Factors Influencing the Recovery of Wounds in Individuals with Peripheral Artery Disease Undergoing Below-the-knee Interventions

Gülden Güven1, Ertan Ural2, Burak Acar2

1Department of Cardiology, Başakşehir Çam ve Sakura City Hospital, İstanbul, Türkiye
2Department of Cardiology, Kocaeli University, Kocaeli, Türkiye

Keywords: Percutaneous transluminal angioplasty; periperipheral artery disease; wound healing.

Abstract

Objectives: This study aimed to explore the elements that impact the healing of wounds in patients suffering from lower limb peripheral arterial disease due to various risk factors who underwent endovascular interventions.

Methods: Conducted at the Cardiology Department of Kocaeli University from January 2015 to August 2019, the study involved 200 patients referred for endovascular revascularization due to stenosis or blockage in the infrapopliteal arteries. A retrospective analysis of medical records was performed. Patients with Burger’s disease were excluded from the study, resulting in 192 participants. Angiography and angioplasty results were reviewed, focusing on vessel conditions and outcomes of the procedures. Wound healing was assessed through follow-up records, and additional information was gathered through phone interviews with patients lacking complete data. Healing assessments occurred at least 3 months post-procedure, categorizing patients based on their healing outcomes.

Results: A comparative analysis of patient demographics and procedural details indicated that factors such as male gender, chronic kidney disease (CKD), smoking history, and lack of flow in the tibialis anterior post-procedure were significantly associated with non-healing outcomes. Multivariate analysis identified CKD, Rutherford class 6 classification, and absence of tibialis anterior flow as negative predictors for healing.

Conclusion: The study highlights that CKD, classification as Rutherford 6 before intervention, and impaired tibialis anterior flow post-procedure are significant negative indicators for wound healing in patients undergoing peripheral interventions.

Introduction

Atherosclerotic diseases are the leading cause of death and disability worldwide, creating a significant economic burden for countries.[1] Coronary artery disease (CAD) is the most common cause of death, but peripheral artery disease (PAD), kidney failure, and cerebrovascular accidents also contribute notably to morbidity and mortality.[2] PAD is among the most widespread conditions, with over 200 million cases globally.[3] Pad refers to a condition affecting blood vessels outside the heart, brain, and other isolated organs. It is characterized by the narrowing of arteries, which reduces blood flow to both the upper and lower limbs. In the lower limbs, PAD becomes an occlusive disease due to thrombosis and thromboembolic events in arteries beyond the aortic bifurcation.[4] PAD is a progressive disorder that can severely affect quality of life, increase the need for prolonged hospital stays, result in amputations, raise mortality rates, and elevate healthcare costs.[5] It is also linked to a higher incidence of cardiovascular events and deaths compared to the general population.[6] PAD is more common in older individuals and those with a greater risk for heart disease. The presence of additional risk factors, such as diabetes, hypertension (HT), high cholesterol, chronic kidney disease (CKD), and smoking, is a significant predictor of development.[5,7–9]

The key event in atherosclerosis involves thickening of the arterial wall and lipid accumulation, which leads to the formation of an atheroma. This process can result in the narrowing or blockage of the blood vessels, disrupting blood flow to vital organs. Ischemia, caused by stenosis and occlusion in arteries supplying the lower extremities, can result in intermittent claudication (pain in the legs that forces the person to stop walking), rest pain, muscle cramps, coldness, pale skin, weakened or absent pulses, numbness, weakness, a burning sensation, nail changes, ulcers, and eventually gangrene in advanced stages.[7–11] Two primary systems are used to classify the severity of PAD and guide treatment decisions. The Fontaine and Rutherford classifications (Table 1) assess how well patients can function, while the Trans-Atlantic Inter-Society Consensus (TASC) classification is used to determine the location and complexity of lesions.[2,7,12] In the 2000 and 2007 TASC I and II guidelines, lesions in the aortoiliac and femoropopliteal regions were categorized from simple to complex (TASC A, B, C, D), with endovascular treatment recommended for types A and B, and open surgery for types C and D. After 2007, advancements in imaging and angioplasty technology, along with increased clinical experience, have enabled many medical centers to treat complex lesions with endovascular procedures instead of traditional surgery. Risk factors for PAD are similar to those for CAD and atherosclerotic diseases, including smoking, dyslipidemia, diabetes, CKD, and HT. However, there is limited evidence to suggest that these risk factors have a distinct impact on specific peripheral arterial regions. Further research is needed to determine the specific factors influencing the development of disease in various areas.[13] Thus, our study aims to identify factors that affect wound healing in patients with lower-extremity peripheral arterial disease who also have risk factors and underwent endovascular treatment.

Table 1. Rutherford and Fontaine classifications

Materials and Methods

Patient Group Characteristics

Approval for this study was obtained from the Clinical Research Ethics Committee of Kocaeli University Faculty of Medicine on May 10, 2019, with project number 2019/126. The study was conducted on 200 patients who presented to the Cardiology Department of Kocaeli University between January 2015 and August 2019 with intermittent claudication (leg pain during physical activity) and critical limb ischemia (leg discomfort at rest or tissue loss) due to peripheral artery disease. These patients underwent endovascular revascularization using standard or drug-coated balloon angioplasty for narrowing or blockage in their below-knee arteries. Patient records were analyzed retrospectively. Individuals with Buerger’s disease were excluded from the study. After excluding eight patients based on exclusion criteria, 192 patients were included in the study.

We retrospectively reviewed the records of patients admitted to our hospital between January 2015 and August 2019 with lower extremity peripheral artery disease who underwent balloon angioplasty. Patients who underwent peripheral endovascular intervention in our center are routinely followed up in outpatient clinics at the 1st, 3rd, 6th, and 12th months. Follow-up records were accessed from the nucleus system archive, and wound healing progress was evaluated. Patients with incomplete information were contacted by phone to assess post-procedure wound healing. Wound healing status was checked at least 3 months after the procedures. Patients were divided into two groups based on their wound healing status after the procedure. Those who underwent early amputation post-procedure were classified as the non-healing group. Demographic data, lesion characteristics, procedural details, and follow-up outcomes were obtained from the hospital registry system. Angiography and balloon angioplasty images of the patients were recorded from the Picture Archiving and Communication System archive system. This included re-evaluating the narrowing and/or blockage in the vessels, identifying which vessels were affected, the number of vessels involved, which vessels were treated, and the success of the balloon angioplasty procedure. TASC classification was performed using all these data. Clinical evaluation during hospitalization was conducted by examining data identified and recorded according to the Rutherford classification.

Procedure Characteristics

In 182 patients, the same-side common femoral artery was used as the access site, while in 10 patients, the opposite-side common femoral artery was utilized. Before the procedure, each patient underwent a detailed medical history and complete physical examination, baseline laboratory tests were conducted, and an electrocardiogram was performed. Body mass index could not be calculated due to incomplete data in the archive system. Patients were administered 300 mg of clopidogrel and 300 mg of acetylsalicylic acid the day before the procedure. Maintenance therapy continued with 75 mg of clopidogrel and 100 mg of acetylsalicylic acid tablets in the following days. Individuals with CKD received isotonic fluid at a dose of 1 cc/ kg of body weight 24 h before the procedure, and treatment continued for at least 24 h afterward. In diagnostic images obtained by catheterizing the femoral vascular sheath or popliteal artery and injecting iodinated contrast material with the help of a pump, stenoses of 50% or more were considered significant. Percutaneous transluminal angioplasty (PTA), with or without atherectomy, was performed in cases with significant stenosis and in occluded below-knee main arterial structures whose distal section could be visualized, depending on the lesion structure. After the procedure, control angiographies were performed to evaluate lumen patency. Technical success was defined as a maximum of 30% residual stenosis after the procedure with increased blood flow. During the treatment, the catheter access site was frequently checked for hemorrhagic complications. After the procedure, patients with foot ulcers received meticulous care, regular foot dressings were performed, and medical treatment was organized.

Definitions

CAD was identified in individuals with at least 50% narrowing of the heart’s blood vessels, as determined by previous coronary imaging for any indication. Hyperlipidemia (HL) was defined as a low-density lipoprotein cholesterol level exceeding 100 mg/dL or the use of cholesterol-lowering therapy. A family history of CAD was defined by the presence of the condition in first-degree female relatives younger than 65 years or first-degree male relatives younger than 55 years. Diabetes mellitus (DM) was characterized by either treatment with insulin or oral glucose-lowering agents or a fasting blood sugar level above 126 mg/dL. CKD was identified by a glomerular filtration rate (GFR) below 60 mg/dL or routine dialysis treatment. The GFR calculation was performed using the Modification of Diet in Renal Disease formula. Body mass index was calculated by dividing body weight (kg) by the square of height (m2 ). Tobacco exposure was categorized into current smokers, former smokers, individuals who had quit, and those exposed to secondhand smoke. HT was defined as a clinic-measured blood pressure above 140/90 mmHg or ongoing antihypertensive therapy.

Statistical Analysis

Data evaluation was conducted using IBM SPSS 20.0 (IBM Corp., Armonk, NY, USA). Continuous variables were presented as mean±standard deviation, while categorical variables were summarized as frequencies and percentages. The normality of numerical data distribution was assessed using the Shapiro–Wilk test. The relationship between categorical variables was determined through chi-square analysis. The Student’s t-test was applied to compare normally distributed continuous variables. Univariate regression analysis was initially performed to identify factors independently influencing wound recovery. Variables with a p-value below 0.1 in the univariate model were included in the multivariate regression analysis. A p<0.05 was considered statistically significant for two-tailed hypothesis testing.

The study was conducted in accordance wıth the declaratıon of 31 Helsinki.

We did not use artificial intelligence–assisted technologies (such as large language models, chatbots, or image creators) in the production of submitted work.

Results

Patient Group Characteristics

A total of 192 individuals with severe leg ischemia were treated with angioplasty (with or without atherectomy) for critical narrowing in the below-knee arterial region. The distribution of patients was as follows: 38.5% (74) were female, and 61.5% (118) were male. The mean age was 67 years, ranging from 32 to 93 years. Among the patients, 80 (41.7%) were active smokers. Diabetes was present in 134 individuals (69.8%), HT in 119 patients (62%), HL in 25 patients (13%), and CAD in 96 patients (50%). CKD was identified in 52 patients (27.1%). The functional classification of patients was based on the Rutherford scale, with 149 individuals (77.6%) categorized as Rutherford 5 and 43 patients (22.4%) classified as Rutherford 6.

When comparing the two subgroups based on demographic factors, statistically significant differences were observed in male prevalence (52.2% vs. 70%, p=0.01), CKD occurrence (16.3% vs. 37%, p=0.01), and tobacco exposure (32.6% vs. 50%, p=0.01). Detailed wound recovery characteristics and subgroup demographic data are presented in (Table 2).

Table 2. Demographic characteristics of the patients

Procedure and Post-treatment Monitoring

During the examination of vascular blockages, it was observed that blood circulation was absent in the popliteal artery in 105 individuals (54.7%), in the anterior tibial artery in 171 cases (89.1%), in the posterior tibial artery in 173 subjects (90.1%), in the peroneal artery in 148 patients (77.1%), and in the distal segments in 164 cases (85.4%). Among these, 78 individuals (40.6%) exhibited a complete absence of blood supply in all lower leg arteries. The anatomical assessment was conducted following the TASC classification, identifying 10 cases (5.2%) as TASC-C and 182 cases (94.8%) as TASC-D.

Further evaluation of endovascular interventions and treatment sites revealed no significant statistical variations concerning blockage location, TASC categorization, clot removal, balloon dilation, or stent placement, and full occlusions in the infrapopliteal region. However, a notable difference was identified in the wound recovery rate in individuals undergoing vessel scraping (atherectomy) and balloon-assisted widening in the posterior tibial artery (Table 3).

Table 3. Target lesion and procedure characteristics

In follow-up imaging conducted through peripheral angiography, persistent vessel blockage was noted in 7 individuals (7%) in the popliteal artery, 52 cases (52%) in the anterior tibial artery, 63 patients (63%) in the posterior tibial artery, 40 cases (40%) in the peroneal artery, and 44 individuals (44%) in the dorsalis pedis among those who exhibited no wound improvement. A comparative evaluation was performed between individuals whose wounds healed and those who did not. No significant disparities were found apart from the anterior tibial artery findings (Table 4).

Table 4. Post-procedure evaluation

A detailed statistical model (multivariate regression) was applied to factors with p<0.1 in the initial single-variable analysis. In this advanced analysis, CKD, Rutherford stage 6 classification, and the absence of blood supply in the anterior tibial artery following the vascular intervention were identified as independent risk factors negatively impacting wound recovery (Table 5).

Table 5. Multivariate analysis table of factors affecting wound healing after endovascular intervention

Discussion

Performing endovascular procedures on the infrapopliteal region in patients with peripheral arterial disease (PAD) presents significant challenges for interventional cardiologists. The presence of extensive calcifications, the involvement of multiple arteries, a higher incidence of complete blockages compared to narrowing, difficulties in vascular access (particularly in more proximal obstructions), and other anatomical complexities all contribute to the difficulty of these interventions.[14] Advances in guidewire and balloon technologies have facilitated the ability to reach and restore blood flow in these small-caliber vessels. However, despite these advancements, the outcomes may not always be favorable for all individuals.

Peripheral artery disease necessitates close monitoring both during and after treatment, requiring careful management by both patients and physicians. In this retrospective study, factors influencing post-procedural wound healing in individuals with intermittent claudication and critical limb ischemia were analyzed. These patients underwent endovascular revascularization to address blockages or complete occlusions in the arteries below the knee. Our findings indicated that the presence of CKD (classified as Rutherford stage 6) and the absence of blood flow in the anterior tibial artery following PTA were independent predictors of poor wound healing.

The risk factors for PAD align with those of other atherosclerotic conditions, including HT, dyslipidemia, diabetes, and kidney dysfunction, in addition to unchangeable variables such as aging and male sex.[11,14,15] A systematic review by Mustapha et al.,[16] which analyzed 52 studies published between 2005 and 2015, found that among patients undergoing PTA for infrapopliteal disease, 75% had diabetes, 75% had high blood pressure, 53% had elevated cholesterol levels, and 34% had kidney impairment.

In this study, a comparison was made between individuals with successful wound healing and those without. The average age in the group with impaired wound recovery was 64.3 years, and 70% were male. Although the differences were not statistically significant, diabetes, HT, HL, and CAD were more prevalent in the non-healing group. A single-center study by Conrad et al.[17] involving 407 individuals found that diabetes was a predictor of shorter limb survival and that kidney disease requiring dialysis was associated with worse outcomes. Similarly, our study identified CKD as an independent determinant of delayed wound healing, supporting the findings of previous research.

Pre-procedural assessments indicated that individuals classified as Rutherford stage 6 had a poorer prognosis for wound healing compared to those classified as Rutherford stage 5, suggesting that the extent of tissue involvement negatively impacts the healing process. Chronic wounds are frequently located in the lower limbs, which can be attributed to relatively slower blood circulation in these regions compared to other parts of the body. Our findings also highlighted that the absence of blood flow in the anterior tibial artery post-intervention had a detrimental impact on wound healing, likely due to the vascular supply this artery provides to critical regions of the foot.

Smoking is a known vasospastic agent that exacerbates atherosclerosis, a relationship well-documented in the Framingham study. This research indicated that smokers have a threefold higher risk of developing peripheral artery disease compared to non-smokers. A meta-analysis of 30 studies conducted by Romiti et al. and another meta-analysis by Mustapha et al.[16–18] found that smoking history was present in 50% and 40% of individuals undergoing. PTA for infrapopliteal disease, respectively. In our study, smoking prevalence was significantly higher among those with poor wound healing. Although smoking was a significant factor in univariate regression analysis, it did not remain statistically significant in the multivariate model.

A study by Kok et al.[19] involving 112 individuals found that at a 3-year follow-up, major amputations were more common in individuals with a history of smoking, stroke, and cardiovascular disease. In our study, 100 patients (52.1%) experienced impaired wound healing post-procedure. Using the updated 2015 TASC II classification, the majority of our patient population consisted of TASC C and D lesions with multiple medical comorbidities. However, no significant difference in wound healing was found between different TASC classifications. Given that most individuals fell within the TASC D category, direct comparisons between groups were somewhat limited. In addition, due to an insufficient number of records, we could not definitively assess the relationship between procedural success and amputation rates. Amputations were identified through an in-depth review of imaging records and categorized as cases with delayed wound healing.

Minimally invasive endovascular techniques offer benefits such as shorter hospital stays, lower morbidity, and reduced mortality. However, procedural success is often limited by long-segment occlusions, extensive calcifications, and multi-level arterial involvement. While newer techniques such as atherectomy, cryoplasty, specialized cutting balloons, and laser angioplasty have been introduced for below-the-knee interventions, studies indicate that these approaches do not provide superior results compared to conventional methods and tend to be more expensive.[20–23] Drug-coated balloons have also been explored in recent years, yet their effectiveness compared to standard balloon angioplasty remains uncertain. In our study, atherectomy combined with PTA did not demonstrate a significant positive effect on wound healing.

Limitations of the Study

The primary limitation of this study is the relatively small sample size. In addition, data regarding the timing of amputations and the extent of wound healing following peripheral endovascular intervention were insufficient. As a result, larger-scale studies are necessary to validate and expand upon these findings.

Conclusion

In summary, an evaluation of factors influencing wound healing after peripheral endovascular intervention identified CKD, a pre-procedural clinical classification of Rutherford stage 6, and the absence of blood flow in the anterior tibial artery following PTA as negative predictors of wound healing.

Cite This Article: Güven G, Ural E, Acar B. Factors Influencing the Recovery of Wounds in Individuals with Peripheral Artery Disease Undergoing Below-the-knee Interventions. Koşuyolu Heart J 2025;28(3):86–92

Ethics Committee Approval

The study was approved by the Kocaeli University Faculty of Medicine Clinical Research Ethics Committee (no: 2019/126, date: 10/05/2019).

Peer Review

Externally peer-reviewed.

Author Contributions

Concept – G.G.; Design – G.G.; Supervision – G.G.; Data collection and/or processing – G.G.; Data analysis and/or interpretation – B.A.; Literature search – G.G.; Writing – G.G.; Critical review – E.U.

Conflict of Interest

The authors have no conflicts of interest to declare.

Use for AI for Writing Assistance

No AI technologies utilized.

Financial Disclosure

The authors declared that this study received no financial support.

References

  1. Mahoney EM, Wang K, Keo HH, Duval S, Smolderen KG, Cohen DJ, et al. Vascular hospitalization rates and costs in patients with peripheral artery disease in the United States. Circ Cardiovasc Qual Outcomes 2010;3:642–51.
  2. Rutherford RB, Baker JD, Ernst C, Johnston KW, Porter JM, Ahn S, et al. Recommended standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg 1997;26:517–38.
  3. Criqui MH, Aboyans V. Epidemiology of peripheral artery disease. Circ Res 2015;116:1509–26.
  4. Shah AM, Banerjee T, Mukherjee D. Coronary, peripheral and cerebrovascular disease: a complex relationship. J Indian Med Assoc 2010;108:292.
  5. Hirsch AT, Criqui MH, Treat-Jacobson D, Regensteiner JG, Creager MA, Olin JW, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA 2001;286:1317–24.
  6. Hirsch AT, Duval S. The global pandemic of peripheral artery disease. Lancet 2013;382:1312–4.
  7. Stoffers HE, Rinkens PE, Kester AD, Kaiser V, Knottnerus JA. The prevalence of asymptomatic and unrecognized peripheral arterial occlusive disease. Int J Epidemiol 1996;25:282–90.
  8. Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, et al. ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease. J Am Coll Cardiol 2006;47:e1–192.
  9. Cengiz M, Sigara PB. Periferik damar hastalıkları. İç: Özyardımcı N, ed. Sigara ve Sağlık. Bursa; 2002. p.332–6. [In Turkish]
  10. Berkow R. The Merck Manual Home Edition. Merck & Company; 1995. p.130–6.
  11. Quriel K, Green RM. Arterial Disease. Schwartz SI, ed. Principles of Surgery. 7th ed. New York: McGraw-Hill; 1999. p.931–8.
  12. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FGR. Inter-society consensus for the management of peripheral arterial disease (TASC II). J Vasc Surg 2007;45:S5–67.
  13. European Stroke Organisation; Tendera M, Aboyans V, Bartelink ML, Baumgartner I, Clément D, Collet JP, et al. ESC Guidelines on the diagnosis and treatment of peripheral artery diseases. Eur Heart J 2011;32:2851–906.
  14. Wiechmann BN. Tibial intervention for critical limb ischemia. Semin Interv Radiol 2009;26:315–23.
  15. De Sanctis JT. Percutaneous interventions for lower extremity peripheral vascular disease. Am Fam Physician 2001;64:1965–72.
  16. Mustapha JA, Finton SM, Diaz-Sandoval LJ, Saab FA, Miller LE. Percutaneous transluminal angioplasty in patients with infrapopliteal arterial disease: systematic review and meta-analysis. Circ Cardiovasc Interv 2016;9:1–27.
  17. Conrad MF, Crawford RS, Hackney LA, Paruchuri V, Abularrage CJ, Patel VI, et al. Endovascular management of patients with critical limb ischemia. J Vasc Surg 2011;53:1020–5.
  18. Romiti M, Albers M, Brochado-Neto FC, Durazzo AES, Pereira CAB, De Luccia N. Meta-analysis of infrapopliteal angioplasty for chronic critical limb ischemia. J Vasc Surg 2008;47:975–81.
  19. Kok HK, Asadi H, Sheehan M, McGrath FP, Given MF, Lee MJ. Outcomes of infrapopliteal angioplasty for limb salvage based on the updated TASC II classification. Diagn Interv Radiol 2017;23:360–4.
  20. Fowkes FGR, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott MM, et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet 2013;382:1329–40.
  21. Bozkurt AK, Tasci I, Tabak O, Gumus M, Kaplan Y. Peripheral artery disease assessed by ankle-brachial index in patients with established cardiovascular disease or at least one risk factor for atherothrombosis (CAREFUL study). BMC Cardiovasc Disord 2011;11:4.
  22. Bozkurt DAK. Ulusal Tedavi Kılavuzu 2016. 2016. p.201. [In Turkish]
  23. Selvin E, Erlinger TP. Prevalence of and risk factors for peripheral arterial disease in the United States: results from the NHANES 1999–2000. Circulation 2004;110:738–43.

Figure and Tables

Table 1. Rutherford and Fontaine classifications
Table 2. Demographic characteristics of the patients
Table 3. Target lesion and procedure characteristics
Table 4. Post-procedure evaluation
Table 5. Multivariate analysis table of factors affecting wound healing after endovascular intervention