Critical Limb Ischemia

INTRODUCTION:

Critical limb ischemia (CLI) is a clinical syndrome of ischemic rest pain or tissue loss such as gangrene or ulcerations due to obstructive peripheral artery disease. Critical limb ischemia differs from acute limb ischemia, which is a sudden loss of limb perfusion (less than 14 days by definition). In contrast, critical limb ischemia occurs over weeks to months.

The Rutherford and Fontaine classification systems are used to categorize patients with peripheral artery disease.¹ The nomenclature allows clinicians to communicate the severity of illness that patients with peripheral artery disease present with. It is noteworthy that patients with critical limb ischemia represent the sickest patients with peripheral artery disease, as they are labeled as Rutherford classes 4, 5, or 6, and as Fontaine classes III, or IV.

Of great concern is that patients presenting with critical limb ischemia have a risk of major amputation (defined as above the ankle) that occurs in 30-50% of patients within 1 year without revascularization.¹ Avoiding major amputations whenever possible is paramount because major amputations are associated with significant functional limitations, and lead to increased morbidity and mortality in CLI patients. On the other hand, minor amputations (defined as toe or forefoot) are often required to treat tissue loss and usually do not limit functional independence significantly.

Despite the adverse outcomes that occur with major amputation in CLI patients, a recent study demonstrated that from 2000-2010, only 38.7% of medicare beneficiaries underwent an invasive angiogram prior to lower extremity amputation.² Because of the large number of patients that proceed to amputation without ever undergoing evaluation for revascularization, protocols to more aggressively evaluate patients for peripheral artery disease with signs of CLI have been proposed in the medical literature. An example of one such algorithm is demonstrated in the video.³ There are several important issues that this algorithm brings forth that should be highlighted.

First of all, this algorithm emphasizes the need to visually define the extent of peripheral artery disease in patients with poorly healing wounds or ischemic rest pain. Due to pressure amplification that can occur with stiff, or calcified arteries, ankle brachial indices are often misleading in CLI patients. A normal ankle brachial index does not rule out obstructive peripheral artery disease in these patients. In a recently published study, 25% of CLI patients referred for endovascular intervention were noted to have a normal ankle brachial index, and 19% of CLI patients referred for surgical revascularization were noted to have a normal ankle brachial index.⁴ Although, the algorithm suggests that CT angiography, MR angiography, or invasive angiography could be performed, the majority of CLI patients will require invasive angiography because the smaller infrapopliteal arteries are often suboptimally visualized using noninvasive techniques.

The second issue of importance illustrated by the algorithm is that endovascular revascularization is favored over surgical revascularization in patients presenting with CLI. Randomized studies examining the outcomes of CLI patients with endovascular versus surgical revascularization are scarce. The BASIL trial, which is considered the landmark study in the field, demonstrated similar rates of amputation-free survival during 4 years of follow up.⁵ An additional observation noted in the BASIL trial was a higher number of periprocedural complications such as myocardial infarctions, strokes, and deaths in patients treated with surgical revascularization compared to endovascular revascularization.⁵ This observation is due to the fact that many patients presenting with CLI also have concomitant advanced coronary artery disease and/or cerebrovascular disease that may not yet be diagnosed at the time they present with CLI.

The third issue of importance illustrated by the algorithm is that if the patient is initially deemed a poor candidate for endovascular revascularization, the patient’s operative risk needs to be evaluated before proceeding with surgical revascularization. As suggested above, many patients with CLI have undiagnosed, but advanced coronary artery disease and/or cerebrovascular disease that may ultimately prohibit surgical revascularization. These patients may require primary amputation. As directed by the algorithm, patients who are at a high risk for surgical complications, should be reconsidered for endovascular intervention-perhaps by a more aggressive operator. This aspect of the algorithm emphasizes the need for endovascular specialists who treat patients with CLI to perform at the highest technical level.

Finally, it should be noted that treatment algorithms for the management of patients with CLI will evolve as further research continues. The National Heart, Lung, and Blood Institute (NHLBI) sponsored BEST-CLI trial is expected to enroll approximately 2100 patients with CLI.⁶ The trial will randomize patients to endovascular or surgical revascularization, and is expected to provide the medical community with valuable new insights for the treatment of CLI patients using contemporary techniques. Of particular interest will be the knowledge that is gained regarding the hypothesis that angiosome targeted revascularization is required to achieve limb salvage. This hypothesis suggests that operators must achieve revascularization in the infrapopliteal vessel that provides blood flow directly to the area of the leg where the ulceration is located.³ Thus far, smaller studies and the experience of most proficient operators suggest that achieving single vessel runoff to the foot in any angiosomal distribution will prevent major amputations in most patients.

ADDRESSING CARDIOVASCULAR RISK IN CLI PATIENTS:

In addition to possessing the highest degree of technical skills demonstrated above, endovascular specialists caring for patients with CLI must also be mindful of the high risk of cardiovascular morbidity and mortality that is present in these patients. In general, patients with peripheral artery disease have an increased risk of death related to myocardial infarction and/or stroke that occurs in 30-50% of patients in the following 5 years.⁹ Patients presenting with critical limb ischemia, face that same level of risk in the following 1 year.⁹ Therefore, a helpful guide for physicians caring for patients with peripheral artery disease is provided with the PAD Treatment Triangle. The obvious foundation of care for these patients involves the two points at the base of the triangle. For patients with claudication, the goal of therapy is to relieve patients of their symptoms with exercise rehabilitation, pharmacologic treatment such as cilostazol, and/or revascularization. For patients with CLI, the goal of therapy is to protect the patient’s feet with aggressive wound care and revascularization (preferably with an endovascular approach). Demonstrated at the top of the PAD Treatment Triangle is the need to prevent cardiovascular morbidity and mortality because keeping these patients alive should always be the priority of the physicians caring for these patients. Although a complete discussion regarding the scientific evidence supporting the suggested strategies to prevent cardiovascular morbidity and mortaility is beyond the scope of this article, the following approaches are recommended in all patients with peripheral artery disease:

• Smoking cessation

• Antiplatelet therapy (ASA or clopidogrel)

• Cholesterol control with statins (target LDL < 70)

• Hypertension control (ACE inhibitors are preferred)

• Diabetes control (target Hgb A1C < 7.0)

• Therapeutic lifestyle changes (heart healthy diet, routine exercise)

• Annual flu shot

Additionally, patients with peripheral artery disease should be directly educated and questioned regarding any potential anginal symptoms and/or stroke symptoms at every follow up opportunity. Providers should maintain a low threshold for pursuing further evaluation of the coronary and/or carotid vasculature if any potential symptoms are reported.

CONCLUSIONS:

Critical limb ischemia is a complex medical problem that requires an aggressive multidisciplinary approach to treatment. Patients presenting with CLI have a high risk for major amputation within 1 year without revascularization. Despite the high risk for amputation, many patients in the United States undergo amputation without ever having undergone angiography to determine if they might be a candidate for revascularization. Recently published algorithms suggest anatomically defining the extent of peripheral artery disease in all patients with poorly healing wounds or ischemic rest pain. Normal ankle-brachial indices should not be used to rule out peripheral artery disease in these high risk patients. After defining the extent of peripheral artery disease in CLI patients, revascularization should be pursued, preferably with endovascular techniques, when possible. Providers should also be mindful of the high risk for cardiovascular morbidity and mortality that is present in CLI patients; strategies should be integrated into the care of CLI patients to reduce their high risk for myocardial infarction, stroke, and death.

REFERENCES

1. TASC II Working Group. Int Angiol. 2007; 26: 81-157.

2. Circ Cardiovasc Qual Outcomes. 2014; 7: 142-150.

3. Circ. Cardiovasc. Interv. 2016; 9. e001946.

4. J Am Coll Cardiol Intv. 2017: 10: 2307-16.

5. Lancet. 2005; 366: 1925-1934.

6. J Am Heart Assoc. 2016 Jul 8;5(7).

7. J Vasc Surgery. 2012; 55: 390-9.

8. J Am Coll Cardiol Intv. 2017: 10: 1344-1354.

9. Circulation. 2006: 113: e463-654.