Leg Ulcers Research Articles

Impact of great saphenous vein ablation on healing and recurrence of venous leg ulcers in patients with post-thrombotic syndrome: A retrospective comparative study

BackgroundThe optimal treatment approach for patients with active venous leg ulcers (VLUs) and post-thrombotic syndrome (PTS) associated with great saphenous vein (GSV) reflux remains unclear. To address this gap, we retrospectively compared the outcomes of patients with post-thrombotic VLU with an intact GSV vs those with a stripped or ablated GSV. MethodsWe retrospectively analyzed data from 48 patients with active VLUs and documented PTS, who were treated at a single center between January 2018 and December 2022. Clinical information, including ulcer photographs, was recorded in a prospectively maintained digital database at the initial and follow-up visits. Two patient groups—group A (with an intact GSV) and group B (with a stripped or ablated GSV)—were compared in terms of time to complete healing, proportion of ulcers achieving complete healing, and ulcer recurrence during the follow-up period. ResultsThere were no significant differences in age, gender, initial ulcer size, or ulcer duration between the two groups. All included patients had femoropopliteal post-thrombotic changes. Group A had significantly more completely healed ulcers (33 of 34 ulcers, 97%) compared with group B (10 of 14 ulcers, 71%) (P = .008). Group A also exhibited a significantly shorter time to complete ulcer healing (median: 42.5 days, interquartile range [IQR]: 65) compared with group B (median: 161 days, IQR: 530.5) (P = .0177), with a greater probability of ulcer healing (P = .0084). Long-term follow-up data were available for 45 of 48 patients (93.7%), with a mean duration of 39.6 months (range: 5.7-67.4 months). The proportion of ulcers that failed to heal or recurred during the follow-up period was significantly lower in group A (9 of 32 ulcers, 27%) compared with group B (11 of 13 ulcers, 85%) (P = .0009). In addition, in a subgroup analysis, patients with an intact but refluxing GSV (12 of 34) had a significantly shorter time to heal (median: 34 days, IQR: 57.25) (P = .0242), with a greater probability of ulcer healing (P = .0091) and significantly fewer recurrences (2 of 12, 16%) (P = .006) compared with group B. ConclusionsOur findings suggest that removal of the GSV through stripping or ablation in patients with post-thrombotic deep venous systems affecting the femoropopliteal segment may result in delayed ulcer healing and increased ulcer recurrence. Patients with an intact GSV had better outcomes, even when the refluxing GSV was left untreated. These findings emphasize the potential impact of GSV treatment on the management of VLUs in individuals with PTS. Further investigation is needed to validate these results and explore alternative therapeutic strategies to optimize outcomes for this patient population.

Development of a core outcome set for use in research evaluations of interventions for venous leg ulceration: International eDelphi consensus

IntroductionVenous leg ulceration (VLU) is a chronic, recurring condition with associated pain, malodour, impaired mobility and susceptibility to infection which in turn significantly impacts an individual's health-related quality of life. Randomised controlled trials (RCTs) aim to determine the efficacy of interventions to improve outcomes. To be useful, these outcomes should be consistently and fully reported across RCTs. A core outcome set (COS) is an agreed-upon standardised set of outcomes which should be, at a minimum, reported in all RCTs for a given indication including that of VLU. AimTo gain consensus on which outcome domains and outcomes should be considered as core and therefore included in all RCTs of interventions in VLU treatment. MethodTwo sequential, two round e-Delphi surveys were completed. The first gained consensus on core outcome domains and the second on core outcomes within those domains. Participants included: people with direct experience of having VLUs and their carers, healthcare professionals whose practice included VLU care and researchers within wound care (clinical, academic, industry). ResultsFive outcome domains; healing, pain, quality of life, resource use and adverse events, and 11 outcomes were rated as core by participants. The patient and not the limb or ulcer was the preferred unit of analysis for reporting. RecommendationsWe recommend investigators report on all five outcome domains, regardless of the type of intervention being evaluated. Future research is needed to identify measurement methods for the 11 identified outcomes. We also recommend investigators follow the CONSORT guidelines (http://www.consort-statement.org/).

Case study on management of non healing venous Ulcer with unripe fruits of carica papaya

Case study on management of non healing venous Ulcer with unripe fruits of carica papaya

Dehydrated human amnion/chorion membrane to treat venous leg ulcers: a cost-effectiveness analysis.

To evaluate the cost-effectiveness of dehydrated human amnion/chorion membrane (DHACM) in Medicare enrolees who developed a venous leg ulcer (VLU). This economic evaluation used a four-state Markov model to simulate the disease progression of VLUs for patients receiving advanced treatment (AT) with DHACM or no advanced treatment (NAT) over a three-year time horizon from a US Medicare perspective. DHACM treatments were assessed when following parameters for use (FPFU), whereby applications were initiated 30-45 days after the initial VLU diagnosis claim, and reapplications occurred on a weekly to biweekly basis until completion of the treatment episode. The cohort was modelled on the claims of 530,220 Medicare enrolees who developed a VLU between 2015-2019. Direct medical costs, quality-adjusted life years (QALYs), and the net monetary benefit (NMB) at a willingness-to-pay threshold of $100,000/QALY were applied. Univariate and probabilistic sensitivity analyses (PSA) were performed to test the uncertainty of model results. DHACM applied FPFU dominated NAT, yielding a lower per-patient cost of $170 and an increase of 0.010 QALYs over three years. The resulting NMB was $1178 per patient in favour of DHACM FPFU over the same time horizon. The rate of VLU recurrence had a notable impact on model uncertainty. In the PSA, DHACM FPFU was cost-effective in 63.01% of simulations at the $100,000/QALY threshold. In this analysis, DHACM FPFU was the dominant strategy compared to NAT, as it was cost-saving and generated a greater number of QALYs over three years from the US Medicare perspective. A companion VLU Medicare outcomes analysis revealed that patients who received AT with a cellular, acellular and matrix-like product (CAMP) compared to patients who received NAT had the best outcomes. Given the added clinical benefits to patients at lower cost, providers should recommend DHACM FPFU to patients with VLU who qualify. Decision-makers for public insurers (e.g., Medicare and Medicaid) and commercial payers should establish preferential formulary placement for reimbursement of DHACM to reduce budget impact and improve the long-term health of their patient populations dealing with these chronic wounds. Support for this analysis was provided by MiMedx Group, Inc., US. JLD, and RAF are employees of MiMedx Group, Inc. WHT, BH, PS, BGC and WVP were consultants to MiMedx Group, Inc. VD, AO, MRK, JAN, NW and GAM served on the MiMedx Group, Inc. Advisory Board. MRK and JAN served on a speaker's bureau. WVP declares personal fees and equity holdings from Stage Analytics, US.

A systematic review of the impact of compression therapy on quality of life and pain among people with a venous leg ulcer.

To gain a greater understanding of how compression therapy affects quality of life, this systematic review appraised existing published studies measuring the impact of compression therapy on health quality of life (HRQoL), and pain, among people with venous leg ulcers (VLU). Five databases were searched, and two authors extracted data and appraised the quality of selected papers using the RevMan risk of bias tool. Due to heterogeneity in the types of compression and instruments used to evaluate HRQoL, meta-analysis was not appropriate; thus, a narrative synthesis of findings was undertaken. Ten studies were included, 9 RCTs and one before-after study. The studies employed nine different HRQoL tools to measure the impact of a variety of compression therapy systems, with or without an additional exercise programme, versus other compression systems or usual care, and the results are mixed. With the use of the Cardiff Cardiff Wound Impact Schedule, the SF-8 and the SF-12, study authors found no differences in QoL scores between the study groups. This is similar to one study using QUALYs (Iglesias et al., 2004). Conversely, for studies using EuroQol-5D, VEINES-QOL, SF-36 and CIVIQ-20 differences in QoL scores between the study groups were noted, in favour of the study intervention groups. Two further studies using QUALYs found results that favoured a two-layer cohesive compression bandage and the TLCCB group, respectively. Results for the five studies that assessed pain are also mixed, with one study finding no difference between study groups, one finding that pain increased over the study period and three studies finding that pain reduced in the intervention groups. All studies were assessed as being at risk of bias in one or more domains. Results were varied, reflecting uncertainty in determining the impact of compression therapy on quality of life and pain among people with a venous leg ulcer. The heterogeneity of the compression systems and the measures used to evaluate HRQoL make it a challenge to interpret the overall evidence. Further studies should strive for homogeneity in design, interventions and comparators to enhance both internal and external validity.

Advancing nursing practice in Ireland: A pathway of care for nurse-led integrated venous leg ulcer management

Approximately 80% of patients presenting with leg ulcers are venous in origin. However, lack of standardisation of care has a human and financial impact for patients and service providers. Increases in the aging population and number of patients entering older age with co-morbidities results in increases in the demand for venous leg ulcer treatments. A joint initiative between a Registered Advanced Nurse Practitioner (RANP) in tissue viability and wound care, and a vascular consultant, identified deficits in patient care delivery and quality of life.A joint initiative Implementing the principles of the ‘Sláintecare’ policy was established as the Leg Ulcer Centre Ireland (LUCI) to deliver a pathway for the treatment and management of lower limb venous ulcers. The RANP provides a “one stop shop” for patients, offering a complete care package from diagnosis to surgical intervention - endovenous ablation, follow-up post operative care and discharge.Audit findings include; reduced hospital admissions and waiting times; increased patient satisfaction; and, improved interdisciplinary integrated referral pathways.The RANP offers an effective, efficient diagnosis-to-end treatment service for patients. The results demonstrate improved treatment, cost outcomes and value-based outcomes for patients. The new integrated service facilitates expansion of the service and further enhancement of the nursing skills and role.

Early term results of venous leg ulcer treatment in chronic venous disease: a Latam perspective

Early term results of venous leg ulcer treatment in chronic venous disease: a Latam perspective

Dehydrated human amnion chorion membrane to treat venous leg ulcers: a cost-effectiveness analysis.

Dehydrated human amnion chorion membrane to treat venous leg ulcers: a cost-effectiveness analysis.

Treatment patterns and outcomes of Medicare enrolees who developed venous leg ulcers.

Treatment patterns and outcomes of Medicare enrolees who developed venous leg ulcers.

Differences in risk profile associated with varicose veins and chronic venous insufficiency - results from the Bonn Vein Study 1.

Background: The aim of this publication is to demonstrate similarities and differences in the association of risk factors with the prevalence of different manifestations of chronic venous disease (CVD), like varicose veins (VV), venous oedema (C3) and severe chronic venous insufficiency (CVI) in the population-based cross-sectional Bonn Vein Study 1 (BVS). Patients and methods: In the BVS 1 between 13.11.2000 and 15.3.2002, 3.072 participants, 1350 men and 1722 women, from a simple random sample of the general population of the city of Bonn and two rural townships aged 18-79 years were included. The overall response proportion was 59%. All participants answered a standardized questionnaire including information about socio-economic data, lifestyle, physical activity, medical history, and quality of life. Venous investigations were performed clinically and by a standardized duplex examination by trained investigators. The CEAP classification in the version of 1996 was used to classify the findings. Logistic regression models were performed for the association of possible risk factors with VV, venous edema (C3) and severe CVI (C4-C6). The predictive risk (PR) describes the association of the diseases and the possible influencing factors. Results: VV, venous oedema (C3) and severe CVI (C4-C6) have common risk factors like higher age, number of pregnancies, family history of VV and overweight or obesity. Female gender is significantly associated with VV and C3 but not with severe CVI (C4-C6). High blood pressure and urban living are only associated with C3 and C4-C6 disease whereas prolonged sitting is associated with C3 and lower social class with C4-C6 exclusively. Discussion: In many epidemiological studies risk factors were associated with chronic venous disorders in general. Our data show that VV, venous edema and severe CVI may have different risk profiles. Venous edema is more often associated with arterial hypertension and sedentary lifestyle whereas lower social class seems to be a risk factor for severe CVI including venous ulcers. Conclusions: The differences in the association of risk factors to VV, venous edema and severe CVI should be considered if prevention and treatment of chronic venous diseases are planned. As examples, compression stockings could be proposed in sitting profession to prevent oedema, VV patients with risk factors like obesity might benefit from early treatment for VV and obesity. More longitudinal evaluation of risk factors is necessary to evaluate the true risk profile of CVD.

Satisfactory result of great saphenous vein endovenous laser ablation until below the knee on active venous leg ulcer: a case series

Background Active venous leg ulcer (VLU) is the most severe manifestation of chronic venous disease which not only affects patients’ health, but also decreases the quality of life, and delivers economic burdens. Treatment of superficial venous reflux with early endovenous laser ablation (EVLA) has been associated with reducing ulcer recurrence levels and promoting faster VLU healing. We reported three cases of patients with active VLU undergoing EVLA with different approaches. Case illustration Three patients came with complaint of leg ulcer, diagnosed with C6sEpAsdPr, with venous clinical severity scores (VCSS) of 15, 23, and 22 respectively. Severe great saphenous veins (GSV) reflux was found in all patients by duplex ultrasound examination. The second patient had undergone above-the-knee EVLA. All patients underwent EVLA using 1470-nano meter wavelength laser device and ELVeS radial fiber (Biolitec, Bonn, Germany). The laser energy protocol used was 6 W linear endovenous energy density (LEED) 50 J/cm for proximal until media ATK GSV ablation, 5 W LEED 40 J/cm for media ATK until proximal below-the-knee (BTK) GSV, and 2 W LEED 20 J/cm for proximal until distal BTK GSV. The third patient was also treated with EVLA for small saphenous vein severe reflux. Follow-up until 6 months post-EVLA showed significant healing of the ulcer with 14, 16, and 17 VCSS reduction consecutively without any complication. Conclusion We’ve reported three cases of patients with active VLU undergoing EVLA until BTK with significant results. The EVLA of GSV until BTK where there is still significant reflux is safe and provides satisfactory results in patients with VLU.

Association between stroke and venous leg ulcers: A Mendelian randomization study.

To investigate any potential bidirectional causal relationships between stroke and venous leg ulcers (VLUs), Mendelian randomization (MR) analyses were carried out in this study. The exposure factor was stroke, the outcome factor was VLUs. The two-sample MR study was carried out based on the online analysis platform (http://app.mrbase.org/). The association of stroke and VLUs was analysed via methods of Inverse Variance Weighted (IVW), Weighted Median, MR-Egger and weighted mode. IVW method suggested no association between stroke and VLUs ((β 1.06; SE 9.321; p = 0.9095)). Weighted median estimator (β 5.906; SE 11.99, p = 0.6223), MR-Egger (β -0.8677; SE 21.89; p = 0.9691) and weighted mode (β 9.336; SE 17.77; p = 0.6089) showed consistent results. Conversely, evidence indicating that the presence of VLUs increased the risk of stroke was lacking. According to this MR study, there is no causal connection between stroke and VLUs, which suggests that therapies targeting stroke may not be effective against VLUs.

Bacterial Species Involved in Venous Leg Ulcer Infections and Their Sensitivity to Antibiotherapy-An Alarm Signal Regarding the Seriousness of Chronic Venous Insufficiency C6 Stage and Its Need for Prompt Treatment.

Venous leg ulcers (VLUs) are a common chronic wound condition susceptible to infection by various bacterial species. Understanding bacterial presence and antibiotic sensitivity is crucial for effective treatment. Methodsː Medical records of 60 patients diagnosed with the C6 chronic venous insufficiency stage were analyzed retrospectively. The patients were divided into an active recurrent VLU group (33 cases) and a first-onset active VLU group (27 cases). Bacterial identification, antibiotic sensitivity, and laboratory markers were assessed. Resultsː Pseudomonas aeruginosa was the most prevalent bacterial species in both the study (72.72%) and control (37.03%) groups, along with other common bacteria such as Proteus mirabilis, Enterococcus sp., Staphylococcus aureus, Acinetobacter baumannii, Klebsiella spp., and Escherichia coli. Furthermore, uncommon bacteria, including Providencia rettgeri, Group B Streptococcus, and Salmonella Paratyphi B, and a fungal infection with Candida albicans, were identified only in the study group, while Morganella morganii was found exclusively in the control group. Pseudomonas aeruginosa showed significant sensitivity to several antibiotics, particularly Amikacin and Meropenem. Nonspecific laboratory markers, such as CRP, fibrinogen, ESR, WBC, CK, neutrophils, and lymphocytes, revealed statistically significant differences between groups, indicating their potential as biomarkers for monitoring recurrent VLUs. Conclusionsː These results highlight the need for comprehensive diagnostic approaches to effectively manage VLU infections and improve patient outcomes. Further research is warranted to explore factors influencing the presence of uncommon bacteria and to develop targeted interventions for VLU management.

Connecting epigenetics and inflammation in vascular senescence: state of the art, biomarkers and senotherapeutics.

Vascular diseases pose major health challenges, and understanding their underlying molecular mechanisms is essential to advance therapeutic interventions. Cellular senescence, a hallmark of aging, is a cellular state characterized by cell-cycle arrest, a senescence-associated secretory phenotype macromolecular damage, and metabolic dysregulation. Vascular senescence has been demonstrated to play a key role in different vascular diseases, such as atherosclerosis, peripheral arterial disease, hypertension, stroke, diabetes, chronic venous disease, and venous ulcers. Even though cellular senescence was first described in 1961, significant gaps persist in comprehending the epigenetic mechanisms driving vascular senescence and its subsequent inflammatory response. Through a comprehensive analysis, we aim to elucidate these knowledge gaps by exploring the network of epigenetic alterations that contribute to vascular senescence. In addition, we describe the consequent inflammatory cascades triggered by these epigenetic modifications. Finally, we explore translational applications involving biomarkers of vascular senescence and the emerging field of senotherapy targeting this biological process.

First clinical evaluation of the safety and efficacy of tarumase for the debridement of venous leg ulcers.

We report the first clinical evaluation of a new enzymatic wound debridement product containing tarumase in venous leg ulcer patients. As a first-in-human study, this was a prospective, open-label, multi-centre, dose escalation study across five dose cohorts and involving a total of 43 patients treated three times weekly for up to 4 weeks (12 applications). The primary and secondary endpoints of the study were to assess the systemic safety, local tolerability, and early proof of concept both for wound debridement and healing. Results indicated that the tarumase enzyme was well tolerated when applied topically to wounds, with no indications of systemic absorption, no evidence of antibody generation, and no systemic effects on coagulation pathways. Locally, there was no evidence of pain on application, no local itching, no increases in erythema, oedema, exudate or bleeding and only a few treatment emergent adverse events were reported. As the concentration of tarumase was escalated, trends towards faster and improved effectiveness of wound debridement were observed, especially in patients with significant slough at baseline. Trends towards faster rates of healing were also noted based on observations of increased granulation tissue, increased linear healing and reduction in surface area over the 4-week treatment period.

Occlusive cutaneous vasculopathies as cause of chronic ulcers.

The term occluding vasculopathies covers a large number of different conditions. These often manifest as skin ulcers. Occluding vasculopathies should be considered in the differential diagnosis of leg ulcers. The term "occlusive vasculopathies" encompasses pathophysiologically related entities that share structural or thrombotic obliteration of small cutaneous vessels. In this article, we will focus on livedoid vasculopathy with and without antiphospholipid syndrome and calciphylaxis with differentiation from hypertonic leg ulcer as the most relevant differential diagnoses of leg ulcer. The term also includes vascular occlusion, for example due to oxalate or cholesterol embolism, and septic vasculopathy. This often leads to acral ulceration and is therefore not a differential diagnosis with classic leg ulcers. It will not be discussed in this article. Occlusive vasculopathy may be suspected in the presence of the typical livedo racemosa or (non-inflammatory) retiform purpura as a sign of reduced cutaneous perfusion in the wound area. Inflammatory dermatoses, especially vasculitides, must be differentiated. This is achieved by histopathological evaluation of a tissue sample of sufficient size and depth taken at the appropriate time. In addition, specific laboratory parameters, particularly coagulation parameters, can support the diagnosis.

Associations Among Wound-Related Factors Including Biofilm, Wound-Related Symptoms and Systemic Inflammation in Older Adults with Chronic Venous Leg Ulcers.

Objective: The purposes of this observational prospective study were to (1) characterize the wound-related factors (wound area, the presence of biofilm, and total bacteria), wound-related symptoms (fatigue, pain, exudate, itching, and edema or swelling), and systemic inflammation (level of serum C-reactive protein [CRP]), and (2) explore associations between wound-related factors, wound-related symptoms, and systemic inflammation in older individuals with chronic venous leg ulcers (CVLUs) over 8 weeks of wound treatment. Approach: A total of 117 participants who received standardized care (weekly sharp debridement) for chronic venous ulcer were enrolled. We collected clinical data every 2 weeks during the 8 weeks of the study period or until the wound was healed (if healed before 8 weeks). Associations among variables were estimated using a Bayesian approach applied to general linear mixed models. Results: Based on Bayes factor (BF) value, there was extremely strong evidence for the association of biofilm with mean total bacteria (BF >1,000). There was moderate evidence of a direct association between biofilm presence and levels of CRP (BF 4.3) and moderate evidence of direct associations between biofilm and wound-related symptoms, pain and exudate (BF 5.12, 8.49, respectively). Innovation: Wound-related symptoms and the level of systemic CRP were associated with biofilm among patients who were receiving weekly sharp debridement. Symptom severity associated with CVLUs requires assessment and management of wound-related factors and levels of inflammation in addition to symptom assessment. Conclusion: This study is the first to examine associations among biofilm, as wound-related factors, systemic inflammation, wound-related symptoms, and wound healing in clinical settings. Symptom severity, level of systemic CRP, and wound-related factors should be considered as well as assessment of biofilm in CVLU in older individuals with CVLU.

Clinical spectrum of fusariosis from a tertiary care center in India- a retrospective study.

Fusarium spp. is an emerging pathogen that presents with varied clinical presentations but there are very few studies from India that elaborate on the spectrum of infection caused by the fungus. Hence, the present study was conducted in our institute to understand the clinical spectrum of fusariosis. The present study was a retrospective study conducted at a tertiary care institute, in Hyderabad, Telangana, India for four years from January 2018 to December 2022. All the patients with clinically significant isolation of Fusarium spp. from various samples were included in the study. There were 25 cases of fusariosis diagnosed during the study period. Fusarium was isolated predominantly from debrided tissue following road traffic accidents in 12/25 (84%) of the cases, nails in 3/25 (12%) and superficial leg ulcer in 1/25 (4%) of the cases. Speciation was done for four patients. Three were Fusarium incarnatum and one was Fusarium solani. The patients were treated surgically and with/without antifungal therapy and were discharged in a stable condition. Traumatic injuries were the major cause of infections in the present study. As Fusarium is a virulent and highly resistant pathogen, an early suspicion and an appropriate diagnosis would lead to a better outcome in these patients.

Clinical and microbiological features of host-bacterial interplay in chronic venous ulcers versus other types of chronic skin ulcers.

Chronic venous ulcers of the lower limbs develop in the context of advanced venous disease and have a significant impact on the patient's quality of life, being associated with depression and worrisome suicide rates, as well as with an economic burden caused by increased medical care costs and high epidemiological risks of healthcare associated infections and emergence of strains resistant to multiple classes of antibiotics and/ or antiseptics. Although numerous studies have investigated the composition of the chronic wounds microbiome, either by culture-dependent or independent methods, there are no data on the association between virulence and resistance profiles of strains isolated from venous ulcers and the clinical picture of this pathology. The elucidation of pathogenic mechanisms, at both phenotypic and molecular level, is crucial in the fight against these important human microbial agents, in order to develop novel biomarkers and discover new therapeutic targets. In this study we aimed to characterize the phenotypic virulence profiles (including the ability to develop biofilms) of microorganisms isolated from chronic skin wounds and to correlate them with the clinical symptomatology. Considering the high incidence of Staphylococcus aureus infections in chronic ulcers, but also the ability of this species to develop multi-drug resistance, we performed an more in-depth study of the phenotypic and genotypic virulence profiles of methicillin-resistant Staphylococcus. The study revealed important differences regarding the clinical evolution and virulence profiles of microorganisms isolated from lower limb wounds, as well as between patients diagnosed with chronic venous ulcers and those with lesions of different etiology.

Association between venous leg ulcers and chronic heart failure: A Mendelian randomization study.

An association between venous leg ulcers (VLU) and chronic heart failure (CHF) has been suggested by observational research. This study used Mendelian randomization (MR) methods to look into any possible bidirectional causal links between VLU and CHF. The 'TwoSampleMR' R package was employed for MR analyses. The association of VLU and CHF was assessed via methods of inverse variance weighted (IVW), weighted mode, MR Egger and weighted median. Results of IVW suggested no association between VLU and CHF (β 0.008356; SE 0.01889; p = 0.6582). The weighted median estimator (β -0.005777; SE 0.02059, p = 0.7791), MR-Egger (β -0.08955; SE 0.04557; p = 0.07296) and weighted mode (β -0.01202; SE 0.02467; p = 0.6341) showed consistent results. Conversely, evidence indicating that the presence of CHF increased the risk of VLU was lacking. In conclusion, there is no bidirectional causal relationship between VLU and CHF. Further studies are required to validate the findings of this study.