Methods, design, and initial results of an angiographic core lab from VOYAGER-PAD.

Background: Anatomy is critical in risk stratification and therapeutic decision making in coronary disease. The relationship between anatomy and outcomes is not well described in PAD. We sought to develop an angiographic core lab within the VOYAGER-PAD trial. The current report describes the methods of creating this core lab, its study population, and baseline anatomic variables. Methods: Patients undergoing lower-extremity revascularization for symptomatic PAD were randomized in VOYAGER-PAD. The median follow up was 2.25 years. Events were adjudicated by a blinded Clinical Endpoint Committee. Angiograms were collected from study participants; those with available angiograms formed this core lab cohort. Angiograms were scored for anatomic and flow characteristics by trained reviewers blinded to treatment. Ten percent of angiograms were evaluated independently by two reviewers; inter-rater agreement was assessed. Clinical characteristics and the treatment effect of rivaroxaban were compared between the core lab cohort and noncore lab participants. Anatomic data by segment were analyzed. Results: Of 6564 participants randomized in VOYAGER-PAD, catheter-based angiograms from 1666 patients were obtained for this core lab. Anatomic and flow characteristics were collected across 16 anatomic segments by 15 reviewers. Concordance between reviewers for anatomic and flow variables across segments was 90.5% (24,417/26,968). Clinical characteristics were similar between patients in the core lab and those not included. The effect of rivaroxaban on the primary efficacy and safety outcomes was also similar. Conclusions: The VOYAGER-PAD angiographic core lab provides an opportunity to correlate PAD anatomy with independently adjudicated outcomes and provide insights into therapy for PAD. (ClinicalTrials.gov Identifier: NCT02504216).

Medical Therapy for Peripheral Artery Disease.

PURPOSE OF REVIEW: Patients with lower extremity peripheral artery disease (PAD) are at high risk for major adverse cardiovascular events (MACE) and major adverse limb events (MALE). This manuscript will review the current evidence for medical therapy in patients with PAD according to different clinical features and the overall cardiovascular (CV) risk. RECENT FINDINGS: The management of PAD encompasses non-pharmacologic strategies, including lifestyle modification such as smoking cessation, supervised exercise, Mediterranean diet and weight loss as well as pharmacologic interventions, particularly for high risk patients. Benefits for reduction of CV and limb outcomes have been demonstrated for new therapies, including antithrombotic therapy (i.e., low-dose rivaroxaban plus aspirin), lipid lowering therapy (i.e., proprotein convertase subtilisin/kexin type 9 inhibitors), and glucose lowering therapy (i.e., sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists). However, the adoption of these therapies in PAD remains suboptimal in practice. Implementation science studies have recently shown promising results in PAD patients. Comprehensive medical and non-medical management of PAD patients is crucial to improving patient outcomes, mitigating symptoms, and reducing the risk of MACE and MALE. A personalized approach, considering the patient's overall risk profile and preference, is essential for optimizing medical management of PAD.

Recent Trends in Clinical Setting and Provider Specialty for Endovascular Peripheral Artery Disease Interventions for the Medicare Population.

PURPOSE: To describe national trends in peripheral endovascular interventions by physician specialty, anatomic segment of disease, and clinical location of service. MATERIALS AND METHODS: Current Procedural Terminology codes were used to identify claims for peripheral vascular interventions (PVIs) in 2011-2017 Physician Supplier Procedure Summary master files, which contain 100% Part B Medicare billing. Market share was defined as enrollment-adjusted proportion of billed PVI services for each specialty. Annual volume of billed services was additionally evaluated by clinical location (inpatient, outpatient, office-based laboratories) and anatomic segment of disease (iliac, femoral/popliteal, infrapopliteal). RESULTS: Aggregate PVI claims increased 31.3%, from 227,091 in 2011 to 298,127 in 2017. Annual market share remained relatively stable for all specialties: surgery, 48.3%-49.6%; cardiology, 37.2%-35.1%; radiology, 12.8%-13.3%. Accounting for Medicare enrollment, the volume of iliac interventions decreased by 18% over the study period, while femoral/popliteal interventions increased modestly (+7.5%) and infrapopliteal interventions increased (+46%). The greatest proportional increase in infrapopliteal claims occurred among radiologists (surgeons +40.4%, cardiologists +32.1%, radiologists +106.6%). Adjusting for enrollment, claims from office-based laboratories increased substantially (+305.7%), while hospital-based billing decreased (inpatient -25.7%, outpatient -12.9%). Office-based laboratory utilization increased dramatically with all specialties (surgery +331.8%, cardiology +256.0%, radiology +475.7%). CONCLUSIONS: Utilization of PVIs continues to increase, while specialty market shares have stabilized since 2011, leaving surgeons and cardiologists as the major providers of endovascular peripheral artery disease care. The greatest relative increases are occurring in infrapopliteal interventions and office-based laboratory procedures, where radiologist involvement has increased dramatically.

Assessment of foot perfusion: Overview of modalities, review of evidence, and identification of evidence gaps.

Patients with critical limb ischemia have nonhealing wounds and/or ischemic rest pain and are at high risk for amputation and mortality. Accurate evaluation of foot perfusion should help avoid unnecessary amputation, guide revascularization strategies, and offer efficient surveillance for patency. Our aim is to review current modalities of assessing foot perfusion in the context of the practical clinical management of patients with critical limb ischemia.

Long-term outcomes of carotid artery stenting in patients with a contralateral carotid artery occlusion.

OBJECTIVES: To examine the association between a contralateral carotid artery occlusion (CCO) and the rates of subsequent target-lesion restenosis and revascularization after carotid artery stenting (CAS). BACKGROUND: Patients with carotid artery disease undergoing revascularization often have a CCO. The association of a CCO with long-term outcomes after CAS is uncertain. METHODS: At two institutions, 267 CAS procedures were performed from 2006 to 2016 including 47 (18%) with a CCO. Regular follow-up with duplex carotid ultrasound was performed to assess for restenosis. Univariate Cox regression analysis was performed to evaluate the association between the presence of a CCO and repeat revascularization. RESULTS: The mean patient age was 70 years. There was no significant difference (P > 0.05) in procedural indication (asymptomatic vs ischemic symptoms) or medical comorbidities between groups. During 5-year follow up, the rate of duplex-derived >80% stenosis was 6% in the non-CCO group and 9% in the CCO group (P = 0.45). Despite similar rates of >80% restenosis, there was a significant association between CCO and subsequent target-lesion revascularization (TLR), with rates of 6.4% vs 0.9% at 5 years (HR 7.2, confidence interval (CI) 1.2-43, P = 0.04). There were no significant differences between groups in the 5-year rates of stroke (4.3% in CCO group vs 4.5% in non-CCO group, HR 0.53, CI 0.07-4.22, P = 1.0) or MACCE (15% vs 18%, HR 0.55, CI 0.2-1.55, P = 0.68). CONCLUSIONS: Patients undergoing CAS with a CCO were more likely to undergo TLR during long-term follow up, but they did not have any differences in procedural success or short- and long-term outcomes.

Ticagrelor in Peripheral Artery Disease Endovascular Revascularization (TI-PAD): Challenges in clinical trial execution.

There is limited evidence to guide clinical decision-making for antiplatelet therapy in peripheral artery disease (PAD) in the setting of lower extremity endovascular treatment. The Ticagrelor in Peripheral Artery Disease Endovascular Revascularization Study (TI-PAD) evaluated the role of ticagrelor versus aspirin as monotherapy in the management of patients following lower extremity endovascular revascularization. The trial failed to recruit the targeted number of patients, likely due to aspects of the design including the lack of option for dual antiplatelet therapy, and inability to identify suitable patients at study sites. In response, the protocol underwent amendments, but these changes did not adequately stimulate recruitment, and thus TI-PAD was prematurely terminated. This article describes the rationale for TI-PAD and challenges in trial design, subject recruitment and trial operations to better inform the conduct of future trials in PAD revascularization. ClinicalTrials.gov Identifier: NCT02227368.

The Contemporary Safety and Effectiveness of Lower Extremity Bypass Surgery and Peripheral Endovascular Interventions in the Treatment of Symptomatic Peripheral Arterial Disease.

BACKGROUND: Treatment for symptomatic peripheral artery disease includes lower extremity bypass surgery (LEB) and peripheral endovascular interventions (PVIs); however, limited comparative effectiveness data exist between the 2 therapies. We assessed the safety and effectiveness of LEB and PVI in patients with symptomatic claudication and critical limb ischemia. METHODS AND RESULTS: In a community-based clinical registry at 2 large integrated healthcare delivery systems, we compared 883 patients undergoing PVI and 975 patients undergoing LEB between January 1, 2005 and December 31, 2011. Rates of target lesion revascularization were greater for PVI than for LEB in patients presenting with claudication (12.3±2.7% and 19.0±3.5% at 1 and 3 years versus 5.2±2.4% and 8.3±3.1%, log-rank P<0.001) and critical limb ischemia (19.1±4.8% and 31.6±6.3% at 1 and 3 years versus 10.8±2.5% and 16.0±3.2%, log-rank P<0.001). However, in comparison with PVI, LEB was associated with increased rates of complications up to 30 days following the procedure (37.1% versus 11.9%, P<0.001). There were no differences in amputation rates between the 2 groups. Findings remained consistent in sensitivity analyses by using propensity methods to account for treatment selection. CONCLUSIONS: In patients with symptomatic peripheral artery disease, in comparison with LEB, PVI was associated with fewer 30-day procedural complications, higher revascularization rates at 1 and 3 years, and no difference in subsequent amputations.

Anatomic runoff score predicts cardiovascular outcomes in patients with lower extremity peripheral artery disease undergoing revascularization.

BACKGROUND: Although the presence, extent, and severity of obstruction in patients with lower extremity peripheral artery disease (LE PAD) affect their functional status, quality of life, and treatment, it is not known if these factors are associated with future cardiovascular events. We empirically created an anatomic runoff score (ARS) to approximate the burden of LE PAD and determined its association with clinical outcomes. METHODS: We evaluated all patients with LE PAD and bilateral angiography undergoing revascularization in a community-based clinical study. Primary clinical outcomes of interest were (1) a composite of all-cause death, myocardial infarction (MI), and stroke and (2) amputation-free survival. Cox proportional hazards models were created to identify predictors of clinical outcomes. RESULTS: We evaluated 908 patients undergoing angiography, and a total of 260 (28.0%) patients reached the composite end point (45 MI, 63 stroke, and 152 death) during the study period. Anatomic runoff score ranged from 0 to 15 (mean 4.7; SD 2.5) with higher scores indicating a higher burden of disease, and an optimal cutpoint analysis classified patients into low ARS (<5) and high ARS (≥5). The unadjusted rates of the primary composite end point and amputation-free survival were nearly 2-fold higher in patients with a high ARS when compared with patients with a low ARS. The most significant predictors of the composite end point (death/MI/stroke) were age (δ 10 years; hazard ratio [HR] 1.53; CI 1.32-1.78; P < .001), diabetes mellitus (HR 1.65; CI 1.26-2.18; P < .001), glomerular filtration rate <30 (HR 2.23; CI 1.44-3.44; P < .001), statin use (HR 0.66; CI 0.48-0.88; P < .001), and ARS (δ 2 points; HR 1.21; CI 1.08-1.35; P < .001). CONCLUSIONS: After adjustment for clinical factors, the LE PAD ARS was an independent predictor of future cardiovascular morbidity and mortality in a broadly representative patient population undergoing revascularization for symptomatic PAD. A clinically useful anatomic scoring system, if validated, may assist clinicians in risk stratification during the course of clinical decision making.

Community-based walking exercise for peripheral artery disease: An exploratory pilot study.

Supervised walking exercise is an effective treatment to improve walking ability of patients with peripheral artery disease (PAD), but few exercise programs in community settings have been effective. The aim of this study was to determine the efficacy of a community-based walking exercise program with training, monitoring and coaching (TMC) components to improve exercise performance and patient-reported outcomes in PAD patients. This was a randomized, controlled trial including PAD patients (n=25) who previously received peripheral endovascular therapy or presented with stable claudication. Patients randomized to the intervention group received a comprehensive community-based walking exercise program with elements of TMC over 14 weeks. Patients in the control group did not receive treatment beyond standard advice to walk. The primary outcome in the intent-to-treat (ITT) analyses was peak walking time (PWT) on a graded treadmill. Secondary outcomes included claudication onset time (COT) and patient-reported outcomes assessed via the Walking Impairment Questionnaire (WIQ). Intervention group patients (n=10) did not significantly improve PWT when compared with the control group patients (n=10) (mean ± standard error: +2.1 ± 0.7 versus 0.0 ± 0.7 min, p=0.052). Changes in COT and WIQ scores were greater for intervention patients compared with control patients (COT: +1.6 ± 0.8 versus -0.6 ± 0.7 min, p=0.045; WIQ: +18.3 ± 4.2 versus -4.6 ± 4.2%, p=0.001). This pilot using a walking program with TMC and an ITT analysis did not improve the primary outcome in PAD patients. Other walking performance and patient self-reported outcomes were improved following exercise in community settings. Further study is needed to determine whether this intervention improves outcomes in a trial employing a larger sample size.

Optimal treatment of extracranial carotid artery disease: carotid endarterectomy, carotid stenting, or optimal medical therapy.

The optimal treatment of extracranial carotid artery disease is more controversial for asymptomatic than for symptomatic patients. Early trials comparing carotid endarterectomy to medical therapy alone demonstrated clear benefit of surgery in both symptomatic and asymptomatic populations. However, some believe that advances in medical therapy now lead to similar outcomes with optimal medical therapy alone and revascularization in asymptomatic patients. The role of carotid stenting is heavily debated, and the evidence base comparing carotid stenting to endarterectomy is limited primarily by inadequate operator experience as well as paucity of data in high surgical risk patients. A useful clinical approach to carotid bifurcation disease is to categorize patients by symptomatic status and revascularization risk. For symptomatic patients, revascularization should be favored over medical therapy alone. For asymptomatic patients, medical therapy alone might be considered, particularly for patients at high risk of revascularization and with anticipated survival <3-5 years.

Late presenting, contained rupture of the superficial femoral artery following atherectomy and stenting: case report and literature review.

Excisional atherectomy alone or followed by stenting is considered an appropriate treatment strategy for patients with lifestyle-limiting claudication due to obstructive infra-inguinal peripheral arterial disease (Ramaiah et al., J Endovasc Ther 2006;13:592-6021). We present a case of a 69-year-old man with eccentric severely calcified disease of the superficial femoral artery (SFA) treated with excisional atherectomy followed by stenting with an interwoven nitinol stent. The procedure was complicated by extravascular stent migration associated with a contained rupture presenting 30 days after the intervention. The complication was successfully treated with a stent graft. Although rare, pseudoaneurysms have been reported at the site of prior atherectomy; however, this case is the first description of a contained rupture post atherectomy associated with erosion of a nitinol stent into an extra-luminal position. The mechanism and management of this complication are discussed.

Community walking programs for treatment of peripheral artery disease.

BACKGROUND: Supervised walking programs offered at medical facilities for patients with peripheral artery disease (PAD) and intermittent claudication (IC), although effective, are often not used due to barriers, including lack of reimbursement and the need to travel to specialized locations for the training intervention. Walking programs for PAD patients that occur in community settings, such as those outside of supervised settings, may be a viable treatment option because they are convenient and potentially bypass the need for supervised walking. This review evaluated the various methods and outcomes of community walking programs for PAD. METHODS: A literature review using appropriate search terms was conducted within PubMed/MEDLINE and the Cochrane databases to identify studies in the English language that used community walking programs to treat PAD patients with IC. Search results were reviewed, and relevant articles were identified that form the basis of this review. The primary outcome was peak walking performance on the treadmill. RESULTS: Ten randomized controlled trials examining peak walking outcomes in 558 PAD patients demonstrated that supervised exercise programs were more effective than community walking studies that consisted of general recommendations for patients with IC to walk at home. Recent community trials that incorporated more advice and feedback for PAD patients in general resulted in similar outcomes, with no differences in peak walking time compared with supervised walking exercise groups. CONCLUSIONS: Unstructured recommendations for patients with symptomatic PAD to exercise in the community are not efficacious. Community walking programs with more feedback and monitoring offer improvements in walking performance for patients with claudication and may bypass some obstacles associated with facility-based exercise programs.

Call for Formalized Pathways in Vascular Medicine Training: JACC Review Topic of the Week.

The burden of vascular diseases and complexity of their management have been growing. Vascular medicine specialists may help to bridge gaps in care, especially as part of multidisciplinary teams. However, there is a limited number of vascular medicine specialists because of constraints in training. Despite established pathways for training in vascular medicine, there are obstacles that restrict completion of training in dedicated programs. A key factor is lack of funding as a result of inadequate recognition by key national accrediting and credentialing organizations. A concerted effort is required to overcome the obstacles to expand vascular medicine training programs and ultimately the pool of vascular medicine specialists. Well-trained vascular medicine specialists will be well positioned to ease the burden of vascular disease and optimize patient outcomes.

Retrograde approach to recanalization of complex tibial disease.

A significant proportion (~ 20%) of patients with complex tibial artery occlusions cannot be treated using a conventional antegrade approach. We report our experience using the retrograde approach for the treatment of complex tibial artery occlusive disease using retrograde pedal/tibial access in 13 limbs from 12 patients. Retrograde pedal/tibial access was achieved in all cases (facilitated by surgical cutdown in one case), and procedural success was achieved in 11 of 13 limbs (85%). Based on this experience, a discussion of clinical and technical aspects of the retrograde pedal/tibial approach is provided, and a new classification for tibial artery occlusive disease is proposed.

Acute Aortic Syndromes.

Acute aortic syndromes, classified into aortic dissection, intramural hematoma, and penetrating aortic ulcer, are associated with high early mortality for which early diagnosis and management are crucial to optimize outcomes. Patients often present with nonspecific clinical symptoms and signs; therefore, it is important for providers to maintain a high index of suspicion for acute aortic syndromes. Electrocardiogram-gated computed tomographic angiography of the chest, abdomen, and pelvis is currently the most practical imaging modality for diagnosis and identification of complications. Evolution in surgical techniques and the development of aortic endografts have improved patient outcomes, but randomized trials are still needed.

Acute Kidney Injury Following In-Patient Lower Extremity Vascular Intervention: From the National Cardiovascular Data Registry.

OBJECTIVES: The authors analyzed data from the NCDR (National Cardiovascular Data Registry) PVI Registry and defined acute kidney injury (AKI) as increased creatinine of ≥0.3 mg/dl or 50%, or a new requirement for dialysis after PVI. BACKGROUND: AKI is an important and potentially modifiable complication of peripheral vascular intervention (PVI). The incidence, predictors, and outcomes of AKI after PVI are incompletely characterized. METHODS: A hierarchical logistic regression risk model using pre-procedural characteristics associated with AKI was developed, followed by bootstrap validation. The model was validated with data submitted after model creation. An integer scoring system was developed to predict AKI after PVI. RESULTS: Among 10,006 procedures, the average age of patients was 69 years, 58% were male, and 52% had diabetes. AKI occurred in 737 (7.4%) and was associated with increased in-hospital mortality (7.1% vs. 0.7%). Reduced glomerular filtration rate, hypertension, diabetes, prior heart failure, critical or acute limb ischemia, and pre-procedural hemoglobin were independently associated with AKI. The model to predict AKI showed good discrimination (optimism corrected c-statistic = 0.68) and calibration (corrected slope = 0.97, intercept of -0.07). The integer point system could be incorporated into a useful clinical tool because it discriminates risk for AKI with scores ≤4 and ≥12 corresponding to the lower and upper 20% of risk, respectively. CONCLUSIONS: AKI is not rare after PVI and is associated with in-hospital mortality. The NCDR PVI AKI risk model, including the integer scoring system, may prospectively estimate AKI risk and aid in deployment of strategies designed to reduce risk of AKI after PVI.

Novel application of the "CART" technique for endovascular treatment of external iliac artery occlusions.

We report the novel application of the Controlled Antegrade and Retrograde subintimal Tracking technique for the endovascular treatment of occlusions of the external iliac artery (EIA). We hypothesized that this technique would limit the extent of subintimal dissection to the length of the EIA occlusion, thus preserving patency of the internal iliac artery proximally and the circumflex iliac artery distally and minimizing the length of stent required to treat the occlusion, including the length of stent placed in the common femoral artery. The technical execution and clinical experience with this technique is reported.

Use of Stingray re-entry system in treatment of complex tibial artery occlusive disease.

One of the mechanisms of technical failure in the treatment of tibial artery occlusive disease includes an inability to re-enter the true lumen of the tibial vessel distal to the occlusion following tracking of the interventional wire into the subintimal space. We report the first case using a coronary 0.014″ re-entry system (Stingray Chronic Total Occlusions Re-entry System, BridgePoint Medical) in the treatment of a complex tibial artery occlusion where the antegrade approach initially failed due to this mechanism. The re-entry system allowed completion of antegrade recanalization of the occlusion and represents an important addition to the interventional armamentarium for the treatment of complex tibial artery disease.

Long-Term Outcomes and Associations With Major Adverse Limb Events After Peripheral Artery Revascularization.

BACKGROUND: Long-term cardiovascular and limb outcomes after revascularization for peripheral artery disease and, in particular, prognosis after post-procedure major adverse limb events (MALE) are not well-studied. OBJECTIVES: This study sought to describe outcomes after peripheral revascularization and assess relationships between post-procedure MALE hospitalization and subsequent events. METHODS: Patients undergoing peripheral artery revascularization between January 1, 2009, and September 30, 2015, in the Premier Healthcare Database were examined for the co-primary outcomes of interest, composite myocardial infarction (MI) or stroke and composite major amputation or peripheral revascularization. Multivariable adjusted Cox proportional hazards models with post-procedure MALE hospitalization included as a time-dependent covariate were developed to estimate hazard ratios for outcomes. RESULTS: Among 393,017 revascularized patients followed for a median of 2.7 years (interquartile range: 1.3 to 4.4 years), the cumulative incidence of MI or stroke was 9.8% and that of major amputation or peripheral revascularization was 41.9%. A total of 50,750 patients (12.9%) had at least 1 post-procedure MALE hospitalization. In time-dependent covariate adjusted models, post-procedure MALE hospitalization was associated with greater risk of subsequent MI or stroke (hazard ratio: 1.34; 95% confidence interval: 1.28 to 1.40) and major amputation or peripheral revascularization (hazard ratio: 8.13; 95% confidence interval: 7.96 to 8.29). After peripheral revascularization with or without post-procedure MALE hospitalization, risk of limb events increased rapidly post-procedure and more slowly after the first year, whereas cardiac risk increased steadily during follow-up. CONCLUSIONS: Revascularized peripheral artery disease patients face earlier limb and later cardiovascular ischemic risk that is heightened among patients with post-procedure MALE hospitalization. Increased provider awareness of these long-term risks may guide efforts to improve post-procedural outcomes.