Intensifying our focus on critical limb ischemia

Abstract

Critical limb ischemia (CLI) is the most advanced clinical presentation of chronic peripheral artery disease (PAD).1,2 Compared to the overall population of PAD, patients with CLI have a dramatically higher risk of major amputation as well as overall mortality.3 CLI also accounts for more than US$20 billion in annual healthcare costs due to the medical complexity of these patients.4 With the increasing prevalence of diabetes, chronic kidney disease (CKD), and an aging population, the prevalence of CLI is expected to increase significantly in the coming decades. For these reasons, CLI has been a significant area of research and clinical advancement over the last decade. In this special issue of Vascular Medicine, leading experts in the field report important advances in the recognition, pathophysiology, and treatment of CLI. Several risk factors and disparities exist in the presentation and identification of CLI. Elbadawi and colleagues report on national trends of CLI with concomitant CKD.5 They found that the prevalence of hospitalization for CLI with CKD has increased between 2002 and 2015, and that patients with concomitant CKD have higher rates of in-hospital mortality and amputation. Interestingly, revascularization was less frequently performed in patients with CKD, but revascularization was associated with lower rates of mortality and amputation. Although diabetes is a well-established risk factor for CLI, the association between CLI prevalence and socioeconomic deprivation among patients with diabetes is less well understood.6 Hurst and colleagues investigated this question using geospatial analysis in a Scottish administrative area. They report a fiveto sevenfold difference in CLI prevalence depending on areas of socioeconomic deprivation. These results highlight the critical interaction between socioeconomic factors and CLI. Such studies will assist with both policy measures and focused health efforts to identify and risk-stratify patients with CLI. In the past year, the coronavirus disease (COVID-19) pandemic has fundamentally changed the timing and processes of care for both CLI and other time-sensitive medical conditions. Stabile and colleagues report that, during lockdown in Italy, hospital admissions for CLI decreased by 66% and the rate of amputation among hospitalized patients increased dramatically after lockdown restrictions were eased.7 These results are consistent with delayed care and subsequent presentation of more advanced disease, which was not salvageable in many cases. Clearly, COVID19 has had significant impact on the outcomes of patients with CLI who are dependent on the availability and coordination of multiple medical/surgical specialists. Calcium is a major limitation for effective treatment of CLI, and patients with CLI often have significant plaque and medial wall calcification.8 Lee et al. investigated the calcifying characteristics of vascular smooth muscle cells isolated from patients with CLI.9 They report that vascular smooth muscle cells isolated from patients with CLI had significantly increased levels of calcium formation compared to human aortic vascular smooth muscle cells. Losurdo and colleagues performed a systematic review and meta-analysis of the association of medial artery calcification with PAD severity and found that medial artery calcification was associated with higher risk of amputation, suggesting that medial artery calcification may be an important risk factor for limb-related outcomes in CLI.10 Identifying methods for interrupting the cycle of calcium development and plaque progression in CLI could be a beneficial step in modifying the disease progression of CLI. Clinical studies have also started to identify optimal treatment options for CLI. Surgical bypass in patients with CLI is often technically complex due to the need for distal targets and poor outflow. Benedetto and colleagues report on their experience with inframalleolar bypass in patients with advanced CLI.11 These findings emphasize the need to consider all available options when attempting limb salvage in CLI. Endovascular techniques and devices have also significantly advanced in the past few years. Huizing and colleagues report on the outcomes of bioresorbable scaffolds for the treatment of infrapopliteal disease, which is a promising new treatment for CLI.12 Together, these surgical and Intensifying our focus on critical limb ischemia