Robustness of Longitudinal Safety and Efficacy After Paclitaxel-Based Endovascular Therapy for Treatment of Femoro-Popliteal Artery Occlusive Disease: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The aims of this study were: i) to assess fragility indices (FIs) of individual randomized controlled trials (RCTs) that compared paclitaxel-based drug-coated balloons (DCBs) or drug-eluting stents (DESs) versus standard endovascular devices, and ii) to meta-analyze mid-term and long-term safety and efficacy outcomes from available RCT data while also estimating the FI of pooled results. METHODS: This systematic review has been registered in the PROSPERO public database (CRD42022304326 http://www.crd.york.ac.uk/PROSPERO). A query of PubMed (Medline), EMBASE (Excerpta Medical Database), Scopus, and CENTRAL (Cochrane Central Register of Controlled Trials) databases was performed to identify eligible RCTs. Rates of primary patency (PP) and target lesion revascularization (TLR) were assessed as efficacy outcomes, while lower limb amputation (LLA) consisting of major amputation that is. below or above the knee and all-cause mortality were estimated as safety outcomes. All outcomes were pooled with a random effects model to account for any clinical and study design heterogeneity. The analyses were performed by dividing the RCTs according to their maximal follow-up length (mid-term was defined as results up to 2-3 years, while long-term was defined as results up to 4-5 years). For each individual outcome, the FI and reverse fragility index (RFI) were calculated according to whether the outcome results were statistically significant or not, respectively. The fragility quotient (FQ) and reverse fragility quotient (RFQ), which are the FI or RFI divided by the sample size, were also calculated. RESULTS: A total of 2,337 patients were included in the systematic review and meta-analysis. There were 2 RCTs examining DES devices and 14 RCTs evaluating different DCBs. For efficacy outcomes, there was evidence that paclitaxel-based endovascular therapy increased the PP rate and reduced the TLR rate at mid-term, with a calculated pooled risk ratio (RR) of 1.66 for patency (95% CI, 1.55-1.86; P < 0.001), with a corresponding number needed-to-treat (NNT) of 3 patients (95% CI, 2.9-3.8) and RR of 0.44 for TLR (95% CI, 0.35-0.54; P = 0.027), respectively. Similarly, there was evidence that paclitaxel-based endovascular therapy both increased PP and decreased TLR rates at long-term, with calculated pooled RR values of 1.73 (95% CI, 1.12-2.61; P = 0.004) and 0.53 (95% CI, 0.45-0.62; P = 0.82), respectively. For safety outcomes, there was evidence that paclitaxel-based endovascular therapy increased all-cause mortality at mid-term, with a calculated pooled RR of 2.05 (95% CI, 1.21-3.24). However, there was no difference between treatment arms in LLA at mid-term (95% CI, 0.1-2.7; P = 0.68). Similarly, neither all-cause mortality nor LLA at long-term differed between treatment arms, with a calculated pooled RR of 0.66, 1.02 (95% CI, 0.31-3.42) and 1.02 (95% CI, 0.30-5.21; P = 0.22), respectively. The pooled estimates of PP at mid-term were robust (FI = 28 and FQ = 1.9%) as were pooled rates of TLR (FI = 18 and FQ = 0.9%). However, when safety outcomes were analyzed, the robustness of the meta-analysis decreased significantly. In fact, the relationship between the use of paclitaxel-coated devices and all-cause mortality at mid-term showed very low robustness (FI = 4 and FQ = 0.2%). At 5 years, only the benefit of paclitaxel-based devices to reduce TLR remained robust, with an FI of 32 and an FQ of 3.1%. CONCLUSIONS: The data supporting clinical efficacy endpoints of RCTs that examined paclitaxel-based devices in the treatment of femoral-popliteal arterial occlusive disease were robust; however, the pooled safety endpoints were highly fragile and prone to bias due to loss of patient follow-up in the original studies. These findings should be considered in the ongoing debate concerning the safety of paclitaxel-based devices.

Risk Factor Analysis for Crossing Failure in Primary Antegrade Wire-Catheter Approach for Femoropopliteal Chronic Total Occlusions.

INTRODUCTION: Antegrade wire-catheter crossing remains the primary approach for femoropopliteal interventions. Nonetheless, data reporting on crossing failure are limited. Aim of this study is to identify risk factors for antegrade crossing failure in patients with femoropopliteal chronic total occlusions (CTOs). METHODS: This is a single-center, retrospective analysis. Patients with femoropopliteal CTOs treated between May 2018 and February 2020 were included into this study. Primary endpoint of this analysis was primary crossing success defined as successful antegrade crossing without the use of retrograde access, crossing or re-entry devices. The assisted crossing success was additionally analyzed. A logistic regression analysis identified risk factors for failed primary antegrade crossing. RESULTS: Data from 300 patients were analyzed. The majority (n=183, 61%) presented with lifestyle limiting claudication. The mean lesion length was 180 mm [interquartile range (IQR) 100-260 mm], whereas the median CTO length was 100 mm (IQR=50-210 mm). A chronic total occlusion crossing approach based on plaque morphology (CTOP) type I configuration was observed in 9% (n=26) of the lesions, type II in 61% (n=183), type III in 8% (n=25), and type IV in 66 CTOs (n= 66, 22%). Severe calcification based on the Peripheral Arterial Calcium Scoring Scale (PACSS), Peripheral Academic Research Consortium (PARC), and 360° grading systems was identified in 17%, 24%, and 28% of the lesions, respectively. A contralateral femoral access was used in 278 cases (93%). The primary crossing success amounted to 70% (n=210). The use of a re-entry device in 28 patients (9%) or of a combined antegrade-retrograde approach in 11% (n=34) of the cases increased the assisted crossing success to 89% (n=267). The presence of calcification (odds ratio [OR]=4.2, 95% CI=1.7-10.2) or of circumferential calcium (OR=2.5, 95% CI=1.3-4.9), a CTOP class ΙΙΙ or ΙV (OR=1.9, 95% CI=1.4-2.6), a proximal superficial femoral artery (SFA) occlusion (OR=3.5, 95% CI=1.7-7.4) and a CTO at P3 (OR=4.1, 95% CI=1.5-10.8) were associated with an increased risk for antegrade crossing failure. CONCLUSIONS: In this study, chronic total occlusions (CTO) morphology, calcification burden, and lesion's location were identified as independent risk factors for failed antegrade crossing. Nonetheless, the use of alternative crossing strategies significantly increased the overall crossing success.

The impact of the SARS-CoV-2 pandemic on the management of chronic limb-threatening ischemia and wound care.

In the wake of the coronavirus pandemic, the critical limb ischemia (CLI) Global Society aims to develop improved clinical guidance that will inform better care standards to reduce tissue loss and amputations during and following the new SARS-CoV-2 era. This will include developing standards of practice, improve gaps in care, and design improved research protocols to study new chronic limb-threatening ischemia treatment and diagnostic options. Following a round table discussion that identified hypotheses and suppositions the wound care community had during the SARS-CoV-2 pandemic, the CLI Global Society undertook a critical review of literature using PubMed to confirm or rebut these hypotheses, identify knowledge gaps, and analyse the findings in terms of what in wound care has changed due to the pandemic and what wound care providers need to do differently as a result of these changes. Evidence was graded using the Oxford Centre for Evidence-Based Medicine scheme. The majority of hypotheses and related suppositions were confirmed, but there is noticeable heterogeneity, so the experiences reported herein are not universal for wound care providers and centres. Moreover, the effects of the dynamic pandemic vary over time in geographic areas. Wound care will unlikely return to prepandemic practices. Importantly, Levels 2-5 evidence reveals a paradigm shift in wound care towards a hybrid telemedicine and home healthcare model to keep patients at home to minimize the number of in-person visits at clinics and hospitalizations, with the exception of severe cases such as chronic limb-threatening ischemia. The use of telemedicine and home care will likely continue and improve in the postpandemic era.

A systematic review of the ipsilateral retrograde approach to the treatment of femoropopliteal arterial lesions.

OBJECTIVE: The endovascular treatment of femoropopliteal lesions is an integral part of managing peripheral arterial disease. The antegrade approach is the most widely used technique with good evidence for its safety and efficacy. However, crossing a lesion, particularly chronic total occlusions (CTO), can be technically challenging and so the retrograde approach is increasingly used to maximize the chances of procedural success. The objective of this systematic review was, therefore, to assess the safety and effectiveness of the ipsilateral retrograde approach to femoropopliteal lesions. METHODS: A systematic review conforming to the PRISMA standards was undertaken. MEDLINE, EMBASE, and The Cochrane Register were searched between January 1, 1988, and January 1, 2020. Full-text, English-language, peer-reviewed articles pertaining to peripheral arterial disease, endovascular intervention and access site were included. RESULTS: A total of 8599 articles were screened, of which 38, involving 1940 patients undergoing 2184 retrograde procedures, were included. The mean number of patients per study was 51.1, with three studies including fewer than 10 and four more than 100 patients. The reported follow-up ranged from 30 days to 3 years, and six articles did not report any long-term outcome data. A retrograde approach was used as the primary access route in 45.% of procedures (648/1438) with relevant data. Primary technical success was achieved in 88% (1920/2184; 64%-100%) with a reported complication rate of 11% (235/2117; 0%-27%). Overall, the quality of evidence was poor, with just seven articles deemed to be of high quality with a low risk of bias. A meta-analysis was not deemed appropriate owing to heterogeneity of data. CONCLUSIONS: An ipsilateral retrograde approach to femoropopliteal lesions has good primary technical success and a low rate of complications. It has a promising role as a bailout, or even a primary access technique, in complex lesions. Patient positioning, puncture site and technique, lesion anatomy, and the size of catheters and devices used are important considerations to achieve the best outcomes. There remains a paucity of robust evidence for its superiority over traditional antegrade approaches, and further work is required to identify the optimal technique and those patients who would benefit most from the approach.

Tibiopedal arterial minimally invasive retrograde revascularization (TAMI) in patients with peripheral arterial disease and critical limb ischemia. On behalf of the Peripheral Registry of Endovascular Clinical Outcomes (PRIME).

OBJECTIVES AND BACKGROUND: Complex peripheral arterial disease (PAD) and critical limb ischemia (CLI) are associated with high morbidity and mortality. Endovascular techniques have become prevalent in treatment of advanced PAD and CLI, and use of techniques such as tibiopedal minimally invasive revascularization (TAMI), have been proven safe in small, single-center series. However, its use has not been systematically compared to traditional approaches. METHODS AND RESULTS: This is a retrospective, multicenter analysis which enrolled 744 patients with advanced PAD and CLI who underwent 1,195 endovascular interventions between January 2013 and April 2018. Data was analyzed based on access used for revascularization: 840 performed via femoral access, 254 via dual access, and 101 via TAMI. The dual access group had the highest median Rutherford Class and lowest number of patent tibial vessels. Median fluoroscopy time, procedure time, hospital stay, and contrast volume were significantly lower in the TAMI access group when compared to both femoral/dual access groups. There was also a significant difference between all groups regarding location of target lesions: Femoropopliteal lesions were most commonly treated via femoral access; infrapopliteal lesions, via TAMI, and multilevel lesions via dual access. CONCLUSIONS: Stand-alone TAMI or tibial access as an integral part of a dual access treatment strategy, is safe and efficacious in the treatment of patients with advanced PAD and CLI who have infrapopliteal lesions. Larger prospective and randomized studies may be useful to further validate this approach.

Digital Subtraction Angiography Prior to an Amputation for Critical Limb Ischemia (CLI): An Expert Recommendation Statement From the CLI Global Society to Optimize Limb Salvage.

Despite recent guideline updates on peripheral artery disease (PAD) and critical limb ischemia (CLI) treatment, the optimal treatment for CLI is still being debated. As a result, care is inconsistent, with many CLI patients undergoing an amputation prior to what many consider to be mandatory: consultation with an interdisciplinary specialty care team and a comprehensive imaging assessment. More importantly, quality imaging is critical in CLI patients with below-the-knee disease. Therefore, the CLI Global Society has put forth an interdisciplinary expert recommendation for superselective digital subtraction angiography (DSA) that includes the ankle and foot in properly indicated CLI patients to optimize limb salvage. A recommended imaging algorithm for CLI patients is included.

Chronic Total Occlusion Crossing Approach Based on Plaque Cap Morphology: The CTOP Classification.

PURPOSE: To present the chronic total occlusion (CTO) crossing approach based on plaque cap morphology (CTOP) classification system and assess its ability to predict successful lesion crossing. METHODS: A retrospective analysis was conducted of imaging and procedure data from 114 consecutive symptomatic patients (mean age 69±11 years; 84 men) with claudication (Rutherford category 3) or critical limb ischemia (Rutherford category 4-6) who underwent endovascular interventions for 142 CTOs. CTO cap morphology was determined from a review of angiography and duplex ultrasonography and classified into 4 types (I, II, III, or IV) based on the concave or convex shape of the proximal and distal caps. RESULTS: Statistically significant differences among groups were found in patients with rest pain, lesion length, and severe calcification. CTOP type II CTOs were most common and type III lesions the least common. Type I CTOs were most likely to be crossed antegrade and had a lower incidence of severe calcification. Type IV lesions were more likely to be crossed retrograde from a tibiopedal approach. CTOP type IV was least likely to be crossed in an antegrade fashion. Access conversion, or need for an alternate access, was commonly seen in types II, III, and IV lesions. Distinctive predictors of access conversion were CTO types II and III, lesion length, and severe calcification. CONCLUSION: CTOP type I lesions were easiest to cross in antegrade fashion and type IV the most difficult. Lesion length >10 cm, severe calcification, and CTO types II, III, and IV benefited from the addition of retrograde tibiopedal access.

Innovations in the Endovascular Management of Critical Limb Ischemia: Retrograde Tibiopedal Access and Advanced Percutaneous Techniques.

PURPOSE OF REVIEW: Retrograde tibiopedal access and interventions have contributed to advance of endovascular techniques to treat critical limb ischemia (CLI) patients. This review encompasses the spectrum from advanced diagnostic imaging and technical therapeutic approaches for infrapopliteal occlusions, to a discussion of current standards and future directions. RECENT FINDINGS: Contemporary studies of infrapopliteal angioplasty show suboptimal short-term and 1-year clinical outcomes. Comparative data is needed to shift the focus from PTA to disruptive treatment modalities that can further improve outcomes. Retrograde pedal access has emerged as an important tool to facilitate successfully percutaneous revascularization and limb salvage in patients with CLI. To efficiently approach the complexity of CLI, new thought processes are needed to change the reigning paradigms. Retrograde tibial-pedal access has shown improvement in the rate of successful revascularizations and is an important tool in the amputation-prevention armamentarium. Additional technologies may further improve success rates. Drug-eluting stents have shown better outcomes than PTA in patients with focal infrapopliteal lesions. Registry data have demonstrated the advantage of several atherectomy devices in the tibial arteries. More recently, bioresorbable vascular scaffolds have been used successfully, and further studies with drug-coated balloons are underway. Interventional operators are now even working in the inframalleolar space to reconstitute the plantar arch. Well-conducted studies are needed to generate high-quality evidence in the field of critical limb ischemia management.

Tibiopedal Access for Crossing of Infrainguinal Artery Occlusions: A Prospective Multicenter Observational Study.

PURPOSE: To report a prospective, multicenter, observational study (ClinicalTrials.gov identifier NCT01609621) of the safety and effectiveness of tibiopedal access and retrograde crossing in the treatment of infrainguinal chronic total occlusions (CTOs). METHODS: Twelve sites around the world prospectively enrolled 197 patients (mean age 71±11 years, range 41-93; 129 men) from May 2012 to July 2013 who met the inclusion criterion of at least one CTO for which a retrograde crossing procedure was planned or became necessary. The population consisted of 64 (32.5%) claudicants (Rutherford categories 2/3) and 133 (67.5%) patients with critical limb ischemia (Rutherford category ≥4). A primary antegrade attempt to cross had been made prior to the tibiopedal attempt in 132 (67.0%) cases. Techniques used for access, retrograde lesion crossing, and treatment were at the operator's discretion. Follow-up data were obtained 30 days after the procedure. RESULTS: Technical tibiopedal access success was achieved in 184 (93.4%) of 197 patients and technical occlusion crossing success in 157 (85.3%) of the 184 successful tibial accesses. Failed access attempts were more common in women (9 of 13 failures). The rate of successful crossing was roughly equivalent between sexes [84.7% (50/59) women compared to 85.6% (107/125) men]. Technical success did not differ significantly based on a prior failed antegrade attempt: the access success rate was 92.4% (122/132) after a failed antegrade access vs 95.4% (62/65) in those with a primary tibiopedal attempt (p=0.55). Similarly, crossing success was achieved in 82.8% (101/122) after a failed antegrade access vs 90.3% (56/62) for patients with no prior antegrade attempt (p=0.19). Minor complications related to the access site occurred in 11 (5.6%) cases; no patient had access vessel thrombosis, compartment syndrome, or surgical revascularization. CONCLUSION: Tibiopedal access appears to be safe and can be used effectively for the crossing of infrainguinal lesions in patients with severe lower limb ischemia.

Tibio-pedal arterial minimally invasive retrograde revascularization in patients with advanced peripheral vascular disease: the TAMI technique, original case series.

BACKGROUND: A tibial-pedal access method is needed for patients with advanced peripheral artery disease (PAD) unable to tolerate common femoral artery (CFA) access and intervention due to body habitus or comorbidities. This is the first case series reporting an alternative technique to revascularize such patients. Using ultrasound (US) and the tibio-pedal arterial minimally invasive retrograde revascularization (TAMI) technique, operators accessed, and revascularized the lower extremity completely via tibial-pedal arterial access. METHODS: This retrospective, single-center, case series recorded on 23 patients who underwent TAMI revascularization during a seven-month period in 2012, demonstrating the feasibility and safety of the TAMI technique. Eighty-three percent had Rutherford Classification IV-VI. Ultrasound guidance aided all tibial access. Demographics, vascular symptoms, disease characteristics, success, procedure length, time to discharge, immediate and 30-day complications were collected. Comparison was sought with 201 unmatched patients treated via traditional CFA access over a similar period. RESULTS: Arterial access was successful in all patients. Thirty-six lesions were treated. Lesion success (ability to cross lesion and achieve post treatment stenosis <30%) was achieved in 95% of patients. 25% of lesions were above the knee. Average prestenosis was 92.5%; average poststenosis 12%. No major complications were noted. Two patients presented within 30 days with access site pain. Access site peroneal artery pseudo-aneurysms were diagnosed and treated percutaneously with covered stents. Both recovered with no sequelae. CONCLUSION: Retrograde tibio-pedal intervention appears to be safe and effective. The TAMI technique offers an alternate revascularization method for critically ill advanced PAD patients.

Utility and feasibility of ultrasound-guided access in patients with critical limb ischemia.

BACKGROUND: Patients with advanced peripheral vascular disease (PVD) and critical limb ischemia (CLI) require immediate revascularization to improve blood flow and prevent amputation. Vascular, and especially tibial, access is arguably a very important part of the procedure. Utilization of ultrasound (US) guidance to access the peripheral vessels will maximize success and decrease the risk of complications. METHODS: This is a retrospective analysis of patients admitted to our institution between 2010 and 2011. Eighty-six patients with 191 lesions underwent revascularization for advanced PVD and CLI. US guidance was utilized to access the vascular bed in an antegrade or retrograde fashion in 100% of these patients. Data collected included success rate and time to access using US. Immediate in hospital and 30 day outcomes were also documented. RESULTS: The average age of patients was 69.8 years, with 69.7% male patients. All tibial access (33.7%) was obtained under US guidance. Obtaining vascular access using US was achieved in 95.3% of patients. At discharge, access site complications were limited to one patient (1.1%) with a pseudoaneurysm; no access complications related to the tibial vessels. At 30 days, there was one major amputation (1.1%) and one vascular access complication (1.1%). CONCLUSION: US guided access is a feasible and safe procedure that can aid in accessing vascular conduits in patients with CLI. Applying this technique across the board in CLI patients decreases the risk of immediate complications and facilitates accessing tibial arteries.

Utilization Rates of Diagnostic and Therapeutic Vascular Procedures Among Patients Undergoing Lower Extremity Amputations in a Rural Community Hospital: A Clinicopathological Correlation.

BACKGROUND: Significant geographical variations exist in amputation rates and utilization of diagnostic and therapeutic vascular procedures before lower extremity amputations in the United States. The purpose of this study was to evaluate the rates of diagnostic and therapeutic vascular procedures in the year prior to amputation in a contemporary population and correlate with pathological findings of the amputation specimens. METHODS: A retrospective analysis was conducted of non-traumatic amputations from 2011 to 2017 at a rural community hospital. We reviewed the proportion of patients undergoing diagnostic (ankle brachial index with duplex ultrasound, computerized tomography angiogram and invasive angiogram) and therapeutic (endovascular and surgical revascularization) vascular procedures in the year prior to amputation. Prevalence of tissue viability and osteomyelitis were evaluated in all amputated specimens and atherosclerotic vascular disease (ASVD) was evaluated in major amputations. We also analyzed primary amputation rates among different subgroups. RESULTS: 698 patients were included with 248 (36%) major amputations and 450 (64%) minor amputations. Any diagnostic procedure was performed in 59% of the major amputations and 49% of the minor amputations (P = 0.01). Any therapeutic revascularization procedure was performed in 34% of the major amputations and 28% of the minor amputations (P = 0.08). The pathology of major amputation specimens revealed severe ASVD in 57% and mild-moderate ASVD in 27% of specimens. Tissue viability was significantly higher in major amputations (90% vs 30%, P = 0.04) and osteomyelitis was significantly higher in minor amputations (50% vs 14%, P = 0.03). Primary amputations were performed in 66% of major amputations, 72% of minor amputations, 81% with mild to moderate ASVD and 54% with severe ASVD. CONCLUSION: Diagnostic and therapeutic vascular procedures appear under-utilized for patients undergoing lower extremity amputations at a rural community hospital. ASVD rates and tissue viability imply that revascularization could be of significant benefit to avoid major amputation.

Can an elderly woman's heart be too strong? Increased mortality with high versus normal ejection fraction after an acute coronary syndrome. The Global Registry of Acute Coronary Events.

BACKGROUND: Coronary artery disease is the leading cause of death in women. We sought to validate previous clinical experience in which we have observed that elderly women with a very high left ventricular ejection fraction (LVEF) are at increased risk of death compared with elderly women with acute coronary syndromes with a normal LVEF. METHODS: Data from 5,127 elderly female patients (age >65 years) enrolled in the Global Registry of Acute Coronary Events were collected. Patients were divided into 3 groups based on their LVEF: group I had a low ejection fraction (<55%), group II had a normal ejection fraction (55%-65%), and group III had a high ejection fraction (>65%). χ² test and multiple logistic regression analysis were performed. The main outcome measures were death in-hospital and death, stroke, rehospitalization, and myocardial infarction at 6-month follow-up. RESULTS: Hospital mortality was 12% in group I. Patients in group III were more likely to die in-hospital than those in group II (P = .003). Multivariable logistic regression showed that high ejection fraction was an independent predictor of hospital death (odds ratio [OR] 2.5, 95% CI [CI] 1.2-5.2, P = .01), 6-month death (OR 2.0, 95% CI 1.1-3.4, P = .01), and cardiac arrest/ventricular fibrillation (OR 2.5, 95% CI 1.2-5.0, P = .01) compared with the normal ejection fraction group. CONCLUSIONS: Having a very high LVEF (> 65%) is associated with worse survival and higher rates of sudden cardiac death than an LVEF considered to be in the reference range.

Intravascular Ultrasound Imaging Versus Digital Subtraction Angiography in Patients with Peripheral Vascular Disease.

OBJECTIVES: The evaluation of arterial plaque morphology and vessel diameter is a vital component of peripheral vascular interventions. Historically, digital subtraction angiography (DSA) has been considered the gold standard for vessel sizing and treatment. However, this modality has the limitation of providing a two-dimensional image of a three-dimensional luminal structure. Utilization of intravascular ultrasound (IVUS) has been incorporated into diagnostic and treatment algorithms to further characterize the arterial vessel. This study compared visual estimation of vessel diameter by angiographic imaging with IVUS measurements. METHODS: A retrospective analysis was conducted on a cohort of 43 patients who underwent an endovascular intervention utilizing DSA and IVUS imaging. Angiographic measurements were determined by an interventionalist blinded to the IVUS findings. RESULTS: Of the 43 patients, 58% were male, the majority (72%) were ages 60-89 years, 58% were Rutherford classification III, and 42% had critical limb ischemia (Rutherford classification IV or V). Arterial access sites were common femoral, posterior tibial, and anterior tibial in 37%, 37%, and 26%, respectively. Tibiopedal arterial minimally invasive (TAMI) retrograde revascularization was utilized in 63% of patients. Vessel sizing was consistently the same or smaller for female subjects with either imaging modality. Overall, measurements estimated from angiographic images were significantly smaller than those obtained from IVUS analysis. CONCLUSION: IVUS appears to offer a greater degree of accuracy in measuring arterial lumen diameter. As measurements obtained from angiographic imaging consistently under-estimated vessel size, utilization of IVUS may aid in the determination of treatment algorithms and lead to improved endovascular outcomes.

Lower extremity revascularization via endovascular and surgical approaches: A systematic review with emphasis on combined inflow and outflow revascularization.

This review is intended to help clinicians and patients understand the present state of peripheral artery disease, appreciate the progression and presentation of critical limb ischemia/chronic limb-threatening ischemia, and make informed decisions regarding inflow and outflow endovascular revascularization and surgical treatment options within the context of current debates in the medical community. A controlled literature search was performed to obtain research on outcomes of critical limb ischemia patients undergoing complete leg revascularization for peripheral artery disease inflow and outflow disease. Data for this review were identified by queries of medical and life science databases, expert referral, and references from relevant papers published between 1997 and 2019, resulting in 48 articles. The literature review herein indicates that endovascular revascularization-including ballooning, stenting, and atherectomy-is an effective peripheral artery disease therapy for both above the knee and below the knee disease, and can safely and effectively treat both inflow and outflow disease. As such, it plays a leading role in the therapy of lower extremity artery disease.

One-Year Outcomes of Peripheral Endovascular Device Intervention in Critical Limb Ischemia Patients: Sub-Analysis of the LIBERTY 360 Study.

BACKGROUND: High-risk patients with advanced peripheral artery disease (PAD), including critical limb ischemia (CLI), are often excluded from peripheral endovascular device intervention clinical trials, leading to difficulty in translating trial results into real-world practice. There is a need for prospectively assessed studies to evaluate peripheral endovascular device intervention outcomes in CLI patients. METHODS: LIBERTY 360 is a prospective, observational, multi-center study designed to evaluate the procedural and long-term clinical outcomes of peripheral endovascular device intervention in real-world patients with symptomatic lower-extremity PAD. One thousand two hundred and four patients were enrolled and stratified based on Rutherford Classification (RC): RC2-3 (N=501), RC4-5 (N=603), and RC6 (N=100). For this sub-analysis, RC5 and RC6 patients (RC5-6; N=404) were pooled and 1-year outcomes were assessed. RESULTS: Procedural complications rarely (1.7%) resulted in post-procedural hospitalization and 89.1% of RC5-6 patients were discharged to home. Considering the advanced disease state in RC5-6 patients, there was a high freedom from 1-year major adverse event rate of 65.5% (defined as target vessel revascularization, death to 30 days, and major target limb amputation). At 1 year, freedom from major amputation was 89.6%. Wounds identified at baseline on the target limb had completely healed in 172/243 (70.8%) of the RC5-6 subjects by 1 year. Additionally, the overall quality of life, as measured by VascuQoL, improved from baseline to 1 year. CONCLUSION: LIBERTY investigated real-world PAD patients with independent oversight of outcomes. This analysis of LIBERTY RC5-6 patients demonstrates that peripheral endovascular device intervention can be successful in CLI patients, with low rates of major amputation and improvement in wound healing and quality of life through 1-year follow-up.LIBERTY 360, https://clinicaltrials.gov/ct2/show/NCT01855412, ClinicalTrials.gov Identifier: NCT01855412.

Interim Results of the PROMISE I Trial to Investigate the LimFlow System of Percutaneous Deep Vein Arterialization for the Treatment of Critical Limb Ischemia.

OBJECTIVE: To investigate the feasibility, safety, and effectiveness of the LimFlow stent-graft system in performing percutaneous deep vein arterialization (pDVA) for treatment of critical limb ischemia (CLI) patients ineligible for conventional endovascular or surgical revascularization procedures. METHODS: Ten no-option CLI patients (mean age, 67 ± 11 years; 30% women) were enrolled. All patients were classified as Rutherford class 5 or 6 and were deemed by a committee of experts to be ineligible for endovascular or surgical procedures to restore blood flow. Eighty percent were categorized as stage 4 (high risk of amputation) based on Society for Vascular Surgery wound, ischemia, and foot infection (SVS WIfI) scoring index. The primary safety endpoint was amputation-free survival (AFS) at 30 days. A secondary safety endpoint evaluated AFS at 6 months. Other secondary endpoints included primary patency, wound healing, and technical success. RESULTS: Amputation-free survival was achieved in 100% of patients, with no deaths or index limb above-ankle amputations observed at 30 days and 6 months. Technical success rate was 100%. No procedural complications were reported. Primary patency rates at 1 month and 6 months were 90% and 40%, respectively, with reintervention performed in 30% of patients. By 6 months, 30% of patients experienced complete (100%) wound healing, half of patients had 84%-93% wound healing, and 20% of patients experienced 60% healing. CONCLUSION: pDVA using the LimFlow system is a novel approach for treating patients with no-option CLI and may reduce amputation in this population for whom it would otherwise be considered inevitable. Initial findings from this early feasibility trial are promising and additional study is warranted.

Orbital atherectomy for calcified femoropopliteal lesions: a current review.

The orbital atherectomy system is a novel form of atherectomy that uses orbital sanding and pulsatile forces, an effective method of treatment for peripheral atherosclerotic lesions with varying levels of occlusion. Although the devices only has a general indication from the FDA to treat atherosclerotic lesions, they are effective in treating all kinds of lesions, and can therefore mitigate effects of all severities of peripheral artery disease. This approach to endovascular therapy involves the use of differential sanding to preferentially ablate fibrous, fibrofatty and calcified lesions, while deflecting healthy intima away from the crown. The eccentrically mounted crown design allows the device to employ rhythmic pulsating forces that penetrate the medial layer, and cause cracking in the lesions in order to facilitate easier balloon inflation and intravascular drug elution. The combination of vessel modification and lumen enlargement through sanding can effectively restore blood flow to the extremities, and can eliminate risk of critical limb ischemia, as well as subsequent amputation. Extensive lab testing and clinical trials have confirmed the high success rates and low major adverse events associated with this form of treatment. The device is economically viable as well, since its cost is offset by the lower frequency of adjunctive therapy sessions when compared to other devices. Considering the results outlined in this manuscript, the Diamondback 360° is an effective form of atherectomy therapy for peripheral artery disease. In-depth understanding of the operation preparation, procedure, and best imaging techniques can help to optimize outcomes.

Drug-Coated vs Uncoated Percutaneous Transluminal Angioplasty in Infrapopliteal Arteries: Six-Month Results of the Lutonix BTK Trial.

OBJECTIVES: We hypothesized that a drug-coated balloon (DCB) could improve treatment efficacy while maintaining safety when compared with percutaneous transluminal angioplasty (PTA) for the treatment of atherosclerotic infrapopliteal arterial lesions. METHODS: A total of 442 patients with angiographically significant lesions were randomized (2:1) to DCB or PTA. The primary safety and efficacy endpoints were freedom from major adverse limb events and perioperative death (MALE-POD) at 30 days, and freedom from vessel occlusion, clinically driven target-lesion revascularization (CD-TLR), and above-ankle amputation measured at 6 months. Success was achieved if safety between groups was non-inferior (margin 12%), and efficacy was statistically significant either for the overall intention-to treat (ITT) or the proximal-segment DCB groups (ie, the proximal two-thirds of the below-knee arterial pathways). RESULTS: Freedom from MALE-POD for the DCB group (99.3%) was non-inferior to PTA (99.4%; non-inferiority P<.001). Proportional analysis of the primary efficacy endpoint was statistically significant for the proximal-segment DCB group (76%) vs PTA (62.9%; one-sided P<.01; Bayesian P-value for success of .0085) while not statistically significant for the overall ITT group (74.5% for DCB vs 63.5% for PTA; one-sided P=.02). Kaplan-Meier analyses demonstrated superior efficacy for DCB in both the overall ITT and proximal-segment groups at 6 months. Primary patency and CD-TLR, hypothesis-tested secondary endpoints, were also statistically better for the DCB group compared with PTA at 6 months (one-sided P<.025). CONCLUSIONS: DCB treatment for symptomatic infrapopliteal arterial lesions produced non-inferior safety at 30 days and a statistically significant difference in the primary efficacy endpoint when compared with PTA at 6 months.

Histopathologic Characterization of Peripheral Arteries in Subjects With Abundant Risk Factors: Correlating Imaging With Pathology.

OBJECTIVES: The aim of this study was to comprehensively evaluate the pathology of the lower extremity arteries across their entire length in subjects dying with abundant risk factors and to evaluate the clinical and imaging implications of the pathological characteristics. BACKGROUND: Lower extremity peripheral arterial disease is a major cause of cardiovascular morbidity, but a systematic characterization of the pathology has never been undertaken. METHODS: Twelve legs were obtained from 8 cadavers with histories of coronary risk factors (median age 82 years, 6 men); 8 of 12 legs were evaluated using computed tomography before the major peripheral arteries were dissected along their entire length. Dissected arteries were cut serially at 3 to 4 mm, and a total of 2,987 sections were examined. RESULTS: Luminal irregularities and stenosis were more commonly seen in computed tomography images of above-the-knee (AK) arteries. Atherosclerotic lesions were histologically confirmed and were more common in AK (95.7%) than below-the-knee (BK) (56.8%) arteries. Occluded vessels were observed at 18 sites, including 8 AK and 10 BK arteries. Pathologically, acute thrombus was observed in all 8 AK sites, of which 3 were associated with plaque rupture and 5 were related to calcified nodules. The 10 occluded BK arteries revealed chronic total occlusions, of which one-half were embolic in origin and one-half were associated with atherosclerotic lesions. Intimal (75.3%) and medial (86.2%) calcifications were commonly encountered. Proportionate to the neointimal atherosclerosis, intimal calcification was more severe in AK arteries; the severity of medial calcification was no different between AK and BK arteries. Calcification was significantly greater in arteries excised from subjects with compared with those without diabetes. CONCLUSIONS: Atherosclerosis occurs more commonly in AK arteries and luminal occlusion from acute thrombosis secondary to rupture or calcified nodules. BK occlusion was chronic in nature, and at least one-half of lesions were embolic in origin. Medial calcification was similarly common in AK and BK arteries but more prevalent in subjects with diabetes.