Risk factors, transcriptomics, and outcomes of myocardial injury following lower extremity revascularization.
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ABSTRACT:
SUBMITTER: Smilowitz NR
PROVIDER: S-EPMC9038775 | biostudies-literature | 2022 Apr
REPOSITORIES: biostudies-literature
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Risk factors, transcriptomics, and outcomes of myocardial injury following lower extremity revascularization.
Smilowitz Nathaniel R NR Cornwell MacIntosh M Offerman Erik J EJ Rockman Caron B CB Shah Svati H SH Newman Jonathan D JD Ruggles Kelly K Voora Deepak D Berger Jeffrey S JS
Scientific reports 20220425 1
Myocardial injury after non-cardiac surgery (MINS) is common. We investigated the incidence and outcomes of MINS, and mechanistic underpinnings using pre-operative whole blood gene expression profiling in a prospective cohort study of individuals undergoing lower extremity revascularization (LER) for peripheral artery disease (PAD). Major adverse cardiovascular and limb events (MACLE) were defined as a composite of death, myocardial infarction, stroke, major lower extremity amputation or reopera ...[more]
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Project description:Lower extremity open revascularization is a treatment option for peripheral artery disease that carries significant peri-operative risks; however, outcome prediction tools remain limited. Using machine learning (ML), we developed automated algorithms that predict 30-day outcomes following lower extremity open revascularization. The National Surgical Quality Improvement Program targeted vascular database was used to identify patients who underwent lower extremity open revascularization for chronic atherosclerotic disease between 2011 and 2021. Input features included 37 pre-operative demographic/clinical variables. The primary outcome was 30-day major adverse limb event (MALE; composite of untreated loss of patency, major reintervention, or major amputation) or death. Our data were split into training (70%) and test (30%) sets. Using tenfold cross-validation, we trained 6 ML models. Overall, 24,309 patients were included. The primary outcome of 30-day MALE or death occurred in 2349 (9.3%) patients. Our best performing prediction model was XGBoost, achieving an area under the receiver operating characteristic curve (95% CI) of 0.93 (0.92-0.94). The calibration plot showed good agreement between predicted and observed event probabilities with a Brier score of 0.08. Our ML algorithm has potential for important utility in guiding risk mitigation strategies for patients being considered for lower extremity open revascularization to improve outcomes.
| S-EPMC10844206 | biostudies-literature
Project description:To determine whether diabetes mellitus has an independent impact on major limb outcomes at 1 year after endovascular treatment of lower extremity peripheral artery disease (PAD).The study involved 1906 consecutive patients (mean age 66 years; 1469 men) enrolled in the observational Excellence in Peripheral Artery Disease (XLPAD) registry ( ClinicalTrials.gov identifier NCT01904851) between January 2005 and October 2015 after undergoing index endovascular procedures in 2426 limbs for arterial occlusive disease. Patient outcomes included 12-month target limb amputation (above ankle) and target limb revascularization as well as all-cause death. Kaplan-Meier analysis and adjusted Cox proportional hazard models were used for time-to-event analysis of outcomes for the entire study sample as well as for the critical limb ischemia (CLI) and claudication subgroups. Results of the Cox regression models are reported as the hazard ratio (HR) and 95% confidence interval (CI).Diabetics undergoing endovascular procedures had higher rates of comorbid conditions (p<0.001), CLI (p<0.001), heavily calcified lesions (p=0.002), multivessel disease (p=0.030), and fewer infrapopliteal runoff vessels (p<0.001). Regression analysis after adjusting for confounders revealed significantly higher target limb major amputation in diabetics compared with nondiabetics (HR 5.02, 95% CI 1.44 to 17.56, p=0.011). However, repeat revascularization rates were similar. When considering CLI and claudication subgroups, diabetes was associated with a nonsignificant increased risk of 12-month major amputation only for patients presenting with CLI (HR 3.48, 95% CI 0.97 to 12.51, p=0.056). Diabetes was also associated with an increased risk of 12-month all-cause mortality in the overall study sample (HR 4.64, 95% CI 2.01 to 10.70, p<0.001) and in the CLI subgroup (HR 14.15, 95% CI 3.16 to 63.32, p<0.001) but not in the claudication subgroup (HR 1.42, 95% CI 0.45 to 4.54, p=0.552).Diabetes increases the risk of major amputation and all-cause death at 12 months following endovascular revascularization in patients with symptomatic PAD. These risks are especially heightened in patients presenting with CLI.
| S-EPMC5624231 | biostudies-literature
Project description:ObjectiveOptimal patient selection for lower extremity revascularization remains a clinical challenge among the hemodialysis-dependent (HD). The purpose of this study was to examine contemporary real world open and endovascular outcomes of HD patients to better facilitate patient selection for intervention.MethodsA regional multicenter registry was queried between 2003 and 2013 for HD patients (N = 689) undergoing open surgical bypass (n = 295) or endovascular intervention (n = 394) for lower extremity revascularization. Patient demographics and comorbidities were recorded. The primary outcome was overall survival. Secondary outcomes included graft patency, freedom from major adverse limb events, and amputation-free survival (AFS). Multivariate analysis was performed to identify independent risk factors for death and amputation.ResultsAmong the 689 HD patients undergoing lower extremity revascularization, 66% were male, and 83% were white. Ninety percent of revascularizations were performed for critical limb ischemia and 8% for claudication. Overall survival at 1, 2, and 5 years survival remained low at 60%, 43%, and 21%, respectively. Overall 1- and 2-year AFS was 40% and 17%. Mortality accounted for the primary mode of failure for both open bypass (78%) and endovascular interventions (80%) at two years. Survival, AFS, and freedom from major adverse limb event outcomes did not differ significantly between revascularization techniques. At 2 years, endovascular patency was higher than open bypass (76% vs 26%; 95% confidence interval [CI], 0.28-0.71; P = .02). Multivariate analysis identified age ≥80 years (hazard ratio [HR], 1.9; 95% CI, 1.4-2.5; P < .01), indication of rest pain or tissue loss (HR, 1.8; 95% CI, 1.3-2.6; P < .01), preoperative wheelchair/bedridden status (HR, 1.5; 95% CI, 1.1-2.1; P < .01), coronary artery disease (HR, 1.5; 95% CI, 1.2-1.9; P < .01), and chronic obstructive pulmonary disease (HR, 1.4; 95% CI, 1.1-1.8; P = .01) as independent predictors of death. The presence of three or more risk factors resulted in predicted 1-year mortality of 64%.ConclusionsOverall survival and AFS among HD patients remains poor, irrespective of revascularization strategy. Mortality remains the primary driver for these findings and justifies a prudent approach to patient selection. Focus for improved results should emphasize predictors of survival to better identify those most likely to benefit from revascularization.
| S-EPMC5315419 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:There is limited evidence regarding risk factors for lower extremity overuse bone injury (LEOBI) in collegiate athletes. The purposes of the study were to: 1) determine incidence of LEOBI in selected sports and its impact on athletic participation and ADL, 2) assess risk relationships between LEOBI and selected risk factors, and 3) establish the viability of using calcaneal densitometry as a screening tool to identify risk for LEOBI. STUDY DESIGN:Prospective analytical cohort design. METHODS:Collegiate athletes in selected sports (swimming/diving, women's soccer, field hockey, cross-country/track) at one university were invited to participate. Consenting athletes completed an initial questionnaire including demographic information, history, and menstrual function. Measurements included height/weight, hip abductor strength, foot posture index, and calcaneal bone mineral density. Athletes were monitored for potential LEOBI for nine months and an algorithm was used to determine if physician referral was required. The primary outcome of interest was the occurrence of physician-diagnosed LEOBI. If LEOBI was diagnosed by the physician, the athlete completed a follow-up visit including a repeat bone mineral density scan. All athletes were invited for a repeat scan at the end of the year and completed a final questionnaire. Athlete demographics were summarized using descriptive statistics and differences in continuous risk factors were analyzed using t-tests and ANOVA. Finally, risk relationships for categorical variables were analyzed using chi-square and relative risk. RESULTS:84 athletes (64 female, 20 male) consented to participate. Over the study period, eight athletes (one male, seven females) were diagnosed with LEOBI (LEOBI group), five with stress fractures and three with medial tibial stress syndrome. The other 76 athletes who did not have a diagnosis of LEOBI were placed in the non-LEOBI group. Five of the eight were cross-country/track athletes; no swimming/diving athletes had bone injury. Sport (cross-country/track) had a significant relative risk value of 2.26 (95% CI = 1.18-4.32) for LEOBI. There was no association between LEOBI occurrence and sex, hip abductor strength, body mass index, foot type, and menstrual function. There was no difference in bone mineral density at initial or follow-up measures between LEOBI and non-LEOBI groups (p>.05) when analyzing all athletes. When analyzing ground-based athletes only at follow-up (n=44), athletes with LEOBI had lower bone mineral density of right (p = .05) and left (p =.07) calcaneus. The relative risk for developing LEOBI based on calcaneal bone mineral density below the mean of the study participants was 2.1 (95%CI = 1.09-3.35) on the left and 1.53 (95% CI=.80- 3.06) on the right. CONCLUSION:The incidence of LEOBI in this population of athletes was approximately 10%. Risk factors were sport (cross-country/track) and decreased left calcaneal bone mineral density. This study supports the use of calcaneal bone mineral density as a screening measurement for LEOBI risk and suggests the need for further investigation into additional LEOBI risk factors. LEVEL OF EVIDENCE:2.
| S-EPMC4387723 | biostudies-other
Project description:AimsThe impact of diabetes mellitus (DM) on outcomes of lower extremity revascularization (LER) for peripheral artery disease (PAD) is uncertain. We characterized associations between DM and post-procedural outcomes in PAD patients undergoing LER.Methods and resultsAdults undergoing surgical or endovascular LER were identified from the 2014 Nationwide Readmissions Database. DM was defined by ICD-9 diagnosis codes and sub-classified based on the presence or absence of complications (poor glycaemic control or end-organ damage). Major adverse cardiovascular and limb events (MACLEs) were defined as the composite of death, myocardial infarction, ischaemic stroke, or major limb amputation during the index hospitalization for LER. For survivors, all-cause 6-month hospital readmission was determined. Among 39 441 patients with PAD hospitalized for LER, 50.8% had DM. The composite of MACLE after LER was not different in patients with and without DM after covariate adjustment, but patients with DM were more likely to require major limb amputation [5.5% vs. 3.2%, P < 0.001; adjusted odds ratio (aOR) 1.22, 95% confidence interval (CI) 1.03-1.44] and hospital readmission (59.2% vs. 41.3%, P < 0.001; aOR 1.44, 95% CI 1.34-1.55). Of 20 039 patients with DM hospitalized for LER, 55.7% had DM with complications. These patients were more likely to have MACLE after LER (11.1% vs. 5.2%, P < 0.001; aOR 1.56 95% CI 1.28-1.89) and require hospital readmission (61.1% vs. 47.2%, P < 0.001; aOR 1.41 95% CI 1.27-1.57) than patients with uncomplicated DM.ConclusionsDM is present in ≈50% of patients undergoing LER for PAD and is an independent risk factor for major limb amputation and 6-month hospital readmission.
| S-EPMC9630873 | biostudies-literature
Project description:Background & aimsRenal disease is a risk factor for peripheral artery disease (PAD), yet its impact on outcomes after lower extremity (LE) revascularization is not well established. We aimed to characterize the association between chronic kidney disease (CKD) and/or end stage renal disease (ESRD) and post-procedural outcomes in PAD patients undergoing LE revascularization in the United States.MethodsAdults age ≥18 years undergoing surgical or endovascular LE revascularization for PAD with and without CKD or ESRD were identified from the 2014 Nationwide Readmissions Database. Major adverse cardiovascular events (MACE), defined as a composite of death, myocardial infarction or ischemic stroke, were identified for patients with and without renal disease. All-cause hospital readmissions within 6 months of discharge were determined for all survivors.ResultsAmong 39,441 patients with PAD hospitalized for LE revascularization, 10,530 had renal disease (26.7%), of whom 69% had CKD without ESRD and 31% had ESRD. Patients with renal disease were more likely to have MACE after LE revascularization (5.2% vs. 2.5%; adjusted OR [aOR] 1.74, 95% CI 1.40-2.16), require LE amputation (26.1% vs. 12.2%; aOR 1.33, 95% CI 1.19-1.50), and require hospital readmission within 6 months (61.0% vs. 43.6%; adjusted HR [aHR] 1.38, 95% CI 1.28-1.48) compared to those without renal disease.ConclusionsRenal disease is common among patients undergoing LE revascularization for PAD and was independently associated with in-hospital MACE, LE amputation, and hospital readmission within 6 months. Additional efforts to improve outcomes of patients with renal disease and PAD requiring LE revascularization are necessary.
| S-EPMC7141968 | biostudies-literature
Project description:BackgroundLower extremity amputations are common, and postoperative neuropathic pain (phantom limb pain or symptomatic neuroma) is frequently reported. The use of active treatment of the nerve end has been shown to reduce pain but requires additional resources and should therefore be performed primarily in high-risk patients. The aim of this study was to identify the factors associated with the development of neuropathic pain following above-the-knee amputation, knee disarticulation, or below-the-knee amputation.MethodsRetrospectively, 1565 patients with an average follow-up of 4.3 years who underwent a primary above-the-knee amputation, knee disarticulation, or below-the-knee amputation were identified. Amputation levels for above-the-knee amputations and knee disarticulations were combined as proximal amputation level, with below-the-knee amputations being performed in 61 percent of patients. The primary outcome was neuropathic pain (i.e., phantom limb pain or symptomatic neuroma) based on medical chart review. Multivariable logistic regression was performed to identify independent factors associated with neuropathic pain.ResultsPostoperative neuropathic pain was present in 584 patients (37 percent), with phantom limb pain occurring in 34 percent of patients and symptomatic neuromas occurring in 3.8 percent of patients. Proximal amputation level, normal creatinine levels, and a history of psychiatric disease were associated with neuropathic pain. Diabetes, hypothyroidism, and older age were associated with lower odds of developing neuropathic pain.ConclusionsNeuropathic pain following lower extremity amputation is common. Factors influencing nerve regeneration, either increasing (proximal amputations and younger age) or decreasing (diabetes, hypothyroidism, and chronic kidney disease) it, play a role in the development of postamputation neuropathic pain.Clinical question/level of evidenceRisk, III.
| S-EPMC10375758 | biostudies-literature
Project description:ObjectiveAntithrombotic therapy improves endovascular intervention outcomes for peripheral artery disease. However, there are limited data guiding the choice and duration of these adjuvant therapies. Thus, we explored current antithrombotic prescribing preferences among vascular interventionalists, hypothesizing that there are varied and inconsistent treatment practices among providers.MethodsWe developed and distributed a de-identified RedCap survey via Twitter and email to Vascular Quality Initiative members (February 2023). Multiple-choice questions queried antithrombotic agents and treatment durations for a clinical vignette (a claudicant on 81 mg aspirin and statin) with different arterial disease locations (iliac, femoropopliteal, or tibial vessels) and different revascularization strategies (angioplasty or stenting, with and without drug-coating). Antithrombotic options included monotherapies with antiplatelet agents or low-dose rivaroxaban; dual therapies with aspirin combined with a P2Y12 inhibitor (dual antiplatelet therapy, DAPT) or low-dose rivaroxaban (dual pathway inhibition or DPI); or triple therapy with aspirin, a P2Y12 inhibitor, and low-dose rivaroxaban. Options for therapy duration included 30, 90, 180, and 365 days, or indefinitely.ResultsThere were 199 respondents (17% female, 68% White race, 63% academic, 88% vascular surgery). Across all treatment scenarios, respondents selected DAPT (n = 171/199; 86%) in at least one revascularization scenario, followed by aspirin monotherapy (n = 83/199; 42%) and DPI (n = 49/199; 25%). Therapy choice did differ by both anatomic location and revascularization strategy (P < .05). DAPT was most selected following femoropopliteal revascularization (n = 165/199, 83%) and bare metal stenting (n = 162/198, 82%). However, aspirin monotherapy was most selected following iliac level revascularization (n = 52/197; 26%) and following percutaneous transluminal angioplasty at any level (n = 51/182; 28%). DPI was most selected following tibial revascularization (n = 39/184; 21%) and following percutaneous transluminal angioplasty (n = 38/182; 21%). Among those who selected DAPT, the 90-day (n = 99/171; 58%) duration was preferred. Those who selected DPI favored indefinite treatment durations (n = 34/49; 69%). Indefinite DAPT and DPI therapy were more commonly selected for distal level revascularization (P < .05). Rivaroxaban utilization was limited secondary to cost (n = 108/178; 61%), lack of demonstrated effectiveness (n = 75/178; 42%), and concern for safety and bleeding (n = 27/178; 15%).ConclusionsFollowing lower extremity endovascular treatment of peripheral artery disease, a 90-day duration of DAPT remains the most commonly selected antithrombotic regimen despite the emergence of DPI as an evidence-based antithrombotic therapy. The variability in provider preferred antithrombotic agent and treatment duration emphasizes the need for high-quality evidence for the medical optimization of revascularization outcomes.
| S-EPMC11774505 | biostudies-literature
Project description:Background The long-term effectiveness of atherectomy treatment for peripheral arterial disease is unknown. We studied 5-year clinical outcomes by endovascular treatment type among patients with peripheral arterial disease. Methods and Results We queried the Medicare-linked VQI (Vascular Quality Initiative) registry for endovascular interventions from 2010 to 2015. The exposure was treatment type: atherectomy (with or without percutaneous transluminal angioplasty [ PTA] ), stent (with or without PTA ), or PTA alone. The outcomes were major amputation, any amputation, and major adverse limb event (major amputation or any reintervention). We used the center-specific proportions of atherectomy procedures performed in the 12 months before a patient's procedure as the instruments to perform an instrumental-variable Cox model analysis. Among 16 838 eligible patients (median follow-up: 1.3-1.5 years), 11% underwent atherectomy, 40% received PTA alone, and 49% underwent stenting. Patients receiving atherectomy commonly underwent femoropopliteal artery treatment (atherectomy: 65%; PTA : 49%; stenting: 43%; P<0.001) and had worse disease severity (Trans-Atlantic Inter-Society Consensus score [TASC] B and greater; atherectomy: 77%; PTA : 68%; stenting: 67%; P<0.001). The 5-year rate of major adverse limb events was 38% in patients receiving atherectomy versus 33% for PTA and 32% for stenting (log rank P<0.001). Controlling for unmeasured confounding using instrumental-variable analysis, patients treated with atherectomy experienced outcomes similar to those of patients treated with PTA , except for a higher risk of any amputation (hazard ratio: 1.51; 95% CI , 1.08-2.13). However, compared with stenting, atherectomy patients had a higher risk of major amputation (hazard ratio: 3.66; 95% CI , 1.72-7.81), any amputation (hazard ratio: 2.73; 95% CI , 1.60-4.76), and major adverse limb event (hazard ratio: 1.61; 95% CI , 1.10-2.38). Conclusions Atherectomy is used to treat severe femoropopliteal and tibial peripheral arterial disease even though long-term adverse outcomes occur more frequently after this treatment modality.
| S-EPMC6645635 | biostudies-literature
Project description:ObjectivesClopidogrel is effective at decreasing cardiovascular events in patients with peripheral artery disease (PAD); however, its effect on limb outcomes are less known. This study investigated the variability in response to clopidogrel and its relationship with clinical limb outcomes.MethodsThree hundred subjects were enrolled in the Platelet Activity and Cardiovascular Events (PACE) study prior to lower extremity revascularization, of whom 104 were on clopidogrel. Light transmission platelet aggregation was measured in response to ADP 2 μm immediately prior to revascularization. Patients were followed longitudinally for a median follow-up of 18 months. The primary endpoint was major adverse limb events (MALE) defined by major amputation or reoperation of the affected limb. Patients were stratified into groups according to percent ADP-induced aggregation. Poor response to clopidogrel was defined by >50% aggregation.ResultsOverall, the median age was 70 (63, 76) and 35.6% were female. Twenty-nine (27.9%) patients experienced MALE during their follow-up. Median aggregation to ADP 2 μ m was 22.5% (Q1-Q3: 10%, 50%) and 27 subjects (26%) were clopidogrel poor responders. Baseline aggregation was higher in subjects who went on to develop a MALE than those without MALE (43% vs 20%, p = .017). Subjects with aggregation > median (22.5%) were more likely to experience MALE than aggregation < median (38.5% vs 17.3%, p = .029). After multivariable adjustment for age, sex, race/ethnicity, BMI, diabetes, coronary artery disease, and aspirin use, aggregation > median was associated with MALE (adjusted HR [aHR] 2.67, 95% CI 1.18-6.01, p = .018). When stratified by established cut-offs for responsiveness to clopidogrel (50% aggregation), poor responders were more likely to experience MALE than normal responders (44.4% vs 22.1%, aHR 2.18, 95% CI 1.00-4.78, p = .051).ConclusionsAmong patients undergoing lower extremity revascularization on clopidogrel, higher baseline percent aggregation is associated with increased risk for major adverse limb events.
| S-EPMC11892801 | biostudies-literature