Hypertension in Patients With Peripheral Artery Disease: An Updated Literature Review.

Peripheral artery disease (PAD), a condition where there is reduced blood flow due to narrowing or blockage of the arteries of the peripheral vasculature, is an epidemic that currently affects eight million people in the United States alone and is a major risk equivalent to having active coronary artery disease (CAD). However, it is commonly underdiagnosed in the general population. Hypertension is a common cardiovascular condition characterized by elevated blood pressure levels. There are several mitigating risk factors that can reduce the risk of complications of PAD, with hypertension playing a major role. This literature review aims to explore the relationship between hypertension and PAD, including their shared risk factors, pathophysiological mechanisms, and management strategies. In addition, we will analyze how this impacts major cardiovascular outcomes, such as critical limb ischemia, vascular amputation, myocardial infarction (MI), ischemic stroke, and cardiovascular-related death by examining relevant studies, current guidelines, and evidence. This literature review is intended to guide practitioners on ideal blood pressure parameters and evidence-based anti-hypertensives that provide overall cardiovascular benefit in both the primary care and hospital-based setting. By understanding the association between hypertension and PAD and the underlying pathophysiological mechanisms, healthcare professionals can improve diagnosis, treatment, and management strategies for affected individuals.

Peripheral Artery Disease among a High-Risk Asian Population with Ischaemic Stroke, Cardiovascular Disease, or Diabetes Mellitus.

Background: Peripheral artery disease (PAD) affects more than 100 million people globally. Most PAD studies have been performed among predominantly White populations-less is known about other ethnicities. The aim of this cross-sectional study was to determine the prevalence and risk factors of PAD in a high-risk Asian population with ischaemic stroke (IS), myocardial infarction, unstable angina (CVD), or diabetes mellitus (DM). Methods: Patients admitted for IS, CVD, or DM were recruited. Data were collected on age, sex, body mass index (BMI), index condition (CVD, IS, DM), history of hypertension, DM, hypercholesterolaemia, cigarette smoking, and claudication. The Edinburgh Claudication Questionnaire was administered, the ankle brachial index (ABI) was determined, and PAD was diagnosed if ABI was ≤0.9. Results: Of the 450 subjects recruited, 150 were placed in each index disease group, the mean age was 61.9 ± 10.32 years, 43.1% were female, and the mean BMI was 23.9 ± 4.3. Hypertension was reported in 59.3%, DM in 63.6%, hypercholesterolaemia in 39.6%, and smoking in 42.9% of patients. The prevalence of PAD was 27.1%, 22.0% in IS, 29.3% in CAD, and 30.0% in DM. PAD was associated with increasing age (adjusted odds ratio (aOR) 1.04/year, 95% confidence interval [CI] 1.01-1.06; p < 0.001), reduced BMI (aOR 0.94, 95% CI 0.89-0.99; p = 0.026), DM (aOR 1.59, 95% CI 1.20-3.18; p = 0.007), and hypercholesterolaemia (aOR 1.82, 95% CI 1.17-2.28; p = 0.007). It was more frequent in non-lacunar versus lacunar acute IS, non-ST segment elevation versus ST-segment elevation acute myocardial infarction, and insulin-treated versus non-insulin-treated DM. Conclusions: Our study showed a high prevalence of PAD among high-risk Asian patients. This was associated with increasing age, DM, and hypercholesterolaemia and inversely associated with BMI. Different rates were found in sub-groups of IS, CVD, and DM. Systematic approaches were used to identify these high-risk individuals and to improve their outcomes.

Ghrelin Expression in Atherosclerotic Plaques and Perivascular Adipose Tissue: Implications for Vascular Inflammation in Peripheral Artery Disease.

Atherosclerosis, a leading cause of peripheral artery disease (PAD), is driven by lipid accumulation and chronic inflammation within arterial walls. Objectives: This study investigates the expression of ghrelin, an anti-inflammatory peptide hormone, in plaque morphology and inflammation in patients with PAD, highlighting its potential role in age-related vascular diseases and metabolic syndrome. Methods: The analysis specifically focused on the immunohistochemical expression of ghrelin in atherosclerotic plaques and perivascular adipose tissue (PVAT) from 28 PAD patients. Detailed immunohistochemical staining was performed to identify ghrelin within these tissues, comparing its presence in various plaque types and assessing its association with markers of inflammation and macrophage polarization. Results: Significant results showed a higher prevalence of calcification in fibro-lipid plaques (63.1%) compared to fibrous plaques, with a notable difference in inflammatory infiltration between the two plaque types (p = 0.027). Complicated plaques exhibited increased ghrelin expression, suggesting a modulatory effect on inflammatory processes, although this did not reach statistical significance. The correlation between ghrelin levels and macrophage presence, especially the pro-inflammatory M1 phenotype, indicates ghrelin's involvement in the inflammatory dynamics of atherosclerosis. Conclusions: The findings propose that ghrelin may influence plaque stability and vascular inflammation, pointing to its therapeutic potential in managing atherosclerosis. The study underlines the necessity for further research to clarify ghrelin's impact on vascular health, particularly in the context of metabolic syndrome and age-related vascular alterations.

The Incidence and Outcomes of Major Limb Amputation in New Zealand from 2010 to 2021.

Background: Major limb amputation (MLA) can be a common outcome due to severe peripheral artery disease (PAD) and diabetic foot disease (DFD), and it carries a significant mortality burden. In New Zealand (NZ), there is little documentation of the incidence rate and mortality after MLA. The aim was to report the national crude and standardised rates and the mortality post MLA. Methods: This retrospective observational study included all MLAs that occurred within NZ from 1/1/2010 to 31/12/2021 due to DFD and/or PAD. Two national databases (National Minimum Dataset and the Australasian Vascular Audit) were utilised. The crude rates were calculated as cases per 100,000 in the NZ population per year including all ages (using the 2013 and 2018 NZ census figures). The age-standardised rates used the World Health Organization standard population. Post-operative mortality was calculated from the date of first hospitalisation for MLA. Results: From 2010 to 2021, there were 5293 MLA procedures in 4242 patients. On average, there were 8.5 MLAs per week and 441.1 MLAs annually. The overall crude rate was 9.44 per 100,000, and the standardised rate was 6.12 per 100,000. Over the 12 years, the crude rate decreased by 22% (p < 0.001), and the standardised rate decreased by 20.4% (p < 0.001). After MLA, the 30-day and 1-year mortality was 9.5% and 29.6%, respectively. From 2010 to 2021, the relative reduction in 30-day mortality was 45.1% (p < 0.001), and the reduction in 1-year mortality was 24.5% (p < 0.001). Increasing age, female sex and end-stage renal failure were predictors of 30-day and 1-year mortality. Conclusions: A considerable number of MLAs occur in NZ, with substantial perioperative mortality; however, the national incidence rates and mortality have improved over the last 12 years. This data might serve as benchmark to further reduce MLAs and improve patient outcomes.

Participation of Arterial Ischemia in Positional-Related Symptoms among Patients Referred for Thoracic Outlet Syndrome.

Objectives: The coexistence of arterial compression with neurogenic thoracic outlet syndrome (TOS) is associated with a better post-surgical outcome. Forearm transcutaneous oxygen pressure (TcpO2) using the minimal decrease from rest of oxygen pressure (DROPmin) can provide an objective estimation of forearm ischemia in TOS. We hypothesized that a linear relationship exists between the prevalence of symptoms (PREVs) and DROPmin during 90° abduction external rotation (AER) provocative maneuvers. Thereafter, we aimed to estimate the proportion of TOS for which arterial participation is present. Methods: Starting in 2019, we simultaneously recorded forearm TcpO2 recordings (PF6000 Perimed®) and the presence/absence of ipsilateral symptoms during two consecutive 30 s AER maneuvers for all patients with suspected TOS. We retrospectively analyzed the relationship between the prevalence of symptoms and DROPmin results. We estimated the number of cases where ischemia likely played a role in the symptoms, assuming that the relationship should start from zero in the absence of ischemia and increase linearly to a plateau of 100% for the most severe ischemia. Results: We obtained 2560 TcpO2 results in 646 subjects (69% females). The correlation between PREVs and DROPmin was 0.443 (p < 0.001). From these results, we estimated the arterial participation in TOS symptoms to be 22.2% of our 1669 symptomatic upper limbs. Conclusions: TcpO2 appears to be an interesting tool to argue for an arterial role in symptoms in TOS. Arterial participation is frequent in TOS. Whether DROPmin could predict treatment outcomes better than the sole presence of compression is an interesting direction for the future.

Applications of SPECT and PET Imaging for the Physiological Evaluation of Lower Extremity Peripheral Artery Disease.

Peripheral artery disease (PAD) is classified as the narrowing or complete occlusion of the lower extremity arteries due to atherosclerosis. The risk of developing PAD increases with increased age and risk factors such as smoking, diabetes, hypertension, and hypercholesterolemia. Current treatment for PAD involves lifestyle and symptom management, statin and antiplatelet therapy, and/or surgical interventions to improve quality of life with varying efficacy. PAD affects approximately 5 to 6 percent of the global population, with this global burden continuing to increase. Despite the increase in disease prevalence, no gold standard functional diagnostic tool has been established for enabling early detection of the disease, appropriate medical management, and prediction of adverse outcomes for PAD patients. The visualization and quantification of the physiological consequences of PAD are possible by way of nuclear imaging: specifically, via scintigraphy, single-photon emission computed tomography (SPECT), and positron emission tomography (PET) imaging. These non-invasive modalities, when combined with targeted radionuclides, possess utility for detecting functional perfusion deficits and provide unique insight into muscle tissue- and vascular-level characteristics of PAD patients. This review discusses the past, present, and emerging applications of hybrid nuclear imaging modalities in the evaluation and monitoring of patients with PAD.

Method for assessing coating uniformity of angioplasty balloons coated with poly(lactic-co-glycolic acid) nanoparticles loaded with quercetin.

In this study, we aim to quantify coating uniformity and correlate fluorescence intensity to drug loading for drug-coated angioplasty balloons (DCB) coated with 5, 10, 15, or 20 layers of poly(lactic-co-glycolic acid) nanoparticles (NPs) entrapped with quercetin. Uniformity was quantified from histograms and horizontal line profiles of microscopic fluorescent images acquired with sample specific parameters, and cracks in the coating were measured and counted. The fluorescence of images acquired with global parameters was correlated with quercetin loading measured via gravimetric/HPLC analysis. More layers on DCBs may be associated with less uniform coatings, as indicated by differences in histogram standard deviations. The line profile percent deviation from average for each sample was <20%. Cracks were present on all balloons, but their length was not significantly different between samples. The 5-layer DCBs had the fewest cracks, whereas the 15-layer DCBs had the most cracks. A strong positive correlation (R = 0.896) was identified between fluorescence intensity and drug loading. A relationship between the number of layers and coating uniformity seems to exist, but further investigations are required for confirmation. Fluorescence intensity appears to strongly predict drug loading, demonstrating that fluorescent imaging may be a viable alternative to drug release studies.

Antimicrobial resistance is not increasing in subsequent cases of ischaemic foot infections, a single-centre cohort from 2012 to 2021.

Patients with chronic limb-threatening ischaemia (CLTI) are at risk of foot infections, which is associated with an increase in amputation rates. The use of antibiotics may lead to a higher incidence of antimicrobial resistance (AMR) in subsequent episodes of ischaemic foot infections (IFI). This retrospective single-centre cohort study included 130 patients with IFI undergoing endovascular revascularisation. Staphylococcus aureus and Pseudomonas aeruginosa were the two most common pathogens, accounting for 20.5% and 10.8% of cases, respectively. The prevalence of antimicrobial resistance (AMR) and multi-drug resistance did not significantly increase between episodes (10.2% vs. 13.4%, p = 0.42). In 59% of subsequent episodes, the identified pathogens were unrelated to the previous episode. However, the partial concordance of identified pathogens significantly increased to 66.7% when S. aureus was identified (p = 0.027). Subsequent episodes of IFI in the same patient are likely to differ in causative pathogens. However, in the case of S. aureus, the risk of reinfection, particularly with S. aureus, is increased. Multi-drug resistance does not appear to change between IFI episodes. Therefore, recommendations for empirical antimicrobial therapy should be based on local pathogen and resistance statistics without the need to broaden the spectrum of antibiotics in subsequent episodes.

The Association Between Triglyceride-Glucose Index and Its Combination with Obesity Indicators and Lower Extremity Peripheral Artery Disease in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study.

Background: Lower extremity peripheral artery disease (LEAD) is a significant chronic complication of type 2 diabetes mellitus (T2DM) that significantly contributes to disability and mortality. The subtle presentation of LEAD symptoms often leads to underrecognition and misdiagnosis. Therefore, identifying simple and effective evaluation indicators is essential for the early detection and management of LEAD. Insulin resistance is closely associated with diabetes and its complications. However, the specific relationship between insulin resistance-measured by the triglyceride-glucose (TyG) index-and obesity indicators in relation to LEAD remains unclear. Objective: This study aims to investigate the association between the TyG index and its combination with obesity indicators in participants with T2DM and LEAD. Methods: We performed a univariate analysis on 3176 T2DM patients to identify risk factors for LEAD. Patients were then divided into quartiles based on the TyG index combined with various obesity indicators. The chi-square test was used to compare the prevalence of LEAD across these groups. Logistic regression analysis was conducted to examine the association between the TyG index, in combination with different obesity indicators, and the occurrence of LEAD. Finally, we assessed the predictive ability of the TyG index combined with obesity indicators for LEAD by comparing the area under the ROC curve (AUC). Results: The study included 3176 T2DM patients (1691 males and 1485 females) with a mean age of 56.16±10.60 years. Among them, 106 individuals had LEAD. The prevalence of LEAD varied significantly across quartiles of the TyG index, TyG-WC, and TyG-WHR (Q4 > Q3 > Q2 > Q1; P < 0.05). Multiple logistic regression analysis showed that the TyG index, TyG-WC, and TyG-WHR were positively associated with the risk of LEAD in T2DM patients. ROC curve analysis identified the best cutoff values for predicting LEAD: 9.8059 for the TyG index (sensitivity: 49.1%, specificity: 67.9%, AUC: 0.583), 808.8397 for TyG-WC (sensitivity: 70.8%, specificity: 47.8%, AUC: 0.603), and 8.8543 for TyG-WHR (sensitivity: 75.5%, specificity: 44.6%, AUC: 0.607). Conclusion: In T2DM patients, the TyG index, TyG-WHR, and TyG-WC are positively associated with the occurrence of LEAD. TyG-WHR and TyG-WC exhibit a stronger correlation with LEAD compared to the TyG index alone, indicating their superior diagnostic value.

Balloon-expandable cobalt chromium stent versus self-expandable nitinol stent for the Atherosclerotic Iliac Arterial Disease (SENS-ILIAC Trial) Trial: a randomized controlled trial.

Iliac artery angioplasty with stenting is an effective alternative treatment modality for aortoiliac occlusive diseases. Few randomized controlled trials have compared the efficacy and safety between self-expandable stent (SES) and balloon-expandable stent (BES) in atherosclerotic iliac artery disease. In this randomized, multicenter study, patients with common or external iliac artery occlusive disease were randomly assigned in a 1:1 ratio to either BES or SES. The primary end point was the 1-year clinical patency, defined as freedom from any surgical or percutaneous intervention due to restenosis of the target lesion after the index procedure. The secondary end point was a composite event from major adverse clinical events at 1 year. A total of 201 patients were enrolled from 17 major cardiovascular intervention centers in South Korea. The mean age of the enrolled patients was 66.8 ± 8.5 years and 86.2% of the participants were male. The frequency of critical limb ischemia was 15.4%, and the most common target lesion was in the common iliac artery (75.1%). As the primary end point, the 1-year clinical patency as primary end point was 99% in the BES group and 99% in the SES group (p > 0.99). The rate of repeat revascularization at 1 year was 7.8% in the BES group and 7.0% in the SES group (p = 0.985; confidence interval, 1.011 [0.341-2.995]). In our randomized study, the treatment of iliac artery occlusive disease with self-expandable versus balloon-expandable stent was comparable in 12-month clinical outcomes without differences in the procedural success or geographic miss rate regardless of the deployment method in the distal aortoiliac occlusive lesion (ClinicalTrials.gov, NCT01834495).

Importance of Using Angiography for the Early Detection of Chronic Limb Ischemia in Diabetic Foot Wounds.

Peripheral artery disease (PAD) affects millions of people worldwide, presenting with varying symptom severity, including chronic total occlusion of arteries, and occasionally, limb amputation. There are various interventions, such as atherectomy and the use of drug-coated balloons and stents, which have been developed to revascularize affected ischemic regions. However, each interventional approach must be individualized due to a patient's unique underlying conditions. Comorbid conditions, especially diabetes, play a significant role in PAD, as poorly controlled diabetes can accelerate PAD progression. For this reason, an early and accurate diagnosis of PAD is crucial, especially when symptoms may present dissimilar to classic PAD symptoms, often leading to misdiagnosis. The presented cases highlight the tailored interventions to revascularize arteries in patients with diabetic foot wounds utilizing catheters, stents, guidewires, and balloons, made possible after early angiogram. These interventions have been promising in treating PAD patients, and highlight the need for early diagnosis and timely and customized interventions to prevent limb amputation and mitigate potential complications.

Association of endothelial function and lower extremity perfusion in peripheral artery disease.

Background: The current study aims to investigate the association between endothelial function and lower extremity perfusion in patients with peripheral artery disease (PAD). Patients and methods: In total 229 patients with PAD (Rutherford stage 0-3) were enrolled in the current study. Endothelial function was assessed by measuring flow-mediated dilation (FMD) and endothelial cell proliferation capacity (ECPC). Lower extremity perfusion was assessed by measuring oscillometry-based ankle brachial index (oABI) and pulse wave index (PWI). In addition, carotid intima-media-thickness (cIMT) was also measured as a surrogate marker for atherosclerosis. Correlations between FMD, ECPC, oABI, PWI, and cIMT were analysed using Pearson correlation coefficient. The relationship between the above variables and the severity of PAD was investigated using ordinal logistic regression analysis. Results: Correlation analysis showed that FMD negatively associated with PWI (r = -0.183, p = 0.005), ECPC positively associated with oABI (r = 0.162, p = 0.014), and oABI negatively associated with PWI (r = -0.264, p < 0.001). Ordinal logistic regression analysis showed that ECPC (ß = -0.009, p = 0.048), oABI (ß = -5.290, p < 0.001), and age (ß = -0.058, p = 0.002) negatively associated with the PAD Rutherford stages. In addition, PWI (ß = 0.006, p < 0.001), cIMT (ß = 18.363, p = 0.043) positively associated with the PAD Rutherford stages. Conclusions: Endothelial function significantly associates with lower extremity perfusion in patients with PAD, and both are related to the severity of PAD.

Comparing the efficacy and safety of endovascular therapy versus surgical revascularization for critical limb-threatening ischemia: A systematic review and meta-analysis.

INTRODUCTION: Critical limb-threatening ischemia (CLTI) is a severe manifestation of peripheral artery disease (PAD) that can lead to limb amputation and significantly reduce the quality of life. In addition to guideline-directed medical therapy (GDMT), endovascular therapy and surgical revascularization are the two revascularization options for CLTI. In recent years, there has been an ongoing debate about the best approach for CLTI patients. The purpose of this meta-analysis is to examine the current evidence and compare the clinical outcomes of endovascular therapy and surgical revascularization for CLTI. METHODS: We conducted a systematic search of electronic databases (PubMed, Embase, Cochrane Library, and Web of Science) for studies comparing the outcomes of endovascular therapy versus surgery in patients with CLTI. The primary outcomes were major adverse limb events (MALE) and major adverse cardiovascular events (MACE), while secondary outcomes included risk of bleeding, wound complications, readmission, unplanned reoperation, acute renal failure, and length of hospital stay. Pooled data was analyzed using the fixed-effect model or the random-effect model in Review Manager 5.3. The Newcastle-Ottawa Scale and Cochrane risk of bias assessment tool were used to assess the bias of included studies. RESULTS: A total of 16 studies (47,609 patients) were included in this meta-analysis. The overall effect favors surgery over endovascular intervention in terms of MALE [odds ratio (OR) 1.13, 95% CI (1.01-1.28), P = 0.04]. Endovascular therapy is associated with lower MACE rates compared to surgery [OR 0.62, 95% CI (0.51-0.76), P < 0.00001]. Furthermore, the risk of bleeding, wound complications, readmission, unplanned reoperation, acute renal failure as well as the length of hospital stay was lower for endovascular intervention. Finally, there was no statistically significant difference in 30-day mortality between the two groups [OR 0.94, 95% CI 0.79-1.12, P = 0.52; Fig. 3i], and the pooled studies were homogeneous [P = 0.39; I2 = 5%]. CONCLUSION: Surgery may be the preferred treatment option for CLTI patients, as it is associated with a lower risk of MALE than endovascular therapy. However, endovascular therapy may be associated with a lower risk of MACE and lower rates of bleeding, wound complications, readmission, unplanned reoperation, acute renal failure, and shorter hospital stays. There was no statistically significant difference in 30-day mortality between the two groups. Ultimately, the decision to use endovascular therapy or surgery as the primary treatment strategy should be based on a multi-disciplinary team approach with careful consideration of patient characteristics and anatomy.

Peripheral artery disease, chronic kidney disease, and recurrent admissions for acute decompensated heart failure: The ARIC study.

BACKGROUND AND AIMS: Peripheral artery disease (PAD) has not only been associated with recurrent hospitalization for acute decompensated heart failure (ADHF) but is also associated with chronic kidney disease (CKD), a known risk factor for worse heart failure outcomes. The interaction of CKD with PAD in post-discharge ADHF outcomes is not well known. METHODS: Since 2005, hospitalizations for ADHF were sampled from 4 US regions by the Atherosclerosis Risk in Communities (ARIC) study and classified by physician review. We examined the adjusted association of PAD with 1-year ADHF readmissions, in patients with and without CKD (defined by glomerular filtration rate [GFR] ≤60 mL/min/1.73 m2 [stage 3a or worse]). RESULTS: From 2005 to 2018, there were 1049 index hospitalizations for patients with ADHF (mean age 77 years, 66 % white) with creatinine data, who were discharged alive. Of these, 155 (15 %) had PAD and 66 % had CKD. In comparison to those without PAD, patients with PAD had more comorbid conditions and higher 1-year ADHF readmission rates, irrespective of CKD status. After adjustment, PAD was associated with a greater risk of 1-year ADHF readmissions, both for patients with concomitant CKD (HR, 1.70; 95 % CI: 1.29-2.24) and those without CKD (HR, 1.97; 95 % CI: 1.14-3.40); p-interaction = 0.8. CONCLUSION: Among patients hospitalized with ADHF, those with concurrent PAD have more prevalent cardiovascular comorbidities and higher likelihood of 1-year ADHF readmission, irrespective of CKD status. Integrating a more holistic approach in management of patients with concomitant heart failure, PAD and CKD may be an important strategy to improve the prognosis in this vulnerable population.

Characterization of Peripheral Artery Disease and Associations with Traditional Risk Factors, Mobility, and Biomarkers in the Project Baseline Health Study.

BACKGROUND: There is a dearth of research on immunophenotyping in peripheral artery disease (PAD). This study aimed to describe the baseline characteristics, immunophenotypic profile, and quality of life (QoL) of participants with PAD in the Project Baseline Health Study (PBHS). METHODS: The PBHS study is a prospective, multi-center, longitudinal cohort study that collected clinical, molecular, and biometric data from participants recruited between 2017 and 2018. In this analysis, baseline demographic, clinical, mobility, QoL, and flow cytometry data were stratified by the presence of PAD (ankle brachial index [ABI] ≤0.90). RESULTS: Of 2,209 participants, 58 (2.6%) had lower-extremity PAD, and only 2 (3.4%) had pre-existing PAD diagnosed prior to enrollment. Comorbid smoking (29.3% vs. 14%, p<0.001), hypertension (54% vs. 30%, p<0.001), diabetes (25% vs. 14%, p=0.031), and at least moderate coronary calcifications (Agatston score >100: 32% vs. 17%, p=0.01) were significantly higher in participants with PAD than in those with normal ABIs, as were high-sensitivity C-reactive protein levels (5.86 vs. 2.83, p<0.001). After adjusting for demographic and risk factors, participants with PAD had significantly fewer circulating CD56-high natural killer cells, IgM+ memory B cells, and CD10/CD27 double-positive B cells (p<0.05 for all). CONCLUSIONS: This study reinforces existing evidence that a large proportion of PAD without claudication may be underdiagnosed, particularly in female and Black or African American participants. We describe a novel immunophenotypic profile of participants with PAD that could represent a potential future screening or diagnostic tool to facilitate earlier diagnosis of PAD. GOV IDENTIFIER: NCT03154346, https://clinicaltrials.gov/ct2/show/NCT03154346.

Impact of hyper-polypharmacy due to non-cardiovascular medications on long-term clinical outcomes following endovascular treatment for lower limb artery disease: A sub-analysis of the I-PAD Nagano registry.

BACKGROUND: Lower limb artery disease (LEAD) is accompanied by multiple comorbidities; however, the effect of hyperpolypharmacy on patients with LEAD has not been established. This study investigated the associations between hyperpolypharmacy, medication class, and adverse clinical outcomes in patients with LEAD. METHODS: This study used data from a prospective multicenter observational Japanese registry. A total of 366 patients who underwent endovascular treatment (EVT) for LEAD were enrolled in this study. The primary endpoints were major adverse cardiac events (MACE), including myocardial infarction, stroke, and all-cause death. RESULTS: Of 366 patients with LEAD, 12 with missing medication information were excluded. Of the 354 remaining patients, 166 had hyperpolypharmacy (≥10 medications, 46.9 %), 162 had polypharmacy (5-9 medications, 45.8 %), and 26 had nonpolypharmacy (<5 medications, 7.3 %). Over a 4.7-year median follow-up period, patients in the hyperpolypharmacy group showed worse outcomes than those in the other two groups (log-rank test, p < 0.001). Multivariate analysis revealed that the total number of medications was significantly associated with an increased risk of MACE (hazard ratio per medication increase 1.07, 95 % confidence interval 1.02-1.13 p = 0.012). Although an increased number of non-cardiovascular medications was associated with an elevated risk of MACE, the increase in cardiovascular medications was not statistically significant (log-rank test, p = 0.002 and 0.35, respectively). CONCLUSIONS: Hyperpolypharmacy due to non-cardiovascular medications was significantly associated with adverse outcomes in patients with LEAD who underwent EVT, suggesting the importance of medication reviews, including non-cardiovascular medications.

Introduction of novel intravascular ultrasound preceding with angled guiding catheter (I-PAD) technique to treat chronic total occlusions in peripheral artery disease.

BACKGROUND: The optimal endovascular treatment (EVT) for chronic total occlusion (CTO) lesions in patients with peripheral artery disease (PAD) has remained unestablished. We encountered a patient with PAD in whom CTO was successfully treated using a novel technique that involved intravascular ultrasound (IVUS) and angled guiding catheter: IVUS Preceding with Angled guiDing catheter (I-PAD) technique. CASE PRESENTATION: A 74-year-old male presented with intermittent claudication attributed to CTO of the right external iliac artery. EVT was performed via the right common femoral artery. We retrogradely advanced the I-PAD system (i.e. partially extending the IVUS transducer portion from the tip of the angled guiding catheter) in the CTO lesion under the real-time guidance of IVUS imaging. We successfully traversed the CTO lesion without the use of a guidewire in approximately three minutes. The procedure concluded successfully without any procedure-related complications, following optimal stenting. CONCLUSIONS: The I-PAD might be an effective technique to accurately, quickly, and safely pass through CTO lesions.

Safety and Effectiveness of Debulking for the Treatment of Infrainguinal Peripheral Artery Disease. Data From the Recording Courses of vascular Diseases Registry in 2910 Patients.

We investigated the safety and efficacy of debulking infrainguinal lesions in patients with peripheral artery disease (PAD) undergoing endovascular revascularization (EVR) as part of the RECording Courses of vascular Diseases (RECCORD) registry. Patient and lesion specific characteristics, including the lesion complexity score (LCS) were analyzed. The primary endpoint encompassed: (i) clinical improvement in Rutherford categories, (ii) index limb re-interventions, and (iii) major amputations during follow-up. The secondary endpoint included the need for bail-out stenting. Overall, 2910 patients were analyzed; 2552 without and 358 with debulking-assisted EVR. Patients were 72 (interquartile range (IQR) = 15) years old and 1027 (35.3%) had diabetes. Overall complication rates were similarly low in the debulking vs the non-debulking group (4.7 vs 3.2%, P = .18). However, peripheral embolizations rates were low but more frequent with debulking vs. non-debulking procedures (3.9 vs 1.1%, P < .001). After adjustment for clinical and lesion-specific parameters, including LCS, no differences were noted for the primary endpoint (odds ration (OR) = 0.99, 95%CI = 0.69-1.41, P = .94). Bail-out stenting was less frequently performed in patients with debulking-assisted EVR (OR = 0.5, 95%CI = 0.38-0.65, P < .0001). Debulking-assisted EVR is currently used in ∼12% of EVR with infrainguinal lesions and is associated with lower bail-out stent rates but higher peripheral embolization rates; no differences were found regarding index limb re-intervention and amputation rates.

Benefits of early vascular provider involvement in wound care center management of patients with underlying arterial disease.

OBJECTIVES: Peripheral arterial disease (PAD) can reduce wound healing rates by ≤30%. Current literature suggests wound outcomes are improved when management is driven by vascular providers. However, whether this benefit is derived solely from early vascular provider involvement remains unclear. METHODS: A retrospective analysis was performed of 80 limbs with chronic wounds and underlying PAD seen at our institution's wound center between July 2022 and July 2023. Arterial disease was defined by the following criteria: (1) prior PAD diagnosis, (2) ankle-brachial-index of <0.9 or toe pressure of <70 mm Hg, or (3) absent peripheral pulses. Patients were divided into early (<6 week) vascular provider exposure (EVE; n = 45) or late/no vascular exposure (LNVE; n = 35). Providers included vascular surgeons and affiliated advanced practitioners. The primary outcome studied was overall time to wound healing. Statistical analysis included χ2 tests, t test, Pearson correlation, Kaplan-Meier analysis, and Cox regression modeling (variables included in a multivariate model if univariate effect on healing was associated at P < .1). RESULTS: Baseline demographic profiles were similar between groups with exception of lower baseline albumin (P = .037), more heart failure (P = .013), and more prior peripheral endovascular interventions (P = .013) in the EVE group. Although the initial wound locations and sizes were similar, EVE wounds had significantly higher WIfI wound scores (1.9 ± 0.1 vs 1.6 ± 0.1; P = .039). Although more LNVE patients developed radiographic osteomyelitis (31.8% vs 55.6%; P = .033), fewer underwent operative debridement or amputation (100% vs 63.2%; P = .008). On univariate analysis, healing time tended to be shorter in EVE, but not significantly (P = .089). When controlled for comorbidities, however, healing rates were nearly two-fold higher in EVE (hazard ratio, 2.42; 95% confidence interval, 1.21-4.84). LNVE wounds also took significantly longer to reach checkpoints including time to >75% granulation (P = .05), 15% weekly size decrease (P = .044), and epithelialization (P = .026). LNVE patients required more wound center visits (P = .024) and procedures (P = .005) with a longer time to intervention (P = .041). All EVE patients obtained ankle-brachial indices, with 90.9% of them available at their first wound care visit (P < .001). Although a slightly greater proportion of patients underwent a major amputation in EVE (15.6% vs 11.4%; P = .595), this difference did not attain significance; additionally, 100% of EVE patients had documented discussion of nonsalvageable limbs before amputation. CONCLUSIONS: Early exposure to vascular practitioners improves wound healing time, timeliness to intervention, and wound center and hospital resource use in patients with PAD. Further investigation into benefits of vascular involvement within community wound center models could significantly improve awareness and accessibility of arterial wound care in smaller/remote communities.

Intravascular Lithotripsy for Treatment of Severely Calcified Common Femoral Artery Disease: Results From the Disrupt PAD III Observational Study.

BACKGROUND: Surgical endarterectomy is currently considered the front-line therapy for the treatment of calcified lesions in the common femoral artery (CFA). Endovascular interventions have evolved, and their use is increasing in frequency. Intravascular lithotripsy (IVL) has shown promising safety and effectiveness in calcified CFA lesions in a small pilot study, but "real-world" evidence from a larger cohort is lacking. METHODS: The Disrupt PAD III Observational Study (NCT02923193) was a prospective, multicenter registry designed to assess the acute safety and effectiveness of IVL treatment for calcified peripheral arterial disease. Any concomitant treatment with other calcium-modifying technologies as well as definitive treatment strategies was at the discretion of the operators. Patients with CFA lesions were evaluated for acute angiographic safety and effectiveness outcomes following IVL treatment as determined by an independent angiographic core lab. RESULTS: Common femoral artery treatment was indicated in 177 patients (n=163 could be analyzed based on core-laboratory data) enrolled at 23 sites. Characteristics for 164 treated lesions included moderate-severe calcification 95.1%, diameter stenosis 74.8±17.7%, and lesion length 53.6±53.1 mm. Concomitant calcium-modifying therapy was used in 32.3% of lesions. Final therapy included drug-coated balloons in 68.9% and stenting in 16.5% of lesions. Post-IVL and final residual stenoses were 29.2±16.5%and 23.6±11.5%, respectively. No vascular complications (flow-limiting dissections, perforations, embolization, slow or no reflow, or abrupt closure) were present at the end of the procedure by core-laboratory assessment, with 1 (0.8%) flow-limiting dissection initially occurring immediately following IVL treatment. CONCLUSION: This study represents the largest real-world experience of IVL treatment in heavily calcified CFA lesions. Intravascular lithotripsy treatment showed significant stenosis reduction and favorable periprocedural safety in this challenging patient population. CLINICAL IMPACT: In this study we show that calcified common femoral artery disease can be safely and effectively treated with shockwave balloon angioplasty with high procedural success and low complication rates and in clinical practice can now be offered as an alternative to surgical treatment in those patients reluctant to or high risk for vascular surgery. This opens another option for clinicians to treat calcified common femoral artery disease without the risk of dissection, perforation or distal embolization that are associated with atherectomy. This study shows that shockwave lithoplasty offers an innovative plaque modification technology to tackle calcified disease in the common femoral artery.