Lower Extremity Revascularization Research Articles

Evaluation of Clot-inducing Fibrinogen Levels in Chronic Kidney Disease Patients Undergoing Lower Extremity Revascularization

Evaluation of Clot-inducing Fibrinogen Levels in Chronic Kidney Disease Patients Undergoing Lower Extremity Revascularization

Single-Center In-Hospital and Outpatient Opioid Use for Lower Extremity Arterial Disease.

The pain associated with lower extremity arterial disease is difficult to treat, even with lower extremity revascularization. We sought to evaluate in-hospital and post-operative opioid usage in patients with different disease severities and treatments for lower extremity vascular disease. A retrospective review was performed for all hospital encounters for patients with an International Classification of Diseases (ICD) code consistent with lower extremity arterial disease admitted to a single center between January 2018 and March 2023. Cases included patients admitted to the hospital with a primary diagnosis of lower extremity arterial disease. These patients were subdivided based on disease severity, treatment type, and comorbid diagnosis of diabetes mellitus. The analysis focused on in-hospital opioid use frequency and dosage among these patients. The control group (CON) included encounters for patients admitted with a secondary diagnosis of lower extremity atherosclerotic disease. A total of 438 patients represented by all the analyzed encounters were then reviewed for the number and type of vascular procedures performed as well as opioid use in the outpatient setting for one year. Critical limb ischemia (CLI) encounters were more likely to use opioids as compared to the CON and peripheral arterial disease (PAD) without rest pain, ulcer or gangrene groups (CLI 67.9% (95% CI: 63.6%-71.6%) versus CON 52.1% (95% CI: 48.5%-55.7%), p < 0.001 and CLI 67.9% (95% CI: 63.6%-71.6%) versus PAD 50.2% (95% CI: 42.6%-57.4%), p < 0.001). Opioid use was also more common in encounters for gangrene and groups treated with revascularization (REVASC) and amputation (AMP) as compared to CON (gangrene 74.5% (95% CI: 68.5%-82.1%) versus CON 52.1% (95% CI: 48.5%-55.7%), p < 0.01; REVASC 58.3% (95% CI: 57.3%-66.4%) versus CON 52.1% (95% CI: 48.5%-55.7%), p =0.01; and AMP 72.3% (95% CI: 62.1%-74.0%) versus CON 52.1% (95% CI: 48.5%-55.7%), p < 0.01). Significantly increased oral opioid doses per day (MME/day) were not noted for any of the investigated groups as compared to the CON. In the outpatient setting, 186 (42.5% (95% CI: 37.2%-46.4%)) patients were using opioids one month after the most recent vascular intervention. By one year, 31 (7.1% (95% CI: 1.30%-7.70%)) patients were still using opioids. No differences in opioid usage were noted for patients undergoing single versus multiple vascular interventions at one year. Patients undergoing certain vascular surgery procedures were more likely to be using opioids at one year. Patients with CLI and gangrene as well as those undergoing vascular treatment have a greater frequency of opioid use during hospital encounters as compared to those patients with less severe disease and undergoing conservative management, respectively. However, these findings do not equate to higher doses of opioids used during hospitalization. Patients undergoing multiple vascular procedures are not more likely to be using opioids long-term (at one year) as compared to those patients treated with single vascular procedures.

Association Between Diagnosis-to-Limb Revascularization Time and Clinical Outcomes in Outpatients With Chronic Limb-Threatening Ischemia: Insights From the CLIPPER Cohort.

The extent and consequences of ischemia in patients with chronic limb-threatening ischemia (CLTI) may change rapidly, and delays from diagnosis to revascularization may worsen outcomes. We sought to describe the association between time from diagnosis to endovascular lower extremity revascularization (diagnosis-to-limb revascularization [D2L] time) and clinical outcomes in outpatients with CLTI. In the CLIPPER cohort, comprising patients between 66 and 86 years old diagnosed with CLTI betweeen 2010 and 2019, we used Medicare claims data to identify patients who underwent outpatient endovascular revascularization within 180 days of diagnosis. We described the risk-adjusted association between D2L time and clinical outcomes. Among 1 130 065 patients aged between 66 and 86 years with CLTI, 99 221 (8.8%) underwent outpatient endovascular lower extremity revascularization within 180 days of their CLTI diagnosis. Among patients with D2L time <30 days, there was no association between D2L time and all-cause death or major lower extremity amputation. However, among patients with D2L time >30 days, each additional 10-day increase in D2L time was associated with a 2.5% greater risk of major amputation (hazard ratio, 1.025 [95% CI, 1.014-1.036]). There was no association between D2L time and all-cause death. A delay of >30 days from CLTI diagnosis to lower extremity endovascular revascularization was associated with an increased risk of major lower extremity amputation among patients undergoing outpatient endovascular revascularization. Improving systems of care to reduce D2L time could reduce amputations.

Real World Application of WIfI Scores in Peripheral Arterial Disease Patients

The Society for Vascular Surgery wound, ischemia, and foot infection (WIfI) classification system aims to risk stratify patients with chronic limb threatening ischemia (CLTI), predicting both amputation rates and the need for revascularization. However, real-world utilization of the system and whether it accurately predicts outcomes following open revascularization and peripheral interventions is unclear. Therefore, we sought to determine the adoption of the WIfI classification system within a contemporary statewide collaborative as well as the impact of patient factor, and WIfI risk assessment on short- and long-term outcomes. Using data from a large statewide collaborative, we identified patients with CLTI undergoing open surgical revascularization or peripheral vascular intervention (PVI) between 2016 - 2022. The primary exposure was preoperative clinical WIfI stage. Patients were categorized according to the SVS Lower Extremity Threatened Limb Classification System into clinical WIfI stages1, 2, 3, or 4. The primary outcomes were 30-day and 1-year amputation and mortality. Multivariable logistic regression was performed to estimate the association of WIfI stage on post-revascularization outcomes. In the cohort of 17,417 patients, 83.4% (n=14,529) had WIfI stage documented. Peripheral vascular interventions (PVIs) were performed on 57.6% of patients, and 42.4% underwent an open surgical revascularization (OSR). 49.5% of patients were classified as stage 1, 19.3% stage 2, 12.8% stage 3 and 18.3% of patients met stage 4 criteria. Stage 3 and 4 patients had higher rates of diabetes, congestive heart failure, and renal failure, and were less likely to be current or former smokers. One-half of stage 3 patients underwent OSR, while stage 1 patients were most likely to have received a PVI (64%). As WIfI stage increased from 1 to 4, 1-year mortality increased from 12% to 21% (p<0.001), 30-day amputation rates increased from 5% to 38% (p<0.001), and 1-year amputation rates increased from 15% to 55% (p<0.001). Finally, patients who did not have WIfI scores classified had significantly higher 30-day and 1-year mortality, as well as higher 30-day and 1-year amputation rates. The Society for Vascular Surgery WIfI clinical stage is significantly associated with 1-year amputation rates in patients with CLTI following lower extremity revascularization. As nearly 55% of stage 4 patients require a major amputation within one year of intervention, this study supports use of the WIfI classification system in clinical decision making for patients with CLTI.

Endovascular therapy versus bypass for chronic limb-threatening ischemia in a real-world practice

The recent BEST-CLI study showed that bypass was superior to endovascular therapy (ET) in patients with chronic limb threatening ischemia (CLTI) deemed suitable for either approach who had an available single segment great saphenous vein (GSV). However, the superiority of bypass among those lacking GSV was not established. We aimed to examine comparative treatment outcomes from a real-world CLTI population using the Vascular Quality Initiative (VQI)-Medicare-Linked database. We queried the VQI-Medicare-Linked database for patients with CLTI who underwent first-time lower extremity revascularization (2010-2019). We performed two one-to-one propensity score matchings (PSM): ET vs. bypass with GSV (BWGSV) and ET vs. bypass with prosthetic graft (BWPG). The primary outcome was amputation-free survival (AFS). Secondary outcomes were freedom from amputation and overall survival (OS). Three cohorts were queried: BWGSV (N=5,279, 14.7%), BWPG (N=2,778, 7.7%), and ET (N=27,977, 77.6%). PSM produced two sets of well-matched cohorts: 4,705 pairs of ET vs. BWGSV and 2,583 pairs of ET vs. BWPG. In the matched cohorts of ET vs. BWGSV, ET was associated with greater hazards of death (Hazard Ratio [HR]=1.34, 95% Confidence Interval [CI], 1.25-1.43; P<.001), amputation (HR=1.30, 95% CI, 1.17-1.44; P<.001) and amputation/death (HR=1.32, 95% CI, 1.24-1.40; P<.001) up to 4-years. In the matched cohorts of ET vs. BWPG, ET was associated with greater hazards of death up to 2-years (HR=1.11, 95% CI, 1.00-1.22; P=.042) but not amputation or amputation/death. In this real-world multi-institutional Medicare-linked PSM analysis, we found that BWGSV is superior to ET in terms of OS, freedom from amputation and AFS up to 4-years. Moreover, BWPG was superior to ET in terms of OS up to 2-years. Our study confirms the superiority of BWGSV to ET as observed in the BEST-CLI trial.

Long-term limb salvage and functional outcomes for patients undergoing partial calcanectomy.

Partial calcanectomy (PC) can be performed to treat chronic heel ulcers in patients with calcaneal osteomyelitis. Patients undergoing PC often have multiple comorbidities, limited mobility, and face high risk of major limb amputation. This study examined the extent of vascular diagnostic testing and interventions as well as long-term outcomes in patients undergoing PC. A retrospective analysis was performed on patients who underwent PC for non-healing calcaneal ulcer over a ten-year period. Demographics, comorbidities, vascular testing, and procedural data were recorded. Additional subgroup analysis was performed according to presence or absence of peripheral arterial disease (PAD). Primary outcomes were major limb amputation (above or below the knee) and mortality. Secondary outcomes included successful wound healing, time to complete wound healing, re-interventions, and change in ambulatory status. A total of 157 patients underwent partial calcanectomies on 162 limbs. 78.3% of patients had diabetes mellitus and 47.8% were diagnosed with PAD. Ankle brachial index with pulse volume recording (ABI/PVR) was performed for 46.5% (73/157) of patients, arterial duplex in 44.6% (70/157), and 19.7% (31/157) had a computed tomography angiogram. Lower extremity revascularization was performed in 28.4% of limbs (46/162). Independent ambulatory status was reported in 40.1% prior to PC and decreased to 17.9% by the time of last recorded follow-up (p < .00001). Long-term amputation-free survival was significantly higher in patients without PAD at 7 years (78.4% vs 57.1%, p = .02). Multivariate logistic regression analysis demonstrated that PAD and end-stage renal disease (ESRD) increased the odds of major limb amputation (OR 3.5 and 2.8, respectively), whereas ESRD and adjuvant podiatric procedures were associated with increased mortality (OR 4.8 and 4.8, respectively). Non-invasive vascular testing should be obtained in all patients undergoing PC, in order to stratify risk of amputation and identify candidates for revascularization. Over the long-term, patients undergoing PC face significant risk of prolonged wound healing, decline in ambulatory status, and major limb amputation.

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

To determine whether diagnosis of asymptomatic (silent) coronary ischemia using coronary computed tomography (CT)-derived fractional flow reserve (FFRCT) together with targeted coronary revascularization of ischemia-producing coronary lesions following lower-extremity revascularization can reduce adverse cardiac events and improve long-term survival of patients with chronic limb-threatening ischemia (CLTI). Prospective cohort study of CLTI patients with no cardiac history or symptoms undergoing elective lower-extremity revascularization. Patients with pre-operative coronary computed tomography angiography (CTA) and FFRCT evaluation with selective post-operative coronary revascularization (FFRCT group) were compared with patients with standard pre-operative evaluation and no post-operative coronary revascularization (control group). Lesion-specific coronary ischemia was defined as FFRCT≤0.80 distal to a coronary stenosis with FFRCT≤0.75 indicating severe ischemia. Endpoints included all-cause death, cardiac death, myocardial infarction (MI) and major adverse cardiovascular (CV) events (MACE=CV death, MI, stroke, or unplanned coronary revascularization) during 5 year follow-up. In the FFRCT group (n=111), FFRCT analysis revealed asymptomatic (silent) coronary ischemia (FFRCT≤0.80) in 69% of patients, with severe ischemia (FFRCT≤0.75) in 58%, left main ischemia in 8%, and multivessel ischemia in 40% of patients. The status of coronary ischemia in the control group (n=120) was unknown. Following lower-extremity revascularization, 42% of patients in FFRCT had elective coronary revascularization with no elective revascularization in controls. Both groups received guideline-directed medical therapy. During 5 year follow-up, compared with control, the FFRCT group had fewer all-cause deaths (24% vs 47%, hazard ratio [HR]=0.43 [95% confidence interval [CI]=0.27-0.69], p<0.001), fewer cardiac deaths (5% vs 26%, HR=0.18 [95% CI=0.07-0.45], p<0.001), fewer MIs (7% vs 28%, HR=0.21 [95% CI=0.10-0.47], p<0.001), and fewer MACE events (14% vs 39%, HR=0.28 [95% CI=0.15-0.51], p<0.001). Ischemia-guided coronary revascularization of CLTI patients with asymptomatic (silent) coronary ischemia following lower-extremity revascularization resulted in more than 2-fold reduction in all-cause death, cardiac death, MI, and MACE with improved 5 year survival compared with patients with standard cardiac evaluation and care (76% vs 53%, p<0.001). Silent coronary ischemia in patients with chronic limb-threatening ischemia (CLTI) is common even in the absence of cardiac history or symptoms. FFRCT is a convenient tool to diagnose silent coronary ischemia perioperatively. Our data suggest that post-surgery elective FFRCT-guided coronary revascularization reduces adverse cardiac events and improves long-term survival in this very-high risk patient group. Randomized study is warranted to finally test this concept.

Perioperative complications of minor and major reinterventions for peripheral arterial disease.

Patients with peripheral arterial disease (PAD) frequently require reinterventions after lower-extremity revascularization (LER) to maintain perfusion. Current Society for Vascular Surgery guidelines define reinterventions as major or minor based on the magnitude of the procedure. While prior studies have compared primary LER procedures of different magnitudes, similar studies for reinterventions have not been performed. The objective of this study is to compare perioperative outcomes associated with major and minor reinterventions. Patients undergoing LER for PAD at a tertiary care center from 2013 to 2017 were included. A retrospective review of electronic medical records was performed, and reinterventions were categorized as major or minor based on the procedure magnitude. Minor reinterventions included endovascular procedures and open revision with patch angioplasty, while major reinterventions were characterized by open surgical or endovascular LER with catheter-directed thrombolysis (CDT). Perioperative outcomes following LER were captured and compared for major and minor reinterventions. An additional subgroup analysis was performed comparing outcomes associated with major reinterventions stratified into open major surgical reinterventions and CDT. This study included 713 patients over a mean follow-up of 2.5years. A total of 291 patients underwent 696 ipsilateral reinterventions (range = 1-12 reinterventions). Most reinterventions were minor (72.1%, N = 502) and 27.9% (N = 194) were major. Patients receiving reinterventions had an average age of 67.2 ± 11.5 and most were white (73.5%) males (60.1%) initially treated for claudication (58.2%) and CLTI (41.8%). There was significantly higher post-operative bleeding (9.8% vs 3.4%, p = .001), arterial thrombosis (3.1% vs 1.0%, p = .047), and acute renal failure (6.2% vs 2.4%, p = .014) after major reinterventions than minor. Additionally, major reinterventions had significantly higher return to the OR (17.0% vs 11.3%, p = .046) and longer hospital stays (7.5 vs 4.3days, p = <.0001). Overall, major reinterventions were associated with significantly increased perioperative morbidity (37.6% vs 19.7%, p ≤ .001) with no difference in perioperative mortality. In the subgroup analysis, open reinterventions resulted in significantly longer hospital stays (8.6days vs 5.5days, p ≤ .001) and more wound infections than CDT (11.0% vs 0%, p = .017). However, there was no other significant difference in morbidity or mortality following treatment with open surgical reinterventions or CDT. In this study, major reinterventions after LER were associated with greater perioperative morbidity than minor reinterventions, with no difference in mortality. Major reinterventions performed via open surgery and CDT had similar morbidity and mortality.

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

ObjectivesPremature 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. MethodsThere were 8,804 patients with premature PAD on pre- and post-operative antiplatelet therapy only and 1,236 patients on pre- and post-operative anticoagulation plus antiplatelet therapy in the Vascular Quality Initiative (VQI) peripheral vascular intervention, infra-, 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 one-year outcomes were analyzed including reintervention, major amputation, and mortality. ResultsPatients on anticoagulation were more likely to have coronary artery disease (48.7% vs 41.2%, P<.001), congestive heart failure (20.2% vs 13.1%, P<.001), and have undergone prior LER (73.9% vs 49.2%, P<.001) compared to patients on antiplatelet therapy only. They were also less likely to be independently ambulatory (74.2% vs 81.8%, P<.001) and be on a statin medication (66.8% vs 74.3%, P<.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<.001), and less likely to be treated with an endovascular procedure (64.8% vs 73.8%, P<.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<.001) and had higher perioperatively mortality (1.1% vs 0.3%, P=.032), but major amputation was not significantly different (1.8% vs 1.6%, P=.798) compared to patients on antiplatelet therapy alone. At one-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=.001). ConclusionAnticoagulation in addition to antiplatelet therapy in patients with premature PAD undergoing lower extremity revascularization is associated with increased reintervention and mortality at one year.

Establishing a Critical Limb Ischemia Outpatient Center: Separating Facts from Myth

Critical Limb Ischemia or chronic limb-threatening ischemia represents the end stage of peripheral artery disease where arterial flow is compromised to the lower extremities and risk of limb loss may become imminent. Revascularization of lower extremities is one of the cornerstones of limb salvage and amputation prevention. Establishing centers of high quality CLI therapy requires creating different foundational pillars in order to be successful. This article discusses critical limb ischemia center creation from the perspective of critical limb ischemia therapists working in an outpatient setting.

Thromboelastography with Platelet Mapping Identifies High Platelet Reactivity is Associated with Obesity, Diabetes, and Thrombotic Events

Identify prothrombotic coagulation profiles associated with diabetes and obesity using Thromboelastography SUMMARY BACKGROUND DATA: Metabolic comorbidities such as diabetes and obesity are considered pro-inflammatory states which theoretically increase the risk of perioperative thrombotic events across many surgical disciplines. Currently, there is a paucity of objective metrics to determine such risk and ideal pharmacologic targets. Thromboelastography with Platelet Mapping (TEG-PM) provides a comprehensive profile of coagulation and may provide insight into clot dysregulation. Patients undergoing lower extremity revascularization underwent serial TEG-PM analysis. The relationship between the TEG-PM metrics and thrombosis was evaluated. Pre-operative TEG-PM samples of patients with BMI≥25 were compared to those of patients with a normal BMI, and between patients with DM and those without. 218 TEG-PM samples from 202 patients were analyzed. The BMI≥25 cohort showed significantly greater platelet aggregation [81.9%(±20.9)vs.68.6%(±27.7), p<.01]. Patients with DM were more frequently on full-dose anticoagulation [47.7%vs.29.7%p=.01] yet demonstrated increased clot strength, or ADP-Maximum Clot Amplitude(MA) [49.1(±16.1)vs.41.5(±17.1) and 37.7(±19.6)vs.31.6(±17.4)p<.01]. 49 patients experienced thrombosis and exhibited greater platelet aggregation [76.6%(±17.8)vs.66.8%(±30.4) p=.03] and greater ADP/AA MA [47.1(±16.6)vs.41.9(±18.8) and 38.2(±17.8)vs.32.5(±19.9) both p=.05]. Patients who thrombosed were more often diabetic [69.5% vs. 51.0% p=.03] and on full-dose anticoagulation [75.0%vs.56.8% p=.02]. Patients with a BMI≥ 25 and those with diabetes demonstrated TEG-PM profiles similar to patients with thrombosis. Diabetes was independently associated with thrombosis, and full-dose anticoagulation was not protective. This suggests the potential utility of TEG-PM for thrombotic risk stratification based on metabolic factors and suggests antiplatelet agents may be effective at prevention of thrombotic events in this population.

Factors associated with Ninety-day Reintervention following Lower Extremity Revascularization

Peripheral artery disease (PAD) represents a high volume, high-cost burden on the healthcare system. The Centers for Medicare and Medicaid Services (CMS) has developed the Bundled Payments for Care Improvement-Advanced program, in which a single payment is provided for all services administered in a postsurgical 90-day episode of care. Factors associated with 30- and 90-day reinterventions after PAD interventions would represent useful data for both payors and stake holders. We conducted a national cohort study of adults 65 years and older in the Vascular Quality Initiative and CMS linked dataset who underwent an open, endovascular, or hybrid revascularization procedure for PAD between January 1, 2010 to December 31, 2018. Procedures for acute limb ischemia and aneurysms were excluded. The primary outcome was 90-day reintervention. Reintervention at 30-days was a secondary outcome. Covariates of interest included demographic, comorbidities, and patient- and facility-level characteristics. Multivariable Cox regression was used to determine the association between patient- and facility-level characteristics and the risk of 30- and 90-day reinterventions. Among 42,429 patients (71.3% endovascular, 23.3% open, and 5.4% hybrid), median [IQR] age was 74 [69-80], 57.9% were male, and 84.3% were White. Chronic limb threatening ischemia (CLTI) was the operative indication in 40.4% of the procedures. Overall, 42.8% were completed in the outpatient setting (40.3% outpatient, 2.5% office-based lab). Over 70% of procedures for CLTI were completed as inpatient while 60% of the claudication interventions were done as outpatient. The 90-day reintervention rate was 14.5% and the 30-day reintervention rate was 5.5%. Compared to inpatient procedures, PAD interventions completed in the outpatient or office-based lab setting had significantly higher 90- and 30--day reintervention rates (ref - inpatient; outpatient 90d reintervention [HR 1.41 (95% CI 1.25-1.60)]; outpatient 30d reintervention [HR 1.90 (95% CI 1.62-2.24)]; office-based lab 90d reintervention [HR 2.09 (95% CI 1.82-2.41)]; office-based lab 30d reintervention [HR 3.54 (95% CI 3.17-3.94)]). Open and hybrid approaches demonstrated lower risk of reintervention compared to endovascular procedures at 30 and 90 days and, compared to aortoiliac disease, all other anatomic segments of disease were associated with higher 90-day reintervention but no difference was noted at 30 days. While outpatient PAD interventions may be convenient for patients and providers, the outpatient setting is associated with a significant risk of subsequent reintervention. Additional work is needed to understand how to improve the longevity of outpatient PAD interventions.

The Use and Impact of Cilostazol on Patients Undergoing Endovascular Peripheral Interventions

ObjectivesCilostazol is used for the treatment of intermittent claudication. The impact of cilostazol on the outcomes of peripheral vascular interventions (PVI) remains controversial. This study assesses the use and impact of cilostazol on patients undergoing PVI for peripheral arterial disease (PAD). MethodsThe Vascular Quality Initiative (VQI) database files for PVI were reviewed. Patients with PAD who underwent PVI for CLTI or claudication were included and divided based on the use of cilostazol preoperatively. After propensity matching for patient demographics and comorbidities, the short-term and long-term outcomes of the two groups (preoperative cilostazol use versus no pre-operative cilostazol use) were compared. The Kaplan-Meier method was used to determine outcomes. ResultsA total of 245,309 patients underwent PVI procedures and 6.6% (N=16,366) were on cilostazol prior to intervention. Patients that received cilostazol were more likely to be male (62% vs 60%; P < .001), White (77% vs 75%; P < .001), and smokers (83% vs 77%; P < .001). They were less likely to have diabetes mellitus (50% vs 56%; P < .001) and congestive heart failure (14% vs 23%; P < .001). Patient on cilostazol were more likely to be treated for claudication (63% vs 40%, P < .001), undergo prior lower extremity revascularization (55% vs 51%, P<.001) and less likely to have undergone prior minor and major amputation (10% vs 19%; P < .001) compared to patients who did not receive cilostazol. After 3:1 propensity matching, there were 50,265 patients included in the analysis with no differences in baseline characteristics. Patients on cilostazol were less likely to develop renal complications and more likely to be discharged home. Patients on cilostazol had significantly lower rates of long-term mortality (11.5% vs 13.4%, P <.001 and major amputation (4.0% vs 4.7%, P=0.022). However, there were no significant differences in rates of reintervention, major adverse limb events, or patency after PVI. Amputation-free survival rates were significantly higher for patients on cilostazol, after four years of follow-up (89% vs 87%, P=0.03). ConclusionCilostazol is underutilized in the VQI database and seems to be associated with improved amputation-free survival. Cilostazol therapy should be considered in all patients with PAD who can tolerate it prior to PVI.

Revascularisation for Peripheral Artery Disease in France: Implications for the Implementation of VOYAGER-PAD

The VOYAGER-PAD trial demonstrated the interest in dual pathway inhibition (DPI) (low dose rivaroxaban plus aspirin) to reduce limb and cardiovascular events after revascularisation for peripheral artery disease (PAD), but its applicability in clinical practice has not yet been assessed. This study aimed to assess the number of patients revascularised in France for PAD and to estimate the proportion of those matching with VOYAGER-PAD trial selection criteria. A secondary objective was to examine the prognosis of revascularised patients in a real world setting. This observational retrospective study was conducted on the national hospital discharge database and included all patients with PAD who underwent lower extremity revascularisation for PAD (without lower extremity revascularisation in the 2 years prior to inclusion) from 1 January 2016 to 31 December 2019. Available VOYAGER-PAD selection criteria were then applied to the study population. In total, 180 870 incident patients were included (mean age 72.0 ± 12.2 years, 30.9% female), with approximately 45 000 patients revascularised yearly. Among them, 90 379 (50.0%) matched the VOYAGER-PAD trial criteria (VOYAGER-PAD eligible subgroup; mean age 69.8 ± 12.1 years, 29.5% female). In the study population and the VOYAGER-PAD eligible subgroup, 33.9% and 26.6% of patients had diabetes, 28.1% and 19.9% had chronic coronary artery disease, and 14.6% and 5.7% had renal failure, respectively. Overall, 73.1% of study patients were treated by an endovascular approach (75.5% in the VOYAGER-PAD eligible subgroup). In patients with ≥ 1 year of follow up, 45.4% of study patients and 36.0% of the VOYAGER-PAD eligible subgroup experienced a limb or cardiovascular event. Median time until the first event and in hospital death was 4.8 months and 7.8 months, respectively (6.7 months and 12.9 months in the VOYAGER-PAD eligible subgroup). The burden of PAD for revascularisation and secondary events is considerable. One half of revascularised patients in France are eligible for DPI therapy. Those patients are younger, with less comorbidities, and better outcomes.

Association between Statin use and Incident Peripheral Artery Disease According to Race, Age, and Presence of Depression in the Multi-Ethnic Study of Atherosclerosis

BackgroundPeripheral artery disease (PAD) is associated with high morbidity and mortality and has been commonly described as a coronary heart disease equivalent. Statin medications are recommended for primary prevention of atherosclerotic cardiovascular disease (ASCVD) among other indications. Therefore, understanding the longitudinal relationship of incident PAD is necessary to inform future research on how to prevent disease. Depression complicates cardiovascular disease (CVD) patients’ ability to properly adhere to their medications, yet the effect of depression on the relationship between statin use and incident PAD is understudied. People with PAD have a higher incidence of depressive symptoms than people without PAD. Black American and Hispanic populations are disproportionately affected by both PAD and depression yet research on the modifying effect of either race or depression on the relationship between statin use and onset of PAD is minimal. While statin utilization is highest for ages 75–84, there is minimal evidence of favorable risk–benefit balance. Consequently, in this project, we examined the relationship between statin use and incident peripheral artery disease and whether this relationship is modified by race/ethnicity, depressive symptoms, or age. MethodsWe used data on participants from the Multi-Ethnic Study of Atherosclerosis (MESA) from visit 1 (2000) through study visit 6 (2020) who had three separate measurements of the ankle-brachial index (ABI) taken at visit 1, visit 3, and visit 5. Incident PAD was defined as 1) incident lower extremity amputation or revascularization or 2) ABI less than 0.90 coupled with ABI decrease greater than 0.15 over the follow-up period. Statin use was noted on the study visit prior to incident PAD diagnosis while depressive symptoms were measured at exam 1, visit 3, and visit 5. Propensity score matching was implemented to create balance between the participants in the two treatment groups, i.e., statin treated and statin untreated groups to reduce the problem of confounding by indication. Propensity scores were calculated using multivariate logistic regression model to estimate the probability of receiving statin treatment. We used Cox proportional hazards regression to investigate the relationship between time-dependent statin use as well as other risk factors with incident PAD, overall and stratified by 1) race,2) depression status, and 3) age ResultsA total 4,210 participants were included in the final matched analytic cohort. There were 810 (19.3%) incident cases of PAD that occurred over an average (mean) of 11.3 (SD=5.7) years of follow-up time. In the statin treated group, and with the average follow-up time of 12.5 (SD=5.6) years. there were 281 (13.4%) cases of incident PAD with the average follow-up time of 10.1 (SD=5.5), whereas in the statin untreated group, there were 531 (25.2%) cases (p<0.001). Results demonstrate a lower risk of PAD event in statin treated group compared to untreated group (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.33-0.62) over the span 18.5 years. The interactions between 1) depression and 2) race with statin use for incident PAD were not significant. However other risk factors which were significant included Black American race that had approximately 30% lower hazard of PAD compared to non-Hispanic White (HR=0.70, 95% CI: 0.58-0.84); Age-stratified models were also fitted, and stain use was still a significant treatment factor for ages 45-54 (HR 0.45, 95% CI: 0.33-0.63), 55-64 (HR 0.61, 95% CI 0.46-0.79), and 65-74 years (HR 0.61, 95% CI: 0.48-0.78) but not for 75-84 years. ConclusionStatin use was associated with a decreased risk of incident PAD for those under age 75. Neither race nor depression significantly modified the relationship between statin use and incident PAD however risk of incident PAD was lower among Blacks Americans. These findings highlight that the benefit of statin may wane for those over the age 75. Findings also suggest statin use may not be compromised in those living with depression.

Intravascular ultrasound use in peripheral arterial and deep venous interventions: Multidisciplinary expert opinion from SCAI/AVF/AVLS/SIR/SVM/SVS

Percutaneous revascularization is the primary strategy for treating lower extremity venous and arterial disease. Angiography is limited by its ability to accurately size vessels, precisely determine the degree of stenosis and length of lesions, characterize lesion morphology, or correctly diagnose postintervention complications. These limitations are overcome with use of intravascular ultrasound (IVUS). IVUS has demonstrated the ability to improve outcomes following percutaneous coronary intervention, and there is increasing evidence to support its benefits in the setting of peripheral vascular intervention. At this stage in its evolution, there remains a need to standardize the use and approach to peripheral vascular IVUS imaging. This manuscript represents considerations and consensus perspectives that emerged from a roundtable discussion including 15 physicians with expertise in interventional cardiology, interventional radiology, and vascular surgery, representing 6 cardiovascular specialty societies, held on February 3, 2023. The roundtable’s aims were to assess the current state of lower extremity revascularization, identify knowledge gaps and need for evidence, and determine how IVUS can improve care and outcomes for patients with peripheral arterial and deep venous pathology.

Combined Prognostic Value of Preprocedural Protein-Energy Wasting and Inflammation Status for Amputation and/or Mortality after Lower-Extremity Revascularization in Hemodialysis Patients with Peripheral Arterial Disease.

Protein-energy wasting is associated with inflammation and advanced atherosclerosis in hemodialysis patients. We enrolled 800 patients who had undergone successful lower-extremity revascularization, and we investigated the association among the Geriatric Nutritional Risk Index (GNRI) as a surrogate marker of protein-energy wasting, C-reactive protein (CRP), and their joint roles in predicting amputation and mortality. They were divided into lower, middle, and upper tertiles (T1, T2, and T3) according to GNRI and CRP levels, respectively. Regarding the results, the amputation-free survival rates over 8 years were 47.0%, 56.9%, and 69.5% in T1, T2, and T3 of the GNRI and 65.8%, 58.7%, and 33.2% for T1, T2, and T3 of CRP, respectively (p < 0.0001 for both). A reduced GNRI [adjusted hazard ratio (aHR) 1.78, 95% confidence interval (CI) 1.24-2.59, p = 0.0016 for T1 vs. T3] and elevated CRP (aHR 1.86, 95% CI 1.30-2.70, p = 0.0007 for T3 vs. T1) independently predicted amputation and/or mortality. When the two variables were combined, the risk was 3.77-fold higher (95% CI 1.97-7.69, p < 0.0001) in patients who occupied both T1 of the GNRI and T3 of CRP than in those who occupied both T3 of the GNRI and T1 of CRP. In conclusion, patients with preprocedurally decreased GNRI and elevated CRP levels frequently experienced amputation and mortality, and a combination of these two variables could more accurately stratify the risk.

Endovascular versus Surgical Lower Extremity Revascularization among Patients with Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) have a high prevalence of peripheral artery disease. How best to manage lower extremity peripheral artery disease remains unclear in this patient population. We therefore sought to compare the outcomes after endovascular versus surgical lower extremity revascularization among patients with CKD. We used data from Optum's de-identifed Clinformatics® Data Mart Database, a nationwide database of commercially insured persons in the United States to study patients with CKD who underwent lower extremity endovascular or surgical revascularization. We used inverse probability of treatment weighting to balance covariates. We employed proportional hazard regression to study the primary outcome of major adverse limb events (MALE), defined as a repeat revascularization or amputation. We also studied each of these events separately and death from any cause. In our cohort, 60,057 patients underwent endovascular revascularization and 9,338 patients underwent surgical revascularization. Endovascular revascularization compared with surgical revascularization was associated with a higher adjusted hazard of MALE (hazard ratio (HR) 1.52; 95% confidence interval (CI) 1.46-1.59). Endovascular revascularization was also associated with a higher adjusted hazard of repeat revascularization (HR 1.65; 95% CI 1.57-1.72) but a lower adjusted risk of amputation (HR 0.71; CI 0.73-0.89). Patients undergoing endovascular revascularization also had a lower adjusted hazard for death from any cause (0.85; CI 0.82-0.88). In this analysis of patients with CKD undergoing lower extremity revascularization, an endovascular approach was associated with a higher rate of repeated revascularization but a lower risk of subsequent amputation and death compared with surgical revascularization. Multiple factors must be considered when counseling patients with CKD, who have a high burden of comorbid conditions. Clinical trials should include more patients with kidney disease, who are often otherwise excluded from participation, to better understand the most effective treatment strategies for this vulnerable patient population.

Disparities in Diagnosis, Treatment, andOutcomes of Peripheral ArteryDisease: JACC Scientific Statement.

Disparities by sex, race, socioeconomic status, and geography exist in diagnosis, treatment, and outcomes for people with lower extremity peripheral artery disease (PAD). PAD prevalence is similar in men and women, but women have more atypical symptoms and undergo lower extremity revascularization at older ages compared to men. People who are Black have an approximately 2-fold higher prevalence of PAD, compared to people who are White and have more atypical symptoms, greater mobility loss, less optimal medical care, and higher amputation rates. Although fewer data are available for other races, people with PAD who are Hispanic have higher amputation rates than White people. Rates of amputation also vary by geography in the United States, with the highest rates of amputation in the southeastern United States. To improve PAD outcomes, intentional actions to eliminate disparities are necessary, including clinician education, patient education with culturally appropriate messaging, improved access to high-quality health care, science focused on disparity elimination, and health policy changes.

Outcomes of atherectomy in patients undergoing lower extremity revascularisation.

There is a paucity of real-world data on the in-hospital (IH) and post-discharge outcomes in patients undergoing lower extremity peripheral vascular intervention (PVI) with adjunctive atherectomy. In this retrospective, registry-based study, we evaluated IH and post-discharge outcomes among patients undergoing PVI, treated with or without atherectomy, in the National Cardiovascular Data Registry PVI Registry. The IH composite endpoint included procedural complications, bleeding or thrombosis. The primary out-of-hospital endpoint was major amputation at 1 year. Secondary endpoints included repeat endovascular or surgical revascularisation and death. Multivariable regression was used to identify predictors of atherectomy use and its association with clinical endpoints. A total of 30,847 patients underwent PVI from 2014 to 2019, including 10,971 (35.6%) treated with atherectomy. The unadjusted rate of the IH endpoint occurred in 524 (4.8%) of the procedures involving atherectomy and 1,041 (5.3%) of non-atherectomy procedures (p=0.07). After adjustment, the use of atherectomy was not associated with an increased risk of the combined IH endpoint (p=0.68). In the 6,889 (22.4%) patients with out-of-hospital data, atherectomy was associated with a reduced risk of amputation (adjusted hazard ratio [aHR] 0.67, 95% confidence interval [CI]: 0.51-0.85; p<0.01) and surgical revascularisation (aHR 0.63, 95% CI: 0.44-0.89; p=0.017), no difference in death rates (p=0.10), but an increased risk of endovascular revascularisation (aHR 1.21, 95% CI: 1.06-1.39; p<0.01) at 1 year. The use of atherectomy during PVI is common and is not associated with an increase in IH adverse events. Longitudinally, patients treated with atherectomy undergo repeat endovascular reintervention more frequently but experience a reduced risk of amputation and surgical revascularisation.