New Horizons in Lower Limb Ischemia- Pathophysiology and Management

Lower limb ischemia (LLI) comprises acute and chronic ischemia. Acute limb ischemia is because of sudden obstruction of arteries due to embolus and thrombosis. Chronic limb ischemia is a slow progressive disease due to obliteration of arteries of the lower limb and is classified as mild, moderate, and critical. The prevalence of chronic LLI is uncommon before the age of 50 years, but it rises with age after that. Despite the improvement in care and treatment, many patients still progress to severe forms of chronic limb-threatening ischemia (CLTI) requiring major amputation. This thematic issue has six papers and covers recent development in epidemiology, pathogenesis, diagnosis, and treatment modalities of LLI, and provides future directions.

Natrajan et al have reviewed the etiology, pathology, and management of acute LLI. Acute LLI is mostly due to in situ thrombosis and cardioembolic. This is an emergency situation, and therefore diagnosis and management should be performed promptly. Initial assessment should focus on staging, severity of ischemic injury, and potential limb salvage. They have discussed the clinical clues to differentiate embolic and in situ thrombosis. Systemic heparin for anticoagulation and pain management should be initiated promptly after diagnosis. The management options include intravascular interventions, surgical bypass, and hybrid approach. Early intervention results in higher success.

Prasad and Bhanumathy have reviewed the role of advanced glycation end products (AGEs) and its cell receptor (RAGE) and soluble receptor (sRAGE) in the pathophysiology of chronic LLI (CLLI) and its treatment. Serum/plasma levels of AGE and tissue levels of RAGE are elevated, whereas the serum levels of sRAGE are reduced in CLLI subjects. AGE, RAGE, and sRAGE have been implicated in the pathogenesis of atherosclerosis. CLLI may be due to AGE–RAGE axis induced atherosclerosis. Treatment targets for CLLI should be lowering of AGE levels through reduction in dietary intake, prevention of AGE formation and degradation of AGE, suppression of RAGE expression, blocking of AGE-RAGE binding, elevation of sRAGE by upregulating expression of sRAGE and administration of sRAGE exogenously, and use of antioxidants for prevention, regression, and slowing of progression of CLLI.

Kim et al in this issue have reviewed in detail the role of lower extremity amputation in CLTI. They describe the epidemiology, indications for minor foot and major leg amputation, patient selection for major amputation in CLTI, and impact and outcome of major amputation. They concluded that despite the improvement in care and treatment, many patients still progress to severe forms of CLTI requiring major amputation. They also conclude that mortality after major amputation remains high, and highlight multiple potential areas for improvement in lower limb salvage.

Nath et al have provided a good review on the topic of transpedal approach in failed antigrade attempt of lower limb peripheral arterial disease. In their review, they describe that recently transpedal access is used routinely to revascularize suprapopliteal lesions because of its high success rate, less complication, and low cost over femoral arterial approach. They conclude that transpedal approach for the revascularization of LLI is safe and feasible, and may prove to be the preferred procedure for future revascularization of LLI.

Anand et al have provided an exceptional review on the topic of single versus multiple vessel endovascular tibial artery revascularization for critical limb ischemia. The literature shows that single vessel tibial artery revascularization has overall no significance differences in wound healing, limb salvage, and amputation -free survival compared with multivessel revascularization. Single-vessel tibial artery revascularization requires less fluoroscopy time and lower contrast dose, and has lower complication rates compared with multivessel endovascular tibial artery revascularization. They concluded that overall single vessel tibial revascularization is superior to multivessel tibial artery revascularization.

Radaiadeh and Shammas have provided a review on “When pedal access is the only way to save limb.” The prevalence of peripheral artery disease is up to 20% in general population. This develops into chronic limb ischemia in 1 to 2% of the general population. The studies by other investigators have shown that pedal access is feasible and can be performed with high success. The present authors have included three cases where pedal access was used to revascularize when there was no traditional access to achieve revascularization. Although there is a risk to the pedal artery at the access site, the benefits outweigh the risks in patients at high risk of amputation and limited alternative access. Access can be obtained either with angiographic or ultrasound guidance, and they believe that the latter is more likely to succeed particularly hibernating pedal vessels.

Publication History

Article published online:
31 August 2020