Toe-brachial Index Research Articles

Developing a multi-center registry of peripheral artery disease using natural language processing: unlocking the power of the electronic health record

Abstract Background Although peripheral artery disease (PAD) is common and associated with a high risk of mortality, contemporary PAD research remains limited due to poor accuracy of diagnosis codes in the electronic health record (EHR). We previously developed and validated a novel natural language processing (NLP) algorithm that can extract ankle brachial index (ABI) and toe-brachial index (TBI) values from clinical documents and identify patients with PAD with high accuracy (positive predictive value 92.4%). Purpose Scale the NLP system for developing a nationwide registry of PAD in the Veterans Health Administration (VHA), the largest integrated health system in the U.S. that provides care to ~9 million Veterans across 130 sites. Describe the baseline characteristics and mortality outcomes among participants and identify predictors of long-term mortality. Methods A total of 1,182,025 documents from vascular and radiology procedures during 2013-2020 were processed by the NLP system. After excluding non-ABI vascular studies, patients with a known diagnosis of PAD prior to 2015, patients younger than 40 years of age, and those who do not regularly follow-up in the VHA, we identified 107,711 patients with newly diagnosed PAD during 2015-2020. Patients were followed longitudinally using the VA’s electronic health record data. The primary outcome was all-cause mortality. We used Cox proportional hazards regression to examine predictors of long-term mortality. Results The mean age was 70.5 years; 97.3% were males, and 18.5% were of Black race. The mean ABI value was 0.78 (SD: 0.26) and the mean TBI value was 0.51 (SD: 0.19). There was a high prevalence of hypertension (83.6%), heart failure (20.8%), diabetes (53.6%), renal failure (22.1%) and chronic obstructive pulmonary disease (32.4%, Table 1). At 1-year, 9.6% of patients had died and this proportion increased to 25.4% at 3 years. Although nearly all patient variables were significantly associated with mortality, older age, severe PAD at diagnosis, diabetes, heart failure, renal failure and COPD were the strongest predictors of long-term mortality. Black race was associated with lower hazard of long-term mortality. Conclusions Using a previously validated novel NLP algorithm that extracts ABI and TBI values from clinical documents, we have successfully developed a registry of newly diagnosed PAD in the VHA. Ongoing studies from our cohort will yield important insights into the association between clinical management of PAD and clinical outcomes, with the goal of identifying opportunities for improving care.

The use of a novel toe-thumb pressure index for assessing arterial status in the lower limb. A reliability and validity study.

This study explored the reliability, validity and perceived comfort of a novel thumb pressure measure and calculation of a toe-thumb index to identify their suitability as an adjunct or alternatives to ankle-brachial and toe-brachial indices. Repeated manual thumb and toe systolic blood pressures were conducted using two raters, over two time points, on 34 healthy participants. Concurrent automated toe, thumb and brachial systolic blood pressures as well as comfort ratings for these measures (using a 10mm visual analogue scale) were captured once by a research assistant. Automated thumb and brachial measures showed fair correlation (ρ=0.36, p=0.03) and a toe-thumb index and toe-brachial index good correlation (ρ=0.62, p<0.01). Intraclass correlation coefficients (ICC) identified moderate intra-rater reliability for manual thumb pressures for Rater 1 and 2 (ICC 0.57, 95% CI [0.14, 0.79] and ICC 0.74, 95% CI [0.49, 0.87], respectively), while inter-rater reliability was poor (ICC=0.16, 95% CI [-0.85, 0.47]). Concurrent validity comparing manual and automated measures for thumb pressure was also poor (ICC -0.05, 95% CI [-1.06, 0.72] and ICC 0.42, 95% CI [-0.16, 0.72] Rater 1 and 2 respectively). Thumb measures were significantly more comfortable than brachial measures (5mm, p<0.00). Thumb systolic pressures are correlated with brachial systolic pressures, with reasonable intra-rater reliability, however, correlation is only fair and measurement error wider than clinically acceptable. Furthermore, manual measures are poorly correlated with automated units. Consequently, caution is required in applying these techniques. As thumb measures were perceived as significantly more comfortable than brachial measures and have an advantage where brachial pressures cannot, or should not, be obtained, further evaluation is warranted.

Leukotrienes E4 and B4 and vascular endothelium – New insight into the link between vascular inflammation and peripheral arterial

Leukotrienes are proinflammatory mediators that participate in the process of atherogenesis and contribute to the development of symptomatic peripheral arterial disease. The aim was to evaluate the relationship between leukotriene E4 (LTE4) and B4 (LTB4) with parameters reflecting endothelial vascular function in patients with chronic lower limb ischemia. This prospective observational study enrolled 50 consecutive patients undergoing endovascular treatment due to chronic lower limb ischemia (Rutherford 3). All participants were followed-up for one year (after 1, 3, 6 and 12 months), with a sequential assessment of urinary LTE4 and LTB4, as well as measures of endothelial and vascular function: Flow-Mediated Dilatation (FMD), Intima-Media Thickness (IMT), corrected Augmentation Index (AI75), Shear Rate (SR), Ankle-Brachial Index (ABI), Toe-Brachial Index (TBI). There was a significant relationship between LTE4 and measures of vascular function: FMD (R2 = 0.69, P < 0.001), IMT (R2 = 0.12, P < 0.01), AI75 (R2 = 0.43, P < 0.001), SR (R2 = 0.48, P < 0.001). Similar findings were noted for LTB4: FMD (R2 = 0.47, p < 0.001), IMT (R2 = 0.23, P < 0.001), AI75 (R2 = 0.61, P < 0.001) and SR (R2 = 0.33, P < 0.001). Alterations in parameters were significantly related: ΔLTE4 vs ΔFMD(R2 = 0.63, P < 0.001), ΔSR (R2 = 0.42, P < 0.001) and ΔLTB4 vs AI75(R2 = 0.40, P < 0.001), SR(R2 = 0. 29, P < 0.001). We conclude, that increasing concentrations of LTE4 and LTB4 are associated with impairment of vascular and endothelial function, which may lead to worse endovascular treatment clinical outcomes.

Relationship of Thyroid Volume and Function with Ankle-Brachial Index, Toe-Brachial Index, and Toe Pressure in Euthyroid People Aged 18-65.

Background and Objectives: The interrelationship between thyroid function and the state of the cardiovascular system has been investigated both in preclinical and human studies. However, it remains unclear whether there is any association between thyroid hormones and features of subclinical cardiovascular dysfunction in euthyroid patients. Material and Methods: This study involved 45 people (females: 57.8%) with no thyroid disease who, during planned hospitalization, underwent thyroid ultrasound, determination of biochemical parameters of thyroid function, and measurement of ankle-brachial index (ABI) and toe-brachial index (TBI). People with signs of acute illness or a deterioration of their health were excluded. Results: Significant correlations were found between free triiodothyronine (FT3) and several parameters of both ABI (R = 0.347; p = 0.019 for the mean ABI taken from right side and left side values) and TBI (R = 0.396; p = 0.007 for the mean TBI taken from right side and left side values), as well as the maximal toe pressure (TP) taken from right side and left side values (R = 0.304; p = 0.045). Thyrotropin (TSH) was shown to be significantly correlated only with the maximal TBI value (taken from right side and left side values) (R = 0.318; p = 0.033), whereas free thyroxin (FT4) was shown to be significantly correlated only with the minimal TBI value (taken from right side and left side values) (R = 0.381; p = 0.01). Thyroid volume (TV) was shown to be correlated with TP (R = 0.4; p = 0.008 for the mean TP taken from right side and left side values) and some parameters of TBI value (R = 0.332; p = 0.028 for the mean TBI taken from right side and left side values), but no significant correlations were found between TVand ABI parameters. Patients with a mean ABI value ≤ 1.0 or a mean TBI value ≤ 0.75 have lower TSH, FT3, FT4, and TV than the rest of the study population, but the difference was statistically significant only for FT3. Conclusions: Even in a population of euthyroid patients with no diagnosed thyroid disease, there are some significant correlations between the volume and function of the thyroid gland and the selected features of subclinical cardiovascular dysfunction such as ABI and TBI.

The Value of Pressure Indexes in Predicting the Outcome of Diabetic Foot Ulcers as a Guide to Further Management.

Diabetic foot ulcers (DFUs) standout as a prevalent and debilitating condition. Furthermore, the progression of diabetes-related hyperglycemia and associated conditions such as peripheral arterial disease exacerbates the risks of DFUs, including complications like infection and gangrene. Given the significant burden of DFUs, there is a pressing need to improve preventive and therapeutic strategies. This study investigates the clinical profiles of patients with DFUs, including the importance of smoking and intermittent claudication, evaluates management strategies based on the vascular status assessed throughDoppler scans, and provides insights into the importance of ankle-brachial pressure index (ABPI) and toe brachial index (TBI) values, which play a vital role in predicting and managing ulcer healing outcomes, highlighting the importance of vascular assessment in treatment planning. The study aims to assess the clinical profile of patients with DFUs based on their vascularity status using Doppler scans, predict the outcome of the ulcer using indexes like ABPI and TBI values, and decide on further management. This prospective study was conducted over 24 months, from August 2022 to July 2024, at the Department of General Surgery, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pimpri, Pune. The study included 50 patients presenting with DFUs. Approval was obtained from the InstitutionalEthics Committee, and informed consent was obtained from all participants. A detailed history was taken, including the history of smoking and intermittent claudication, and a thorough examination of the ulcer was performed. HbA1c levels were measured, Doppler scans of the lower limbs were done, and the ABPI and TBI values were calculated. Management strategies were determined based on the assessed vascular status, leading to either medical or surgical interventions. Twenty-one (42%) patients who presented with DFUs had a positive history of intermittent claudication, demonstrating a significant association between the history of intermittent claudication and the Doppler findings. Thirty-seven (74%) patients gave a positive history of smoking, which revealed a significant association between the history of smoking and Doppler findings. Thirty-eight (76%) patients had an ABPI of <0.9, out of which 33 (66%)patients showed an improved outcome of the ulcer after necessary management. There is also a statistically significant association between the ABPI and Doppler findings. Sixteen (32%) of patients had a TBI of <0.65, of which all showed an improvement. There is a highly significant association between TBI and the Doppler findings. This study concludes that integrated routine assessment of ABPI and TBI into DFU management protocols is necessary to guide treatment decisions and monitor response to therapy. Treatment and prevention of diabetes-related complications affecting the lower extremities require a dedicated interdisciplinary approach.

Inflammatory Protein Panel: Exploring Diagnostic Insights for Peripheral Artery Disease Diagnosis in a Cross-Sectional Study.

Cytokine-induced neutrophil chemoattractant 1 (CINC-1), a cluster of differentiation 95 (CD95), fractalkine, and T-cell immunoglobulin and mucin domain 1 (TIM-1) are circulating proteins known to be involved in inflammation. While their roles have been studied in neurological conditions and cardiovascular diseases, their potential as peripheral artery disease (PAD) biomarkers remain unexplored. We conducted a cross-sectional diagnostic study using data from 476 recruited patients (164 without PAD and 312 with PAD). Plasma levels of CINC-1, CD95, fractalkine, and TIM-1 were measured at baseline. A PAD diagnosis was established at recruitment based on clinical exams and investigations, defined as an ankle-brachial index < 0.9 or toe-brachial index < 0.67 with absent/diminished pedal pulses. Using 10-fold cross-validation, we trained a random forest algorithm, incorporating clinical characteristics and biomarkers that showed differential expression in PAD versus non-PAD patients to predict a PAD diagnosis. Among the proteins tested, CINC-1, CD95, and fractalkine were elevated in PAD vs. non-PAD patients, forming a 3-biomarker panel. Our predictive model achieved an AUROC of 0.85 for a PAD diagnosis using clinical features and this 3-biomarker panel. By combining the clinical characteristics with these biomarkers, we developed an accurate predictive model for a PAD diagnosis. This algorithm can assist in PAD screening, risk stratification, and guiding clinical decisions regarding further vascular assessment, referrals, and medical/surgical management to potentially improve patient outcomes.

Determinants of vascular impairment in type 1 diabetes–impact of sex and connexin 37 gene polymorphism: A cross-sectional study

BackgroundThe associations of risk factors with vascular impairment in type 1 diabetes patients seem more complex than that in type 2 diabetes patients. Therefore, we analyzed the associations between traditional and novel cardiovascular risk factors and vascular parameters in individuals with T1D and modifications of these associations according to sex and genetic factors.MethodsIn a cross-sectional study, we analyzed the association of risk factors in T1D individuals younger than 65 years using vascular parameters, such as ankle brachial index (ABI) and toe brachial index (TBI), duplex ultrasound, measuring the presence of plaques in carotid and femoral arteries (Belcaro score) and intima media thickness of carotid arteries (CIMT). We also used photoplethysmography, which measured the interbranch index expressed as the Oliva-Roztocil index (ORI), and analyzed renal parameters, such as urine albumin/creatinine ratio (uACR) and glomerular filtration rate (GFR). We evaluated these associations using multivariate regression analysis, including interactions with sex and the gene for connexin 37 (Cx37) polymorphism (rs1764391).ResultsIn 235 men and 227 women (mean age 43.6 ± 13.6 years; mean duration of diabetes 22.1 ± 11.3 years), pulse pressure was strongly associated with unfavorable values of most of the vascular parameters under study (ABI, TBI, Belcaro scores, uACR and ORI), whereas plasma lipids, represented by remnant cholesterol (cholesterol – LDL-HDL cholesterol), the atherogenic index of plasma (log (triglycerides/HDL cholesterol) and Lp(a), were associated primarily with renal impairment (uACR, GFR and lipoprotein (a)). Plasma non-HDL cholesterol was not associated with any vascular parameter under study. In contrast to pulse pressure, the associations of lipid factors with kidney and vascular parameters were modified by sex and the Cx37 gene.ConclusionIn addition to known information, easily obtainable risk factor, such as pulse pressure, should be considered in individuals with T1D irrespective of sex and genetic background. The associations of plasma lipids with kidney function are complex and associated with sex and genetic factors. The decision of whether pulse pressure, remnant lipoproteins, Lp(a) and other determinants of vascular damage should become treatment targets in T1D should be based on the results of future clinical trials.Graphical

Long-term Outcomes of Peripheral Artery Disease In Veterans: Analysis of the PEripheral ARtery Disease Long-term Survival Study (PEARLS).

Contemporary research in peripheral artery disease (PAD) remains limited due to lack of a national registry and low accuracy of diagnosis codes to identify PAD patients in electronic health records. Leveraging a novel natural language processing (NLP) system that identifies PAD with high accuracy using ankle brachial index (ABI) and toe-brachial index (TBI) values, we created a registry of 103,748 patients with new onset PAD patients in the Veterans Health Administration (VHA). Study endpoints include mortality, cardiovascular (hospitalization for acute myocardial infarction or stroke) and limb events (hospitalization for critical limb ischemia or major amputation) and were identified using VA and non-VA encounters. The mean age was 70.6 years; 97.3% were males, and 18.5% self-identified as Black race. The mean ABI value was 0.78 (SD: 0.26) and the mean TBI value was 0.51 (SD: 0.19). Nearly one-third (32.4%) patients were currently smoking and 35.4% formerly smoked. Prevalence of hypertension (86.6%), heart failure (22.7%), diabetes (54.8%), renal failure (23.6%), and chronic obstructive pulmonary disease (35.4%) was high. At 1-year, 9.4% of patients had died. The 1-year incidence of cardiovascular events was 5.6 per 100 patient-years and limb events was 4.5 per 100 patient-years. We have successfully launched a registry of >100,000 patients with a new diagnosis of PAD in the VHA, the largest integrated health system in the U.S. The ncidence of death and clinical events in our cohort is high. Ongoing studies will yield important insights regarding improving care and outcomes in this high-risk group.

Determining the Best Noninvasive Test for Peripheral Arterial Disease Diagnosis to Predict Diabetic Foot Ulcer Healing in Patients Following Endovascular Revascularization.

To analyze the best noninvasive tests prognosis marker in patients with diabetic foot ulcer (DFU) who underwent endovascular revascularization based on clinical outcomes, such as healing rate, time to heal, and free amputation survival after at least a six-month follow-up. A multicentric prospective observational study was performed with 28 participants with ischemic or neuroischemic DFU who came to the participant centers and underwent endovascular revascularization between January 2022 and March 2023. Toe systolic pressure (TP), ankle systolic pressure (AP), the ankle brachial pressure index (ABPI), the toe brachial pressure index (TBPI), transcutaneous pressure of oxygen (TcPO2), and skin perfusion pressure (SPP) were evaluated using PeriFlux 6000 System, Perimed, Sweden, before (Visit 0) and four weeks after revascularization (Visit 1). The primary clinical outcome was an evaluation of the clinical evolution of noninvasive tests comparing Visit 0 and Visit 1, estimating the sensitivity for predicting wound healing of noninvasive tests at six months following initial recruitment. After six months, 71.43% (n = 20) of DFU healed, four patients (14.3%) received major amputations, and one (3.5%) died. The two tests that best predicted wound healing after revascularization according to the ROC curve were TcPO2 and TP with sensitivities of 0.89 and 0.70 for the cut-off points of 24 mmHg and 46 mmHg, respectively. TcPO2 and TP were the two tests that best predicted wound healing in patients who underwent endovascular revascularization. Clinicians should consider the importance of the evaluation of microcirculation in the healing prognosis of patients with diabetic foot ulcers.

Toe-brachial index is more strongly associated with prognosis of diabetic nephropathy than ankle-brachial index in type 2 diabetic patients

Toe-brachial index is more strongly associated with prognosis of diabetic nephropathy than ankle-brachial index in type 2 diabetic patients

Integrating Toe Brachial Index and longitudinal strain echocardiography for detecting coronary artery disease in patients with diabetic foot syndrome.

Coronary artery disease (CAD) is a common problem amongst diabetic foot syndrome (DFS) patients, associated with peripheral arterial disease. This analytic cross-sectional study investigates the diagnostic efficacy of the Toe Brachial Index (TBI) in the detection of CAD in 62 DFS patients. The presence of CAD was assessed by longitudinal strain echocardiography, a sensitive method that provides a more accurate measure of intrinsic left ventricular contractility than left ventricular ejection fraction, especially in diabetic patients. Univariate and multivariate logistic regression identified CAD-associated factors. Receiver operating characteristic curve evaluated TBI and toe pressure's diagnostic performance for CAD. p-Values < 0.05 were considered significant. There was a significant association between TBI and CAD, with each 0.01 increase in TBI associated with a 15% decrease in the odds of CAD development (odds ratio = 0.85, 95% CI: 0.72-0.99, p = 0.039). TBI demonstrated an area under the curve of 0.854, a sensitivity of 80.0% and a specificity of 66.7% at a cut-off of 0.69. Additionally, toe pressure exhibited an area under the curve of 0.845, sensitivity of 74.0% and specificity of 75.0% at a cut-off of 68.0 mmHg. Overall accuracy for TBI and toe pressure was 77.4% and 74.2%, respectively, indicating their potential for CAD risk stratification in the DFS population. This study highlights a significant association between low TBI and the presence of CAD in DFS patients. Consequently, TBI emerges as a valuable screening tool for identifying CAD within this population.

The impact of revascularization strategy on clinical failure, hemodynamic failure, and chronic limb-threatening ischemia symptoms in the BEST-CLI Trial

ObjectiveSustained clinical and hemodynamic benefit after revascularization for chronic limb-threatening ischemia (CLTI) is needed to resolve symptoms and prevent limb loss. We sought to compare rates of clinical and hemodynamic failure as well as resolution of initial and prevention of recurrent CLTI after endovascular (ENDO) vs bypass (OPEN) revascularization in the Best-Endovascular-versus-best-Surgical-Therapy-in-patients-with-CLTI (BEST-CLI) trial. MethodsAs planned secondary analyses of the BEST-CLI trial, we examined the rates of (1) clinical failure (a composite of all-cause death, above-ankle amputation, major reintervention, and degradation of WIfI stage); (2) hemodynamic failure (a composite of above-ankle amputation, major and minor reintervention to maintain index limb patency, failure to an initial increase or a subsequent decrease in ankle brachial index of 0.15 or toe brachial index of 0.10, and radiographic evidence of treatment stenosis or occlusion); (3) time to resolution of presenting CLTI symptoms; and (4) incidence of recurrent CLTI. Time-to-event analyses were performed by intention-to-treat assignment in both trial cohorts (cohort 1: suitable single segment great saphenous vein [SSGSV], N = 1434; cohort 2: lacking suitable SSGSV, N = 396), and multivariate stratified Cox regression models were created. ResultsIn cohort 1, there was a significant difference in time to clinical failure (log-rank P < .001), hemodynamic failure (log-rank P < .001), and resolution of presenting symptoms (log-rank P = .009) in favor of OPEN. In cohort 2, there was a significantly lower rate of hemodynamic failure (log-rank P = .006) favoring OPEN, and no significant difference in time to clinical failure or resolution of presenting symptoms. Multivariate analysis revealed that assignment to OPEN was associated with a significantly lower risk of clinical and hemodynamic failure in both cohorts and a significantly higher likelihood of resolving initial and preventing recurrent CLTI symptoms in cohort 1, including after adjustment for key baseline patient covariates (end-stage renal disease [ESRD], prior revascularization, smoking, diabetes, age >80 years, WIfI stage, tissue loss, and infrapopliteal disease). Factors independently associated with clinical failure included age >80 years in cohort 1 and ESRD across both cohorts. ESRD was associated with hemodynamic failure in cohort 1. Factors associated with slower resolution of presenting symptoms included diabetes in cohort 1 and WIfI stage in cohort 2. ConclusionsDurable clinical and hemodynamic benefit after revascularization for CLTI is important to avoid persistent and recurrent CLTI, reinterventions, and limb loss. When compared with ENDO, initial treatment with OPEN surgical bypass, particularly with available saphenous vein, is associated with improved clinical and hemodynamic outcomes and enhanced resolution of CLTI symptoms.

Effect of alprostadil plus cilostazol on the treatment outcomes and inflammatory factors in patients with lower extremity arteriosclerosis obliterans receiving evidence-based care.

This study aims to elucidate the effect of alprostadil (ALP) plus cilostazol (CIL) on the treatment outcomes and inflammatory factors in patients with lower extremity arteriosclerosis obliterans (LEASO) receiving evidence-based care. Firstly, 130 patients with LEASO were selected from February 2020 to February 2023 and then randomly divided into two groups with 65 patients each. Excluding the dropouts, 59 patients in the control group (6 cases of dropout) received ALP and 62 patients in the research group (3 cases of dropout) received ALP plus CIL. Both groups were cared for in accordance with the evidence-based care model. Treatment outcomes, arteriosclerosis indexes (blood flow of dorsalis pedis artery [DPA], ankle-brachial index [ABI] and toe-brachial index [TBI]), hemorheological parameters (erythrocyte aggregation index [EAI], erythrocyte deformation index [EDI], high blood viscosity [HBV] and haematocrit [HCT]), inflammatory factors (interleukin [IL]-6, IL-8 and tumour necrosis factor [TNF]-α) and complications (nausea, diarrhoea, headache and transaminase elevation) were compared between the control and research groups. Results show that the overall response rate was markedly higher in the research group (90.32%) than in the control group (74.58%). Additionally, the blood flow of DPA, ABI and TBI in the research group significantly increased after the treatment and were higher than those in the control group. Meanwhile, the EAI, EDI, HBV, HCT, IL-6, IL-8 and TNF-α were significantly lower. The two groups did not differ markedly in the complication rate. The above findings suggest that ALP plus CIL is effective for patients with LEASO receiving evidence-based care. It can significantly improve arteriosclerosis indexes and hemorheological parameters while inhibiting serum inflammatory responses, with some certain safety.

Utility of Toe-Brachial Index for CME Credit June 2024

Utility of Toe-Brachial Index for CME Credit June 2024

Sensitivity and Specificity of the Toe-brachial Index Compared to the Ankle-brachial Index, as a Screening Tool for Peripheric Arterial Disease in Patients With Chronic Renal Disease

Sensitivity and Specificity of the Toe-brachial Index Compared to the Ankle-brachial Index, as a Screening Tool for Peripheric Arterial Disease in Patients With Chronic Renal Disease

Pedal Acceleration Time An Alternative Tool To Ankle-Brachial Index In Peripheral Arterial Disease.

Ankle-Brachial Index (ABI) is a well-established diagnostic tool for evaluating peripheral arterial disease (PAD). Limitations in its application led to the development of alternative diagnostic methods, including Toe-Brachial Index (TBI) and Transcutaneous Pressure of Oxygen (TcPO2), yet these are not as widely available as ABI. Recently, Pedal Acceleration Time (PAT), has gained popularity as a new tool to assess PAD, requiring only an ultrasound. This study seeks to further establish the correlation between ABI and PAT, determining whether PAT can be a reliable alternative for diagnosing and assessing the severity of PAD. ABI and PAT were measured in patients attending our consult with no history of vascular or endovascular surgery. Limbs with unmeasurable ABI were excluded. Patients were categorized into groups based on their PAD stage according to the Fontaine classification. Patient demographics, comorbidities and respective ABI and PAT were analysed. Sixty-nine patients (114 limbs) were included in the study. Mean age 68 ± 11.7 years, 78.3% male and 33.3% diabetic patients. Fifty-three claudicant limbs (46.5%) and 26 limbs (22.8%) with chronic limb threatening ischemia. Pearson correlation coefficient between ABI and PAT, showed a strong negative correlation (r= -0.78; p<0.01). Mean ABI and PAT for limbs in Fontaine stage I were 0.94 ± 0.17 and 82.0 ± 27.4 ms; Fontaine stage IIa 0.69 ± 0.21 and 141.3 ± 57.8 ms; Fontaine stage IIb 0.54 ± 0.14 and 173.4 ± 65.1 ms; Fontaine stage III 0.43 ± 0.15 and 216 ± 33.2 ms; Fontaine stage IV 0.49 ± 0.17 and 206.7 ± 78.1 ms, respectively. Our study suggests an inverse correlation between ABI and PAT, in accordance with the findings published in the literature, thus supporting the use of PAT as an easily reproducible and efficient alternative to ABI for evaluating the severity of PAD.

Utility of Toe-Brachial Index

Introduction: The toe-brachial index is typically an adjunctive examination to the ankle-brachial index, which has long been the primary physiologic modality for diagnosing peripheral arterial disease. The goal of this project was to determine toe-brachial index reliability, particularly with patients with diabetes. Methods: We compared duplex ultrasound to the ankle-brachial index and toe-brachial index on 100 patients (200 legs) with suspected symptomatic peripheral arterial disease. Duplex ultrasound stenosis in the femoral/popliteal/infrapopliteal arteries was at least a doubling of velocity between adjacent segments. A blunted systolic Doppler waveform was consistent with proximal occlusive disease. Normal physiologic ranges were arbitrarily set as ankle-brachial index 1.2 to 0.9 and toe-brachial index 0.9 to 0.5. We calculated overall sensitivity/specificity values by averaging. Results: Both physiologic modalities had overall low sensitivity (ankle-brachial index 62%, toe-brachial index 56%). In diabetics, ankle-brachial index sensitivity was 61% and toe-brachial index sensitivity was 57%. Sensitivity improved in the presence of inflow disease (ankle-brachial index 78%, toe-brachial index 63%). Both modalities had good overall specificity (ankle-brachial index 96%, toe-brachial index 86%). In patients with diabetes, the ankle-brachial index specificity was 94% and toe-brachial index specificity was 79%. Both physiologic modalities had identical accuracy (0.43) in comparison to duplex ultrasound. Conclusion: Routine toe-brachial index in conjunction with the ankle-brachial index may not be clinically productive.

Does PAD and microcirculation status impact the tissue availability of intravenously administered antibiotics in patients with infected diabetic foot? Results of the DFIATIM substudy.

The aim of this substudy (Eudra CT No:2019-001997-27)was to assess ATB availability in patients with infected diabetic foot ulcers(IDFUs)in the context of microcirculation and macrocirculation status. For this substudy, we enrolled 23 patients with IDFU. Patients were treated with boluses of amoxicillin/clavulanic acid(AMC)(12patients) or ceftazidime(CTZ)(11patients). After induction of a steady ATB state, microdialysis was performed near the IDFU. Tissue fluid samples from the foot and blood samples from peripheral blood were taken within 6 hours. ATB potential efficacy was assessed by evaluating the maximum serum and tissue ATB concentrations(Cmax and Cmax-tissue)and the percentage of time the unbound drug tissue concentration exceeds the minimum inhibitory concentration (MIC)(≥100% tissue and ≥50%/60% tissue fT>MIC). Vascular status was assessed by triplex ultrasound, ankle-brachial and toe-brachial index tests, occlusive plethysmography comprising two arterial flow phases, and transcutaneous oxygen pressure(TcPO2). Following bolus administration, the Cmax of AMC was 91.8 ± 52.5 μgmL-1 and the Cmax-tissue of AMC was 7.25 ± 4.5 μgmL-1(P<0.001). The Cmax for CTZ was 186.8 ± 44.1 μgmL-1 and the Cmax-tissue of CTZ was 18.6 ± 7.4 μgmL-1(P<0.0001). Additionally, 67% of patients treated with AMC and 55% of those treated with CTZ achieved tissue fT>MIC levels exceeding 50% and 60%, respectively. We observed positive correlations between both Cmax-tissue and AUCtissue and arterial flow. Specifically, the correlation coefficient for the first phase was r=0.42; (P=0.045), and for the second phase, it was r=0.55(P=0.01)and r=0.5(P=0.021). Bactericidal activity proved satisfactory in only half to two-thirds of patients with IDFUs, an outcome that appears to correlate primarily with arterial flow.

Peripheral artery disease patients with chronic kidney disease have lower muscle strength and mitochondrial function compared to those with normal kidney function

Introduction: Chronic kidney disease is a significant risk factor for both the development of peripheral artery disease (PAD) and major adverse limb events. However, little is known about how the coalescence of these two conditions impacts limb muscle pathophysiology. The objective of the current study was to determine the impact of CKD on skeletal muscle strength and mitochondrial health in patients with and without PAD. Methods: A cross-sectional prospective study design was employed to assess plantar flexor muscle strength, muscle fiber cross-sectional area (CSA), and mitochondrial health in four groups of patients (61 males and 29 females): PAD only (Toe brachial index, TBI&lt;0.5 and eGFR&gt;60 mL/min), CKD only (TBI&gt;0.75 and eGFR:15-45 mL/min), PAD with CKD (TBI&lt;0.5 and eGFR:15-45 mL/min), and adult controls without PAD and CKD (TBI&gt;0.75 and eGFR&gt;60 mL/min). Results: Plantar flexor muscle strength was lowest in PAD patients with CKD compared to adult controls ( P&lt;0.0001), PAD only ( P=0.001), and CKD only ( P=0.003). No differences in the mean muscle fiber CSA were detected. The percentage of COX+ fibers was significantly lower in PAD patients with CKD compared to adult controls ( P=0.03). High resolution respirometry analysis of mitochondrial oxidative phosphorylation (OXPHOS) function demonstrated that CKD has a significant negative impact on muscle bioenergetics. PAD patients with CKD had lower OXPHOS function than adult controls ( P=0.0016) and PAD patients without CKD ( P=0.0015). Notably, CKD patients without PAD also had lower OXPHOS function than adult controls ( P=0.0054) and PAD patients without CKD ( P=0.005). Conclusion: The current results demonstrate a profound negative impact of CKD on the associated myopathy of PAD patients. This study was supported by National Institutes of Health (NIH) grant R01-HL149704 (T.E.R.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract 3027: Home-based, High-pressure Intermittent Limb Compression Following Lower Extremity Revascularization In Patients With Severe Peripheral Artery Disease: A Pilot Trial

Objective: Many patients who undergo lower extremity revascularization (LER) for peripheral artery disease (PAD) continue to experience mobility impairment despite adequate revascularization. High-pressure intermittent limb compression (HPILC) has been shown to augment leg blood flow and improve walking endurance in symptomatic PAD patients. This pilot trial aimed to examine the feasibility of home-based HPILC for 2 hours daily over 3 consecutive months in patients who underwent LER for PAD. The primary outcome was the change in 6-minute walk distance from baseline to 3-month follow-up. Methods: Three months following LER, 9 participants were randomly assigned to either HPILC (n=5) or a sham (n=4) group. Participants were provided with a portable pneumatic air pump and inflatable cuffs that were wrapped around the feet, ankles, and calves (ArtAssist, ACI Medical). The inflation pressures were 120 mmHg and 30 mmHg in the HPILC and sham devices, respectively. A built-in timer, inaccessible to participants, provided one estimate of treatment compliance. Outcomes were assessed before and after the completion of the 3-month interventions. Results: Among the 9 randomized participants, one individual required reintervention and was withdrawn from the study. Adherence to treatment was 74% for HPILC and 92% for sham. As shown in Figure 1, the change in 6-minute walk distance from baseline tended to be higher in the HPILC group compared to the sham-treated group (HPILC: 35.2±38.7 m vs. Sham: -14.7±25 m, p=0.07). There were no group differences in the secondary outcomes, including the changes in the ankle-brachial index, the toe-brachial index, and the Vascular Quality of Life questionnaire scores. Conclusions: Home-based HPILC following LER for PAD is feasible, well-tolerated, and appears to improve walking performance. These preliminary findings indicate that HPILC may be a useful adjunct therapy to enhance lower extremity functioning in patients recovering from LER.