Endovascular salvage of failing arterio-venous fistulas utilising sirolimus eluting balloons: Six months results from the ISABELLA trial.

BACKGROUND: Aim of this pilot clinical study was to evaluate the safety and efficacy of the Selution Sustained Limus Release (SLR)™ sirolimus-eluting balloon (SEB) for improving failing arterio-venous fistulas (AVF) patency in Asian haemodialysis patients. METHODS: Prospective single-centre, multi-investigator, non-consecutive, non-blinded single arm trial. Forty end-stage renal failure Asian patients with a dysfunctional AVF underwent SEB angioplasty between May and November 2020. All stenotic lesions were prepared with high pressure non-compliant balloon angioplasty prior to SEB angioplasty. Endpoints of interest included target lesion primary patency and circuit access patency and safety through 30 days. All patients received dual antiplatelet therapy for 1 month and were followed up with Duplex ultrasound at 6 months. RESULTS: There was one subject dropout so final n = 39 patients (mean age 65.0 ± 11.9; males = 26 (66.7%)) and n = 43 target lesions treated. Main indication for intervention was dropping access flow (24/39; 61.5%) and most common target lesion was in the juxta-anastomosis (24/43; 54.5%). There was 100% technical and procedural success. There were no adverse events related to the SEB. Target lesion primary patency rates at 3 and 6 months were 39/41 (95.1%) and 28/39 (71.8%) respectively. Access circuit patency rates at 3 and 6 months were 35/37 (94.6%) and 22/35 (62.9%) respectively. There were 3 (7.7%) deaths all attributable to patients' underlying co-morbidities. CONCLUSIONS: Fistuloplasty using the novel Selution SLR™ SEB for dysfunctional AVF circuits seems a safe and effective modality in Asian haemodialysis patients at 6 months but larger randomised controlled studies are required now to determine its true efficacy against plain balloon angioplasty.

Ranger™ paclitaxel-coated balloon versus conventional balloon angioplasty for treatment of failing arteriovenous fistulas and grafts in haemodialysis patients: A retrospective cohort study.

BACKGROUND: Aim was to compare the safety and patency efficacy outcomes between Ranger™ paclitaxel-coated balloon (PCB)- versus conventional balloon angioplasty (POBA) in the treatment of haemodialysis access-related conduit stenosis. METHODS: Retrospective single-centre, multi-investigator, consecutive, double-arm comparative cohort study. About 130 end-stage renal failure Asian patients with dysfunctional arteriovenous fistula (AVF) or arteriovenous graft underwent PCB or POBA fistuloplasty between November 2018 and June 2020. All stenotic lesions were prepared with high pressure non-compliant balloon angioplasty prior to PCB angioplasty. All patients received at least one antiplatelet agent for 3 months duration post procedure. RESULTS: Mean age was 66.0 ± 10 years and 79/130 (61%) were males. PCB arm (n = 65) versus POBA arm (n = 65). Majority were AVFs circuits (122/130, 94%). Main indication for intervention was dropping access flow (98/130, 76%). About 172 lesions were treated (56% POBA, 44% PCB), and the juxta-anastomosis (JAS) was the main target lesion (87/172, 51%). There were no significant differences in safety outcomes (30-day adverse events, access thrombosis, abandoned AVF and death) between treatment groups. Mean time to target lesion reintervention (TLR) was longer in PCB-treated lesions (7.1 ± 2.7 vs 5.8 ± 3.2 months, p = 0.03), especially amongst recurrent lesions (7.3 ± 2.4 vs 5.7 ± 3.2, p = 0.02). Mean time to circuit reintervention was also longer in PCB-treated circuits (6.9 ± 2.8 vs 5.8 ± 3.7months, p = 0.04). There were 16 deaths (12%), all attributed to patient's underlying comorbidities. CONCLUSIONS: Fistuloplasty with Ranger™ PCB for failing arteriovenous circuits in end-stage renal failure patients, is a safe and efficacious modality compared to POBA in terms of longer freedom from TLR.

Factors Affecting Residual Stump Length Following Endovenous Laser Ablation.

BACKGROUND: Current instruction for endovenous laser ablation (EVLA) recommends that the laser fibre tip should be at least 2 cm caudal to the saphenofemoral or saphenopopliteal junction. This is to reduce risk of deep vein thrombosis (DVT) whilst ensuring that the Great Saphenous Vein (GSV)/Short saphenous vein (SSV) occlusion (residual stump) is close to the SFJ/SPJ to reduce recurrence rates. Our aim was to primarily assess the effects of pre-operative junction distance of the laser fibre on stump length but also look at other factors affecting this. PATIENT AND METHODS: This was a retrospective analysis of an electronic collected database performing EVLA of the GSV and SSV under local anaesthesia. Patients with previous venous thromboembolic events and incomplete data were excluded. Patients were reviewed at 6 weeks with venous Duplex scan to assess for the residual stump distance and DVT. Multivariable logistic regression was used to account for confounders. RESULTS: Between 2012 and 2018, 2341 patients underwent EVLA and complete data were available on 825 (35.2%) patients. All patients were scanned 6 weeks after procedure. Sixty-nine patients (8.4%) had flush occlusion, 3 patients (.4%) had extension into femoral or popliteal vein but not considered to be a DVT and 1 patient had a DVT. High BMI and increasing length of the pre-operative junction was associated with lower incidence of flush occlusion; higher rates of flush occlusions were noted in patients undergoing short saphenous vein (SSV) EVLT (OR 4.11, 95% CI 2.34-7.20; P < .001). CONCLUSIONS: Consideration should be given to increase the intra-procedure laser tip junction to more than 2 cm particularly in patients undergoing SSV treatment to ensure that residual stump is sufficiently distal to SPJ and SFJ reducing risks of thrombus into the femoral or popliteal veins. Lower BMI may be associated with higher risk of this though the reasons for this are unclear.

Combination therapy using scoring and sirolimus drug-coated balloons during lower limb endovascular revascularization for chronic limb threatening ischaemia: A case series.

The aim of this case series was to document our early experience using combination therapy with UltraScore™ Focused Force percutaneous transluminal angioplasty balloon (BD Interventional, New Jersey, US) and Selution Sustained Limus Release (SLR)™ (M.A. MedAlliance SA, Nyon, Switzerland) sirolimus-coated balloon catheter for anti-restenotic drug elution, in the setting of multifocal high-grade stenosis for chronic limb threatening ischaemia. Our anecdotal experience was that preparing the lesion with scoring balloon and then using sirolimus drug-eluting balloon may have synergistic effect when used in tandem, especially in the setting of calcified arterial lesions, where the scoring wires may achieve deeper clefts within the atheromatous plaque to allow better drug absorption into the arterial wall. We report two cases with high-grade multifocal stenosis affecting the superficial femoral and anterior tibial arteries, respectively. Combination therapy using the scoring balloon to first prepare the lesion followed by sirolimus elution achieved technical and procedural success in both cases and a 100% 30-day primary patency. There were no complications related to flow-limiting dissections, vessel perforation or acute recoil. However, whether this combination therapy leads to better primary vessel patency with longer freedom from target lesion revascularization in the medium term remains to be determined.

Slow-flow phenomena following lower limb paclitaxel- and sirolimus-coated balloon angioplasty in the setting of chronic limb threatening ischaemia-a case series.

The Achilles heel of plain old balloon angioplasty (POBA) is neointimal hyperplasia (NIH) and restenosis, caused from the barotrauma of ballooning. Drug-coated balloons using a paclitaxel-based platform (PCB) have been shown to retard the restenotic process, using the anti-proliferative effects of paclitaxel, and give longer vessel patency. This is important in the setting of chronic limb threatening ischemia (CLTI) and for the protracted wound healing process in these frail patients. However, during PCB application, more than 50% of the drug is lost downstream, a phenomenon termed particulate embolization. This is thought to account for the slow- or no-flow phenomenon encountered after PCB use. Recent data suggest that slow-flow phenomenon was associated with a lower target lesion revascularisation rate and worse amputation free survival (AFS). The use of sirolimus coated balloons (SCB) to impede the NIH cascade has been less well studied but recent data suggested excellent short-term efficacy and found no slow flow phenomenon with their use in the tibial arteries in CLTI patients. Aim of this case series is to highlight the difference in flow phenomena using PCB and SCB elution in the setting of CLTI. We evaluated the use of parametric colour coding and time attenuation curves (TAC) as a quantitative measure of blood flow. SCB may have an advantage over PCB use in the peripheral vasculature because of a reduced incidence of slow flow phenomenon following drug elution.

The modified frailty index-11 predicts medium-term outcomes after endovascular revascularisation for chronic limb threatening ischaemia in Asian patients.

OBJECTIVE: The aim was to evaluate the utility of frailty, as defined by the modified Frailty Index-1 1 (mFI-11) on predicting outcomes following endovascular revascularisation in Asian patients with chronic limb-threatening ischaemia (CLTI). METHODS: CLTI patients who underwent endovascular revascularisation between January 2015 and March 2017 were included. Patients were retrospectively scored using the mFI-11 to categorise frailty as low, medium or high risk. Observed outcomes included 30-day complication rate and unplanned readmissions, 1-, 6- and 12-month mortality, and ambulation status at 6- and 12 months post-intervention. RESULTS: A total of 233 patients (250 procedures) were included; 137 (58.8%) were males and the mean age was 69.0 (±10.7) years. 202/233 (86.7%) were diabetic and 196/233 (84.1%) had a prior diagnosis of peripheral arterial disease (PAD). The mean mFI-11 score was 4.2 (±1.5). 28/233 (12.0%), 155/233 (66.5%), and 50/233 (21.5%) patients were deemed low (mF-11 score 0-2), moderate (mFI-11 score 3-5) and high (mFI-11 score 5-7) frailty risk, respectively. High frailty was associated with an increased 12-month mortality (OR 8.54, 95% CI 1.05-69.5; p = 0.05), 30-day complication rate (OR 9.41, 95% CI 2.01-44.1; p < 0.01) and 30-day unplanned readmission (OR 5.06, 95% CI 1.06-24.2; p = 0.04). Furthermore, a high score was associated with a significantly worse 6- (OR 0.320, 95% CI 0.120-0.840; p = 0.02) and 12-month (OR 0.270, 95% CI 0.100-0.710; p < 0.01) ambulatory status. CONCLUSION: The mFI-11 is a useful, non-invasive tool that can be readily calculated using readily available patient data, for prediction of medium-term outcomes for Asian CLTI patients following endovascular revascularisation. Early recognition of short- and mid-term loss of ambulation status amongst high-frailty patients in this challenging cohort of patients could aid decision-making for whether a revascularisation or amputation-first policy is appropriate, and manage patient and caregiver expectations on potential improvement in functional outcome.

Treatment of cephalic arch stenosis in dysfunctional arteriovenous fistulas with paclitaxel-coated versus conventional balloon angioplasty.

BACKGROUND: Treatment of cephalic arch stenosis (CAS) with standard plain old balloon angioplasty (POBA) in dysfunctional arteriovenous fistulas (AVF), is associated with early re-stenosis and higher failure rates compared to other lesions. Paclitaxel-coated balloons (PCB) may improve patency rates. This is a retrospective cohort study. Patients who underwent POBA or PCB for CAS over a 3-year period were included. Outcomes compared were circuit primary patency rates (patency from index procedure to next intervention), circuit primary assisted-patency rates (patency from index procedure to thrombosis), and target lesion (CAS) patency rates (stenosis > 50%) at 3, 6 and 12 months. RESULTS: Ninety-one patients were included. Sixty-five (71.4%) had POBA, while 26 (28.6%) had PCB angioplasty. There were 62 (68.1%) de-novo lesions. CAS was the only lesion that needed treatment in 24 (26.4%) patients. Circuit primary patency rates for POBA versus PCB groups were 76.2% vs. 60% (p = 0.21), 43.5% vs. 36% (p = 0.69) and 22% vs. 9.1% (p = 0.22) at 3, 6 and 12-months respectively. Circuit assisted-primary patency rates were 93.7% vs. 92% (p = 1.00), 87.1% vs. 80% (p = 0.51) and 76.3% vs. 81.8% (p = 0.77), whilst CAS target lesion intervention-free patency rates were 79.4% vs. 68% (p = 0.40), 51.6% vs. 52% (p = 1.00) and 33.9% vs. 22.7% (p = 0.49) at 3, 6 and 12-months respectively. Estimated mean time to target lesion intervention was 215 ± 183.2 days for POBA and 225 ± 186.6 days for PCB (p = 0.20). CONCLUSION: Treatment of CAS with PCB did not improve target lesion or circuit patency rates compared to POBA.

Use of Blue Light in the Management of Chronic Venous Ulcer in Asian Patients: A Case Series.

Chronic venous ulcers, often complicated by late diagnosis and persistent infections, present major clinical and financial challenges. Recently, photobiomodulation therapy (PBMT) has been shown to be effective in overcoming physiological impairments such as hemostasis and inflammation, accelerating the wound healing process. This case series summarises our experience in the treatment of two Asian patients with lower-extremity chronic venous ulcers using PBMT with blue light. Case 1 was a 71-year-old male with a history of hypertension, chronic venous insufficiency and previous deep vein thrombosis. Prior to blue light therapy, the average duration of treatment until wound closure with compression dressings used to be 10-12 weeks. Complete wound closure with the blue light therapy was eight weeks, with a total reduction of 67% of wound size by week 4. Case 2 was a 77-year-old male with a background of hypertension and ischaemic heart disease. Prior to blue light therapy, the patient had also underwent iliac venoplasty and stenting for his recurring bilateral malleolus venous ulcers. By week 4, the right malleolus wound had healed, while the left malleolus wound had a size reduction of 38%. Complete closure of both the wounds was noted at week 6. Blue light was administered to the wounds of both patients for 120 seconds per session, as an adjunct to compression therapy. Both patients reported no additional wound pain during the administration of blue light therapy, with an overall reduction of wound pain at three weeks. The cases demonstrated that PBMT with blue light was well-tolerated, safe, and efficacious in improving wound healing with an adjunct to standard treatment of chronic venous ulcers.

Distribution of Peripheral Arterial Disease in Patients Undergoing Endovascular Revascularization for Chronic Limb Threatening Ischaemia: Insights from the Vascular Quality Initiative in Singapore.

This study aimed to examine the distribution of lower limb atherosclerotic lesions in a multi-ethnic Asian cohort with chronic limb threatening ischemia (CLTI) from Singapore. The Society for Vascular Surgery Vascular Quality Initiative registry database was used to identify 265 CLTI patients who underwent percutaneous angioplasty between June 2019 and December 2019, of whom 171 (64.5%) were male, and the mean age was 67.9±11.0 years. The majority were diabetic (84.5%) and 145 (54.7%) had chronic kidney disease (CKD). The majority of the lower limb atherosclerotic lesions were de novo lesions (598/797, 75.0%), predominantly TransAtlantic Inter-Society Consensus II C/D (451/797, 56.6%), and were moderately to severely calcified (76.3%). The anterior tibial artery and femoral-popliteal artery were the most commonly affected vessels. The mean length of the treated lesions was 14.5±13.7 cm. There was a tendency, albeit insignificant, of multi-level disease in those who were diabetic or had CKD.

Safety and efficacy of Luminor™ balloon and Angiolite™ stent on TASC C/D tibial occlusive lesions in CLI patients: 12-month results. The MERLION trial.

BACKGROUND: The aim of MERLION (NCT04073121) was to evaluate the outcomes of the mono or combination therapy of the iVascular Luminor™ drug-coated balloon (DCB) and Angiolite™ drug-eluting stent for treatment of TASC II C/D tibial occlusive lesions in Asian patients presenting with chronic limb threatening ischemia (CLTI) from Singapore. METHODS: MERLION was a prospective, non-randomized, single arm, observational, multicenter clinical study. Complication-free survival at one month was the safety endpoint. Immediate technical success, 12-month primary vessel patency, limb salvage, freedom from target lesion revascularization (TLR) and amputation free survival (AFS) were the efficacy endpoints of interest. RESULTS: Fifty patients were included. There were 32 males (64% males; mean age 66.4±8.9 years). Majority were Rutherford 5 severity (41/50; 82%). Co-morbidities included diabetes mellitus (47/50; 94.0%), end-stage renal failure (25/50; 50.0%), and hypertension (44/50; 88%). 66 atherosclerotic lesions were treated (47 de novo and 19 restenotic; 60.6% TASC C and 39.4% TASC D). Mean lesion length treated was 13.7±9.5 cm. There was 100% technical success. There were 3/66 (4.5%) bailout stenting for severe flow limiting dissections. Twelve-month primary tibial patency was 34/49 (69.4%) and freedom from TLR was 40/49 (81.5%). AFS was 74.0% (37/50). At 12 months, mean Rutherford scores improved from 100% (Rutherford score >3) at baseline to 31% at 12 months (P<0.05) and wound healing rate was 65.7%. CONCLUSIONS: The iVascular Luminor™ DCB is safe and efficacious in treating highly complex infra-popliteal atherosclerotic lesions in an otherwise challenging frail population of CLTI patients from Singapore.

One-year outcome using cyanoacrylate glue to ablate truncal vein incompetence: A Singapore VenaSeal™ real-world post-market evaluation study (ASVS).

OBJECTIVE: We present 12 months efficacy data from A Singapore VenaSeal™ real-world post-market evaluation Study (ASVS), a prospective single-arm Asian population registry aimed to evaluate cyanoacrylate glue (CAG) closure of refluxing truncal veins. METHODS: Duplex ultrasound was used to assess truncal vein closure. The revised Venous Clinical Severity Score (rVCSS) and three quality of life (QoL) questionnaires were completed to assess improvement in venous disease symptoms. RESULTS: 90/100 (90%) patients (136 legs; 140 truncal veins) completed evaluation at 6- and 12 months. The truncal closure rates at 6 and 12 months were 139/140 (99.3%) and 137/140 (97.9%), respectively. rVCSS and QoL questionnaires scores were sustained from the 3 to 12 months visits, although there were no futher significant improvement. No serious adverse events were reported between 3 and 12 months. CONCLUSIONS: CAG remains a safe and efficacious venous ablative technology at 12 months and is associated with a high rate of target vein occlusion and sustained QoL improvement.

Editor's Choice - Decrease in Mortality from Abdominal Aortic Aneurysms (2001 to 2015): Is it Decreasing Even Faster?

OBJECTIVE: The early twenty first century witnessed a decrease in mortality from abdominal aortic aneurysms (AAA), which was associated with variations in the prevalence of cardiovascular risk factors. This study investigated whether these trends continued into the second decade of the twenty first century. METHODS: Information on AAA mortality (2001 - 2015) using International Classification of Diseases codes was extracted from the World Health Organization (WHO) mortality database. Data on risk factors were extracted from the Institute of Health Metrics and Evaluation and WHO InfoBase, and data on population from the World Development Indicators database. Regression analysis of temporal trends in cardiovascular risk factors was done independently for correlations with AAA mortality trends. RESULTS: Seventeen countries across four continents met the inclusion criteria (Australasia, two; Europe, 11; North America, two; Asia, two). Male AAA mortality decreased in 13 countries (population weighted average: -2.84%), while female AAA mortality decreased in 11 countries (population weighted average: -1.64%). The decrease in AAA mortality was seen in both younger (< 65 years) and older (> 65 years) patients. The decrease in AAA mortality was more marked in the second decade of the twenty first century (2011 - 2015) compared with the first decade (2001 - 2005 and 2006 - 2010). Trends in AAA mortality positively correlated with smoking (males: p = .03X, females: p = .001) and hypertension (males: p = .001, females: p = .01X). Conversely, AAA mortality negatively correlated with obesity (males: p = .001, females: p = .001), while there was no significant correlation with diabetes. CONCLUSION: AAA mortality has continued to decline and seems to have declined at an even faster rate in the second decade of the twenty first century, albeit with heterogeneity among countries. These variations are multifactorial in origin but further efforts targeting smoking cessation and blood pressure control will probably contribute to continued reductions in AAA mortality.

DEep VEin Lesion OPtimisation (DEVELOP) trial: protocol for a randomised, assessor-blinded feasibility trial of iliac vein intervention for venous leg ulcers.

BACKGROUND: Venous leg ulceration is a widespread, debilitating pathology with high recurrence rates. Conservative treatment using graduated compression dressings may be associated with unacceptable ulcer recurrence rates. Early superficial venous ablation encourages ulcer healing and reduces recurrence. However, many of this cohort display concomitant ilio-caval stenosis, which further contributes to lower limb venous hypertension and ulceration. An approach that combines early superficial venous ablation with early treatment of ilio-caval stenotic disease may significantly improve ulcer healing and recurrence rates. We question whether early iliac vein interrogation with intravascular ultrasound (IVUS), stenting of significant occlusive disease plus superficial venous ablation, in patients with active venous leg ulceration, will produce superior ulcer healing to standard therapy. METHODS: This is a prospective, multi-centre, randomised controlled, feasibility trial recruiting patients with lower limb venous ulceration and saphenous venous incompetence. Patients will be randomised to undergo either truncal ablation and compression therapy or truncal ablation, simultaneous iliac interrogation with intravascular ultrasound and stenting of significant (> 50%) iliac vein lesions plus compression therapy. The primary feasibility outcome will be the rate of eligible patient participation while the primary clinical outcomes will be ulcer healing and procedural safety. Secondary outcomes include time to healing, quality of life and clinical scores, ulcer recurrence rates and rates of post-thrombotic syndrome. Follow-up will be over a 5-year period. This feasibility trial is designed to include 60 patients. Should it be practicable a total of 594 patients would be required to adequately power the trial to definitively address ulcer-healing rates. DISCUSSION: This trial will be the first randomised trial to examine the role iliac interrogation and intervention in conjunction with standard operative therapy in the management of venous ulceration related to superficial truncal venous incompetence. ETHICAL COMMITTEE REFERENCE: C.A. 2111 Galway Clinical Research Ethics Committee REGISTRATION: Clinical Trials.gov registration NCT03640689 , Registered on 21 August 2018.

Use of the VENOVO™ and Sinus Obliquus™ venous stents in the treatment of non-thrombotic or post-thrombotic iliac vein lesions - Short-term results from a multi-centre Asian cohort.

OBJECTIVES: Deep venous stenting with intravascular ultrasound (IVUS) guidance is gaining favour as the treatment modality of choice for symptomatic ilio-femoral venous occlusive disease. The aim was to determine the short-term patency and symptomatic relief gained using the Bard Venovo™ and Optimed Sinus Obliquus™ stents in the endovascular treatment of non-thrombotic iliac vein lesions (NIVL) and post-thrombotic venous obstruction (PTO) from two Asian tertiary vascular centres. METHODS: Sixty patients (males = 21/60 (35.0%); median age 67 years (interquartile range 54-77)) who underwent IVUS interrogation and ilio-femoral stenting (June 2018-May 2019) in two Asian centres were prospectively followed. Clinical improvement was determined by the revised Venous Clinical Severity Score (rVCSS), pain using the Visual Analogue Scale (VAS) and ulcer healing rate. Patency rates were evaluated using Duplex ultrasound and computer tomography venogram. RESULTS: Seventy-one legs were interrogated and stented; 11/60 (18.3%) patients had a bilateral procedure. Indications for surgery were PTO (n = 11/71 (15.5%)) and NIVL (n = 60/71 (84.5%)). Twenty-seven of 71 (38.0%) patients had CEAP 6 disease. The median follow-up was 283 (interquartile range 211-370) days. Technical and procedural success was both 100%. Twenty-one of 71 (29.6%) legs had a combination of Venovo™ and Sinus Obliquus™ stents inserted for concurrent ilio-caval and iliac lesions. There were no major post-operative complications. Six-month primary, assisted primary and secondary patency rates were 94.1, 97.1 and 100%, respectively. There were no stent fractures. Mean rVCSS and VAS improved from 12.26 (±3.31) to 4.33 (±2.78) and 6.97 (±1.38) to 2.03 (±1.65), respectively, at three months (p < 0.01). Complete ulcer healing was seen in 27/27 (100%) patients at three months. CONCLUSION: Use of Venovo™ and Sinus Obliquus™ stents for symptomatic ilio-femoral venous disease showed excellent six-month primary patency rate with no stent fractures. There were significant clinical improvement and low-device-related complications. Longer follow-up is awaited to see how these dedicated venous stents perform.