Assessing Mid to Long Term Amputation-Free Survival Rates in Chronic Limb-Threatening Ischemia; A Study of Hybrid Vascular Techniques

Highlights

✓

The study on chronic limb-threatening ischemia underscores the paramount importance of amputation-free survival as a critical outcome measure in vascular surgery.

✓

It highlights the efficiency of hybrid revascularization techniques for limb loss prevention as well as its role in complex wound healing.

Abstract

Introduction. Chronic limb-threatening ischemia (CLTI) is a debilitating condition characterized by inadequate blood supply to the lower extremities, often leading to tissue damage, ulcers, and limb loss. Amputation-free survival (AFS) serves as a crucial measure in evaluating interventions and managing CLTI, emphasizing limb preservation, functional restoration, and prevention of recurrent ischemic events. Objectives. This study aimed to assess mid to long term AFS in CLTI patients treated with hybrid vascular techniques. Materials and Methods. Conducted over 24 months at the Emergency Hospital of Saint Pantelimon in Bucharest, Romania, the study enrolled 62 adult CLTI patients, tracking them postoperatively. Kaplan Meyer survival curves were used to assess AFS rates. Results. Findings revealed a high prevalence of cardiovascular risk factors among participants, with most undergoing infrainguinal bypass revascularization in association with proximal and/or distal angioplasty with or without stenting. Prior to intervention, the majority of patients exhibited advanced stages of ischemia, with trophic lesions predominantly confined to the toes. Analysis of AFS revealed a decline over time, with the majority of amputations occurring within three months post-revascularization. Notably, 64.5% of patients achieved amputation free complete wound healing within the first year, with 90% of them achieving this within the first six months. Complex wounds were associated with prolonged healing. Conclusions. The study shows a 75.2% AFS rate at 24 months, highlighting the effectiveness of hybrid revascularization techniques and proper wound care in optimizing outcomes for CLTI patients.

Introduction

Chronic limb-threatening ischemia (CLTI) is a severe condition characterized by inadequate blood supply to the lower extremities, leading to tissue damage, ulcers, gangrene, and ultimately, the threat of limb loss. It poses a significant challenge in vascular medicine, affecting millions worldwide and representing a major cause of morbidity and mortality while imposing substantial burdens on healthcare systems [1]. The condition arises from advanced peripheral arterial disease, often compounded by diabetes, hypertension, and other comorbidities and it manifests with severe pain, non-healing wounds and tissue necrosis. Patients with CLTI face a myriad of challenges, including impaired mobility, chronic pain, increased risk of infection, and diminished quality of life while also facing a dire prognosis, with a high risk of major amputations and mortality [2].

Amputation-free survival (AFS) serves as a metric in assessing the effectiveness of revascularization interventions and the overall management of CLTI. It encompasses not only the preservation of the affected limb but also the restoration of functionality and the prevention of recurrent ischemic events. Achieving and maintaining amputation-free survival is paramount in preventing disability, reducing healthcare costs, and improving patient well-being [3]. Timely diagnosis and intervention are essential to halt disease progression and salvage affected limbs. Revascularization techniques, including endovascular interventions and surgical bypass grafting, aim to restore adequate blood flow to ischemic tissues, promoting wound healing and limb salvage. Moreover, interdisciplinary approaches involving wound care, medical therapy, and lifestyle modifications are integral to optimizing outcomes in CLTI patients [4]. Despite advancements in treatment modalities, challenges persist in optimizing outcomes for CLTI patients. Access to specialized care, resource limitations, and patient factors can impact treatment efficacy and amputation-free survival rates [5]. Chronic limb-threatening ischemia represents a complex vascular disorder, posing significant challenges to patients, clinicians, and healthcare systems. Amputation-free survival serves as a critical endpoint in evaluating the success of interventions and guiding treatment strategies. By prioritizing limb preservation and optimizing vascular health, we can mitigate the devastating consequences of CLTI and enhance patients’ overall well-being and longevity.

Our objective was to assess the mid to long term amputation free survival rate for patients with chronic limb-threatening ischemia treated by hybrid techniques.

Materials and Methods

An observational study took place at the Emergency Hospital of Saint Pantelimon in Bucharest, Romania, from 2019 to 2022. This study enrolled 62 adult patients diagnosed with CLTI treated by hybrid vascular techniques (either infrainguinal bypass or common femoral thromboendarterectomy associated with distal and/or proximal balloon angioplasty with or without stenting) who were followed postoperatively for a period of 24 months. Standard follow-up appointments were scheduled at 3, 6, 12, and 24 months after revascularization.

Data collection took place both before revascularization and during follow-up examinations thereafter. Upon admission, general demographics, risk factors, and associated morbidities were evaluated. The incidence of subsequent minor and major amputations was closely monitored as the primary endpoint of this study. Minor amputations are defined as below the ankle amputations and major amputations include transtibial and transfemoral amputations.

We included adult patients diagnosed with CLTI presenting trophic ulcers or gangrene, with disease staging following international standards by using the Fontaine and WIFi classifications. The patients enrolled in this study also demonstrated effective communication and decision-making abilities and lacked any other documented conditions that significantly impaired their mobility such as paralysis, spinal cord injury, multiple sclerosis, cerebral palsy, et cetera.

Data analysis utilized the Kaplan-Meier survival function for assessing AFS. It’s important to acknowledge that the collected data only pertains to moderate to high-risk patients who underwent hybrid revascularization techniques, which could introduce bias.

Approval for this study was granted by the research ethics committee of the Emergency Hospital of Saint Pantelimon in Bucharest, Romania.

Results

The average age was 74.5 years, with significantly more male participants. There was a high prevalence of cardiovascular risk factors and pre-existing conditions, most notably hypertension (82.3%), dyslipidemia (77.4%), smoking (69.4%) and diabetes (48.4%). All patients were classified as Fontaine stage IV at admission and more than two thirds underwent infrainguinal bypass revascularization with associated transluminal angioplasty with or without stenting. Detailed demographics, associated morbidities and risk factors can be found in

Table 1. General demographics, associated morbidities and risk factors (n = 62).

.

Prior to revascularization, patients were classified using the WIFi system to estimate amputation risk and revascularization benefit (

Table 2. WIFi classification - Estimate risk of amputation at 12 months in the absence of treatment.

and

Table 3. WIFi classification - Revascularization benefit.

). Out of our 62 patients with trophic lesions, 71% were at a high risk of amputation without treatment, 27.4% had a moderate risk, and only one patient was deemed to have a low risk. More than three-quarters exhibited advanced stages of ischemia, with 16.1% showing moderate ischemia and 6.5% demonstrating mild ischemia. The majority of patients had trophic lesions confined to their toes, while another 12.9% had extensive lesions on the forefoot. In 9.7% of cases, lesions were severe, extending to the ankle joint or heel. A significant benefit from revascularization was anticipated for the vast majority of patients, while a moderate benefit was expected for the remaining 6.4%. No patients fell into the categories of minor or minimal benefit.

We tracked limb amputation-free survival in our patients and found that the majority required amputations before the 3-month mark, leaving only 83.9% (95% CI: 0.72 - 0.91) of patients free from amputation. There was a moderate decrease at the 6 and 12-month intervals to 82.2% (95% CI: 0.70 - 0.90) and 75.2% (95% CI: 0.62 - 0.84), respectively. Following this interval, a plateau phase ensued during which no additional amputations occurred (Figure 1). A total of 27 amputations were performed, including 7 major amputations and 20 minor ones. Intraoperatively, 12 amputations of one or more digits were performed in addition to the revascularization procedure, with no transtibial or transfemoral amputations conducted. The remaining 15 amputations occurred within the first year postoperatively. Of the major amputations, more than half occurred within the first 30 days following revascularization, with three more within a 12-month interval.

Among the 8 postoperative minor amputations, 3 occurred within the first month, 2 within the first 3 months, and 3 more by the end of the first year (

Table 4. Total amputations.

). The healing of trophic lesions played a crucial role in limb amputation-free survival. Of 12 limbs with amputations associating revascularization procedures, 41.7% required additional amputation. Of the remaining 50 patients with trophic lesions, 40 healed completely, representing 64.5% of the total wounds at admission (

Table 5. Healed trophic lesions.

). All remaining lesions healed completely within the first year postoperatively. More than half healed within the first 3 months, and 90% of them within the first 6 months (Figure 2). Difficult, prolonged healing was associated with complex wounds involving deep fascia, tendons, and foot joints (Figure 3 and Figure 4).

Discussions

Amputations represent a significant burden on patients, impacting them functionally, socially, and psychologically. Therefore, the primary aim of arterial vascular surgery is to prevent such procedures whenever possible. Patients afflicted with severe limb ischemia accompanied by gangrene or ulcers face a daunting amputation risk, which can soar up to 50% within the initial year without timely revascularization [6]. Major amputations, such as above or below the knee, have far-reaching implications for individuals afflicted by CLTI. Beyond the physical loss of limb, amputations engender profound psychological distress, functional impairment, and social isolation. Moreover, major amputations serve as an independent risk factor, contributing to an alarming rise in perioperative mortality by as much as 20%, with a staggering 85% mortality rate within five years [7].

The spectrum of amputation-free survival spans a range of factors, influenced by multiple independent variables. Interestingly, this metric doesn’t always align with measures of primary, secondary, or assisted patency, underscoring the complexity of vascular outcomes. Furthermore, intriguing observations reveal that certain patients with previously healed trophic lesions following revascularization may remain asymptomatic even when re-occlusion of treated segments occurs, thanks to the compensatory mechanism of collateral circulation.

To contextualize our findings, we embarked on an extensive review of relevant studies investigating amputation-free intervals among individuals grappling with critical ischemia. Our analysis sought to categorize these studies based on the modality of revascularization employed, shedding light on the efficacy and nuances of different treatment approaches. For instance, one study meticulously tracking 111 patients who underwent endovascular revascularization revealed a sobering outcome: merely 59% ± 1% retained viable limbs after the span of twelve months [8]. In a separate investigation involving a sizable cohort of 3505 patients with chronic limb-threatening ischemia, revascularization emerged as a crucial determinant of amputation-free survival. Notably, the two-year amputation-free survival rate stood at 63.7% for endovascular interventions and 67.8% for surgical interventions, suggesting a noteworthy correlation with oncological factors [9]. Adding depth to our understanding, landmark trials like the BASIL study provided invaluable insights through a randomized controlled trial involving 452 patients with infrainguinal arterial lesions treated either surgically or endovascularly. The results delineated an intricate pattern of amputation-free survival rates at various intervals, showcasing the nuanced interplay between treatment modalities and patient outcomes [10]. Furthermore, a breadth of literature underlines the pivotal role of endovascular revascularization in securing favorable amputation-free survival rates, with reports citing impressive figures such as a two-year amputation-free survival rate of 75.4% [11]. These findings are echoed by other studies, which corroborate the sustained efficacy of endovascular approaches over extended periods, underscoring their potential to mitigate the burden of critical ischemia [12,13].

In our patient cohort, we observed an amputation-free survival rate of 75.2%, mirroring and even exceeding the trends identified in existing literature. This convergence with established data reinforces the validity and generalizability of our findings, offering optimism for improved patient outcomes in the realm of arterial vascular surgery.

Wound healing in CLTI patients is crucial for improving AFS and is influenced by multiple factors, including impaired perfusion, tissue hypoxia, inflammation, infection, and comorbidities such as diabetes and renal disease [14,15]. The compromised blood flow to the affected limb impedes the delivery of oxygen, nutrients, and immune cells essential for proper wound healing, resulting in delayed or non-healing ulcers and a heightened risk of infection and amputation [16,17,18]. CLTI-associated wounds present unique challenges due to the underlying vascular pathology and the presence of multiple comorbidities. These wounds often exhibit poor granulation tissue formation, impaired epithelialization, and a protracted inflammatory phase, making them resistant to standard wound care interventions [19]. Moreover, the chronic nature of CLTI exacerbates wound complexity and diminishes the likelihood of spontaneous healing, necessitating aggressive and multidisciplinary approaches to wound management and, in some cases, not requiring revascularization [20,21]. After revascularization, wound care strategies should be tailored for each patient. Advanced wound care modalities, including negative pressure wound therapy, bioengineered skin substitutes, growth factors, and hyperbaric oxygen therapy, play a pivotal role in augmenting wound healing in CLTI patients [22,23,24,25]. These interventions aim to create a conducive wound environment, stimulate cellular proliferation and angiogenesis, and expedite tissue regeneration [18]. Furthermore, addressing comorbidities such as diabetes, hypertension, and renal insufficiency is critical for optimizing wound healing outcomes [14,26]. Glycemic control, blood pressure management, and aggressive infection control measures are integral components of a comprehensive treatment strategy aimed at mitigating risk factors and promoting wound resolution [26,27]. Future research endeavors should focus on refining diagnostic algorithms, exploring novel therapies, and addressing healthcare disparities to improve CLTI management and outcomes globally.

Conclusions

The amputation-free survival rate at 24 months was 75.2%, with over half of the major amputations occurring within the initial 30 days following revascularization. Within the first year, 64.5% of patients attained amputation-free full wound healing after revascularization, with 90% of them achieving this milestone within the first 6 months.