Jihad Mustapha

Comparison of Orbital Atherectomy Plus Balloon Angioplasty vs. Balloon Angioplasty Alone in Patients With Critical Limb Ischemia: Results of the CALCIUM 360 Randomized Pilot Trial

Purpose To evaluate the role of orbital atherectomy in calcified infrapopliteal arteries in patients with critical limb ischemia compared to balloon angioplasty (BA) alone. Methods A randomized multicenter study was undertaken to evaluate short and 1-year outcomes in 50 patients (32 men; mean age 71 years, range 40–90) with confirmed calcified lesions using 1:1 randomization to the Diamondback 360° Orbital Atherectomy System followed by BA vs. BA alone. All patients had severe (≥50% stenosis) peripheral artery disease (Rutherford classification 4–6) in the popliteal, tibial, and/or peroneal arteries. The primary endpoint was defined as restoration of a normal lumen (residual stenosis ≤30%) with no bailout stenting or dissection types C through F. Scheduled follow-up visits were conducted according to a common protocol at 1, 6, and 12 months. Results Procedural success was 93.1% (27/29 lesions) for atherectomy + BA patients and 82.4% (28/34 lesions) for BA alone (p = 0.27). Bailout stenting was needed in 2 (6.9%) of the 29 atherectomy + BA lesions and in 5 (14.3%) of the 35 BA-treated lesions (p = 0.44). At 1 year, there were no amputations in either group related to the index procedure. Estimates for freedom from target vessel revascularization and all-cause mortality were 93.3% and 100% in the atherectomy + BA group vs. 80.0% (p = 0.14) and 68.4% (p = 0.01) in the BA group, respectively. Proportional hazard models evaluating survival time vs. status of residual stenosis determined a hazard ratio for major adverse events of 5.6 for patients with an acute post-procedure residual stenosis >30% (p = 0.01). Conclusion Debulking with orbital atherectomy appeared to increase the chance of reaching a desirable angioplasty result, with less acute need for bailout stenting and a higher procedure success. A negative association between procedure success and risk of serious adverse outcomes should encourage larger confirmatory studies.

Technique Optimization of Orbital Atherectomy in Calcified Peripheral Lesions of the Lower Extremities: The CONFIRM Series, A Prospective Multicenter Registry

The purpose of CONFIRM registry series was to evaluate the use of orbital atherectomy (OA) in peripheral lesions of the lower extremities, as well as optimize the technique of OA.

Stellarex drug-coated balloon for treatment of femoropopliteal disease: Twelve-month outcomes from the randomized ILLUMENATE pivotal and pharmacokinetic studies

Background: Drug-coated balloons (DCBs) are a predominant revascularization therapy for symptomatic femoropopliteal artery disease. Because of the differences in excipients, paclitaxel dose, and coating morphologies, varying clinical outcomes have been observed with different DCBs. We report the results of 2 studies investigating the pharmacokinetic and clinical outcomes of a new DCB to treat femoropopliteal disease. Methods: In the ILLUMENATE Pivotal Study (Prospective, Randomized, Single-Blind, U.S. Multi-Center Study to Evaluate Treatment of Obstructive Superficial Femoral Artery or Popliteal Lesions With A Novel Paclitaxel-Coated Percutaneous Angioplasty Balloon), 300 symptomatic patients (Rutherford class 2–4) were randomly assigned to DCB (n=200) or standard angioplasty (percutaneous transluminal angioplasty [PTA]) (n=100). The primary safety end point was freedom from device- and procedure-related death through 30 days, and freedom from target limb major amputation and clinically driven target lesion revascularization through 12 months. The primary effectiveness end point was primary patency through 12 months. In the ILLUMENATE PK study (Pharmacokinetic Study of the Stellarex Drug-Coated Angioplasty Balloon), paclitaxel plasma concentrations were measured after last DCB deployment and at prespecified times (at 1, 4, 24 hours and at 7 and 14 days postprocedure) until no longer detectable. Results: In the ILLUMENATE Pivotal Study, baseline characteristics were similar between groups: 50% had diabetes mellitus, 41% were women, mean lesion length was 8.3 cm, and 44% were severely calcified. The primary safety end point was met (92.1% for DCB versus 83.2% for PTA, P=0.025 for superiority) and the primary patency rate was significantly higher with DCB (76.3% for DCB versus 57.6% for PTA, P=0.003). Primary patency per Kaplan-Meier estimates at day 365 was 82.3% for DCB versus 70.9% for PTA (P=0.002). The rate of clinically driven target lesion revascularization was significantly lower in the DCB cohort (7.9% versus 16.8%, P=0.023). Improvements in ankle-brachial index, Rutherford class, and quality of life were comparable, but the PTA cohort required twice as many revascularizations. Pharmacokinetic outcomes showed that all patients had detectable paclitaxel levels after DCB deployment that declined within the first hour (54.4±116.9 ng/mL to 1.4±1.0 ng/mL). Conclusions: The data demonstrate superior safety and effectiveness of the Stellarex DCB in comparison with PTA, and plasma levels of paclitaxel fall to low levels within 1 hour. Clinical Trial Registration: URL: http://clinicaltrials.gov. Unique identifiers: NCT01858428 and NCT01912937.

Percutaneous Transluminal Angioplasty in Patients With Infrapopliteal Arterial Disease: Systematic Review and Meta-Analysis

Background—Contemporary outcomes of percutaneous transluminal angioplasty for the treatment of infrapopliteal atherosclerotic lesions are not well characterized. Hence, a systematic review and meta-analysis was performed to determine the safety and effectiveness of this approach in patients with advanced below-the-knee arterial disease. Methods and Results—MEDLINE and EMBASE databases were searched for contemporary studies (2005–2015) on the effects of percutaneous transluminal angioplasty for the treatment of infrapopliteal lesions. A random effects meta-analysis model was used to analyze procedural (technical success, flow-limiting dissection, provisional stent placement) and long-term (primary patency, repeat revascularization, major amputation, all-cause mortality) outcomes. Ultimately, 52 studies encompassing 6769 patients with 9399 below-the-knee lesions were included in the analysis. Technical success was 91.1% (95% confidence interval [CI], 88.8–93.0), and the incidence of flow-limiting dissections and bailout stenting was 5.6% (95% CI, 3.2–9.8) and 9.1% (95% CI, 6.3–12.9), respectively. Outcomes at 1 year were primary patency, 63.1% (95% CI, 57.3–68.6); repeat revascularization, 18.2% (95% CI, 14.5–22.6); major amputation, 14.9% (95% CI, 12.3–18.0); and all-cause mortality, 15.1% (95% CI, 12.8–17.7). Significant heterogeneity and publication bias were observed for most percutaneous transluminal angioplasty outcomes. Conclusions—Contemporary studies of the use of percutaneous transluminal angioplasty as primary treatment for patients with infrapopliteal arterial disease reveal suboptimal procedural and 1-year clinical outcomes.

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.

Midterm Outcomes From a Pilot Study of Percutaneous Deep Vein Arterialization for the Treatment of No-Option Critical Limb Ischemia:

Purpose: To report the initial clinical experience with percutaneous deep vein arterialization (PDVA) to treat critical limb ischemia (CLI) via the creation of an arteriovenous fistula. Methods: Seven patients (median age 85 years; 5 women) with CLI and no traditional endovascular or surgical revascularization options (no-option CLI) were recruited in a pilot study to determine the safety of PDVA. All patients were diabetic; 4 had Rutherford category 6 ischemia. Six were classified at high risk of amputation based on the Society for Vascular Surgery WIfI (wound, ischemia, and foot infection) classification. The primary safety endpoints were major adverse limb events and major adverse coronary events through 30 days and serious adverse events through 6 months. Secondary objectives included clinical efficacy based on outcome measures including thermal measurement, transcutaneous partial pressure of oxygen (TcPO2), clinical improvement at 6 months, and wound healing. Results: The primary safety endpoints were achieved in 100% of patients, with no deaths, above-the-ankle amputations, or major reinterventions at 30 days. The technical success rate was 100%. Two myocardial infarctions occurred within 30 days, each with minor clinical consequences. All patients demonstrated symptomatic improvement with formation of granulation tissue, resolution of rest pain, or both. Complete wound healing was achieved in 4 of 7 patients and 5 of 7 patients at 6 and 12 months, respectively, with a median healing time of 4.6 months (95% confidence interval 84–192). Median postprocedure peak TcPO2 was 61 mm Hg compared to a preprocedure level of 8 mm Hg (p=0.046). At the time of wound healing, 4 of 5 of patients achieved TcPO2 levels of >40 mm Hg. There were 2 major amputations, 1 above the knee after PDVA thrombosis and 1 below the knee for infection. Three patients died of causes unrelated to the procedure or study device at 6, 7, and 8 months, respectively. Limb salvage was 71% at 12 months. Conclusion: PDVA is an innovative approach for treating no-option CLI and represents an alternative option for the “desert foot,” potentially avoiding major amputation. Our results demonstrate its safety and feasibility, with promising early clinical results in this small cohort.

Impact of lesion location on procedural and acute angiographic outcomes in patients with critical limb ischemia treated for peripheral artery disease with orbital atherectomy: A CONFIRM registries subanalysis.

This analysis compares the procedural and acute angiographic outcomes in patients with critical limb ischemia (CLI) treated with orbital atherectomy in above‐the‐knee (ATK)/popliteal (POP) lesions versus below‐the‐knee (BTK) lesions.

Pooled Analysis of the CONFIRM Registries Impact of Gender on Procedure and Angiographic Outcomes in Patients Undergoing Orbital Atherectomy for Peripheral Artery Disease

Purpose: To compare the acute procedure and angiographic outcomes of peripheral artery disease (PAD) patients treated with orbital atherectomy stratified by gender. Methods: The CONFIRM I, II, and III registries are US multicenter, nonrandomized, all-comers registries of PAD patients who were treated with orbital atherectomy. All patients with gender specified in the registry database were included in the current analysis, which compared the final residual stenosis achieved after atherectomy and the rate of acute complications in female and male patients. The 3 registries included 3131 patients with 4761 lesions: 1261 women (mean age 73.2±10.7 years) with 1874 lesions and 1870 men (mean age 70.4±10.2) with 2887 lesions. Results: The women were older (p<0.001) and had a higher but nonsignificant prevalence of critical limb ischemia (p=0.075). After treatment, the final residual stenosis in women vs. men was 9%±11% vs. 11%±11%, respectively (p<0.001). Women had a higher rate of all types of dissection (13.3% vs. 9.9%, p<0.001). However, both genders had similar rates of flow-limiting dissections (1.6% vs. 1.4%, p=0.61), perforation, slow flow, vessel closure, spasm, embolism, and thrombus formation. Conclusion: The gender analysis of the CONFIRM registries revealed that there was successful lesion modification with orbital atherectomy in both men and women; however, women had a higher rate of dissection (all types). This difference is likely because of the older age and higher percentage of critical limb ischemia in women in this cohort. These results, however, suggest that additional studies should be completed to further understand the increased risks for women vs. men during endovascular procedures.

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.

Below-the-Knee Retrograde Access for Peripheral Interventions: A Systematic Review

Purpose: To investigate the hypothesis that interventions involving retrograde below-the-knee (BTK) vessel punctures have an acceptably low complication rate and high procedural success. Methods: A systematic review was performed of the MEDLINE and Scopus databases for articles describing the results of BTK retrograde access for peripheral interventions. Outcome measures were access success, procedure success, and complications. A predefined subgroup analysis was performed of prospective studies to reduce the influence of possible reporting bias on outcomes. Results: Nineteen articles, including 3 prospective studies, were selected, including a total of 1905 interventions in 1395 patients (mean age 69.5 years; 918 men). The BTK vessels were punctured in 1168 (61.3%) of these interventions. Access was successful in 94.0% of BTK attempts, 86.0% of all lesions were successfully crossed using a retrograde access, and 84.0% of interventions achieved technical success. Forty-eight (4.1%) distal access site complications were reported. Vessel perforations were seen in 13 (1.1%) interventions, vasospasm in 5 (0.4%), and acute distal occlusions in 5 (0.4%). Predefined subgroup analysis of prospective studies showed similar results (p=0.24). Conclusion: A retrograde approach to facilitate peripheral endovascular interventions is a safe and successful technique and should be considered when an antegrade approach is not possible or fails to cross the lesion. Because of missing data on long-term outcomes and methodological shortcomings, real world data of retrograde access in nonexpert centers remains necessary before this technique can be advised to all interventionists dealing with peripheral artery disease.