Abstract Background The clinical benefit and safety of drug-coated devices in chronic limb-threatening ischemia remain debated, particularly after recent randomized evidence questioning paclitaxel-coated technologies. We evaluated wound healing, limb outcomes, and mortality after infrainguinal endovascular therapy with uncoated, paclitaxel-coated, and sirolimus-coated devices. Methods Consecutive patients with chronic limb-threatening ischemia undergoing successful infrainguinal endovascular therapy in a prospective single-center service evaluation were analyzed. The primary exposure was use of any drug-coated device during the index procedure. Inverse probability of treatment weighting and multivariable Cox models were used to adjust for baseline differences. Exploratory analyses compared paclitaxel-coated, sirolimus-coated, and uncoated devices. Results Among 341 patients, 244 (71.6%) received at least one drug-coated device. After weighting, drug-coated device use was associated with more frequent wound healing, whereas major amputation, clinically driven target lesion revascularization, major adverse limb events, and death did not differ significantly between groups. In weighted multivariable models, drug-coated device use remained associated with wound healing (HR, 1.86; 95% CI, 1.14–3.02), but not with mortality or major limb events. Exploratory drug-specific analyses suggested the highest wound-healing rates among patients treated with sirolimus-coated devices, while mortality was comparable between paclitaxel-coated and uncoated devices. Conclusion In this real-world cohort of patients with chronic limb-threatening ischemia undergoing infrainguinal endovascular therapy, drug-coated device use was not associated with increased adjusted 1-year mortality and was associated with improved wound healing. Exploratory analyses suggested favourable wound-healing outcomes with sirolimus-coated balloons, with a lower observed mortality signal that warrants confirmation in larger comparative studies. What is Known Drug-coated devices are widely used in endovascular therapy to prevent restenosis, but their clinical benefit in patients with chronic limb-threatening ischemia remains uncertain. Recent randomized evidence has questioned the effectiveness of paclitaxel-coated devices in chronic limb-threatening ischemia and has raised ongoing concerns regarding long-term mortality. What the Study Adds In a real-world cohort of patients with chronic limb-threatening ischemia undergoing infrainguinal endovascular therapy, drug-coated device use was not associated with increased adjusted 1-year mortality and was associated with improved wound healing. Wound healing may be a clinically sensitive, patient-relevant endpoint for evaluating endovascular strategies in CLTI. Exploratory drug-specific analyses suggested favourable outcomes with sirolimus-coated devices, supporting dedicated comparative studies of limus-based technologies in CLTI.

Background:Dyslipidemia may contribute to pathogenesis and disease complications in limited cutaneous systemic sclerosis (lcSSc), while data about its associations with endothelial dysfunction and clinical lcSSc-specific parameters as well as its predictive role on disease complications are limited. This study investigated the relationship between lipid parameters, endothelial dysfunction, and disease complications in patients with lcSSc. Methods:38 patients with lcSSc and 38 matched controls with primary Raynaud's phenomenon were analyzed at baseline regarding lipid parameters, parameters of endothelial dysfunction and clinical lcSSc-specific parameters. During a subsequent 3-year follow-up period, patients with lcSSc were prospectively observed for disease complications. Results:Patients with lcSSc exhibited lower high-density lipoprotein (HDL) levels (p = 0.032) and total HDL particles (p = 0.001) as well as higher triglyceride levels (p = 0.018), triglycerides/HDL ratio (p = 0.013) and atherogenic index (p = 0.012) compared to controls. Large low-density lipoprotein (LDL) particles correlated positively with endothelial microparticles (r = 0.464, p = 0.044), while very low-density lipoprotein size correlated negatively with symmetric dimethylarginine (r = -0.480, p = 0.033). No significant correlations were observed between lipid parameters and clinical lcSSc-specific parameters. Incidence of macrovascular events and interstitial lung disease were associated with a few selected lipid parameters (all p < 0.05). Conclusion:Patients with lcSSc showed a more pro-atherogenic lipid profile. Although statistically significant, these results were of modest magnitude and should be interpreted in the context of the exploratory design. Associations with endothelial dysfunction and clinical disease parameters were minimal or non-significant. Selected lipid parameters may be associated with disease complications in lcSSc, but these findings require confirmation in larger, adequately powered studies due to the small sample size and exploratory analyses.

The randomised SIRONA trial showed that sirolimus-coated balloon (SCB) angioplasty was non-inferior to paclitaxel-coated balloon angioplasty (PCB) regarding femoropopliteal primary patency. There was no difference in clinically driven target lesion revascularisation (cdTLR) rates between the treatment groups. This post-hoc analysis aimed to assess whether the overall results were consistent across different subgroups and selected post-baseline factors. Primary patency at 12 months was assessed using duplex ultrasound and adjudicated by a core laboratory for 203 and 199 participants in the SCB and PCB groups, respectively (available-case intention-to-treat analysis). Data on 12-month cdTLR were available for 238 and 244 participants in the SCB and PCB groups, respectively. Odds ratios (ORs) for primary patency and hazard ratios (HRs) for cdTLR after SCB compared to PCB in non-pre-specified subgroups were assessed using generalised linear mixed models to control for centre effects, and Cox proportional hazards models, respectively. Primary patency and cdTLR were generally consistent across the analysed subgroups. Two nominal interaction signals were observed. For cdTLR, a nominal interaction with age was identified (interaction p = 0.047); among participants older than 70 years, the estimated hazard ratio favoured SCB (HR 0.52, 95 https://clinicaltrials.gov/study/NCT4475783 .

BACKGROUND:Paclitaxel-coated balloon (PCB) angioplasty is effective for femoropopliteal interventions. However, the increased mortality risk associated with PCB has not yet been cleared, and alternative antiproliferative drugs may offer additional advantages. OBJECTIVES:The authors aimed to investigate whether sirolimus-coated balloon (SCB) angioplasty achieves noninferior primary vessel patency and clinical efficacy and safety compared with PCB angioplasty. METHODS:SIRONA is a multicenter randomized, controlled, noninferiority trial comparing SCB with PCB angioplasty in patients with symptomatic femoropopliteal artery disease. The study was conducted at 25 centers in Germany and Austria. Patients aged 18 years or older with a single target lesion were randomized 1:1 using permuted blocks, stratified by center. Participants and outcome assessors were masked to allocation. Primary endpoints were primary patency and the composite clinical endpoint of freedom from clinically driven target vessel revascularization, major target limb amputation, and device- or procedure-related death at 12 months based on available case intention-to-treat analysis. Prespecified noninferiority margins were 10%. Long-term follow-up is ongoing. RESULTS:Between April 21, 2021, and September 23, 2022, 482 patients were assigned to SCB (n = 238) or PCB (n = 244) groups. The mean age was 68.0 ± 8.9 years; 311 participants (64.5%) were male; and 464 participants (96.3%) presented with intermittent claudication. Mean lesion length was 8.4 ± 6.1 cm and 160 lesions (33.2%) were chronic total occlusions. Primary patency was achieved in 150 of 203 participants (73.9%) with SCBs and in 149 of 199 participants (74.9%) with PCBs (risk difference: -1.0%; 95% CI: -9.6% to 7.6%; Pnoninferiority = 0.019). However, sensitivity analyses revealed that noninferiority was achieved but statistically not robust. The primary clinical endpoint was achieved in 199 of 220 participants (90.5%) with SCBs and in 202 of 218 participants (92.7%) with PCBs (risk difference: -2.2% (95% CI: -7.7% to 3.2%.); Pnoninferiority = 0.003). These results were confirmed by sensitivity analyses. CONCLUSIONS:Among patients with femoropopliteal artery disease, SCBs demonstrated noninferior clinical important outcomes and comparable improvement in vascular quality of life compared with PCBs. Although the noninferiority of primary patency was not statistically robust, this suggests that SCBs may be a valuable alternative to PCBs. (Sirolimus- vs Paclitaxel-Drug Coated Balloons in Patients With Peripheral Artery Disease [SIRONA]; NCT04475783]; Head-to-Head Comparison of Sirolimus vs Paclitaxel Drug-Eluting Balloon Angioplasty in the Femoropopliteal Artery [SIRONA]; DRKS00022452).

Purpose:Long-term outcomes of paclitaxel-coated drug-coated balloons (DCBs) in patients with diabetes mellitus (DM) and infrainguinal peripheral arterial disease (PAD) are incompletely defined. In the current study, we evaluated 5-year outcomes in the diabetic cohort of BIOLUX P-III. Patients and Methods:BIOLUX P-III was a prospective, international, multicenter, post-market, single-arm study evaluating the Passeo-18 Lux DCB in routine practice. Between October 2014 and January 2017, 877 patients with infrainguinal lesions were treated at 47 centers, of whom 418 (47.7%) had DM. The primary clinical endpoint was 6-month freedom from major adverse events (MAEs), defined as freedom from procedure- or device-related death through 30 days, major target-limb amputation, or clinically driven target-lesion revascularization (CD-TLR). The primary performance endpoint was 12-month freedom from CD-TLR. Time-to-event outcomes were analyzed using Kaplan-Meier methods and the Log rank test. Results:Among 877 treated patients, 418 had DM. Follow-up completion was 81.6%, 86.4%, 82.3%, and 31.3% at 6, 12, 24, and 60 months, respectively. At 5 years, freedom from MAE was lower in patients with DM than in those without DM (71.2% vs 74.7%; P = 0.0359), whereas freedom from CD-TLR was similar between groups (79.8% vs 79.6%; P = 0.535). Patients with DM also had lower overall survival (56.3% vs 73.8%; P < 0.0001), lower freedom from major target-limb amputation (92.4% vs 98.8%; P < 0.0001), and lower amputation-free survival (53.0% vs 73.6%; P < 0.0001). Conclusion:In this real-world registry, the Passeo-18 Lux DCB was associated with durable freedom from reintervention through 5 years, with similar CD-TLR rates in patients with and without DM. Patients with DM had poorer long-term survival and limb outcomes. However, these findings should be interpreted in the context of baseline between-group differences and limited 60-month follow-up (ClinicalTrials.gov number, NCT02276313).

PURPOSE:To provide recommendations for the most appropriate endovascular intervention of femoropopliteal (FP) arterial disease based on plaque characterization. MATERIALS AND METHODS:A panel of 22 physicians from multiple disciplines participated in a modified Delphi consensus, leveraging the RAND/UCLA Appropriateness Method. Panelists engaged in 2 rounds of voting, following a literature review, with an in-person discussion prior to the second round of voting. A rigorous statistical approach was used to analyze the points of agreement and disagreement. Consensus-based recommendations on the most appropriate endovascular approaches for treating patients with FP lesions, stratified by lesion morphology, were generated. RESULTS:Overall, 490 individual items were included in the voting, 458 (93%) of which achieved consensus and 32 (7%) were nonconsensus items, based on a priori criteria under the following categories: (a) recommendations on method for determining plaque morphology, (b) preferred endovascular devices for vessel preparation and definitive treatment stratified by (i) plaque morphology and (ii) Tosaka classification of in-stent restenosis, and (c) vessel preparation device safety-related considerations. CONCLUSIONS:This international, multidisciplinary consensus provides evidence- and expert-informed recommendations for vessel preparation and definitive treatment of FP arterial disease, tailored to plaque morphology. These consensus recommendations aim to support clinical decision making and promote best interventional practices by serving as an expert opinion supplement to existing guideline-based care pathways.

BACKGROUND:Drug-coated balloons improve outcomes after femoropopliteal angioplasty, but concerns regarding the long-term safety of paclitaxel-coated devices have prompted interest in alternative antiproliferative strategies. OBJECTIVES:This study sought to evaluate the 2-year patient-centered and clinical outcomes of sirolimus-coated balloon (SCB) versus paclitaxel-coated balloon (PCB) angioplasty. METHODS:SIRONA was a prospective, multicenter, randomized, controlled, noninferiority trial comparing SCB with PCB angioplasty in patients with femoropopliteal artery disease (96.5% intermittent claudication). The present analysis reports prespecified outcomes at 2 years. Effectiveness endpoints included patient-reported outcomes (VascuQol, clinical improvement, and EQ-5D-3L), primary patency, and freedom from clinically driven target lesion revascularization. Safety endpoints included major amputation and all-cause mortality. Longer-term follow-up is ongoing to assess durability and safety up to 5 years. RESULTS:A total of 482 patients was randomized (SCB: n = 238; PCB: n = 244). Improvements in vascular quality of life were sustained through 2 years and were similar between groups (between-group difference: 0.05, 95% CI: -0.15 to 0.24; P = 0.63). Clinical improvement (≥1 Rutherford category) occurred in 88% of the SCB group and 89% of the PCB group (P = 0.89). Kaplan-Meier estimates of primary patency were 64.6% for SCB and 67.2% for PCB (log-rank P = 0.34). Freedom from clinically driven target lesion revascularization was 91.2% for SCB and 88.1% for PCB (log-rank P = 0.42). Major amputation was rare (0.4% in both groups). All-cause mortality occurred in 6.3% and 3.7%, respectively (P = 0.21), with no device- or procedure-related deaths. CONCLUSIONS:SCB angioplasty resulted in sustained patient-reported and clinical outcomes comparable to PCB angioplasty through 2 years, with similar patency, revascularization, and safety.

This trial evaluates whether transcutaneous gaseous carbon dioxide therapy (CO2 therapy) combined with standard of care (SOC) improves healing of hard-to-heal recurrent diabetic foot ulcers (DFUs) compared with SOC alone. A total of 30 participants with recurrent hard-to-heal DFUs were included and randomized 1:1 to an intervention (CO2 therapy plus SOC) or a control group (SOC only). The intervention consisted of 20 daily 50-minute CO2 therapy sessions over 4 weeks. After 4 weeks, 46.7% of ulcers in the intervention group were completely healed, versus 0% in the control group (p = 0.005). The intervention group showed a median area reduction of 85.7% (IQR 54.9-100) compared to 17.2% (IQR 0.88-33.5) in controls (p < 0.001), with significantly better Falanga wound-bed scores (p < 0.001). The intervention group demonstrated a significant relative increase in StO2 (29.6 ± 19.6%), whereas the control group exhibited a decrease (-2.2 ± 6.9%), resulting in a between-group difference of 31.8% (95% CI 20.5%-43.0%; p < 0.001). Pain intensity significantly decreased in the intervention group only (p = 0.002). This trial suggests that CO2 therapy in combination with SOC is superior to SOC alone in healing recurrent, hard-to-heal DFUs.

Background Endovascular treatment of below-the-knee disease in chronic limb-threatening ischemia remains challenging, with limited durability of balloon angioplasty and constraints associated with permanent metallic implants. Drug-eluting resorbable scaffolds (DRS) provide temporary vessel support with local drug delivery followed by bioresorption, representing a promising alternative. However, the optimal clinical scenarios for DRS use remain undefined. This study aimed to establish consensus on DRS use in infrapopliteal revascularization. Methods A multidisciplinary steering committee developed a structured questionnaire addressing lesion characteristics, patient-level clinical factors, and health-system considerations. Using the RAND/UCLA Appropriateness Method and a modified Delphi process, 114 clinical scenarios were evaluated by an international panel of experts in vascular surgery, interventional cardiology, interventional radiology, and vascular medicine. Experts rated each scenario using a 5-point Likert scale. Consensus strength was defined as strong (>80% agreement), partial (60% to 80%), or absent (<60%). Results Thirty-five international experts completed the survey. Strong consensus was achieved for 44 scenarios (38.6%), partial consensus for 35 (30.7%), and no consensus for 35 (30.7%). Strong agreement supported DRS use in patients with CLTI (Rutherford 4-6), vessel diameter ≥3 mm, lesions ≤60 mm, and following adequate vessel preparation, particularly in centers with high procedural expertise and advanced imaging capabilities. Partial consensus emerged for longer or moderately complex lesions and certain clinical contexts. Lack of consensus was observed in small-vessel disease, complex bifurcations, long-segment disease requiring multiple scaffolds, thrombotic lesions, and scenarios involving interruption of antiplatelet therapy. Conclusions This consensus defines appropriate clinical scenarios for BTK DRS use, while areas of disagreement identify evidence gaps and research priorities as scaffold technologies evolve.

The aim of this clinical consensus statement of the European Society of Cardiology Working Group on Aorta and Peripheral Vascular Diseases, the Working Group on Cardiovascular Pharmacotherapy, the Working Group on Pulmonary Circulation & Right Ventricular Function, and the European Society of Vascular Medicine is to summarize existing evidence on lipid-lowering therapy (LLT) in primary and secondary prevention of venous thromboembolism (VTE). VTE, which comprises deep vein thrombosis (DVT) and pulmonary embolism (PE), shares common risk factors with atherosclerotic cardiovascular disease (ASCVD). While anticoagulation is the mainstay in the management of patients with VTE, it may be appropriate to define LLT as risk modifier in primary prevention of VTE in populations at high cardiovascular risk. In patients with VTE, assessment of cardiovascular risk factors, including lipid levels, is commonly part of routine cardiovascular care in accordance with existing ESC Guidelines. Finally, this clinical consensus statement highlights the gaps in evidence and the need for large-scale studies directly investigating the role of LLT in secondary prevention of recurrent VTE in high-risk populations.

PURPOSE:To evaluate the safety and effectiveness of intravascular lithotripsy (SEISMIQ intravascular lithotripsy [IVL] system; Boston Scientific Corporation, Marlborough, Massachusetts) for treating calcified above-the-knee (ATK) lesions in patients with peripheral artery disease. MATERIALS AND METHODS:RESTORE ATK was a prospective, single-arm study that enrolled from 10 sites between January 20, 2023, and December 13, 2023. Ninety-five patients with de novo, moderate to severe calcifications of the femoropopliteal segments were treated using the tested device to modify calcium. Adjunctive drug-eluting technology was not permitted. Primary endpoints were <50% residual diameter stenosis after IVL treatment (by independent core laboratory-adjudicated angiography) and 30-day incidence of major adverse events (MAEs): death, clinically driven target lesion revascularization (CD-TLR), or major amputation. Secondary endpoints included patency, ankle-brachial index, and Rutherford classification (RC) through 6 months. RESULTS:Baseline RC included RC2 (23.2%), RC3 (70.5%), or RC4 (6.3%). Lesions averaged 96.0 mm in length, with 93.7% severely calcified and a mean baseline diameter stenosis of 93.7%. Postprocedural residual stenosis of <50% was achieved in all patients, meeting the predefined performance goal. Three patients (3.2%) received provisional stent placement. Patients had a mean residual stenosis of 21.2% and acute luminal gain of 3.2 mm. No MAEs occurred through 30-day follow-up. At 6 months, target lesion patency was 66.3%, and freedom from CD-TLR was 97.9%. A high proportion of patients demonstrated ≥1 RC improvement at 30-day (93.5%) and 6-month (91.2%) follow-up. CONCLUSIONS:This IVL system demonstrated effective treatment of calcified ATK lesions by successfully reducing calcific stenoses with minimal complications and sustained clinical improvement through 6 months.

Background/objectives:Evidence for the first-line treatment of venous thromboembolism (VTE) by use of direct oral anticoagulants (DOACs) is based on stratification by body-mass index (BMI) and total body weight, but does not consider body composition - defined as the distribution of fat mass (FM) and fat-free mass (FFM). Variability in body composition exists among patients with normal BMI, but is anticipated to be markedly greater in the context of overweight and obesity. Methods:The BIARIVA prospective, single-center, cross-sectional study was conducted to assess whether body composition affects blood coagulation monitoring parameters in patients on therapeutic-dose anticoagulant treatment for VTE with oral factor (F.) Xa inhibitors rivaroxaban or edoxaban. Patients were qualified for inclusion into the study if they were categorized into one of the specified BMI categories; 18-25, 30-35, or > 35 kg/m2. Body composition was determined by two bioelectrical impedance analysis (BIA) methods. The primary endpoint was the association between body composition parameters and coagulation measurements in patients treated with rivaroxaban or edoxaban, assessed by correlation analysis. Results:Thirty-six patients on rivaroxaban and 35 patients on edoxaban were finally analyzed. The main finding in this study was a significant negative correlation observed in the edoxaban group for the absolute FFM with anti-F.Xa and plasma concentration peak levels (BIA method 1: rs = -0.439, p = 0.008; BIA method 2: rs = -0.431, p = 0.010) and with the absolute increase from trough to peak in plasma concentration levels (BIA method 1 and 2: rs = -0.446, p = 0.007) and in anti-F.Xa levels (BIA method 1: rs = -0.445, p = 0.007; BIA method 2: rs = -0.444, p = 0.008). No significant correlations of body composition measures with coagulation parameters were found in the rivaroxaban group. Conclusions:This study suggests that body composition might influence specific coagulation measurements in patients treated with edoxaban, but further research is required to finally determine the role of body composition in this context and to evaluate clinical implications.

Background: Vascular medicine/angiology plays a crucial role in managing vascular diseases, yet its recognition, training, and practice vary across Europe. To understand these disparities, the European Society for Vascular Medicine (ESVM) conducted a survey among young trainees to assess their attitudes and perception towards vascular medicine training. Methods: A cross-sectional survey was distributed among trainees and young specialists from European countries, including nations with and without vascular medicine as a recognized specialty. The survey was published on the ESVM website and shared through national vascular medicine societies. Participants provided insights into their training experiences, opinions of the specialty, and priorities for improvement. Statistical analysis compared responses based on specialty recognition. Findings: Among 210 respondents, 36.2% (n=76) were from countries without formal specialty recognition. Training was more structured in countries with a recognized specialty (p<.001). Multidisciplinary team meetings were deemed critical by 98.1% but were more common in countries with a recognized specialty (p=.003). Overall, 80.5% (n=169) expressed interest in training abroad. Core vascular domains were well-covered, while areas like lymphatic and microvascular diseases lacked sufficient training both in countries where the specialty was recognized and where it was not. Respondents from countries with a recognized specialty rated their training significantly higher (p=.001). Despite challenges, 85.2% (n=179) would choose the specialty again, and 90.4% (n=190) supported a unified European certification. Interpretation: These findings highlight the need for a harmonized training framework in Europe ensuring a shared foundational curriculum in vascular medicine while enhancing professional mobility and improving patient care across the whole spectrum of vascular diseases.

Evaluating the predictive role of endothelial dysfunction in the development of vasculopathy-mediated complications in patients with limited cutaneous systemic sclerosis (lcSSc). 38 patients with lcSSc who were naïve for vasculopathy-mediated complications, defined as absent pre-existing digital ulcers (DU), pulmonary hypertension (PH) and symptomatic atherosclerotic cardiovascular diseases, were prospectively observed during a 3-years follow-up period. At study enrolment, functional and laboratory parameters of endothelial dysfunction were assessed. Microvascular events, defined as the development of DU and PH, macrovascular events, defined as newly symptomatic atherosclerotic cardiovascular diseases, and clinical events, defined as additional interstitial lung disease (ILD), renal crisis and esophageal dysfunction, were recorded annually. 33 patients (86.8

PurposeOur study aimed to investigate the prevalence and timing of ocular surface manifestations in hospitalized COVID-19 patients, providing insights into the occurrence of eye involvement before, during, or after the illness. This study contributes to understanding the extent of ocular involvement in COVID-19, which has been suggested to occur due to potential viral entry through the eyes.Methods451 confirmed COVID-19 patients had a history of hospitalization in Styria, Austria. The study included 176 patients aged 18-95 years who tested positive for SARS-CoV-2 in nasopharyngeal swabs by RT-PCR and received treatment at two hospitals. Telephone interviews were conducted after recovery, focusing on ocular symptoms and medical history (openMEDOCS).ResultsSeventeen percent (n=30) reported new-onset ocular symptoms in the context of COVID-19. Patients with ocular symptoms were younger (p<0.001). Sore throat (p=0.013) and high fever (p=0.038) were significantly more prevalent in patients with new-onset ocular symptoms. Persistent ocular symptoms beyond the duration of hospitalization affected more than half (56.7%) of the participants with new-onset ocular symptoms. However, there were no differences in blood parameters, lung imaging, or comorbidities between groups with and without ocular symptoms.ConclusionsIn hospitalized COVID-19 patients, ocular symptoms occur with a significant prevalence of 17%. Younger age (p<0.001) and the presence of sore throat (p=0.013) are associated with an increased risk of developing new-onset ocular symptoms in the context of COVID-19.