Advanced Treatment of Hemodynamically Unstable Acute Pulmonary Embolism and Clinical Follow-up.

High-risk acute pulmonary embolism (PE), defined as acute PE associated with hemodynamic instability, remains a significant contributor to cardiovascular morbidity and mortality in the United States and worldwide. Historically, anticoagulant therapy in addition to systemic thrombolysis has been the mainstays of medical therapy for the majority of patients with high-risk PE. In efforts to reduce the morbidity and mortality, a wide array of interventional and surgical therapies has been developed and employed in the management of these patients. However, the most recent guidelines for the management of PE have reserved the use of these advanced therapies in scenarios where thrombolytic therapy plus anticoagulation are unsuccessful. This is due largely to the lack of prospective, randomized studies in this population. Stemming from this, the approach to treatment of these patients varies widely depending on institutional experience and resources. Furthermore, morbidity and mortality remain unacceptably high in this population, with estimated 30-day mortality of at least 30%. As such, development of a standardized approach to treatment of these patients is paramount to improving outcomes. Early and accurate risk stratification in conjunction with a multidisciplinary team approach in the form of a PE response team is crucial. With the advent of novel therapies for the treatment of acute PE, in addition to the growing availability of and familiarity with mechanical circulatory support systems, such a standardized approach may now be within reach.

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

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

Ultrasound-assisted versus conventional catheter-directed thrombolysis for acute pulmonary embolism: A multicenter comparison of patient-centered outcomes.

Both catheter-directed thrombolysis (CDT) and ultrasound-assisted thrombolysis (USAT) are novel treatment modalities for patients presenting with acute pulmonary embolism (PE). The objective of this study was to compare clinical and quality-of-life (QOL) outcomes for patients undergoing either treatment modality. We retrospectively studied 70 consecutive patients treated with either CDT or USAT over 3 years at a multicenter health system. The primary clinical efficacy endpoint was right ventricular systolic pressure (RVSP) reduction post-procedurally. Safety endpoints were mortality and bleeding incidents based on Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries (GUSTO) criteria. Long-term QOL was assessed using the 36-Item Short-Form Health Survey (SF-36) via phone interview. Thirty-seven patients (53%) in our study underwent USAT and 33 (47%) patients were treated with conventional CDT. Among all patients studied, 96% had echocardiographic evidence for right ventricular strain on admission. Mean RVSP decreased by 18 ± 13 mmHg in the USAT group post-procedurally as compared to 14 ± 16 mmHg in the CDT group, without significant difference between groups ( p = 0.31). Rates of moderate and severe bleeding were largely identical between USAT and CDT groups (USAT: 3%; CDT: 0%; p = 0.09). There was no death in either group during admission. At long-term follow-up, there was no significant difference in QOL between both treatment modalities in all eight functional domains of SF-36. Our retrospective study demonstrated using USAT over conventional CDT for acute submassive or massive PE did not yield additional clinical, safety, or long-term QOL benefit.

Peripheral vascular interventional advances in 2017.

Aim of this review is to inform major clinical trials in peripheral vascular interventions in the year of 2017.

Unprotected carotid artery stenting in modern practice.

BACKGROUND & PURPOSE: Embolic protection devices (EPD) may provide a mechanism to reduce peri-procedural strokes. They are advocated by consensus guidelines and mandated for Medicare reimbursement. However, outcomes data remain mixed. We aimed to characterize the population of patients undergoing unprotected carotid artery stenting (CAS) and assess the utility of distal filter EPD (F-EPD) in elective CAS. METHODS: We analyzed patients enrolled in the CARE Registry® undergoing CAS between May, 2005 and January, 2012. We assessed the relationship between distal F-EPD use versus no use (No-EPD) and the composite of in-hospital death or stroke (MAE) in unadjusted and 1:3 propensity-matched analyses. RESULTS: Embolic protection was not attempted in a total of 579 out of 13,263 cases performed (4.4%). Patients in the No-EPD group had worse preprocedure neurologic risk factors including higher rates of acute evolving stroke, prior TIA/stroke, symptomatic lesion status, spontaneous carotid artery dissection, and use of general anesthesia intraprocedurally (all Standardized Differences{sd} >10). After exclusion of nonelective cases there was no significant difference in MAE between the No-EPD and F-EPD groups (1.6% vs. 2.3%, sd = 4.72). Additionally, after propensity matching, rates of MAE did not differ between the No-EPD (n = 355) and F-EPD (n = 1065) groups (1.7% vs. 2.5%, sd = 5.87). CONCLUSIONS: Patients selected to undergo unprotected CAS in contemporary practice have high rates of adverse preprocedure neurologic risk factors. Our propensity-matched analysis did not demonstrate evidence of significant benefit or harm associated with use of F-EPD in elective CAS patients.

The Role of IVC Filters in the Management of Acute Pulmonary Embolism.

Venous thromboembolism (VTE), comprising deep venous thrombosis (DVT) and pulmonary embolism (PE), is a prevalent cardiovascular condition, ranking third globally after myocardial infarction and stroke. The risk of VTE rises with age, posing a growing concern in aging populations. Acute PE, with its high morbidity and mortality, emphasizes the need for early diagnosis and intervention. This review explores prognostic factors for acute PE, categorizing it into low-risk, intermediate-risk, and high-risk based on hemodynamic stability and right ventricular strain. Timely classification is crucial for triage and treatment decisions. In the contemporary landscape, low-risk PE patients are often treated with Direct Oral Anticoagulants (DOACS) and rapidly discharged for outpatient follow-up. Intermediate- and high-risk patients may require advanced therapies, such as systemic thrombolysis, catheter-directed thrombolysis, mechanical thrombectomy, and IVC filter placement. The latter, particularly IVC filters, has witnessed increased usage, with evolving types like retrievable and convertible filters. However, concerns arise regarding complications and the need for timely retrieval. This review delves into the role of IVC filters in acute PE management, addressing their indications, types, complications, and retrieval considerations. The ongoing debate surrounding IVC filter use, especially in patients with less conventional indications, reflects the need for further research and data. Despite complications, recent studies suggest that clinically significant issues are rare, sparking discussions on the appropriate and safe utilization of IVC filters in select PE cases. The review concludes by highlighting current trends, gaps in knowledge, and potential avenues for advancing the role of IVC filters in future acute PE management.

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

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Mechanical Thrombectomy for High-Risk Pulmonary Embolism: Insights From the US Cohort of the FLASH Registry.

Background: Acute mortality for high-risk, or massive, pulmonary embolism (PE) is almost 30% even when treated using advanced therapies. This analysis assessed the safety and effectiveness of mechanical thrombectomy (MT) for high-risk PE. Methods: The prospective, multicenter FlowTriever All-comer Registry for Patient Safety and Hemodynamics (FLASH) study is designed to evaluate real-world PE patient outcomes after MT with the FlowTriever System (Inari Medical). In this study, acute outcomes through 30 days were evaluated for the subset of patients with high-risk PE as determined by the sites and following European Society of Cardiology guidelines. An independent medical monitor adjudicated adverse events (AEs), including major AEs: device-related mortality, major bleeding, or intraprocedural device-related or procedure-related AEs. Results: Of the 799 patients in the US cohort, 63 (7.9%) were diagnosed with high-risk PE; 30 (47.6%) patients showed a systolic blood pressure <90 mm Hg, 29 (46.0%) required vasopressors, and 4 (6.3%) experienced cardiac arrest. The mean age of patients with high-risk PE was 59.4 ± 15.6 years, and 34 (54.0%) were women. At baseline, 45 (72.6%) patients were tachycardic, 18 (54.5%) showed elevated lactate levels of ≥2.5 mM, and 21 (42.9%) demonstrated depressed cardiac index of <2 L/min/m2. Immediately after MT, heart rate improved to 93.5 ± 17.9 bpm. Twenty-five (42.4%) patients did not require an overnight stay in the intensive care unit, and no mortalities or major AEs occurred through 48 hours. Moreover, no mortalities occurred in 61 (96.8%) patients followed up through the 30-day visit. Conclusions: In this cohort of 63 patients with high-risk PE, MT was safe and effective, with no acute mortalities reported. Further prospective data are needed in this population.

Anatomic correlates of supra-normal ankle brachial indices.

BACKGROUND: Supra-normal ankle brachial index (ABI) (>1.40), poses diagnostic challenges to determine the presence, location, and severity of peripheral artery disease (PAD). The anatomic distribution of PAD in patients with elevated ABI has not been previously described. METHODS: A retrospective review of all patients referred to the Massachusetts General Hospital vascular diagnostic laboratory from 5 January 2006 to 12 January 2011 who had both a supra-normal ABI and contrast arteriography (CA) within 3 months of each other is reported. Angiographic patterns were described using the Trans Atlantic Inter Society Consensus II (TASC II) classification. RESULTS: One-hundred sixteen limbs were analyzed in 92 patients. Mean age was 71.6 years (± 11.2); 81.5% (75/92) were male; 85.9% Caucasian (79/92); 67.4% diabetics (62/92); 78.3% hypertensive (72/92); 67.4% hypercholesterolemic (62/92); and 64.1% were current or former tobacco users (59/92). Chronic hemodialysis was present in 18.5% (17/92) and 15.2% (14/92) received chronic corticosteroids. Intermittent claudication was present in 46.7% (43/92) and critical limb ischemia in 52.2% (48/92). Aortoiliac, femoral and infra-popliteal involvement per angiography occurred in 14.9% (15/101), 56.1% (60/107), and 84.0% (84/100), respectively. Multilevel disease was present in 48.8% (42/86) of patients. PAD was absent in 4.7% (4/86) of patients. Toe brachial index <0.7 was found in 92% (92/100) of patients with angiographically confirmed PAD. CONCLUSION: In symptomatic patients referred to a vascular laboratory who were found to have supra-normal ABI, nearly one half exhibited multilevel PAD, and over 80% had infrapopliteal involvement. A supra-normal ABI in such patients mandates evaluation for the presence and extent of PAD.

Prevalence and Predictors of Cardiogenic Shock in Intermediate-Risk Pulmonary Embolism: Insights From the FLASH Registry.

BACKGROUND: Patients with acute pulmonary embolism (PE) and hypotension (high-risk PE) have high mortality. Cardiogenic shock can also occur in nonhypotensive or normotensive patients (intermediate-risk PE) but is less well characterized. OBJECTIVES: The authors sought to evaluate the prevalence and predictors of normotensive shock in intermediate-risk PE. METHODS: Intermediate-risk PE patients in the FLASH (FlowTriever All-Comer Registry for Patient Safety and Hemodynamics) registry undergoing mechanical thrombectomy with the FlowTriever System (Inari Medical) were included. The prevalence of normotensive shock (systolic blood pressure ≥90 mm Hg but cardiac index ≤2.2 L/min/m2) was assessed. A composite shock score consisting of markers of right ventricular function and ischemia (elevated troponin, elevated B-type natriuretic peptide, moderately/severely reduced right ventricular function), central thrombus burden (saddle PE), potential additional embolization (concomitant deep vein thrombosis), and cardiovascular compensation (tachycardia) was prespecified and assessed for its ability to identify normotensive shock patients. RESULTS: Over one-third of intermediate-risk PE patients in FLASH (131/384, 34.1%) were in normotensive shock. The normotensive shock prevalence was 0% in patients with a composite shock score of 0 and 58.3% in those with a score of 6 (highest score). A score of 6 was a significant predictor of normotensive shock (odds ratio: 5.84; 95% CI: 2.00-17.04). Patients showed significant on-table improvements in hemodynamics post-thrombectomy, including normalization of the cardiac index in 30.5% of normotensive shock patients. Right ventricular size, function, dyspnea, and quality of life significantly improved at the 30-day follow-up. CONCLUSIONS: Although hemodynamically stable, over one-third of intermediate-risk FLASH patients were in normotensive shock with a depressed cardiac index. A composite shock score effectively further risk stratified these patients. Mechanical thrombectomy improved hemodynamics and functional outcomes at the 30-day follow-up.

Longer-Term Outcomes Following Mechanical Thrombectomy for Intermediate- and High-Risk Pulmonary Embolism: 6-Month FLASH Registry Results.

Background: Mechanical thrombectomy provides rapid hemodynamic improvements after acute pulmonary embolism (PE), but long-term benefits are uncertain. Methods: FlowTriever All-comer Registry for Patient Safety and Hemodynamics is a prospective, single-arm, multicenter registry of patients with acute PE treated with the FlowTriever System (Inari Medical). Six-month outcomes including modified Medical Research Council dyspnea scores (MMRCD), right ventricular (RV) function, 6-minute walk test distances, and PE quality-of-life scores (QoL) were assessed. Results: In total, 799 patients were enrolled and 75% completed the study with a mean follow-up of 204 ± 46 days. Demographic characteristics included 54.1% men, mean age of 61.2 years, 77.1% intermediate-high-risk PE, and 8.0% high-risk PE. All-cause mortality was 4.6% at study completion. The proportion of patients with normal echocardiographic RV function increased from 15.1% at baseline to 95.1% at 6 months (P < .0001). MMRCD score improved from 3.0 at baseline to 0.0 at 6 months (P < .0001). 6-minute walk test distances increased from 180 m at 48 hours to 398 m at 6 months (P < .001). Median PE QoL total scores were 9.38 at 30 days and 4.85 at 6 months (P < .001). Prevalence of site-reported chronic thromboembolic pulmonary hypertension was 1.0% and chronic thromboembolic disease was 1.9%. Conclusions: In this large diverse group of PE patients, 6-month all-cause mortality, chronic thromboembolic pulmonary hypertension, and chronic thromboembolic disease were low following thrombectomy with the FlowTriever system. Significant improvements in RV function, patient symptoms, exercise capacity, and QoL were observed at 6 months, suggesting that rapid extraction of thrombus may prevent long-term sequelae in patients with PE.

Acute outcomes for the full US cohort of the FLASH mechanical thrombectomy registry in pulmonary embolism.

BACKGROUND: Evidence supporting interventional pulmonary embolism (PE) treatment is needed. AIMS: We aimed to evaluate the acute safety and effectiveness of mechanical thrombectomy for intermediate- and high-risk PE in a large real-world population. METHODS: FLASH is a multicentre, prospective registry enrolling up to 1,000 US and European PE patients treated with mechanical thrombectomy using the FlowTriever System. The primary safety endpoint is a major adverse event composite including device-related death and major bleeding at 48 hours, and intraprocedural adverse events. Acute mortality and 48-hour outcomes are reported. Multivariate regression analysed characteristics associated with pulmonary artery pressure and dyspnoea improvement. RESULTS: Among 800 patients in the full US cohort, 76.7% had intermediate-high risk PE, 7.9% had high-risk PE, and 32.1% had thrombolytic contraindications. Major adverse events occurred in 1.8% of patients. All-cause mortality was 0.3% at 48-hour follow-up and 0.8% at 30-day follow-up, with no device-related deaths. Immediate haemodynamic improvements included a 7.6 mmHg mean drop in mean pulmonary artery pressure (-23.0%; p<0.0001) and a 0.3 L/min/m2 mean increase in cardiac index (18.9%; p<0.0001) in patients with depressed baseline values. Most patients (62.6%) had no overnight intensive care unit stay post-procedure. At 48 hours, the echocardiographic right ventricle/left ventricle ratio decreased from 1.23±0.36 to 0.98±0.31 (p<0.0001 for paired values) and patients with severe dyspnoea decreased from 66.5% to 15.6% (p<0.0001).  Conclusions: Mechanical thrombectomy with the FlowTriever System demonstrates a favourable safety profile, improvements in haemodynamics and functional outcomes, and low 30-day mortality for intermediate- and high-risk PE.

Current interventional therapies in acute pulmonary embolism.

Pulmonary embolism (PE) is the third leading cause of cardiovascular mortality. The management of PE is currently evolving given the development of new technologies and team-based approaches. This document will focus on risk stratification of PEs, review of the current interventional therapies, the role of clinical endpoints to assess the effectiveness of different interventional therapies, and the role for mechanical circulatory support in the complex management of this disease.

Objective Outcome Measures for Trials in Patients With Chronic Limb-Threatening Ischemia Across 2 Decades: Analysis and Recommendations.

Chronic limb-threatening ischemia (CLTI) is prevalent and associated with morbidity and mortality. The published research concerning CLTI therapeutics is evolving. The goals of this review are to: 1) summarize the endpoints that are being used in trials assessing interventions for patients with CLTI; and 2) review gaps and discrepancies in current outcome definitions. A search was conducted of the PubMed database and ClinicalTrials.gov to identify studies published between January 2000 and March 2020 that evaluated treatment options for patients with CLTI. Meta-analyses, case series, case reports, abstracts, and expert opinion were excluded. Forty-nine studies (n = 11,667) were identified that fulfilled the inclusion criteria. Most trials reported clinical outcomes (mortality, 69.4%; limb events, 87.8%; target lesion revascularization, 83.7%). Mean follow-up duration was 23.7 months. In investigational device exemption trials, total follow-up and follow-up to primary outcomes were discordant (12 months vs 6 months; P = 0.0018). Hemodynamic testing was reported in 71.4%, usually ankle-brachial index. Patency was assessed in 89.8% of trials; ultrasound was used in 65.3% and invasive angiography in 85.7%, at baseline and/or during follow-up. Wound assessment was performed in 49.0% of studies, qualitative in 28.6% and quantitative in 20.4%. Finally, quality of life assessment was performed in 55% of studies. Definitions for many outcomes varied across studies. Consensus regarding which outcomes to study, uniform definitions, and optimal methods to measure some of these outcomes are yet to be established. A comprehensive effort by all stakeholders is needed to move the field of CLTI forward.

Contemporary outcomes of rescue percutaneous coronary intervention for acute myocardial infarction: comparison with primary angioplasty and the role of distal protection devices (EMERALD trial).

BACKGROUND: The value of distal protection devices during rescue PCI has not been studied. METHODS: The population enrolled in a prospective, randomized multicenter trial of distal microcirculatory protection in ST-elevation MI, was stratified for those undergoing rescue (n = 93) or primary (n = 408) PCI; we performed the prespecified comparisons of distal protection in rescue and primary PCI. RESULTS: Compared to primary PCI, rescue patients had higher baseline rates of TIMI-3 flow, but lower rates of post PCI TIMI-3 flow. However, no differences in the primary endpoints of complete ST-segment resolution (STR) at 30 minutes or infarct size, or 6 month mortality were present. In rescue PCI patients, randomization to distal protection did not significantly affect infarct size, STR, mortality or other clinical events. CONCLUSION: Despite reduced rates of post-procedural TIMI-3 flow, patients undergoing rescue PCI compared to primary PCI have similar myocardial perfusion, infarct size and clinical outcomes. Distal protection did not offer any detectable benefit in this patient population.

Pulmonary embolism: Care standards in 2018.

Pulmonary embolism (PE) is a leading cause of cardiovascular mortality worldwide. Clinical presentation can be diverse, and clinicians should have a high index of suspicion regarding the diagnosis. Evaluation should include detailed history of possible risk factors, physical examination and laboratory tests that would support the diagnosis and help risk-stratify patients. Finally, a dedicated imaging study should be performed in order to make a definitive diagnosis. Decisions regarding short-term, immediate, treatment are dictated by PE risk category. Treatment of low and high-risk PE is relatively straightforward. But treating moderate risk PE is challenging since aggressive treatment is not devoid of potential harm. This review focuses on the acute and chronic treatment of PE. We present risk stratification, guidance as to treatment choice and insights into chronic treatment with available anticoagulants.

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score.

Pulmonary embolism (PE) is a major cause of morbidity and mortality world-wide, and the use of thrombolytic therapy has been associated with favourable clinical outcomes in certain patient subsets. These potential benefits are counterbalanced by the risk of bleeding complications, the most devastating of which is intracranial haemorrhage (ICH). We retrospectively evaluated 9703 patients from the 2003-2012 nationwide in-patient sample database (NIS) who received thrombolytics for PE. All patients with ICH during the PE hospitalisation were identified and a clinical risk score model was developed utilizing demographics and comorbidities. The dataset was divided 1:1 into derivation and validation cohorts. During 2003-2012, 176/9705 (1.8 %) patients with PE experienced ICH after thrombolytic use. Four independent prognostic factors were identified in a backward logistic regression model, and each was assigned a number of points proportional to its regression coefficient: pre-existing Peripheral vascular disease (1 point), age greater than 65 years (Elderly) (1 point), prior Cerebrovascular accident with residual deficit (5 points), and prior myocardial infarction (Heart attack) (1 point). In the derivation cohort, scores of 0, 1, 2 and ≥ 5 points were associated with ICH risks of 1.2 %, 1.9 %, 2.4 % and 17.8 %, respectively. Rates of ICH were similar in the validation cohort. The C-statistic for the risk score was 0.65 (0.61-0.70) in the derivation cohort and 0.66 (0.60-0.72) in the validation cohort. A novel risk score, derived from simple clinical historical elements was developed to predict ICH in PE patients treated with thrombolytics.

Building a Critical Limb Ischemia Program.

OPINION STATEMENT: The need to develop highly qualified, multidisciplinary critical limb ischemia (CLI) programs has gained significant momentum. Due to the systemic nature of the disease, patients with CLI are inherently medically complex and often present with multiple comorbidities. Successful care for these patients depends on community screening, early referral, accurate diagnosis, risk stratification, risk factor modification, invasive and non-invasive treatment strategies, and appropriate surveillance. Patients with CLI are often treated by multiple subspecialists-often lacking a unified team which could lead to inefficiencies and redundancy. Establishing an effective critical limb ischemia program relies on the joint efforts of multiple physician specialists, nurses, technicians, wound care specialists, researchers, and administrators who together form an integrated network that is easily accessible to the patient. This article will focus on the various modalities needed to build an advanced critical limb ischemia program, while addressing the challenges facing the medical community in caring for this population.

Peripheral artery disease. Part 1: clinical evaluation and noninvasive diagnosis.

Peripheral artery disease (PAD) is a marker of systemic atherosclerosis. Most patients with PAD also have concomitant coronary artery disease (CAD), and a large burden of morbidity and mortality in patients with PAD is related to myocardial infarction, ischemic stroke, and cardiovascular death. PAD patients without clinical evidence of CAD have the same relative risk of death from cardiac or cerebrovascular causes as those diagnosed with prior CAD, consistent with the systemic nature of the disease. The same risk factors that contribute to CAD and cerebrovascular disease also lead to the development of PAD. Because of the high prevalence of asymptomatic disease and because only a small percentage of PAD patients present with classic claudication, PAD is frequently underdiagnosed and thus undertreated. Health care providers may have difficulty differentiating PAD from other diseases affecting the limb, such as arthritis, spinal stenosis or venous disease. In Part 1 of this Review, we explain the epidemiology of and risk factors for PAD, and discuss the clinical presentation and diagnostic evaluation of patients with this condition.