Page 2426 - Hematology_ Basic Principles and Practice ( PDFDrive )

2166 Part XII Hemostasis and Thrombosis

A B C D
Fig. 148.5 CONVENTIONAL CONTRAST ANGIOGRAPHY ILLUSTRATING USE OF A SELF-
EXPANDING NITINOL STENT TREATMENT OF AN OCCLUSION OF THE SUPERFICIAL
FEMORAL ARTERY. (A) Occlusion in the mid-superficial femoral artery. (B) Balloon angioplasty. (C) Stent
24
deployment in the lesion. (D) Angiogram after stent deployment (Reproduced from Thukkani and Kinlay .)

Surgical revascularization remains the gold standard for peripheral Therapeutic Angiogenesis
revascularization with the choice of operation depending on the
location of the stenosis. Options include (1) aortoiliac or aortofemoral Several clinical trials have explored the utility of angiogenic growth
reconstruction for proximal disease involving the aorta or iliofemoral factors for improvement of walking time in patients with claudication
vessels, (2) femoral-popliteal bypass (either above- or below-knee or for promotion of healing and preservation of limb viability in
popliteal) for superficial femoral artery or popliteal artery disease, and patients with CLI. Angiogenic factors investigated have included
(3) femoral-distal (tibial or peroneal) bypass for distal arterial stenosis. vascular endothelial growth factor, fibroblast growth factor, hepato-
28
Aortobiiliac or aortobifemoral bypass graft surgery for aortoiliac cyte growth factor, and hypoxia inducible factor-1α. Despite
occlusive disease (“inflow”) produces excellent long-term results with encouraging results with these agents in animal models of hind-limb
5-year patency rates ranging from 85% to 90%. Surgical treatment ischemia, none of the human studies has demonstrated a benefit of
of infrainguinal disease (“outflow”) also produces durable results, gene therapy. It is not known whether the lack of success is because
although outcomes depend on the type of bypass conduit used. Vein of the choice of gene, mode of delivery, or other factors.
grafts are the most durable; femoral-popliteal vein bypass grafts have Early data on infusion of endothelial progenitor cells (EPCs) have
an expected 5-year patency rate of approximately 66%. The 5-year been mixed. In experimental models, EPC infusion in hind-limb
patency rate for prosthetic grafts, such as polytetrafluoroethylene ischemia models promoted angiogenesis, as indicated by capillary
1
(PTFE), is lower, about 47%. Limitations of surgical interventions density, and reduced the need for amputation. Preliminary studies in
include the need for general anesthesia and the attendant risk of humans suggested that infusion of autologous CD34 cells may reduce
cardiovascular events and death associated with major noncardiac amputation rates in patients with CLI. In a pilot study, intramuscular
surgery in patients with atherosclerosis. Given the potential for injection of CD34 cells in patients with CLI was also shown to be
coexistent cardiovascular disease, preoperative assessment is important safe with a nonsignificant trend towards improved amputation-free
to identify and limit the risk of cardiovascular events in vascular survival. A meta-analysis of 12 trials showed that while there was an
surgery patients. 26 overall benefit of bone marrow–derived cell therapy, these benefits
Whereas revascularization is indicated for most patients with CLI were considerably less and nonsignificant when only placebo-
to preserve limb viability, the comparative efficacy and safety of controlled randomized trials were assessed. In fact, more recent data
endovascular revascularization and surgical reconstruction for CLI is from the placebo-controlled JUVENTAS study found that repetitive
not known. A contemporary registry has sought to evaluate the infusion of bone marrow mononuclear cells into the common femoral
comparative safety and effectiveness of surgical and endovascular artery did not reduce amputation rates in patients with severe limb
26a
interventions in patients with symptomatic PAD. The BEST-CLI ischemia not amenable to revascularization. A recent meta-analysis
Trial (Best Endovascular versus Best Surgical Therapy in Patients with reviewed the existing literature on cell-based therapies in the treat-
Critical Limb Ischemia) is an ongoing trial that is comparing the ment of critical limb ischemia and demonstrated improved amputa-
relative benefits of surgical versus endovascular treatment in this tion free survival and wound healing without significant impact on
population. 27 mortality. 29