Vascular Growth in Ischemic Limbs: A Review of Mechanisms and Possible Therapeutic Stimulation

Stimulation of vascular growth to treat limb ischemia is promising, and early results obtained from uncontrolled clinical trials using angiogenic agents, e.g., vascular endothelial growth factor, led to high expectations. However, negative results from recent placebo-controlled trials warrant further research. Here, current insights into mechanisms of vascular growth in the adult, in particular the role of angiogenic factors, the immune system, and bone marrow, were reviewed, together with modes of its therapeutic stimulation and results from recent clinical trials. Three concepts of vascular growth have been described to date-angiogenesis, vasculogenesis, and arteriogenesis (collateral artery growth)-which represent different aspects of an integrated process. Stimulation of arteriogenesis seems clinically most relevant and has most recently been attempted using autologous bone marrow transplantation with some beneficial results, although the mechanism of action is not completely understood. Better understanding of the highly complex molecular and cellular mechanisms of vascular growth may yet lead to meaningful clinical applications. © 2008 Annals of Vascular Surgery Inc

Limited value of digital subtraction angiography in the evaluation of cell-based therapy in patients with limb ischemia

Cell-based therapy has been proposed as a novel strategy for patients with severe peripheral arterial disease by stimulating vascular growth. In clinical studies of this therapy, the emphasis has been on demonstrating recovery of clinical parameters, rather than on evaluation of blood flow recovery. Angiography is still the gold standard for the assessment of lower leg arteries. Therefore, we studied the usefulness of angiography in the evaluation of cell-based therapy. Sixteen patients with critical leg ischemia (ischemic rest pain or ulcers), or persistent (>12 months) profound disabling claudication were unilaterally treated with autologous bone marrow-derived mononuclear cells. Pre- and 6 months post-treatment digital subtraction angiographies (DSA) were assessed and compared in a blinded fashion twice by a panel of seven vascular surgeons and interventional radiologists. Inter- and intraobserver variability on qualitative (poor/moderate/rich) and semi-quantitative (increase/no difference/decrease) assessment of collateral circulation were evaluated. Agreement was expressed inter- and intraclass correlation coefficients (CC). Inter- and intraobserver agreement was moderate for the qualitative grading of collateral extent (CC = 0.46 and 0.60, respectively). Agreement was moderate (inter-CC = 0.60) to good (intra-CC = 0.73) for comparing pre- and post-treatment DSA. Clinical response was based on limb salvage, pain-free walking distance, ankle-brachial pressure index and pain scores. No difference was observed in the extent of collateral circulation between pre- and post treatment DSA after separate analysis of clinical responding and non-responding patients (P = 0.92). DSA is not a suited modality for the evaluation of therapeutic angiogenesis.Development and application of statistical models for medical scientific researc

Limited value of digital subtraction angiography in the evaluation of cell-based therapy in patients with limb ischemia

Cell-based therapy has been proposed as a novel strategy for patients with severe peripheral arterial disease by stimulating vascular growth. In clinical studies of this therapy, the emphasis has been on demonstrating recovery of clinical parameters, rather than on evaluation of blood flow recovery. Angiography is still the gold standard for the assessment of lower leg arteries. Therefore, we studied the usefulness of angiography in the evaluation of cell-based therapy. Sixteen patients with critical leg ischemia (ischemic rest pain or ulcers), or persistent (> 12 months) profound disabling claudication were unilaterally treated with autologous bone marrow-derived mononuclear cells. Pre- and 6 months post-treatment digital subtraction angiographies (DSA) were assessed and compared in a blinded fashion twice by a panel of seven vascular surgeons and interventional radiologists. Inter- and intraobserver variability on qualitative (poor/moderate/rich) and semi-quantitative (increase/no difference/decrease) assessment of collateral circulation were evaluated. Agreement was expressed inter- and intraclass correlation coefficients (CC). Inter- and intraobserver agreement was moderate for the qualitative grading of collateral extent (CC = 0.46 and 0.60, respectively). Agreement was moderate (inter-CC = 0.60) to good (intra-CC = 0.73) for comparing pre- and post-treatment DSA. Clinical response was based on limb salvage, pain-free walking distance, ankle-brachial pressure index and pain scores. No difference was observed in the extent of collateral circulation between pre- and post treatement DSA after separate analysis of clinical responding and non-responding patients (P = 0.92). DSA is not a suited modality for the evaluation of therapeutic angiogenesis

A comparison of the Doppler-derived maximal systolic acceleration versus the ankle-brachial pressure index or detecting and quantifying peripheral arterial occlusive disease in diabetic patients

Aim The aim of this study was to assess the diagnostic accuracy of the Doppler derived maximal systolic acceleration (ACC(max)) as a novel technique for evaluating peripheral arterial occlusive disease (PAOD) in patients with diabetes mellitus, who are known for a falsely elevated ankle-brachial index (ABI). Methods. In this retrospective analysis ACC(max) was measured at ankle level in a series of 163 consecutive patients referred to the vascular laboratory for initial assessment of PAOD. Patients were classified according to the presence or absence of diabetes. In the non-diabetic patients PAOD was defined as ABI 10 m/s(2) was found to be highly predictive for the exclusion of PAOD (negative predictive value 95%). In addition, the ACC(max) cut-off value of <6.5 m/s(2) was highly predictive for the detection of PAOD (positive predictive value 99%). A strong quadratic association was found between ACC(max) and ABI in the non-diabetic group (R-2=0.85). In the diabetic patients R-2 values were 0.81 and 0.79 after ABI and TBI measurement respectively. Conclusion. DUS-derived ACC(max) an accurate marker that could offer significant benefits for the diagnosis of PAOD, especially in diabetic patients.Vascular Surger

A Systemic Evaluation of the Costs of Elective EVAR and Open Abdominal Aortic Aneurysm Repair Implies Cost Equivalence

Objective: The suggested high costs of endovascular aneurysm repair (EVAR) hamper the choice of insurance companies and financial regulators for EVAR as the primary option for elective abdominal aortic aneurysm (AAA) repair. However, arguments used in this debate are impeded by time related aspects such as effect modification and the introduction of confounding by indication, and by asymmetric evaluation of outcomes. Therefore, a re-evaluation minimising the impact of these interferences was considered.Methods: A comparative analysis was performed evaluating a period of exclusive open repair (OR; 1998-2000) and a period of established EVAR (2010-2012). Data from four hospitals in The Netherlands were collected to estimate resource use. Actual costs were estimated by benchmark cost prices and a literature review. Costs are reported at 2019 prices. A break even approach, defining the costs for an endovascular device at which cost equivalence for EVAR and OR is achieved, was applied to cope with the large variation in endovascular device costs.Results: One hundred and eighty-six patients who underwent elective AAA repair between 1998 and 2000 (OR period) and 195 patients between 2010 and 2012 (EVAR period) were compared. Cost equivalence for OR and EVAR was reached at a break even price for an endovascular device of (sic)13 190. The main cost difference reflected the longer duration of hospital stay (ward and Intensive Care Unit) of OR ((sic)11 644). Re-intervention rates were similar for OR (24.2%) and EVAR (24.6%) (p = .92).Conclusion: Cost equivalence for EVAR and OR occurs at a device cost of (sic)13 000 for EVAR. Hence, for most routine repairs, EVAR is not costlier than OR until at least the five year follow up.Vascular Surger

Saccular Abdominal Aortic Aneurysms Patient Characteristics, Clinical Presentation, Treatment, and Outcomes in the Netherlands

Objective: The aim of this was to analyze differences between saccularshaped abdominal aortic aneurysms (SaAAAs) and fusiform abdominal aortic aneurysms (FuAAAs) regarding patient characteristics, treatment, and outcome, to advise a threshold for intervention for SaAAAs.Background: Based on the assumption that SaAAAs are more prone to rupture, guidelines suggest early elective treatment. However, little is known about the natural history of SaAAAs and the threshold for intervention is not substantiated.Methods: Observational study including primary repairs of degenerative AAAs in the Netherlands between 2016 and 2018 in which the shape was registered, registered in the Dutch Surgical Aneurysm Audit (DSAA). Patients were stratified by urgency of surgery; elective versus acute (symptomatic/ruptured). Patient characteristics, treatment, and outcome were compared between SaAAAs and FuAAAs.Results: A total of 7659 primary AAA-patients were included, 6.1% (n = 471) SaAAAs and 93.9% (n = 7188) FuAAAs. There were 5945 elective patients (6.5% SaAAA) and 1714 acute (4.8% SaAAA). Acute SaAAApatients were more often female (28.9% vs 17.2%, P = 0.007) compared with acute FuAAA-patients. SaAAAs had smaller diameters than FuAAAs, in elective (53.0mm vs 61 mm, P = 0.000) and acute (68mm vs 75 mm, P = 0.002) patients, even after adjusting for sex. In addition, 25.2% of acute SaAAA-patients presented with diameters <55mm and 8.4% <45 mm, versus 8.1% and 0.6% of acute FuAAA-patients (P = 0.000). Postoperative outcomes did not significantly differ between shapes in both elective and acute patients.Conclusions: SaAAAs become acute at smaller diameters than FuAAAs in DSAA patients. This study therefore supports the current idea that SaAAAs should be electively treated at smaller diameters than FuAAAs. The exact diameter threshold for elective treatment of SaAAAs is difficult to determine, but a diameter of 45mm seems to be an acceptable threshold.Vascular Surger