and Cox proportional hazards models, with interaction terms added for CKD. For amputation, cumulative incidence functions and Fine-Gray models were used to account for the competing risk of death, with interaction terms for CKD added. RESULTS: Of 4084 patients (2042 per group), the mean age was 71.0 ± 10.8 years, and 69.0% were male. Irrespective of CKD status, 30-day mortality (hazard ratio [HR]: 0.94, 95% confidence interval [CI]: 0.63-1.42, P = .78) was similar for LEB vs PVI, but LEB was associated with a lower risk of 30-day amputation (sub-HR [sHR]: 0.66, 95% CI: 0.44-0.97, P = .04). CKD status, however, did not modify these results. Similarly, LEB vs PVI was associated with a lower risk of 5-year mortality (HR: 0.79, 95% CI: 0.71-0.88, P < .001) but no difference in 5-year amputation (sHR: 1.03, 95% CI: 0.89-1.20, P = .67). CKD status did not modify these results. CONCLUSIONS: Regardless of CKD status, patients had a lower risk of 5-year all-cause mortality and 30-day amputation with LEB vs PVI. Results may help inform preference-sensitive treatment decisions on LEB vs PVI for patients with CLTI and CKD, who may commonly be deemed too high risk for surgery.

The 5-Factor Modified Frailty Index is a Succinct yet Effective Predictor of Adverse Outcomes in Patients Undergoing Open Surgery for Abdominal Aortic Aneurysm.

BACKGROUND: Frailty is an age-related, clinically recognizable state marked by increased susceptibility. The 5-item Modified Frailty Index (mFI-5) offers a concise assessment of frailty and has demonstrated its efficacy in various surgical fields. While the mFI-5 has been validated for endovascular aneurysm repair for abdominal aortic aneurysm (AAA), its applicability in open surgical repair (OSR) for AAA remains largely unexplored. This study sought to evaluate the utility of mFI-5 in predicting 30-day outcomes following OSR for AAA. METHODS: Patients underwent OSR for AAA were identified in American College of Surgeons National Surgical Quality Improvement Program-targeted database from 2012 to 2021. Patients were stratified into 3 cohorts: mFI-5 score of 0 (control), 1, and 2+. Multivariable logistic regression was used to compare 30-day perioperative outcomes between frail patients and controls adjusting preoperative variables with P value <0.1. RESULTS: Of the 5,249 patients who underwent OSR for AAA, 1,043 were controls, 2,938 had an mFI-5 score of 1 and 1,268 had an mFI-5 score of 2+. When compared to the control group, patients with an mFI-5 = 1 were more likely to have pulmonary events (adjusted odds ratio (aOR) = 1.452, P < 0.01), bleeding events (aOR = 1.33, P < 0.01), wound complications (aOR = 2.214, P < 0.01), ischemic colitis (aOR = 1.616, P = 0.01), and unplanned reoperation (aOR = 1.292, P = 0.04). Those with an mFI-5 = 2+ demonstrated higher risks of mortality (aOR = 1.709, P < 0.01), major adverse cardiovascular events (aOR = 1.347, P = 0.04), pulmonary events (aOR = 2.045, P < 0.01), renal dysfunction (aOR = 1.568, P < 0.01), sepsis (aOR = 1.587, P = 0.01), bleeding events (aOR = 1.429, P < 0.01), wound complications (aOR = 2.338, P < 0.01), ischemic colitis (aOR = 1.775, P = 0.01), unplanned reoperation (aOR = 1.445, P = 0.01), operation over 4 hours (aOR = 1.34, P < 0.01), length of stay over 7 days (aOR = 1.324, <0.01), discharge not to home (aOR = 1.547, P < 0.01), 30-day readmission (aOR = 1.657, P = 0.01). CONCLUSIONS: The mFI-5 emerges as a succinct yet effective indicator of frailty for patients undergoing OSR for AAA. Especially, an mFI-5 score of 2+ is linked with increased 30-day mortality and complications. As such, mFI-5 can be used as a valuable screening tool for frailty in patients undergoing OSR for AAA.

Long-term outcomes in the smoking claudicant after peripheral vascular interventions.

OBJECTIVE: Emphasis on tobacco cessation, given the urgent and emergent nature of vascular surgery, is less prevalent than standard elective cases such as hernia repairs, cosmetic surgery, and bariatric procedures. The goal of this study is to determine the effect of active smoking on claudicating individuals undergoing peripheral vascular interventions (PVIs). Our goal is to determine if a greater emphasis on education should be placed on smoking cessation in nonurgent cases scheduled through clinic visits and not the Emergency Department. METHODS: This study was performed using the multi-institution de-identified Vascular Quality Initiative/Medicare-linked database (Vascular Implant Surveillance and Interventional Outcomes Network [VISION]). Claudicants who underwent PVI for peripheral arterial occlusive disease between 2004 and 2019 were included in our study. Our final sample consisted of a total of 18,726 patients: 3617 nonsmokers (19.3%) (NSs), 9975 former smokers (53.3%) (FSs), and 5134 current smokers (27.4%) (CSs). We performed propensity score matching on 29 variables (age, gender, race, ethnicity, treatment setting [outpatient or inpatient], obesity, insurance, hypertension, diabetes, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease, previous coronary artery bypass graft, carotid endarterectomy, major amputation, inflow treatment, prior bypass or PVI, preoperative medications, level of treatment, concomitant endarterectomy, and treatment type [atherectomy, angioplasty, stent]) between NS vs FS and FS vs CS. Outcomes were long-term (5-year) overall survival (OS), limb salvage (LS), freedom from reintervention (FR), and amputation-free survival (AFS). RESULTS: Propensity score matching resulted in 3160 well-matched pairs of NS and FS and 3750 well-matched pairs of FS and CS. There was no difference between FS and NS in terms of OS (hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.82-1.09; P = .43), FR (HR, 0.96; 95% CI, 0.89-1.04; P = .35), or AFS (HR, 0.90; 95% CI, 0.79-1.03; P = .12). However, when compared with CS, we found FS to have a higher OS (HR, 1.18; 95% CI, 1.04-1.33; P = .01), less FR (HR, 0.89; 95% CI, 0.83-0.96; P = .003), and greater AFS (HR, 1.16; 95% CI, 1.03-1.31; P = .01). CONCLUSIONS: This multi-institutional Medicare-linked study looking at elective PVI cases in patients with peripheral artery disease presenting with claudication found that FSs have similar 5-year outcomes in comparison to NSs in terms of OS, FR, and AFS. Additionally, CSs have lower OS and AFS when compared with FSs. Overall, this suggests that smoking claudicants should be highly encouraged and referred to structured smoking cessation programs or even required to stop smoking prior to elective PVI due to the perceived 5-year benefit.

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.

Comparison of direct oral anticoagulants and warfarin in chronic limb-threatening ischemia.

OBJECTIVE: The role of direct oral anticoagulants (DOACs) in chronic limb-threatening ischemia after revascularization is unknown. Current evidence-based guidelines do not provide clear guidance on the role of anticoagulation or the selection of anticoagulant. Current practice is highly varied and based on provider and patient preference. The purpose of this study was to measure the impact of different anticoagulants on the incidence of major adverse limb events (MALEs) after revascularization for chronic limb-threatening ischemia, major adverse cardiovascular events (MACEs), all-cause mortality, and hospitalization for major bleeding events. METHODS: This was a single-center, observational, retrospective cohort study. Subjects were eligible if they were 18 years or older; underwent endovascular or open revascularization for chronic limb-threatening ischemia, rest pain, or tissue loss; and were subsequently prescribed apixaban, rivaroxaban, or warfarin. The primary end point was the incidence of MALEs, including above-ankle amputation or major index-limb reintervention, within 1 year of index event. Secondary end points included the rate of all-cause mortality, MACEs, and incidence of International Society on Thrombosis and Haemostasis (ISTH) major bleeding. RESULTS: From January 1, 2017, to September 20, 2022, 141 patients met the inclusion and exclusion criteria and were reviewed. The median age was 67 years, with 92 patients prescribed apixaban or rivaroxaban and 49 patients prescribed warfarin. Of these, 42 patients were prescribed triple antithrombotic therapy, 88 dual antithrombotic therapy, and 13 anticoagulant monotherapy. The primary outcome of 1-year MALEs occurred in 36.7% of the warfarin group and 33.7% of the DOAC group (relative risk [RR], 1.09; 95% CI, 0.53-2.25; P = .72). Secondary outcomes of 1-year MACEs (10.2% vs 4.3%; RR, 2.35; 95% CI, 0.60-9.18; P = .18) and 1-year all-cause mortality (26.5% vs 16.3%; RR, 1.63; 95% CI, 0.70-3.78; P = .15) did not differ between the groups. The secondary safety outcome of 1-year ISTH major bleeding occurred in 16.3% of the warfarin group and 4.3% of the DOAC group (RR, 3.76; 95% CI, 1.07-13.19; P = .015). CONCLUSIONS: In patients with chronic limb-threatening ischemia who were revascularized and prescribed anticoagulation with apixaban, rivaroxaban, or warfarin on discharge, no difference in MALEs, MACEs, or all-cause mortality was found. However, 1-year admissions for ISTH major bleeding were significantly higher among patients prescribed warfarin. A randomized trial may confirm these findings.

Validation of JCLIMB, SPINACH, and VQI Calculators for Prediction of Two Year Survival in Patients With Chronic Limb Threatening Ischaemia After Infra-Inguinal Surgical or Endovascular Revascularisation.

OBJECTIVE: This study aimed to evaluate three survival prediction models: the JAPAN Critical Limb Ischaemia Database (JCLIMB), Surgical Reconstruction Versus Peripheral Intervention in Patients With Critical Limb Ischaemia (SPINACH), and Vascular Quality Initiative (VQI) calculators. METHODS: Multicentre data of patients who underwent infrainguinal revascularisation for chronic limb threatening ischaemia between 2018 and 2021 were analysed retrospectively. The prediction models were validated using a calibration plot analysis with the intercept and slope. The discrimination was evaluated using area under the curve (AUC) analysis. The observed two year overall survival (OS) was evaluated by the Kaplan - Meier method. The two year OS predicted by each model at < 50%, 50 - 70%, and > 70% was defined as high, medium, and low risk, respectively. RESULTS: A total of 491 patients who underwent infra-inguinal revascularisation were analysed. The rates of surgical revascularisation, endovascular therapy, and hybrid therapy were 26.5%, 70.1%, and 5.5%, respectively. The average age was 75.6 years, and the percentages of patients with diabetes mellitus and dialysis dependent end stage renal disease were 66.6% and 44.6%, respectively. The tissue loss rate was 85.7%. The intercept and slope were -0.13 and 1.18 for the JCLIMB, 0.11 and 0.82 for the SPINACH, and -0.15 and 1.10 for the VQI. The AUC for the two year OS of JCLIMB, SPINACH, and VQI were 0.758, 0.756, and 0.740, respectively. The observed two year OS rates of low, medium, and high risk using the JCLIMB calculator were 80.1%, 61.1%, and 28.5%, respectively (p < .001), using the SPINACH calculator were 81.0%, 57.0%, and 38.1%, respectively (p < .001), and using the VQI calculator were 77.8%, 45.8%, and 49.6%, respectively (p < .001). CONCLUSION: The JCLIMB, SPINACH, and VQI survival calculation models were useful, although the OS predicted by the VQI model appeared to be lower than the observed OS.

Long-term results following atrioventricular septal defect repair.

BACKGROUND: Atrioventricular septal defects (AVSD) represent 4-7% of congenital cardiac malformations. Definitive early repair is favored over prior pulmonary artery banding and delayed definitive repair in many centers. The aim of this study was to analyze long-term outcomes following AVSD repair over a 21-year period. METHODS: A total of 202 consecutive patients underwent surgical AVSD correction between June 1999 and December 2020. Surgery was performed using the double-patch technique. The study data were prospectively collected and retrospectively analyzed. Primary outcomes were In-hospital mortality and overall long-term freedom from reoperation. RESULTS: Median age at operation was 120 days (IQR 94-150), median weight was 5.0 kg (4.2-5.3). None of the patients died within the first 30 postoperative days. In-hospital mortality was 0.5% (1/202 patients). Median follow-up was 57 months (11-121). Overall freedom from reoperation at 5, 10 and 15 years was 91.8%, 86.9% and 86.9%, respectively. CONCLUSION: AVSD repair with the double-patch technique is a safe and effective procedure with good early postoperative outcomes and low long-term reoperation rates.

Induction of CD73 prevents death after emergency open aortic surgery for a ruptured abdominal aortic aneurysm: a randomized, double-blind, placebo-controlled study.

Mortality remains high after emergency open surgery for a ruptured abdominal aortic aneurysm (RAAA). The aim of the present study was to assess, if intravenous (IV) Interferon (IFN) beta-1a improve survival after surgery by up-regulating Cluster of differentiation (CD73). This is a multi-center phase II double-blind, 2:1 randomized, parallel group comparison of the efficacy and safety of IV IFN beta-1a vs. placebo for the prevention of death after open surgery for an infra-renal RAAA. All study patients presented a confirmed infra-renal RAAA, survived the primary emergency surgery and were treated with IFN beta-1a (10 µg) or matching placebo for 6 days after surgery. Major exclusion criteria included fatal hemorrhagic shock, chronic renal replacement therapy, diagnosed liver cirrhosis, severe congestive heart failure, advanced malignant disease, primary attempt of endovascular aortic repair (EVAR), and per-operative suprarenal clamping over 30 min. Main outcome measure was all-cause mortality at day 30 (D30) from initial emergency aortic reconstruction. The study was pre-maturely stopped due to a reported drug-drug interaction and was left under-powered. Out of 40 randomized patients 38 were included in the outcome analyses (27 IFN beta-1a and 11 placebo). There was no statistically significant difference between treatment groups at baseline except more open-abdomen and intestinal ischemia was present in the IFN beta-1a arm. D30 all-cause mortality was 22.2% (6/27) in the IFN beta-1a arm and 18.2% (2/11) in the placebo arm (OR 1.30; 95% CI 0.21-8.19). The most common adverse event relating to the IFN beta-1a was pyrexia (20.7% in the IFN beta-1a arm vs. 9.1% in the placebo arm). Patients with high level of serum CD73 associated with survival (P = 0.001) whereas the use of glucocorticoids and the presence of IFN beta-1a neutralizing antibodies associated with a poor CD73 response and survival. The initial aim of the trial, if postoperative INF beta-1a treatment results on better RAAA survival, could not be demonstrated. Nonetheless the anticipated target mechanism up-regulation of CD73 was associated with 100% survival. According to present results the INF beta-1a induced up-regulation of serum CD73 was blocked with both use of glucocorticoids and serum IFN beta-1a neutralizing antibodies. The study was pre-maturely stopped due to interim analysis after a study concerning the use if IV IFN beta-1a in ARDS suggested that the concomitant use of glucocorticoids and IFN beta-1a block the CD73 induction. Trial registration: ClinicalTrials.gov NCT03119701. Registered 19/04/2017 (retrospectively registered).

Total anomalous pulmonary venous connection: Influence of heterotaxy and venous obstruction on outcomes.

BACKGROUND: Previous studies have demonstrated increased early mortality and pulmonary vein reintervention for patients with total anomalous pulmonary venous connection (TAPVC) and heterotaxy syndrome (HTX+) compared with patients with TAPVC without heterotaxy syndrome (HTX-). We aimed to evaluate the longitudinal risk of pulmonary vein reintervention and mortality in HTX + patients. METHODS: A retrospective review was performed to identify longitudinal interventions in patients with TAPVC seen at a single center from 1995 to 2019. The mean cumulative interventions were described for all patients using the Nelson-Aalen estimator. Survival with TAPVC was described using Kaplan-Meier estimates. RESULTS: A total of 336 patients were identified with TAPVC, of whom 118 (35%) had heterotaxy syndrome. Functional single ventricles were identified in 106 of these 118 HTX + patients (90%) and in 14 of 218 HTX- patients (6%) (P < .001). Obstructed TAPVC (OBS+) was present in 49 of 118 HTX + patients (42%) and in 87 of 218 HTX- patients (40%) (P = .89). The median duration of follow-up was 6.5 years. Five-year survival was 69% for HTX+/OBS + patients, 72% for HTX+/OBS- patients, 86% for HTX-/OBS + patients, and 95% for HTX-/OBS- patients (P < .0001, log-rank test). The mean number of pulmonary vein interventions at the median follow-up time was greater in the HTX+/OBS + patients compared with HTX+/OBS- patients (mean, 2.0 vs 1.1; P = .030), HTX-/OBS + patients (mean, 1.3; P = .033), and HTX-/OBS- patients (mean, 1.3; P = .029). CONCLUSIONS: Among the 4 cohorts, HTX+ was associated with a higher rate of mortality, and HTX+/OBS+ was associated with a greater number of pulmonary vein interventions. This may be due in part to the high prevalence of single ventricle physiology in the HTX + cohort.

Extensive cell salvage and postoperative outcomes following thoracoabdominal and descending aortic repair.

OBJECTIVE: Cell salvage (CS) reduces intraoperative blood transfusion. However, it may cause deformity of the red blood cells and loss of coagulation factors, which may lead to unwanted sequelae. Thus, we hypothesized that extensive CS would lead to adverse outcomes after descending/thoracoabdominal aortic aneurysm (D/TAAA) repair. METHODS: Between 1991 and 2017, 2012 patients undergoing D/TAAA repair were retrospectively reviewed. After we excluded patients without reported intraoperative CS amount, patients were enrolled in the study (N = 1474) and divided into 2 groups: low CS (salvaged units <40, N = 983) and high CS (salvaged units ≥40, N = 491). Analyses were performed to verify the extensive CS as the risk factor for adverse outcomes. RESULTS: Preoperative demographics showed that the high-CS group had a significantly greater incidence of male patients (72% vs 58%), heritable aortic disease (24% vs 17%), redo (27% vs 20%), greater glomerular filtration rate (mL/min/1.73 m2, 75 vs 66) and more extensive aneurysms (TAAA extent II-IV). The high-CS group had significantly more postoperative complications compared with the low-CS group, including respiratory failure, renal failure, cardiac complications, neurologic deficits, bleeding, and 30-day mortality. Multivariable analysis confirmed high CS was an independent risk factor for renal failure along with long bypass time, older age, and extent of repairs. There was an incremental risk of renal failure and 30-day mortality proportional to salvaged cell unit (P < .001 in both). CONCLUSIONS: Increased salvaged cell units were associated with adverse postoperative outcomes after D/TAAA repairs. Risk of renal failure and mortality increased proportionally to the salvaged cell units.

Gait speed is a preoperative indicator of postoperative events after elective proximal aortic surgery.

OBJECTIVE: The study objective was to evaluate whether 5-m gait speed, an established marker of frailty, is associated with postoperative events after elective proximal aortic surgery. METHODS: We performed a retrospective review of 435 patients aged more than 60 years who underwent elective proximal aortic surgery, defined as surgery on the aortic root, ascending aorta, or aortic arch through median sternotomy. Patients completed a 5-m gait speed test within 30 days before surgery. We evaluated the association between categoric (slow, ≤0.83 m/s and normal, >0.83 m/s) and continuous gait speed and the likelihood of experiencing the composite outcome before and after adjustment for European System for Cardiac Operative Risk Evaluation II. The composite outcome included in-hospital mortality, renal failure, prolonged ventilation, and discharge location. Secondary outcomes were 1-year mortality and 5-year survival. RESULTS: Of the study population, 30.3% (132/435) were categorized as slow. Slow walkers were significantly more likely to have in-hospital mortality, prolonged ventilation, and renal failure, and were less likely to be discharged home (all P < .05). The composite outcome was 2 times more likely to occur for slow walkers (gait speed categoric adjusted odds ratio, 2.08; 95% confidence interval, 1.27-3.40; P = .004). Moreover, a unit (1 m/s) increase in gait speed (continuous) was associated with 73% lower risk of experiencing the composite outcome (odds ratio, 0.27; 95% confidence interval, 0.11-0.68; P = .006). CONCLUSIONS: Slow gait speed is a preoperative indicator of risk for postoperative events after elective proximal aortic surgery. Gait speed may be an important tool to complement existing operative risk models, and its application may identify patients who may benefit from presurgical and postsurgical rehabilitation.

Cohort Study Examining the Association of Immunosuppressant Drug Prescription With Major Adverse Cardiovascular and Limb Events in Patients With Peripheral Artery Disease.

AIM: Immune activation is strongly implicated in atherosclerotic plaque instability, however, the effect of immunosuppressant drugs on cardiovascular events in patients with peripheral artery disease (PAD) is not known. The aim of this study was to assess whether prescription of one or more immune suppressant drugs was associated with a lower risk of major adverse cardiovascular (MACE; i.e. myocardial infarction, stroke or cardiovascular events) or limb events (MALE; i.e. major amputation or requirement for peripheral revascularization) in patients with PAD. METHODS: A total of 1506 participants with intermittent claudication (n = 872) or chronic limb threatening ischemia (CLTI; n = 634) of whom 53 (3.5%) were prescribed one or more immunosuppressant drugs (prednisolone 41; methotrexate 17; leflunomide 5; hydroxychloroquine 3; azathioprine 2; tocilizumab 2; mycophenolate 1; sulfasalazine 1; adalimumab 1) were recruited from 3 Australian hospitals. Participants were followed for a median of 3.9 (inter-quartile range 1.2, 7.3) years. The association of immunosuppressant drug prescription with MACE or MALE was examined using Cox proportional hazard analyses. RESULTS: After adjusting for other risk factors, prescription of an immunosuppressant drug was associated with a significantly greater risk of MACE (Hazard ratio, HR, 1.83, 95% confidence intervals, CI, 1.11, 3.01; P = 0.017) but not MALE (HR 1.32, 95% CI 0.90, 1.92; P = 0.153). In a sub-analysis restricted to participants with CLTI findings were similar: MACE (HR 2.44, 95% CI 1.32, 4.51; P = 0.005); MALE (HR 1.38, 95% CI 0.87, 2.19; P = 0.175); major amputation (HR 1.37, 95% CI 0.49, 3.86; P = 0.547). CONCLUSIONS: This cohort study suggested that immunosuppressant drug therapy is associated with a greater risk of MACE amongst patients with PAD.

Surgeon volume and established hospital perioperative mortality rate together predict for superior outcomes after open abdominal aortic aneurysm repair.

BACKGROUND: In 2018, the Society for Vascular Surgery (SVS) published hospital volume guidelines for elective open abdominal aortic aneurysm (AAA) repair, recommending that elective open surgical repair of AAAs should be performed at centers with an annual volume of ≥10 open aortic operations of any type and a documented perioperative mortality of ≤5%. Recent work has suggested a yearly surgeon volume of at least seven open aortic cases for improved outcomes. The objective of the present study was to assess the importance of hospital volume and surgeon volume at these cut points for predicting 1-year mortality after open surgical repair of AAAs. METHODS: We evaluated patients who had undergone elective open AAA repair using the New York Statewide Planning and Research Cooperative System database from 2003 to 2014. The effect of the SVS guidelines on postoperative mortality and complications was evaluated. Confounding between the hospital and surgeon volumes was identified using mixed effects multivariate Cox proportional hazards analysis. The effect of the interactions between hospital volume, established hospital perioperative survival, and surgeon volume on postoperative outcomes was also investigated. RESULTS: The cohort consisted of 7594 elective open AAA repairs performed by 542 surgeons in 137 hospitals during the 12-year study period. Analysis of the 2018 guidelines using the Statewide Planning and Research Cooperative System database revealed 1-year and 30-day mortality rates of 9.2% (range, 8.3%-10.1%) and 3.5% (range, 2.9%-4.1%) for centers that were within the SVS guidelines and 13.6% (range, 12.5%-14.7%) and 6.9% (range, 6.1%-7.8%) for those that were outside the guidelines, respectively (P < .001 for both). Multivariate survival analysis revealed a hazard ratio for a surgeon volume of ≥7, hospital volume of ≥10, and hospital 3-year perioperative mortality of ≤5% of 0.80 (95% confidence interval [CI], 0.70-0.93; P = .003), 0.91 (95% CI, 0.77-1.08; P = .298), and 0.72 (95% CI, 0.62-0.82; P < .001), respectively. Additionally, procedures performed by surgeons with a yearly average volume of open aortic operations of at least seven and at hospitals with an established elective open AAA repair perioperative mortality rate of ≤5% showed improved 1-year (33.2% relative risk reduction; P < .001) and 30-day (P = .001) all-cause survival and improved postoperative complication rates. CONCLUSIONS: These data have demonstrated that centers that meet the SVS AAA volume guidelines are associated with improved 1-year and 30-day all-cause survival. However, the results were confounded by surgeon volume. A surgeon open aortic volume of at least seven procedures and an established hospital perioperative mortality of ≤5% each independently predicted for 1-year survival after open AAA repair, with the hospital volume less important. These results indicate that surgeons with an annual volume of at least seven open aortic operations of any type should perform elective open AAA repair at centers with a documented perioperative mortality of ≤5%.

Outcome Analysis Using the Modified Frailty Index-5 in Patients With Complex Aortoiliac Disease.

OBJECTIVES: Vascular surgery patients commonly have several comorbidities that cumulatively lead to a frailty status. The cumulative comorbidities disproportionately increase the risk of adverse events and are also associated with worsened long-term prognosis. In recent years, several tools have been elaborated with the objective of quantifying a patient's frailty. One of them is the modified frailty index-5 (mFI-5), a simplified and easy to use index. There is scarce data regarding its value as a prognostic factor in aortoiliac occlusive disease. The aim of this work is to validate mFI-5 as a potential postoperative prognostic indicator in this population. METHODS: From January 2013 to January 2020, 109 patients who underwent elective revascularizations, either endovascular or open surgery, having Trans-Atlantic Inter-Society Consensus II type D aortoiliac lesions in a tertiary and a regional hospital were selected from a prospective vascular registry. Demographic data was collected including diabetes mellitus, chronic heart failure, chronic obstructive pulmonary disease, arterial hypertension requiring medication and functional status. The 30-d and subsequent long-term surveillance outcomes were also collected including major adverse cardiovascular events (MACE), major adverse limb events (MALE) and all-cause mortality were assessed in the 30-d post-procedure and in the subsequent long-term surveillance period. The mFI-5 was applied to this population to evaluate the prognostic impact of this frailty marker on mortality and morbidity. RESULTS: In the long-term follow-up, mFI-5 was significantly associated with MACE (hazard ratio [HR] 2.469; 95% confidence interval [CI]: 1.267-4.811; P = .008) and all-cause mortality (HR 2.585; 95% CI: 1.270-5.260; P = .009). However, there was no significant association with 30-day outcomes. Along with the presence of chronic kidney disease, mFI-5 was the prognostic factor better able of predicting MACE. No prognostic value was found regarding short-term outcomes. CONCLUSION: The mFI-5 index may have a role in predicting long term outcomes, namely MACE and all-cause mortality, in the subset of patients with extensive aortoiliac occlusive disease. Its ease of use can foster its application in risk stratification and contribute for the decision-making process.

The Impact of Anemia on One-Year Amputation-Free Survival in Patients Undergoing Revascularization for Chronic Limb-Threatening Ischemia: A Retrospective Cohort Study.

BACKGROUND: Anemia is potentially associated with increased morbidity and mortality following vascular surgery procedures. This study investigated whether peri-procedural anemia is associated with reduced 1-year amputation-free survival (AFS) in patients undergoing revascularization for chronic limb-threatening ischemia (CLTI). METHODOLOGY: A retrospective analysis of patients diagnosed with CLTI between February 2018-February 2019, who subsequently underwent revascularization, was conducted. Hemoglobin concentration measured at index assessment was recorded and stratified by WHO criteria. Subsequent peri-procedural red blood cell transfusions (RBC) were also recorded. The primary outcome was 1-year AFS. Kaplan Meier survival analysis and Cox's proportional hazard modelling were conducted to assess the effect of anemia and peri-procedure transfusion on outcomes. RESULTS: 283 patients were analyzed, of which 148 (52.3%) were anemic. 53 patients (18.7%) underwent RBC transfusion. Patients with anemia had a significantly lower 1-year AFS (64.2% vs. 78.5%, P = 0.009). A significant difference in 1-year AFS was also observed based upon anemia severity (P = 0.008) and for patients who received RBC transfusion (45.3% vs 77.0%, P < 0.001). On multivariable analysis, moderately severe anemia was independently associated with increased risk of major amputation/death (aHR 1.90, 95% CI 1.06-3.38, P = 0.030). After adjusting for severity of baseline anemia, peri-procedural RBC transfusion was associated with a significant increase in the combined risk of major amputation/death (aHR 3.15, 95% CI 1.91-5.20, P < 0.001). CONCLUSION: Moderately severe peri-procedural anemia and subsequent RBC transfusion are independently associated with reduced 1-year AFS in patients undergoing revascularization for CLTI. Future work should focus on investigating alternative measures to managing anemia in this cohort.