Long-Term Mortality Predictors Using a Machine-Learning Approach in Patients With Chronic Limb-Threatening Ischemia After Peripheral Vascular Intervention.

BACKGROUND: Patients with chronic limb-threatening ischemia (CLTI) face a high long-term mortality risk. Identifying novel mortality predictors and risk profiles would enable individual health care plan design and improved survival. We aimed to leverage a random survival forest machine-learning algorithm to identify long-term all-cause mortality predictors in patients with CLTI undergoing peripheral vascular intervention. METHODS AND RESULTS: Patients with CLTI undergoing peripheral vascular intervention from 2017 to 2018 were derived from the Medicare-linked VQI (Vascular Quality Initiative) registry. We constructed a random survival forest to rank 66 preprocedural variables according to their relative importance and mean minimal depth for 3-year all-cause mortality. A random survival forest of 2000 trees was built using a training sample (80% of the cohort). Accuracy was assessed in a testing sample (20%) using continuous ranked probability score, Harrell C-index, and out-of-bag error rate. A total of 10 114 patients were included (mean±SD age, 72.0±11.0 years; 59% men). The 3-year mortality rate was 39.1%, with a median survival of 1.4 years (interquartile range, 0.7-2.0 years). The most predictive variables were chronic kidney disease, age, congestive heart failure, dementia, arrhythmias, requiring assisted care, living at home, and body mass index. A total of 41 variables spanning all domains of the biopsychosocial model were ranked as mortality predictors. The accuracy of the model was excellent (continuous ranked probability score, 0.172; Harrell C-index, 0.70; out-of-bag error rate, 29.7%). CONCLUSIONS: Our random survival forest accurately predicts long-term CLTI mortality, which is driven by demographic, functional, behavioral, and medical comorbidities. Broadening frameworks of risk and refining health care plans to include multidimensional risk factors could improve individualized care for CLTI.

Lower extremity arterial disease vs. coronary artery disease: mortality differences after revascularization.

BACKGROUND AND AIMS: Patients undergoing revascularization for lower extremity arterial disease (LEAD) may face a higher risk of mortality than those with coronary artery disease (CAD). This study aimed to characterize the difference in mortality risk between patients undergoing revascularization for LEAD and CAD and identify associated factors. METHODS: The 1-year database of 10 754 patients undergoing revascularization for CAD (n = 6349) and LEAD (n = 4405) was analysed. Poisson regression models were used to characterize interpopulation differences in mortality, adjusting for baseline clinical features, including age, sex, polyvascular disease, comorbidities, medications, and vulnerabilities. RESULTS: Individuals with LEAD were older, were more likely to have polyvascular disease, had more comorbidities, and received fewer cardioprotective drugs than those with CAD. Vulnerabilities remained more common in the LEAD group even after adjusting for these clinical features. The crude risk ratio of mortality incidence for LEAD vs. CAD was 2.91 (95% confidence interval, 2.54-3.34), attenuated to 2.14 (1.83-2.50) after controlling for age, sex, and polyvascular disease. The percentage attenuation in the excessive mortality associated with LEAD was 29%. The stepwise addition of comorbidities, medications, and vulnerabilities as adjusting factors attenuated the incidence risk ratio to 1.48 (1.26-1.72), 1.33 (1.12-1.58), and 1.17 (0.98-1.39), respectively, and increased the percentage attenuation to 64%, 73%, and 86%, respectively. CONCLUSIONS: Mortality risk was almost three-fold higher in patients undergoing revascularization for LEAD than in those with CAD. The excessive mortality was considerably attributable to inter-group differences in baseline characteristics, including potentially clinically or socially modifiable factors.

Infrapopliteal Bypass In Patients On Dialysis: Patency And Survival.

INTRODUCTION: Portugal has one of the highest prevalence of patients on a regular dialysis program. This population has a higher incidence of peripheral arterial disease with higher rates of postoperative morbidity and mortality. Our goal was to compare outcomes between dialysis and non-dialysis patients with chronic limb threatening ischemia (CLTI) submitted to infrapopliteal bypass. MATERIALS AND METHODS: A retrospective single-center study of infrapopliteal bypass for CLTI was performed between 2012 and 2019. Patients were divided in two groups based on dialysis status (group 1 incorporated patients on dialysis). Primary end point was 1-year freedom from CLTI. Secondary end points were limb-salvage, survival and primary (PP) and tertiary patency (TP) rates at 3 years of follow-up. RESULTS: A total of 352 infrapopliteal bypasses were performed in 310 patients with CLTI. Fourteen percent of the revascularizations were performed on dialysis patients (48/352). Median age was 73 years (interquartile range - IQR 15) and 74% (259/352) were male. Median follow-up was 26 months (IQR 42). Overall, 92% (325/352) had tissue loss and 44% (154/352) had some degree of infection. The majority of revascularization procedures were performed with vein grafts (61%, 214/352). The 30-day mortality was 4% (11/310), with no difference between groups (p = 0.627). Kaplan-Meier analysis showed no difference between groups regarding freedom from CLTI (76% vs. 79%; HR 0.96, CI 0.65-1.44, p=0.857), limb-salvage (70% vs. 82%; HR 1.40, CI 0.71-2.78, p=0.327) and survival (62% vs. 64%; HR 1.08, CI 0.60-1.94, p=0.799). PP rates were 39% in group 1 and 64% in group 2 (HR 1.71, CI 1.05-2.79, p=0.030). TP rates were not different between groups (57% and 78%; HR 1.79, CI 0.92-3.47, p=0.082). CONCLUSION: Infrapopliteal bypass for CLTI, on dialysis patients, resulted in lower PP rates. No differences were observed in freedom from CLTI, TP, limb salvage and survival.

Ten-year mortality after treating obstructive coronary atherosclerosis with contemporary stents in patients with or without concomitant peripheral arterial disease.

BACKGROUND AND AIMS: Previous studies in percutaneous coronary intervention (PCI) patients showed a higher 3-year adverse event risk, including all-cause mortality, in those with concomitant peripheral arterial disease (PADs). Ten-year data of mortality and causes of death are scarce. This analysis assessed PCI patients, treated with contemporary drug-eluting stents, the impact of concomitant PADs on very long-term mortality, and causes of death. METHODS: We assessed PCI all-comers from our center who participated in the TWENTE and DUTCH PEERS trials (clinicaltrials.gov:NCT01066650, NCT01331707), comparing patients with versus without PADs. Life status was checked in the Dutch Personal Records Database; causes of death were obtained from medical records. RESULTS: Of 2705 study patients, 668 (24.7%) died during follow-up: 88/212 (41.5%) patients with PADs and 580/2493 (23.1%) without PADs. In PADs patients, the 10-year rate of all-cause mortality was about twice as high as in patients without PADs (41.5% vs.23.1%, HR: 2.05, 95%-CI: 1.64-2.57, p<0.001). For both groups, the rates of patients dying from various causes of death were: cardiac (14.1% vs.6.8%), vascular (2.8% vs. 1.1%), non-cardiovascular (17.4% vs. 9.8%), and unclear causes (7.1% vs. 5.3%), without a statistically significant between-group difference. When multivariate analysis was adjusted for between-group differences in cardiovascular risk profile, PADs remained predictor of all-cause mortality (adjusted HR: 1.38, 95%-CI: 1.08-1.75, p=0.01). CONCLUSIONS: The 10-year all-cause mortality rate in PCI patients with concomitant PADs was almost twice as high as in those without PADs. Age and other traditional cardiovascular risk factors were higher in patients with PADs, but after correction for these confounders PADs still accounted for almost 40% increase in mortality.

Arm and ankle blood pressure indices, and peripheral artery disease, and mortality: a cohort study.

BACKGROUND AND AIMS: Few studies have compared arm and ankle blood pressures (BPs) with regard to peripheral artery disease (PAD) and mortality. These relationships were assessed using data from three large prospective clinical trials. METHODS: Baseline BP indices included arm systolic BP (SBP), diastolic BP (DBP), pulse pressure (arm SBP minus DBP), ankle SBP, ankle-brachial index (ABI, ankle SBP divided by arm SBP), and ankle-pulse pressure difference (APPD, ankle SBP minus arm pulse pressure). These measurements were categorized into four groups using quartiles. The outcomes were PAD (the first occurrence of either peripheral revascularization or lower-limb amputation for vascular disease), the composite of PAD or death, and all-cause death. RESULTS: Among 40 747 participants without baseline PAD (age 65.6 years, men 68.3%, diabetes 50.2%) from 53 countries, 1071 (2.6%) developed PAD, and 4955 (12.2%) died during 5 years of follow-up. Incident PAD progressively rose with higher arm BP indices and fell with ankle BP indices. The strongest relationships were noted for ankle BP indices. Compared with people whose ankle BP indices were in the highest fourth, adjusted hazard ratios (95% confidence interval) for each lower fourth were 1.64 (1.31-2.04), 2.59 (2.10-3.20), and 4.23 (3.44-5.21) for ankle SBP; 1.19 (0.95-1.50), 1.66 (1.34-2.05), and 3.34 (2.75-4.06) for ABI; and 1.41 (1.11-1.78), 2.04 (1.64-2.54), and 3.63 (2.96-4.45) for APPD. Similar patterns were observed for mortality. Ankle BP indices provided the highest c-statistics and classification indices in predicting future PAD beyond established risk factors. CONCLUSIONS: Ankle BP indices including the ankle SBP and the APPD best predicted PAD and mortality.

Regional variation in cause of death in patients with type 2 diabetes: Insights from EXSCEL.

AIMS: Type 2 diabetes (T2D) is a risk factor for cardiovascular and non-cardiovascular mortality. However, global distribution of cause-specific deaths in T2D is poorly understood. We characterized cause-specific deaths by geographic region among individuals with T2D at risk for cardiovascular disease (CVD). METHODS AND RESULTS: The international EXSCEL trial included 14,752 participants with T2D (73% with established CVD). We identified the proportion of deaths over 5-year follow-up attributed to cardiovascular and non-cardiovascular causes, and associated risk factors. During median 3.2-year follow-up, 1,091 (7.4%) participants died. Adjudicated causes of death were 723 cardiovascular (66.3% of deaths), including 252 unknown, and 368 non-cardiovascular (33.7%). Most deaths occurred in North America (N = 356/9.6% across region) and Eastern Europe (N = 326/8.1%), with fewest in Asia/Pacific (N = 68/4.4%). The highest proportional cause-specific deaths by region were sudden cardiac in Asia/Pacific (23/34% of regional deaths) and North America (86/24%); unknown in Eastern Europe (90/28%) and Western Europe (39/21%); and non-malignant non-cardiovascular in Latin America (48/31%). Cox proportional hazards model for adjudicated causes of death showed prognostic risk factors (hazard ratio [95% CI]) for cardiovascular and non-cardiovascular deaths, respectively: heart failure 2.04 (1.72-2.42) and 1.86 (1.46-2.39); peripheral artery disease 1.83 (1.54-2.18) and 1.78 (1.40-2.26); and current smoking status 1.61 (1.29-2.01) and 1.77 (1.31-2.40). CONCLUSIONS: In a contemporary T2D trial population, with and without established CVD, leading causes of death varied by geographic region. Underlying mechanisms leading to variability in cause of death across geographic regions and its impact on clinical trial endpoints warrant future research.

Delayed Closure of Guillotine Lower Extremity Amputation in Obese Patients is Associated with Increased Mortality.

BACKGROUND: Staged surgery with open guillotine amputation (OGA) prior to a definitive major lower extremity amputation (LEA) has been shown to be effective for sepsis control and improving wound healing. Studies have evaluated postoperative complications including infection, return to the operating room for re-amputation, and amputation failure following OGA. However, the role of timing to close OGA for predictive outcomes remains poorly understood. We aim to assess outcomes of major LEA related to the time of OGA closure. METHODS: Data from patients who underwent major LEA from 2015 to 2021 were collected retrospectively. The study included all patients undergoing below-knee, through-knee, or above-knee amputations. Next, patients who had OGA prior to a definitive amputation were selected. Patients who died before amputation closure were excluded. Postamputation outcomes such as surgical site infection, postoperative sepsis, postoperative ambulation, hospital length of stay, and 30-day, 1-year, and 5-year mortality were reviewed. The study cohort was stratified by demographics and comorbidities. Receiver operating characteristic curve analysis was performed to determine the time of closure (TOC) cutoff value. Univariate and multivariate analysis was performed to assess outcomes. Statistical significance was set at P < 0.05. RESULTS: Of 688 patients who underwent major LEA, 322 underwent staged amputation with OGA before the formalization procedure and were included. The TOC ranged from 1-47 days with a median of 4 days (interquartile range from 3 to 7). The optimal TOC point of 8 days (ranging from 2-42 days) in obese patients (199/322) for predicting mortality showed the largest area under the curve (0.709) with 64.71% sensitivity and 78.3% specificity. Patients who are obese and grouped in TOC less than 8 days had no 30-day mortality, significantly lower 1-year mortality, better survival, and a lower rate of deep venous thrombosis complication. There was no significant difference in length of stay, postoperative surgical site infection, sepsis, and ambulation between the 2 subgroups of obese patients. Multivariable analysis showed that gender, chronic kidney disease, and postoperative ambulation independently predict overall mortality in obese patients. CONCLUSIONS: TOC cutoff in obese patients showed statistically significant results in predicting mortality. Our findings indicated better survival in obese patients with a lower TOC (less than 8 days). This emphasizes the importance of earlier closure of OGA in obese patients.

Reconsidering the Impact of Endovascular Repair on Short-Term and Mid-Term Outcomes in Peripheral Arterial Disease: A Retrospective Analysis.

BACKGROUND: The aim of the study is to compare the short-term and medium-term outcomes in patients who underwent open repair (OR) or endovascular repair (ER) for peripheral arterial disease (PAD) also including stratifications based on severity and year of the first intervention. METHODS: We conducted an observational retrospective single-center cohort study. We evaluated patients with PAD that primarily underwent ER, OR, minor, and major amputations in a single center from 2005 to 2020. The patients were then subdivided according to the type of intervention (OR versus ER), and stratified according to the International Classification of Diseases 9 code reported in the operating documents and to the year intervention. Mortality, minor, and major amputation rates occurring at 30 days, 2 years, and 5 years after the first intervention were evaluated as primary outcomes and compared between patient groups in both stratifications. Moreover, Kaplan-Maier curves were analyzed for these outcomes. RESULTS: One thousand four hundred ninety two patients (67.0% males) with PAD were evaluated. Their clinical presentations were intermittent claudication in 51.4% of cases, rest pain in 16.8%, ulcers in 10.3%, and gangrene in 21.5%. Nine hundred ninety seven (66.8%) underwent OR and 495 (33.2%) ER as first intervention for PAD. No statistical differences were observed in terms of mortality in the 2 groups (OR versus ER, P = 1,000, P = 0.357, and P = 0.688 at 30 days, 2 years, and 5 years, respectively). The rate of minor amputations was significantly higher (P < 0.012, P < 0.002, and P < 0.007 at 30 days, 2 years, and 5 years, respectively) for ER group in any of the observed follow-up periods. Also, we have observed that OR and ER do not have any significant short-term and medium-term major amputation rate differences. CONCLUSIONS: In our experience, the impact of ER does not significantly change short-term and mid-term major outcomes in patients with PAD.

Association of antiplatelet therapy with clinical outcomes in patients with peripheral artery disease.

BACKGROUND: The beneficial role of dual anti-platelet therapy (DAPT) in coronary artery disease is well established. However, there is limited data describing the effects of DAPT in patients with atherosclerotic peripheral artery disease (PAD). The aim of this meta-analysis is to compare clinical outcomes associated with DAPT versus single anti-platelet therapy (SAPT) in patients with symptomatic PAD. METHODS: We performed a literature search for studies assessing the risk of adverse cardiovascular and limb events in cohorts receiving either DAPT or SAPT. The primary endpoint was all cause mortality. The secondary endpoints included graft failure, amputation, total bleeding, severe bleeding and fatal bleeding. The search included the following databases: Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar. The search was not restricted to time or publication status. RESULTS: A total of 11 studies with 54,331 participants (24,449 on SAPT and 29,882 on DAPT) were included. Patients with PAD treated with SAPT had higher all-cause mortality compared to patients treated with DAPT (OR 1.37, 95 % CI 1.09-1.74; p < 0.01). There was no difference in risk of graft failure or amputation between patients treated with SAPT or DAPT (OR 0.9, 95 % CI 0.77-1.06; p = 0.19; OR 1.11, 95 % CI 0.88-1.41; p = 0.37). Patients treated with SAPT had lower total bleeds compared to patients treated with DAPT (OR 0.53, 95 % CI 0.36-0.77; p < 0.01). However, For SAPT plus AC vs SAPT, a total of 8 studies with 17,100 participants (3447 with SAPT plus AC and 8619 with only SAPT) were included. Patients on SAPT plus AC did not have a statistically significant difference in risk for all-cause mortality, (OR 0.91, 95 % CI 0.67-1.24; p = 0.56). SAPT plus AC had significantly lower risk of MI (OR 0.82, 95 % CI 0.69-0.97; p = 0.02), amputation (OR 0.72, 95 % CI 0.53-0.97; p = 0.03), and graft failure (OR 0.66, 95 % CI 0.48-0.93; p = 0.02). There was no significant different in risk of fatal bleeding be-tween the two groups (OR 1.60, 95 % CI 0.76-3.35; p = 0.22). CONCLUSIONS: In patients with symptomatic PAD, a strategy of DAPT may confer a mortality benefit when compared to SAPT without significantly increasing the risk of serious bleeding events.

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.

C-Reactive Protein and Risk of Cardiovascular Events and Mortality in Patients with Various Cardiovascular Disease Locations.

Anti-inflammatory drugs reduce the risk of cardiovascular events in patients with coronary artery disease (CAD), but less is known about the relation between inflammation and outcomes in patients with cerebrovascular disease (CeVD), peripheral artery disease (PAD), and abdominal aortic aneurysm (AAA). This study assessed the association between C-reactive protein (CRP) and clinical outcomes in patients with CAD (n = 4,517), CeVD (n = 2,154), PAD (n = 1,154), and AAA (n = 424) from the prospective Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease study. The primary outcome was recurrent cardiovascular disease (CVD), defined as myocardial infarction, ischemic stroke, or cardiovascular death. Secondary outcomes were major adverse limb events and all-cause mortality. Associations between baseline CRP and outcomes were assessed using Cox proportional hazards models adjusted for age, sex, smoking, diabetes mellitus, body mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, and glomerular filtration rate. Results were stratified by CVD location. During a median follow-up of 9.5 years, 1,877 recurrent CVD events, 887 major adverse limb events, and 2,341 deaths were observed. CRP was independently associated with recurrent CVD (hazard ratio [HR] per 1 mg/L 1.08, 95% confidence interval [CI] 1.05 to 1.10), and all secondary outcomes. Compared with the first quintile of CRP, HRs for recurrent CVD were 1.60 (95% CI 1.35 to 1.89) for the last quintile ≤10 mg/L and 1.90 (95% CI 1.58 to 2.29) for the subgroup with CRP >10 mg/L. CRP was associated with recurrent CVD in patients with CAD (HR per 1 mg/L 1.08, 95% CI 1.04 to 1.11), CeVD (HR 1.05, 95% CI 1.01 to 1.10), PAD (HR 1.08, 95% CI 1.03 to 1.13), and AAA (HR 1.08, 95% CI 1.01 to 1.15). The association between CRP and all-cause mortality was stronger for patients with CAD (HR 1.13, 95% CI 1.09 to 1.16) than for patients with other CVD locations (HRs 1.06 to 1.08; p = 0.002). Associations remained consistent beyond 15 years after the CRP measurement. In conclusion, greater CRP is independently associated with an increased risk of recurrent CVD and mortality, irrespective of previous CVD location.

Mortality differences by race over 20 years in individuals with peripheral artery disease.

INTRODUCTION: Racial disparities exist in patients with peripheral artery disease (PAD), with Black individuals having worse PAD-specific outcomes. However, mortality risk in this population has been mixed. As such, we sought to evaluate all-cause mortality by race among individuals with PAD. METHODS: We analyzed data from the National Health and Nutrition Examination Survey (NHANES). Baseline data were obtained from 1999 to 2004. Patients with PAD were grouped according to self-reported race. Multivariable Cox proportional hazards regression was performed to calculate adjusted hazard ratios (HR) by race. A separate analysis was performed to study the effect of burden of social determinants of health (SDoH) on all-cause mortality. RESULTS: Of 647 individuals identified, 130 were Black and 323 were White. Black individuals had more premature PAD (30% vs 20%, p < 0.001) and a higher burden of SDoH compared to White individuals. Crude mortality rates were higher in Black individuals in the 40-49-year and 50-69-year age groups compared to White individuals (6.7% vs 6.1% and 8.8% vs 7.8%, respectively). Multivariable analysis demonstrated that Black individuals with both PAD and coronary artery disease (CAD) had a 30% higher hazard of death over 20 years compared to White individuals (HR = 1.3, 95% CI: 1.0-2.1). The cumulative burden of SDoH marginally (10-20%) increased the risk of all-cause mortality. CONCLUSIONS: In a nationally representative sample, Black individuals with PAD and CAD had higher rates of mortality compared to their White counterparts. These findings add further proof to the ongoing racial disparities among Black individuals with PAD and highlight the necessity to identify ways to mitigate these differences.

Transcatheter Arterialization of Deep Veins in Chronic Limb-Threatening Ischemia.

BACKGROUND: Approximately 20% of patients with chronic limb-threatening ischemia have no revascularization options, leading to above-ankle amputation. Transcatheter arterialization of the deep veins is a percutaneous approach that creates an artery-to-vein connection for delivery of oxygenated blood by means of the venous system to the ischemic foot to prevent amputation. METHODS: We conducted a prospective, single-group, multicenter study to evaluate the effect of transcatheter arterialization of the deep veins in patients with nonhealing ulcers and no surgical or endovascular revascularization treatment options. The composite primary end point was amputation-free survival (defined as freedom from above-ankle amputation or death from any cause) at 6 months, as compared with a performance goal of 54%. Secondary end points included limb salvage, wound healing, and technical success of the procedure. RESULTS: We enrolled 105 patients who had chronic limb-threatening ischemia and were of a median age of 70 years (interquartile range, 38 to 89). Of the patients enrolled, 33 (31.4%) were women and 45 (42.8%) were Black, Hispanic, or Latino. Transcatheter arterialization of the deep veins was performed successfully in 104 patients (99.0%). At 6 months, 66.1% of the patients had amputation-free survival. According to Bayesian analysis, the posterior probability that amputation-free survival at 6 months exceeded a performance goal of 54% was 0.993, which exceeded the prespecified threshold of 0.977. Limb salvage (avoidance of above-ankle amputation) was attained in 67 patients (76.0% by Kaplan-Meier analysis). Wounds were completely healed in 16 of 63 patients (25%) and were in the process of healing in 32 of 63 patients (51%). No unanticipated device-related adverse events were reported. CONCLUSIONS: We found that transcatheter arterialization of the deep veins was safe and could be performed successfully in patients with chronic limb-threatening ischemia and no conventional surgical or endovascular revascularization treatment options. (Funded by LimFlow; PROMISE II study ClinicalTrials.gov number, NCT03970538.).

Demographic and regional trends of peripheral artery disease-related mortality in the United States, 2000 to 2019.

INTRODUCTION: Peripheral artery disease (PAD) is a common progressive atherosclerotic disease associated with significant morbidity and mortality in the US; however, data regarding PAD-related mortality trends are limited. This study aims to characterize contemporary trends in mortality across sociodemographic and regional groups. METHODS: The Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research (CDC WONDER) was queried for data regarding PAD-related deaths from 2000 to 2019 in the overall sample and different demographic (age, sex, race/ethnicity) and regional (state, urban-rural) subgroups. Crude and age-adjusted mortality rates (CMR and AAMR, respectively) per 100,000 people were calculated. Associated annual percentage changes (APC) were computed using Joinpoint Regression Program Version 4.9.0.0 trend analysis software. RESULTS: Between 2000 and 2019, a total of 1,959,050 PAD-related deaths occurred in the study population. Overall, AAMR decreased from 72.8 per 100,000 in 2000 to 32.35 per 100,000 in 2019 with initially decreasing APCs followed by no significant decline from 2016 to 2019. Most demographic and regional subgroups showed initial declines in AAMRs during the study period, with many groups exhibiting no change in mortality in recent years. However, men, non-Hispanic (NH) Black or African American individuals, people aged ⩾ 85 years, and rural counties were associated with the highest AAMRs of their respective subgroups. Notably, there was an increase in crude mortality rate among individuals 25-39 years of age from 2009 to 2019. CONCLUSION: Despite initial improvement, PAD-related mortality has remained stagnant in recent years. Disparities have persisted across several demographic and regional groups, requiring further investigation.

Association of neutrophil-to-lymphocyte ratio with thirty-day mortality in acute peripheral arterial ischemia.

BACKGROUND: Acute peripheral arterial ischemia (APAI) is an acute ischemic condition that develops as a result of embolism or thrombosis, and its morbidity and mortality are still high today. The objective of this study is to determine the effect of preoperative Neutrophil-to-Lymphocyte ratio (NLR) on mortality in patients admitted with the diagnosis of APAI. METHODS: 178 patients who were diagnosed with acute peripheral arterial occlusion and underwent emergency embolectomy were evaluated retrospectively over a 7-year period. Patient demographics, clinical history, risk factors, comorbidity, and hemogram sub-parameters were documented. The endpoint of the patients was determined as death. RESULTS: A total of 178 patients were identified with a mean age 74.29±14.71 (range 28-111) years; among them, 105 (59%) were female. 18% patients (32/178) died within 30 days. Lower extremity involvement was present in 124 (69.7%) of the patients. A statistically significant difference was found between the mortality rates and blood parameters of the patients included in the study in terms of white blood count C-reactive protein (CRP), and age among those with normal distribution. Neutrophil, NLR, procalcitonin, lactate, aspartate aminotransferase, and urea; It was statistically significant in terms of mortality in our patients with APAI. NLR values of the deceased were determined as 7.98 ± 6.85. CONCLUSIONS: APAI patients with high NLRs had significantly higher risks of 30-day mortality. The NLR can be used as a prognostic marker in these patients and warrants further investigation.

Assessment of Sirolimus- vs. paCLitaxEl-coated balloon angioPlasty In atherosclerotic femoropopliteal lesiOnS (ASCLEPIOS Study): preliminary results.

BACKGROUND: There appears to be an association between paclitaxel-coated devices and increased 5-year all-cause mortality. METHODS: We are conducting a prospective, randomized, controlled, single-center, noninferiority study. All consecutive patients with femoropopliteal arterial disease who fulfilled the inclusion/exclusion criteria are sequentially and consecutively assigned to either paclitaxel (Ranger, Boston Scientific) or sirolimus (MagicTouch, Concept Medical) coated balloon angioplasty treatment. The primary outcome are procedural success and primary vessel patency at index procedure. The secondary outcomes are 30-day and 12-month freedom from MAEs (amputation, death, TLR/TVR, MI, distal embolization that requires a separate intervention or hospitalization), procedural success (≤30% residual diameter stenosis or occlusion after the procedure), Rutherford category improvement (reduction ≤1 category) and ABI improvement (increase ≥0.10 from baseline). RESULTS: A total of six patients have been enrolled in the present study up to now. The mean age was 72.6 years old and five were male. All patients had angiographic evidence of isolated occlusion in the transition segment of the distal femoral superficial artery in the popliteal artery. The mean length was 109 mm. Three patients were treated by sirolimus-coated (group A) and three by paclitaxel coated balloon angioplasty (group B). The primary patency and procedural success was in two of three and three of three patients, for group A and B, respectively. CONCLUSIONS: Preliminary results show safety and feasibility of the Sirolimus-coated balloon angioplasty. Further investigation and increase of sample size will allow for more sustained conclusions regarding patency and procedural success of this type of balloons for the endovascular treatment of peripheral arterial disease.

Four-year patient-level pooled mortality analysis of the ILLUMENATE US Pivotal and EU randomized controlled trials.

OBJECTIVE: To perform a meta-analysis of two concordant randomized controlled trials (RCTs) examining the long-term, 4-year safety profile of the Stellarex drug-coated balloon (DCB) vs percutaneous transluminal angioplasty (PTA) for the treatment of peripheral artery disease. METHODS: An independent, third-party, meta-analysis of homogeneous, patient-level data from the ILLUMENATE Pivotal and ILLUMENATE EU RCTs was performed to assess mortality (time to death) in patients treated for symptomatic femoropopliteal disease. The Kaplan-Meier (KM) methodology was used to estimate hazard rates [HRs] of all-cause mortality, and Cox proportional hazard modeling was used to assess predictors of mortality. All serious adverse events, including deaths, were adjudicated by an independent, blinded clinical events committee. RESULTS: In total, 589 (419 DCB; 170 PTA) patients were included in the pooled analysis of the ILLUMENATE Pivotal and ILLUMENATE EU RCTs. The median follow-up was 1735 days (interquartile range, 1434-1829 days), equivalent to 4.75 years. Vital status compliance was >95% in each RCT. The total number of deaths through 4 years was 81 of 589 (13.8%): 58 of 419 (13.8%) in the DCB arm and 23 of 170 (13.5%) in the PTA arm. The 1-year KM estimate of all-cause mortality was 1.9% ± 0.7% (estimate ±standard error) in those treated with DCB vs 1.2% ± 0.9% in those treated with PTA. At 2, 3, and 4 years, the respective KM estimates were 6.6% ± 1.2% vs 4.9% ± 1.7%, 9.3% ± 1.4% vs 9.9% ± 2.4%, and 14.0% ± 1.7% vs 14.4% ± 2.8% (P = .864). There were no significant differences in clinical events committee-adjudicated deaths between the two cohorts. In multivariate analysis, predictors of 4-year mortality were age (HR, 1.048; 95% confidence interval [CI], 1.026-1.071; P < .0001), renal insufficiency (HR, 2.440; 95% CI, 1.566-3.800; P < .0001), and lesion length (HR, 1.004; 95% CI, 1.000-1.008; P = .041). Neither paclitaxel exposure (DCB vs PTA; HR, 1.086; 95% CI, 0.709-1.664; P = .705) nor dose (mg; HR, 1.043; 95% CI, 0.971-1.119; P = .248) was the predictor of all-cause mortality at 4 years. CONCLUSIONS: This systematic meta-analysis of two concordant ILLUMENATE RCTs shows no difference in all-cause mortality through 4 years between Stellarex DCB and PTA, confirming the acceptable, long-term safety profile of the Stellarex DCB.

Symptomatic human immunodeficiency virus infection is associated with advanced presentation and perioperative mortality in patients undergoing surgery for peripheral arterial disease.

OBJECTIVE: Prior studies have demonstrated an increased risk of developing cardiovascular and peripheral arterial disease (PAD) in patients with human immunodeficiency virus (HIV). However, the effect of chronic HIV infection in patients with preexisting PAD and requiring vascular intervention is unclear. In the present study, we assessed the differences in clinical presentation and perioperative outcomes for patients with PAD who had undergone revascularization or amputation with and without HIV infection. METHODS: International Classification of Diseases, 9th and 10th Revisions, Clinical Modification, codes were used to identify patients with a prior diagnosis of PAD who had undergone lower extremity revascularization or amputation in the National Inpatient Sample (2003-2017). From this group, the patients were divided for analysis into those with and without HIV infection. Of the patients with HIV infection (PWHs), we identified additional subsets of patients: those with any prior or current diagnosis of an HIV-related illness, including acquired immunodeficiency syndrome, designated as symptomatic HIV, and those without such a diagnosis, designated as asymptomatic HIV infection. Propensity score matching was performed to create matched cohorts. Population-based comparative analyses were performed of the clinical characteristics of the HIV-infected and HIV-uninfected groups. Univariate and multivariate logistic regression analyses of the perioperative in-hospital outcomes were performed on the matched cohorts. RESULTS: A total of 224,912 patients aged 18 to 85 years were identified who had been admitted with an established diagnosis of PAD and had undergone a lower extremity procedure. Of these patients, 1264 (0.56%) also had a diagnosis of HIV infection. Symptomatic PWHs were more likely to present with critical limb ischemia than were the HIV-uninfected patients or asymptomatic PWHs (66.2% vs 46.3% and 43.6%; P < .01). However, both asymptomatic and symptomatic PWHs were more likely to have required minor (7.5% and 6.7% vs 2.6%; P < .01) and major (12.9% and 27.4% vs 7.0%; P < .01) amputations than were matched HIV-uninfected controls. Although adjusted multivariate logistic regression analysis demonstrated symptomatic HIV infection to be a significant, independent predictor of in-hospital mortality (odds ratio, 2.46; 95% confidence interval, 1.37-4.40; P = .003), the perioperative mortality for the asymptomatic PWH was comparable to that of matched HIV-uninfected controls. CONCLUSIONS: Symptomatic PWHs, including patients living with acquired immunodeficiency syndrome, who had required a PAD-related procedure had presented with more advanced vascular disease and were most at risk of early perioperative mortality. However, the presentation and mortality between asymptomatic PWHs with well-controlled disease and HIV-uninfected patients were comparable. All PWHs with PAD were more likely to undergo lower extremity amputations than were HIV-uninfected matched controls. Asymptomatic, well-controlled HIV infection should not be a contraindication to elective PAD-related procedures because the mortality was similar to that of HIV-uninfected controls. However, the limb salvage rates might be lower for all PWHs with PAD, regardless of HIV disease severity. Taken together, these findings can improve perioperative risk stratification and surgical management of PAD in this high-risk population.

Reinterventions in Patients with Claudication and Chronic Limb Threatening Ischemia.

BACKGROUND: Patients with peripheral artery disease (PAD) present with claudication or chronic limb threatening ischemia (CLTI). CLTI patients have a more advanced stage of atherosclerosis and increased comorbidities compared to claudicants, and are at an elevated risk of major amputation and mortality after lower extremity revascularization (LER). However, the frequency of reinterventions for claudication and CLTI have not been compared. Our hypothesis is that patients with CLTI undergo more frequent reinterventions to prevent major amputation. METHODS: A single-center retrospective chart review of consecutive patients undergoing lower extremity revascularization (LER) for PAD in 2013-2015 was performed. Patients were stratified based on indication for revascularization into claudication or CLTI. Patient characteristics, outcomes, and reinterventions were compared between the 2 groups. RESULTS: There were 826 patients undergoing LER and 44% (N = 361) had CLTI. Patients treated for CLTI were more likely to be smokers (P < 0.001), to have diabetes (P< 0.001), chronic renal insufficiency (P< 0.001), end stage renal disease (P< 0.001), and cardiac disease (P< 0.001). CLTI patients were less likely to be on optimal medical management as reflected by decreased rate of aspirin (P< 0.001), ADP receptor/P2Y12 inhibitors (P< 0.001), and statins (P< 0.001) compared to patients with claudication. Patients with CLTI had significantly higher major amputation (3.7% vs. 0.2%, P< 0.001) and mortality (1.4% vs. 0.2%, P = 0.092) at 30 days. At long-term follow up, patients with CLTI had higher rates of major amputation (15.5% vs. 1.3%, P < 0.001) and mortality (37.1% vs. 18.1%, P < 0.001) compared to patients with claudication. There was a significant difference in mean follow-up time between the 2 cohorts (claudication: 3.7 ± 1.5 years versus CLTI: 2.6 ± 1.8 years, P < 0.001). There was no significant difference in the ipsilateral reintervention rate between the 2 groups (claudication: 39.6% vs. CLTI: 42.7%, P = 0.37) or the mean number of ipsilateral reinterventions (claudication: 2.0 ± 1.6 vs. CLTI: 2.0 ± 1.7). However, after adjusting for follow-up time, the mean number of reinterventions per year was significantly higher for CLTI patients compared to patients with claudication (1.4 ± 2.2 vs. .6 ± 0.7 intervention per year, P < 0.001). CONCLUSIONS: Patients undergoing LER for CLTI undergo more frequent reinterventions over time compared to patients treated for claudication. Research on reinterventions after LER should include reporting of the frequency of reintervention adjusted for the follow up period in addition to the reintervention rate defined as the percentage of patients undergoing reintervention.