Jason Q. Alexander

Evaluation of Cell Therapy on Exercise Performance and Limb Perfusion in Peripheral Artery Disease: The CCTRN PACE Trial (Patients with Intermittent Claudication Injected with ALDH Bright Cells)

Background: Atherosclerotic peripheral artery disease affects 8% to 12% of Americans >65 years of age and is associated with a major decline in functional status, increased myocardial infarction and stroke rates, and increased risk of ischemic amputation. Current treatment strategies for claudication have limitations. PACE (Patients With Intermittent Claudication Injected With ALDH Bright Cells) is a National Heart, Lung, and Blood Institute–sponsored, randomized, double-blind, placebo-controlled, phase 2 exploratory clinical trial designed to assess the safety and efficacy of autologous bone marrow–derived aldehyde dehydrogenase bright (ALDHbr) cells in patients with peripheral artery disease and to explore associated claudication physiological mechanisms. Methods: All participants, randomized 1:1 to receive ALDHbr cells or placebo, underwent bone marrow aspiration and isolation of ALDHbr cells, followed by 10 injections into the thigh and calf of the index leg. The coprimary end points were change from baseline to 6 months in peak walking time (PWT), collateral count, peak hyperemic popliteal flow, and capillary perfusion measured by magnetic resonance imaging, as well as safety. Results: A total of 82 patients with claudication and infrainguinal peripheral artery disease were randomized at 9 sites, of whom 78 had analyzable data (57 male, 21 female patients; mean age, 66±9 years). The mean±SEM differences in the change over 6 months between study groups for PWT (0.9±0.8 minutes; 95% confidence interval [CI] −0.6 to 2.5; P=0.238), collateral count (0.9±0.6 arteries; 95% CI, −0.2 to 2.1; P=0.116), peak hyperemic popliteal flow (0.0±0.4 mL/s; 95% CI, −0.8 to 0.8; P=0.978), and capillary perfusion (−0.2±0.6%; 95% CI, −1.3 to 0.9; P=0.752) were not significant. In addition, there were no significant differences for the secondary end points, including quality-of-life measures. There were no adverse safety outcomes. Correlative relationships between magnetic resonance imaging measures and PWT were not significant. A post hoc exploratory analysis suggested that ALDHbr cell administration might be associated with an increase in the number of collateral arteries (1.5±0.7; 95% CI, 0.1–2.9; P=0.047) in participants with completely occluded femoral arteries. Conclusions: ALDHbr cell administration did not improve PWT or magnetic resonance outcomes, and the changes in PWT were not associated with the anatomic or physiological magnetic resonance imaging end points. Future peripheral artery disease cell therapy investigational trial design may be informed by new anatomic and perfusion insights. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01774097.Background: Atherosclerotic peripheral artery disease affects 8% to 12% of Americans >65 years of age and is associated with a major decline in functional status, increased myocardial infarction and stroke rates, and increased risk of ischemic amputation. Current treatment strategies for claudication have limitations. PACE (Patients With Intermittent Claudication Injected With ALDH Bright Cells) is a National Heart, Lung, and Blood Institute–sponsored, randomized, double-blind, placebo-controlled, phase 2 exploratory clinical trial designed to assess the safety and efficacy of autologous bone marrow–derived aldehyde dehydrogenase bright (ALDHbr) cells in patients with peripheral artery disease and to explore associated claudication physiological mechanisms. Methods: All participants, randomized 1:1 to receive ALDHbr cells or placebo, underwent bone marrow aspiration and isolation of ALDHbr cells, followed by 10 injections into the thigh and calf of the index leg. The coprimary end points were change from baseline to 6 months in peak walking time (PWT), collateral count, peak hyperemic popliteal flow, and capillary perfusion measured by magnetic resonance imaging, as well as safety. Results: A total of 82 patients with claudication and infrainguinal peripheral artery disease were randomized at 9 sites, of whom 78 had analyzable data (57 male, 21 female patients; mean age, 66±9 years). The mean±SEM differences in the change over 6 months between study groups for PWT (0.9±0.8 minutes; 95% confidence interval [CI] −0.6 to 2.5; P =0.238), collateral count (0.9±0.6 arteries; 95% CI, −0.2 to 2.1; P=0.116), peak hyperemic popliteal flow (0.0±0.4 mL/s; 95% CI, −0.8 to 0.8; P =0.978), and capillary perfusion (−0.2±0.6%; 95% CI, −1.3 to 0.9; P=0.752) were not significant. In addition, there were no significant differences for the secondary end points, including quality-of-life measures. There were no adverse safety outcomes. Correlative relationships between magnetic resonance imaging measures and PWT were not significant. A post hoc exploratory analysis suggested that ALDHbr cell administration might be associated with an increase in the number of collateral arteries (1.5±0.7; 95% CI, 0.1–2.9; P =0.047) in participants with completely occluded femoral arteries. Conclusions: ALDHbr cell administration did not improve PWT or magnetic resonance outcomes, and the changes in PWT were not associated with the anatomic or physiological magnetic resonance imaging end points. Future peripheral artery disease cell therapy investigational trial design may be informed by new anatomic and perfusion insights. Clinical Trial Registration: URL: . Unique identifier: [NCT01774097][1]. # Clinical Perspective {#article-title-36} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01774097&atom=%2Fcirculationaha%2F135%2F15%2F1417.atom

Endovascular Retrieval of Inferior Vena Cava Filter Penetrating Into Aorta: An Unusual Presentation of Abdominal Pain

Inferior vena cava filters are commonly used in patients with contraindications to or failures of treatment with anticoagulation. However, these are not without complications. Serious complications include penetration of the filter struts into adjacent structures, including the aorta. The design of permanent filters makes retrieval in the instance of life-threatening complication complex, often requiring extensive surgical exploration. Retrievable filters may be more easily removed via endovascular methods, reducing the morbidity of surgical approaches.

Hyperbaric Oxygen Treatment Outcome for Different Indications from a Single Center

BACKGROUND Hyperbaric oxygen (HBO) is used as an adjunctive therapy for a variety of indications. However, there is a lack of high-quality research evaluating HBO treatment outcomes for different indications available in the current literature. METHODS We retrospectively reviewed all patients who underwent HBO therapy at a single hyperbaric center from January 2010 to December 2013 using predetermined criteria to analyze successful, improved, or failed treatment outcomes for the following indications: chronic refractory osteomyelitis, diabetic foot ulcer, failed flap or skin graft, osteoradionecrosis, soft tissue radiation necrosis, and multiple coexisting indications. RESULTS Among the included 181 patients treated with adjunctive HBO at our center, 81.8% had either successful or improved treatment outcomes. A successful or improved outcome was observed in 82.6% of patients treated for chronic refractory osteomyelitis (n = 23), 74.1% for diabetic foot ulcer (n = 27), 75.7% for failed flap or skin graft (n = 33), 95.7% for osteoradionecrosis (n = 23), 88.1% for soft tissue radiation necrosis (n = 42), and 72.4% for multiple coexisting indications (n = 29). Among 4 patients treated for other indications, 100% of the cases were either successful or improved. CONCLUSIONS This study has provided a comprehensive outcome survey of using HBO for the previously mentioned indications at our center. It supplements the literature with more evidence to support the consideration of HBO in different indications.

An Analysis of Variables Affecting Aortic Neck Length with Implications for Fenestrated Endovascular Repair of Abdominal Aortic Aneurysm

BACKGROUND A major factor in the selection of patients for endovascular aneurysm repair (EVAR) is the character of the aortic neck, and studies suggest that many patients are treated outside of the instructions for use (IFU) criteria. By analyzing aortic neck morphology, we hope to identify factors that may influence decision making about the use of fenestrated endografts as an alternative to extending the neck limitations of traditional endografts. METHODS A retrospective analysis was completed on 111 patients who underwent computed tomography angiography (CTA) scans between May 1, 2009 and January 3, 2011 for the evaluation of abdominal aortic aneurysm (AAA). Individual characteristics of neck and aneurysm morphology were analyzed to establish whether certain factors determined suitability for EVAR with traditional nonfenestrated endografts. In considering augmented neck lengths (ANL), anatomic measurements of distance from the start of aortic dilatation to the lowest renal artery (LRA) and highest renal artery (HRA) were analyzed. Measurements were analyzed using Stata software (version 11.2; StataCorp, College Station, TX). RESULTS There were 86 men and 25 women in the patient population, with an average age of 72.9 years. In 46 patients, the proximal neck length was <15 mm, with 26 patients having neck lengths <10 mm. There was a negative relationship between AAA maximum diameter and proximal neck length (rs = -0.2237; P = 0.018), indicating that as aneurysm size increases, proximal neck length decreases. There was a significant correlation between proximal neck length and proximal neck diameter (rs = -0.2585; P = 0.006) and between proximal neck length and angle (rs = -0.2355; P = 0.013), and between proximal neck diameter and right iliac maximum diameter (rs = 0.2329; P = 0.014). Using fenestration to place an endograft above the LRA would create an ANL of >15 mm in 20 of 40 patients with aortic necks deemed too short to be eligible for EVAR using conventional infrarenal graft positioning. Extending the graft above the HRA would create an ANL of >15 mm in 36 of 40 patients. DISCUSSION In this study, 41% of patients presented with neck lengths outside that of the traditional IFU for most aortic endografts. While there was wide variation from patient to patient, there was a general correlation between increasing AAA size and aneurysms that have shorter, wider, and more angulated proximal necks. Fenestration of even 1 renal artery could substantially increase the ANL. Additional study is warranted to determine if an increase in ANL in patients with otherwise short necks will positively impact long-term EVAR outcomes.

Unique Case of Takayasu Arteritis with Severe Distal Aortic Stenosis and Iliac Thrombosis

Takayasu arteritis is a rare, chronic large vessel vasculitis of unknown etiology which predominantly affects women younger than 40 years of age. Symptoms are highly variable based on the location and extent of the stenosis, arterial occlusion, aneurysm, and thrombosis. Diagnosis is based on clinical presentation, relevant laboratory work-up, and imaging findings of wall thickening and stenosis of medium and large vessels. Management includes glucocorticoid therapy, frequently paired with adjunctive immunosuppressants, and sometimes surgical intervention in severe cases. Here, we present a unique case of Takayasu arteritis with critical distal aortic stenosis with very severe wall thickening involving the bilateral common iliac artery and leading to left iliac artery thrombosis. Based on our literature review, our article represents a very rare presentation of Takayasu arteritis with severe iliac artery thrombosis.

Arterial Embolisms and Thrombosis in Upper Extremity Ischemia

Objective: Upper extremity ischemia (UEI) is an uncommon condition that can lead to permanent disability. There is a limited understanding of the etiology, management, and outcomes of the disease. Methods: We retrospectively reviewed the charts of all patients who were diagnosed with “embolism and/or thrombosis of arteries of upper extremity” at our institution from January 2005 to December 2013. Results: Patients diagnosed with embolisms were older (P < .001), more likely to undergo thromboembolectomy (P < .001), had higher rates of hypertension (P = .001), and had longer lengths of hospital stay (P = .002). There were no significant differences in complications or mortality at 30 days and up to 1 year. Conclusion: At our center, embolism was found to be the most common etiology for UEI followed by thrombosis and stenosis. Patients presented with embolism were older, were more likely to undergo thromboembolectomy, and had higher rates of hypertension and longer hospital stays.

Evaluation of Cell Therapy on Exercise Performance and Limb Perfusion in Peripheral Artery Disease: The CCTRN Patients with Intermittent Claudication Injected with ALDH Bright Cells (PACE) Trial

Background: Atherosclerotic peripheral artery disease affects 8% to 12% of Americans >65 years of age and is associated with a major decline in functional status, increased myocardial infarction and stroke rates, and increased risk of ischemic amputation. Current treatment strategies for claudication have limitations. PACE (Patients With Intermittent Claudication Injected With ALDH Bright Cells) is a National Heart, Lung, and Blood Institute–sponsored, randomized, double-blind, placebo-controlled, phase 2 exploratory clinical trial designed to assess the safety and efficacy of autologous bone marrow–derived aldehyde dehydrogenase bright (ALDHbr) cells in patients with peripheral artery disease and to explore associated claudication physiological mechanisms. Methods: All participants, randomized 1:1 to receive ALDHbr cells or placebo, underwent bone marrow aspiration and isolation of ALDHbr cells, followed by 10 injections into the thigh and calf of the index leg. The coprimary end points were change from baseline to 6 months in peak walking time (PWT), collateral count, peak hyperemic popliteal flow, and capillary perfusion measured by magnetic resonance imaging, as well as safety. Results: A total of 82 patients with claudication and infrainguinal peripheral artery disease were randomized at 9 sites, of whom 78 had analyzable data (57 male, 21 female patients; mean age, 66±9 years). The mean±SEM differences in the change over 6 months between study groups for PWT (0.9±0.8 minutes; 95% confidence interval [CI] −0.6 to 2.5; P=0.238), collateral count (0.9±0.6 arteries; 95% CI, −0.2 to 2.1; P=0.116), peak hyperemic popliteal flow (0.0±0.4 mL/s; 95% CI, −0.8 to 0.8; P=0.978), and capillary perfusion (−0.2±0.6%; 95% CI, −1.3 to 0.9; P=0.752) were not significant. In addition, there were no significant differences for the secondary end points, including quality-of-life measures. There were no adverse safety outcomes. Correlative relationships between magnetic resonance imaging measures and PWT were not significant. A post hoc exploratory analysis suggested that ALDHbr cell administration might be associated with an increase in the number of collateral arteries (1.5±0.7; 95% CI, 0.1–2.9; P=0.047) in participants with completely occluded femoral arteries. Conclusions: ALDHbr cell administration did not improve PWT or magnetic resonance outcomes, and the changes in PWT were not associated with the anatomic or physiological magnetic resonance imaging end points. Future peripheral artery disease cell therapy investigational trial design may be informed by new anatomic and perfusion insights. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01774097.Background: Atherosclerotic peripheral artery disease affects 8% to 12% of Americans >65 years of age and is associated with a major decline in functional status, increased myocardial infarction and stroke rates, and increased risk of ischemic amputation. Current treatment strategies for claudication have limitations. PACE (Patients With Intermittent Claudication Injected With ALDH Bright Cells) is a National Heart, Lung, and Blood Institute–sponsored, randomized, double-blind, placebo-controlled, phase 2 exploratory clinical trial designed to assess the safety and efficacy of autologous bone marrow–derived aldehyde dehydrogenase bright (ALDHbr) cells in patients with peripheral artery disease and to explore associated claudication physiological mechanisms. Methods: All participants, randomized 1:1 to receive ALDHbr cells or placebo, underwent bone marrow aspiration and isolation of ALDHbr cells, followed by 10 injections into the thigh and calf of the index leg. The coprimary end points were change from baseline to 6 months in peak walking time (PWT), collateral count, peak hyperemic popliteal flow, and capillary perfusion measured by magnetic resonance imaging, as well as safety. Results: A total of 82 patients with claudication and infrainguinal peripheral artery disease were randomized at 9 sites, of whom 78 had analyzable data (57 male, 21 female patients; mean age, 66±9 years). The mean±SEM differences in the change over 6 months between study groups for PWT (0.9±0.8 minutes; 95% confidence interval [CI] −0.6 to 2.5; P =0.238), collateral count (0.9±0.6 arteries; 95% CI, −0.2 to 2.1; P=0.116), peak hyperemic popliteal flow (0.0±0.4 mL/s; 95% CI, −0.8 to 0.8; P =0.978), and capillary perfusion (−0.2±0.6%; 95% CI, −1.3 to 0.9; P=0.752) were not significant. In addition, there were no significant differences for the secondary end points, including quality-of-life measures. There were no adverse safety outcomes. Correlative relationships between magnetic resonance imaging measures and PWT were not significant. A post hoc exploratory analysis suggested that ALDHbr cell administration might be associated with an increase in the number of collateral arteries (1.5±0.7; 95% CI, 0.1–2.9; P =0.047) in participants with completely occluded femoral arteries. Conclusions: ALDHbr cell administration did not improve PWT or magnetic resonance outcomes, and the changes in PWT were not associated with the anatomic or physiological magnetic resonance imaging end points. Future peripheral artery disease cell therapy investigational trial design may be informed by new anatomic and perfusion insights. Clinical Trial Registration: URL: . Unique identifier: [NCT01774097][1]. # Clinical Perspective {#article-title-36} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01774097&atom=%2Fcirculationaha%2F135%2F15%2F1417.atom

Endoluminal Control of the Inferior Vena Cava During Resection of a Level III Tumor Thrombus Associated With Renal Cell Carcinoma: A Case Report and Review of the Literature

Removal of tumor thrombus in the inferior vena cava (IVC) associated with renal cell carcinoma (RCC) presents a surgical challenge. Traditional techniques for vena caval control and thrombectomy for level III and IV thrombi require considerable added surgical morbidity. We present a case employing an endoluminal approach using balloon occlusion for vascular control and subsequent tumor resection. We also review other minimally invasive techniques described recently in the literature and compare these techniques with our own.

Single-center experience with complex abdominal aortic aneurysms treated by open or endovascular repair using fenestrated/branched endografts

Objective: The objective of this study was to evaluate outcomes of patients with complex abdominal aortic aneurysms (cAAAs) treated with open repair (OR) or fenestrated/branched endovascular aneurysm repair (F/B‐EVAR) from a single center. Methods: A retrospective analysis of consecutive patients with cAAAs treated electively by OR or F/B‐EVAR between January 2010 and February 2017 was conducted. Demographics of the patients, cardiovascular risk factors, procedure time, number of vessels incorporated, radiation dose, estimated blood loss, intensive care unit (ICU) length of stay (LOS), and hospital LOS were recorded. End points included target vessel patency, aneurysm rupture, freedom from reintervention, and major adverse events (MAEs). Results: During this period, 153 patients (OR, 69; F/B‐EVAR, 84) underwent repair of cAAA. The majority were male (OR, 55; F/B‐EVAR, 64), with a mean age of 75.8 ± 7.6 years (F/B‐EVAR) and 71.2 ± 7.9 years (OR). Patients in the F/B‐EVAR group were more likely to be American Society of Anesthesiologists class 3 and 4 (60% vs 0%; P < .001) and had a higher median Society for Vascular Surgery/American Association for Vascular Surgery comorbidity severity score (15 vs 7; P < .001). A total of 235 vessels were targeted in the F/B‐EVAR group, with a technical success of 97.6%. Thirty‐one patients in the OR group required concomitant renal artery revascularization. Transfusion requirements (100% vs 1.2%), MAEs (40.6% vs 13.1%), procedure length (304 minutes vs 140 minutes), estimated blood loss (2246 mL vs 165 mL), ICU LOS (3 days vs 1 day), and hospital LOS (7 days vs 2 days) were higher (P < .001) in the OR group compared with the F/B‐EVAR group. The 30‐day mortality was 2.9% and 2.4% (P = .84) in the OR group and F/B‐EVAR group, respectively. Supraceliac clamp site was associated with increased incidence of postoperative renal insufficiency. A decrease in procedure time, contrast volume, fluoroscopy time, and fluoroscopy dose was noted in the F/B‐EVAR group with increasing experience even as case complexity increased. More patients were discharged home after F/B‐EVAR (97.6% vs 59.4%; P < .001). With a mean follow‐up of 31 months (F/B‐EVAR, 17 months; OR, 48 months), the rate of secondary intervention was 3.7% and 5.8% (P = NS) for F/B‐EVAR and OR, respectively. Freedom from branch instability and reintervention was 99% (95% confidence interval, 96.2%‐99.8%) and 96% (95% confidence interval, 87.1%‐98.6%), respectively. Conclusions: Results of this “real‐world” experience suggest that the use of F/B‐EVAR for the treatment of cAAAs in high‐risk surgical patients is safe and effective and has comparable short‐term results to those of low‐risk patients undergoing OR. Patients treated by F/B‐EVAR had shorter ICU and hospital LOS, lower MAEs, and faster convalescence. A decrease in procedure time and radiation dose was noted as experience was gained, even as complexity increased.

Evaluation of Cell Therapy on Exercise Performance and Limb Perfusion in Peripheral Artery DiseaseClinical Perspective: The CCTRN PACE Trial (Patients With Intermittent Claudication Injected With ALDH Bright Cells)

Background: Atherosclerotic peripheral artery disease affects 8% to 12% of Americans >65 years of age and is associated with a major decline in functional status, increased myocardial infarction and stroke rates, and increased risk of ischemic amputation. Current treatment strategies for claudication have limitations. PACE (Patients With Intermittent Claudication Injected With ALDH Bright Cells) is a National Heart, Lung, and Blood Institute–sponsored, randomized, double-blind, placebo-controlled, phase 2 exploratory clinical trial designed to assess the safety and efficacy of autologous bone marrow–derived aldehyde dehydrogenase bright (ALDHbr) cells in patients with peripheral artery disease and to explore associated claudication physiological mechanisms. Methods: All participants, randomized 1:1 to receive ALDHbr cells or placebo, underwent bone marrow aspiration and isolation of ALDHbr cells, followed by 10 injections into the thigh and calf of the index leg. The coprimary end points were change from baseline to 6 months in peak walking time (PWT), collateral count, peak hyperemic popliteal flow, and capillary perfusion measured by magnetic resonance imaging, as well as safety. Results: A total of 82 patients with claudication and infrainguinal peripheral artery disease were randomized at 9 sites, of whom 78 had analyzable data (57 male, 21 female patients; mean age, 66±9 years). The mean±SEM differences in the change over 6 months between study groups for PWT (0.9±0.8 minutes; 95% confidence interval [CI] −0.6 to 2.5; P=0.238), collateral count (0.9±0.6 arteries; 95% CI, −0.2 to 2.1; P=0.116), peak hyperemic popliteal flow (0.0±0.4 mL/s; 95% CI, −0.8 to 0.8; P=0.978), and capillary perfusion (−0.2±0.6%; 95% CI, −1.3 to 0.9; P=0.752) were not significant. In addition, there were no significant differences for the secondary end points, including quality-of-life measures. There were no adverse safety outcomes. Correlative relationships between magnetic resonance imaging measures and PWT were not significant. A post hoc exploratory analysis suggested that ALDHbr cell administration might be associated with an increase in the number of collateral arteries (1.5±0.7; 95% CI, 0.1–2.9; P=0.047) in participants with completely occluded femoral arteries. Conclusions: ALDHbr cell administration did not improve PWT or magnetic resonance outcomes, and the changes in PWT were not associated with the anatomic or physiological magnetic resonance imaging end points. Future peripheral artery disease cell therapy investigational trial design may be informed by new anatomic and perfusion insights. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01774097.Background: Atherosclerotic peripheral artery disease affects 8% to 12% of Americans >65 years of age and is associated with a major decline in functional status, increased myocardial infarction and stroke rates, and increased risk of ischemic amputation. Current treatment strategies for claudication have limitations. PACE (Patients With Intermittent Claudication Injected With ALDH Bright Cells) is a National Heart, Lung, and Blood Institute–sponsored, randomized, double-blind, placebo-controlled, phase 2 exploratory clinical trial designed to assess the safety and efficacy of autologous bone marrow–derived aldehyde dehydrogenase bright (ALDHbr) cells in patients with peripheral artery disease and to explore associated claudication physiological mechanisms. Methods: All participants, randomized 1:1 to receive ALDHbr cells or placebo, underwent bone marrow aspiration and isolation of ALDHbr cells, followed by 10 injections into the thigh and calf of the index leg. The coprimary end points were change from baseline to 6 months in peak walking time (PWT), collateral count, peak hyperemic popliteal flow, and capillary perfusion measured by magnetic resonance imaging, as well as safety. Results: A total of 82 patients with claudication and infrainguinal peripheral artery disease were randomized at 9 sites, of whom 78 had analyzable data (57 male, 21 female patients; mean age, 66±9 years). The mean±SEM differences in the change over 6 months between study groups for PWT (0.9±0.8 minutes; 95% confidence interval [CI] −0.6 to 2.5; P =0.238), collateral count (0.9±0.6 arteries; 95% CI, −0.2 to 2.1; P=0.116), peak hyperemic popliteal flow (0.0±0.4 mL/s; 95% CI, −0.8 to 0.8; P =0.978), and capillary perfusion (−0.2±0.6%; 95% CI, −1.3 to 0.9; P=0.752) were not significant. In addition, there were no significant differences for the secondary end points, including quality-of-life measures. There were no adverse safety outcomes. Correlative relationships between magnetic resonance imaging measures and PWT were not significant. A post hoc exploratory analysis suggested that ALDHbr cell administration might be associated with an increase in the number of collateral arteries (1.5±0.7; 95% CI, 0.1–2.9; P =0.047) in participants with completely occluded femoral arteries. Conclusions: ALDHbr cell administration did not improve PWT or magnetic resonance outcomes, and the changes in PWT were not associated with the anatomic or physiological magnetic resonance imaging end points. Future peripheral artery disease cell therapy investigational trial design may be informed by new anatomic and perfusion insights. Clinical Trial Registration: URL: . Unique identifier: [NCT01774097][1]. # Clinical Perspective {#article-title-36} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01774097&atom=%2Fcirculationaha%2F135%2F15%2F1417.atom