Cath Lab Digest

The prevalence of patients in the United States with critical limb ischemia (CLI) is estimated to be 50 to 100 per 100,000 yearly and is on the rise.1 It is estimated that within 1 year after clinical diagnosis, 30% of patients will undergo a major amputation, and 25–30% will be deceased.² CLI is associated with the presence of rest pain, tissue loss, ulcerations and gangrene of the foot or toes. Traditionally, CLI has been categorized as Rutherford Classification Stages: 3 (severe claudication) 4 (ischemic rest pain); 5 (minor tissue loss); 6 (major tissue loss).³ Patients with CLI have severe disease involving most of the tibial pedal arterial tree. Early detection and treatment of CLI can prevent amputation and save lives.

There are many associated risk factors contributing to the increasing number of patients with CLI — our aging population, obesity, diabetes and tobacco consumption being the most significant. Patients over 80 years of age are at a much higher risk for CLI due to an increased sedentary lifestyle. The continuation of tobacco consumption triples the risk of CLI, and diabetes mellitus (DM) is known to exacerbate the risk of CLI four-fold.⁴ Diabetic patients present a significant challenge for both surgical and endovascular therapy. These patients with CLI often have severe distal high-grade stenosis and chronic total occlusions (CTOs). It is well known that a diabetic patient with CLI is ten times more likely to undergo an amputation when compared to non-diabetics.⁵

Presentation

CLI presentation is becoming more widely recognized with its course of initial, predominantly nocturnal, ischemic rest pain involving the foot. Patients often complain of having to dangle their feet over the side of the bed to get pain relief. CLI often progresses to tissue loss from minor injury or trauma to the skin or nails. It is now well understood that this minor trauma can initiate a cascade of ischemic tissue loss. The tissue loss can progress into a non-healing ulcer. If the lack of blood supply continues and the tissue’s metabolic demands are not met, the ulcer progresses to gangrene. The ischemic area becomes susceptible to infection and sepsis, contributing to an increase in cardiac events and possibly death.

Diagnosis

Patient history and physical examination continue to play a pivotal role during the diagnostic work-up of CLI. Ankle-brachial pressure indices (ABI) are the standard for detection of peripheral vascular disease, but are not applicable for all patients. This is especially true in patients with DM and end-stage renal disease (ESRD) or in other patients prone to severely calcified arteries who are likely to have a falsely elevated ABI. The ABI in this subset of patients is less likely to detect occlusive tibio-pedal arterial disease, in which palpation for the pedal pulses provides accurate detection of pulsatile blood flow in the tibio-pedal arteries. Otherwise, an ABI of < 0.40 is consistent with a diagnosis of CLI.⁶

Following physical examination, precise angiographic diagnostic evaluation is a crucial step in the therapeutic algorithm during the preintervention phase. A pig-tail catheter placed in the distal aorto-iliac junction followed by contrast injection and distal runoff evaluation has been the most common method of peripheral diagnostic angiography. In CLI patients who are undergoing revascularization, the anatomical visualization and description should be obtained from a catheter placed near the target lesion (selective angiography). When comparing the selective angiography to the standard aorto-iliac runoff, it is clear that significant data regarding the tibio-pedal anatomical description can be missed when utilizing the aorto-iliac pig-tail method alone. Selective angiography is far more accurate, especially in the presence of tibio-pedal occlusive disease.

Pathophysiology

Atherosclerosis involves several highly interrelated processes including lipid disturbances, platelet activation, thrombosis, endothelial dysfunction, inflammation, oxidative stress, vascular smooth cell activation, altered matrix metabolism, remodeling and genetic factors.⁷ In early atherogenesis, recruitment of inflammatory cells and the accumulation of lipids lead to the formation of a lipid-rich core. Oxidized low-density lipoprotein (LDL) stimulates the production of chemokines and growth factors, resulting in smooth muscle cell proliferation. Oxidized LDL also stimulates the production of osteopontin, resulting in calcification. The spectrum of lesion morphology can range from fibrotic to fibrocalcific. Heavily calcified vessels are associated with extremely complex intervention as well as a higher risk of complications and therapeutic failures.

Treatment

Treatment of CLI can include endovascular therapy, surgical grafting or amputation. A large meta-analysis performed by Romiti et al⁸ on infrapopliteal angioplasty for chronic CLI indicated that percutaneous transluminal angioplasty (PTA) has become an acceptable form of treatment for patients with CLI. This meta-analysis, which reviewed endovascular and vascular surgical interventional data from 1981 to 2006, showed a transitional evolution preferential for endovascular therapy to treat CLI. Early on, patients with below-the-knee (BTK) CLI received PTA only when short proximal non-CTO tibial disease was present. Over time, the analysis demonstrated that the course of therapy had changed significantly. Operators moved toward treating long tibial disease, including CTO segments, more regularly with endovascular techniques. The positive progress of evolving CLI therapy is a necessary adaptation to the increased complexity of CLI.