Intra-arterial Fractional Flow Reserve Measurements Provide an Objective Assessment of the Functional Significance of Peripheral Arterial Stenoses.

OBJECTIVE: Peripheral arterial stenoses (PAS) are commonly investigated with duplex ultrasound (DUS) and angiography, but these are not functional tests. Fractional flow reserve (FFR), a pressure based index, functionally assesses the ischaemic potential of coronary stenoses, but its utility in PAS is unknown. FFR in the peripheral vasculature in patients with limb ischaemia was investigated. METHODS: Patients scheduled for angioplasty and or stenting of isolated iliac and superficial femoral artery stenoses were recruited. Resting trans-lesional pressure gradient (Pd/Pa) and FFR were measured after adenosine provoked hyperaemia using an intra-arterial 0.014 inch flow and pressure sensing wire (ComboWire XT, Philips). Prior to revascularisation, exercise ABPI (eABPI) and DUS derived peak systolic velocity ratio (PSVR) of the index lesion were determined. Calf muscle oxygenation was measured using blood oxygenation level dependent cardiovascular magnetic resonance prior to and after revascularisation. RESULTS: Forty-one patients (32, 78%, male, mean age 65 ± 11 years) with 61 stenoses (iliac 32; femoral 29) were studied. For lesions < 80% stenosis, resting Pd/Pa was not influenced by the degree of stenosis (p = .074); however, FFR was discriminatory, decreasing as the severity of stenosis increased (p = .019). An FFR of < 0.60 was associated with critical limb threatening ischaemia (area under the curve [AUC] 0.87; 95% CI 0.75 - 0.95), in this study performing better than angiographic % stenosis (0.79; 0.63 - 0.89), eABPI (0.72; 0.57 - 0.83), and PSVR (0.65; 0.51 - 0.78). FFR correlated strongly with calf oxygenation (rho, 0.76; p < .001). A greater increase in FFR signalled resolution of symptoms and signs (ΔFFR 0.25 ± 0.15 vs. 0.13 ± 0.09; p = .009) and a post-angioplasty and stenting FFR of > 0.74 predicted successful revascularisation (combined sensitivity and specificity of 95%; AUC 0.98; 0.91 - 1.00). CONCLUSION: This pilot study demonstrates that FFR can objectively measure the functional significance of PAS that compares favourably with visual and DUS based assessments. Its role as a quality control adjunct that confirms optimal vessel patency after angioplasty and or stenting also merits further investigation.

Multicenter trans-Atlantic experience with fenestrated-branched endovascular aortic repair of chronic post-dissection thoracoabdominal aortic aneurysms.

OBJECTIVE: This multicenter international study aimed to describe outcomes of fenestrated-branched endovascular aortic repairs (FB-EVAR) in a cohort of patients treated for chronic post-dissection thoracoabdominal aortic aneurysms (PD-TAAAs). METHODS: We reviewed the clinical data of all consecutive patients treated by FB-EVAR for repair of extent I to III PD-TAAAs in 16 centers from the United States and Europe (2008-2021). Data were extracted from institutional prospectively maintained databases and electronic patient records. All patients received off-the-shelf or patient-specific manufactured fenestrated-branched stent grafts. Endpoints were any cause mortality and major adverse events at 30 days, technical success, target artery (TA) patency, freedom from TA instability, minor (endovascular with <12 Fr sheath) and major (open or ≥12 Fr sheath) secondary interventions, patient survival, and freedom from aortic-related mortality (ARM). RESULTS: A total of 246 patients (76% male; median age, 67 years [interquartile range, 61-73 years]) were treated for extent I (7%), extent II (55%), and extent III (35%) PD-TAAAs by FB-EVAR. The median aneurysm diameter was 65 mm (interquartile range, 59-73 mm). Eighteen patients (7%) were octogenarians, 212 (86%) were American Society of Anesthesiologists class ≥3, and 21 (9%) presented with contained ruptured or symptomatic aneurysms. There were 917 renal-mesenteric vessels targeted by 581 fenestrations (63%) and 336 directional branches (37%), with a mean of 3.7 vessels per patient. Technical success was 96%. Mortality and rate of major adverse events at 30 days was 3% and 28%, including disabling complications such as new onset dialysis in 1%, major stroke in 1%, and permanent paraplegia in 2%. Mean follow-up was 24 months. Kaplan-Meier (KM) estimated patient survival at 3 and 5 years was 79% ± 6% and 65% ± 10%. KM estimated freedom from ARM was 95% ± 3% and 93% ± 5% at the same intervals. Unplanned secondary interventions were needed in 94 patients (38%), including minor procedures in 64 (25%) and major procedures in 30 (12%). There was one conversion to open surgical repair (<1%). KM estimated freedom from any secondary intervention was 44% ± 9% at 5 years. KM estimated primary and secondary TA patency were 93% ± 2% and 96% ± 1% at 5 years, respectively. CONCLUSIONS: FB-EVAR for chronic PD-TAAAs was associated with high technical success and a low rate of mortality (3%) and disabling complications at 30 days. Although the procedure is effective in the prevention of ARM, patient survival was low at 5 years (65%), likely due to the significant comorbidities in this cohort of patients. Freedom from secondary interventions at 5 years was 44%, although most procedures were minor. The significant rate of reinterventions highlights the need for continued patient surveillance.

Editor's Choice - Estimated Radiation Dose to the Operator During Endovascular Aneurysm Repair.

OBJECTIVE: To estimate operator organ doses from fluoroscopically guided infrarenal endovascular aneurysm repair (EVAR) procedures, using the detailed exposure information contained in radiation dose structured reports. METHODS: Conversion factors relating kerma area product (PKA) to primary operator organ doses were calculated using Monte Carlo methods for 91 beam angles and seven x-ray spectra typical of clinical practice. A computer program was written, which selects the appropriate conversion factor for each exposure listed in a structured report and multiplies it by the respective PKA. This system was used to estimate operator doses for 81 EVAR procedures for which structured reports were available. The impact of different shielding scenarios and variations in operator position was also investigated. RESULTS: Without any shielding, the median estimated effective dose was 113 µSv (interquartile range [IQR] 71, 252 µSv). The highest median organ doses were for the colon (154 µSv, IQR 81, 343) and stomach (133 µSv, IQR 76, 307). These dose estimates represent all exposures, including fluoroscopy and non-fluoroscopic digital acquisitions. With minimal shielding provided by 0.25 mm of Pb covering the torso and upper legs, the effective dose was reduced by a factor of around 6. With additional shielding from ceiling and table shields, a 25 to 50 fold reduction in dose is achievable. Estimated doses were highest where the primary beam was pointed directly away from the operator. CONCLUSION: The models suggest that with optimal use of shielding, operator doses can be reduced to levels equivalent to one to two days of natural background exposure and well below statutory dose limits.

Carbon dioxide flushing versus saline flushing of thoracic aortic stents (INTERCEPTevar): protocol for a multicentre pilot randomised controlled trial.

INTRODUCTION: Thoracic endovascular aortic repair (TEVAR) carries a 3%-6.1% stroke risk, including risk of 'silent' cerebral infarction (SCI). Stent-grafts are manufactured in room air and retain air. Instructions for use recommend saline flushing to 'de-air' the system prior to insertion, but substantial amounts of air are released when deploying them, potentially leading to downstream neuronal injury and SCI. Carbon dioxide (CO2) is more dense and more soluble in blood than air, without risk of bubble formation, so could be used in addition to saline to de-air stents. This pilot trial aims to assess the feasibility of a full-scale randomised controlled trial (RCT) investigating the neuroprotective benefit against SCI with the use of CO2-flushed aortic stent-grafts. METHODS AND ANALYSIS: This is a multicentre pilot RCT, which is taking place in vascular centres in the UK, USA and New Zealand. Patients identified for TEVAR will be enrolled after informed written consent. 120 participants will be randomised (1:1) to TEVAR-CO2 or TEVAR-saline, stratified according to TEVAR landing zone. Participants will undergo preoperative neurocognitive tests and quality of life assessments, which will be repeated at 6 weeks, or first outpatient appointment, and 6 months. Inpatient neurological testing will be performed within 48 hours of return to level 1 care for clinical stroke or delirium. Diffusion-weighted MRI will be undertaken within 72 hours postoperatively (1-7 days) and at 6 months to look for evidence and persistence of SCI. Feasibility will be assessed via measures of recruitment and retention, informing the design of a full-scale trial. ETHICS AND DISSEMINATION: The study coordination centre has obtained approval from the London Fulham Research Ethics Committee (19/LO/0836) and Southern Health and Disability Ethics Committee (NZ) and UK's Health Regulator Authority (HRA). The study has received ethical approval for recruitment in the UK (Fulham REC, 19/LO/0836), New Zealand (21/STH/192) and the USA (IRB 019-264, Ref 378630). Consent for entering into the study will be taken using standardised consent forms by the local study team, led by a local PI. The results of the trial will be submitted for publication in an open access journal. TRIAL REGISTRATION NUMBER: NCT03886675.

Acute Kidney Injury in Patients with Acute Type B Aortic Dissection.

OBJECTIVE: Acute kidney injury (AKI) is common in patients with aortic diseases; however, it has not been extensively studied in acute type B aortic dissection (TBAD). AKI is known to be associated with adverse kidney outcomes and premature death. This study investigated the incidence and impact of AKI in patients with acute TBAD. METHODS: This was a retrospective study including data from two tertiary vascular centres in the UK. Case notes and electronic records were reviewed for consecutive patients presenting with acute symptomatic TBAD. Patients were managed according to a uniform clinical protocol; both patients who underwent surgery and those managed conservatively were included in this analysis. Serum creatinine values were used to calculate the number of patients who developed AKI, based on validated Kidney Disease Improving Global Outcomes definitions. Associations between incidence of AKI, death, and Major Adverse Kidney Events (MAKE; defined as death, dialysis and/or drop in estimated glomerular filtration rate > 25%) were explored. RESULTS: Overall, 66 (42.6%) of 155 patients developed AKI within one week of presenting with TBAD. Of these, 23 patients (34.8%) had stage 1, 26 patients (39.4%) stage 2, and 17 patients (25.8%) stage 3 AKI. MAKE at 30 and 90 days occurred in 17 (11.0%) and 12 patients (7.7%), respectively. AKI was associated with significantly worse outcomes, with a 24.2% mortality rate in the AKI group compared with 7.8% among those with no AKI (p <.001); this association was also significant in adjusted analyses, both in patients who did and did not undergo surgery. CONCLUSION: AKI is very common among patients presenting with acute TBAD, even in clinically uncomplicated disease. There was a significant association with mortality and MAKE, whether patients underwent surgery or not. This warrants further investigation to better understand the underlying causes of the AKI and investigate management strategies which may improve outcomes.

Outcomes of off-the-shelf multibranched stent grafts with intentional occlusion of directional branches using endovascular plugs during endovascular repair of complex aortic aneurysms.

OBJECTIVE: To evaluate the technique and outcomes of intentional occlusion of directional branches (DBs) using endovascular plugs during branched endovascular aortic repair using off-the-shelf Zenith t-Branch thoracoabdominal (TAAA) stent grafts. METHODS: We reviewed the clinical data and outcomes of all consecutive patients treated by branched endovascular aortic repair using off-the-shelf Zenith t-Branch TAAA stent-graft (Cook Medical, Bloomington, Ind) in seven academic centers from 2013 to 2019. All patients had at least one DB intentionally occluded using extension of the branch with balloon or self-expandable covered stent, followed by placement of endovascular plugs. Intentional occlusion was indicated in patients with variations in the normal four-vessel renal-mesenteric anatomy, pre-existing dialysis, or in those who failed catheterization of a target vessel. End points were 30-day/in-hospital mortality, major adverse events, secondary interventions, target artery (TA) patency, TA instability, and patient survival. RESULTS: There were 100 patients, 65 male and 35 female, with median age of 71 years (interquartile range [IQR], 66-75 years). Of these, 31 patients (31%) had urgent/emergent operations for symptomatic/contained ruptured aneurysms. The median aneurysm diameter was 72 mm (IQR, 61-85 mm). A total of 290 renal-mesenteric arteries were incorporated with a median of three (IQR, 3-3) vessels/patient. Indications for DB occlusion were less than four suitable renal-mesenteric targets in 84 patients or pre-existing dialysis and inability to catheterize a target vessel in eight patients each. There were 110 DBs occluded by vascular plugs, including 48 celiac axis, one superior mesenteric artery, and 61 renal DBs. Thirty-day/in-hospital mortality was 10%, including 9% for elective and 13% for urgent/emergent procedures. Major adverse events occurred in 44 patients (44%), including acute kidney injury in 19 patients (19%), estimated blood loss >1 L in 12 patients (12%), respiratory failure and new onset dialysis in six patients (6%) each, bowel ischemia in five patients (5%), and myocardial infarction and paraplegia in two patients (2%) each. The median follow-up was 5 months (range, 1-13 months). Eighteen patients (18%) required secondary interventions, none for problems related to the occluded DB. There were no endoleaks related to the occluded DB. At 2 years, primary and secondary patency and freedom from TA instability were 93% ± 3%, 97% ± 2%, and 91% ± 4%, respectively. Freedom from secondary interventions and patient survival were 75% ± 6% and 63% ± 7%, respectively. CONCLUSIONS: Intentional occlusion of DBs using endovascular plugs allows versatile use of a four-vessel off-the-shelf multi-branched TAAA stent graft in patients with variations in the normal renal and mesenteric anatomy or when technical difficulties prevent successful target vessel stenting. There were no endoleaks or secondary interventions associated with the occluded DB.

Mutations in EPHB4 cause human venous valve aplasia.

Venous valve (VV) failure causes chronic venous insufficiency, but the molecular regulation of valve development is poorly understood. A primary lymphatic anomaly, caused by mutations in the receptor tyrosine kinase EPHB4, was recently described, with these patients also presenting with venous insufficiency. Whether the venous anomalies are the result of an effect on VVs is not known. VV formation requires complex "organization" of valve-forming endothelial cells, including their reorientation perpendicular to the direction of blood flow. Using quantitative ultrasound, we identified substantial VV aplasia and deep venous reflux in patients with mutations in EPHB4. We used a GFP reporter in mice to study expression of its ligand, ephrinB2, and analyzed developmental phenotypes after conditional deletion of floxed Ephb4 and Efnb2 alleles. EphB4 and ephrinB2 expression patterns were dynamically regulated around organizing valve-forming cells. Efnb2 deletion disrupted the normal endothelial expression patterns of the gap junction proteins connexin37 and connexin43 (both required for normal valve development) around reorientating valve-forming cells and produced deficient valve-forming cell elongation, reorientation, polarity, and proliferation. Ephb4 was also required for valve-forming cell organization and subsequent growth of the valve leaflets. These results uncover a potentially novel cause of primary human VV aplasia.

Preoperative comprehensive geriatric assessment and optimisation prior to elective arterial vascular surgery: a health economic analysis.

BACKGROUND: increasing numbers of older people are undergoing vascular surgery. Preoperative comprehensive geriatric assessment and optimisation (CGA) reduces postoperative complications and length of hospital stay. Establishing CGA-based perioperative services requires health economic evaluation prior to implementation. Through a modelling-based economic evaluation, using data from a single site clinical trial, this study evaluates whether CGA is a cost-effective alternative to standard preoperative assessment for older patients undergoing elective arterial surgery. METHODS: an economic evaluation, using decision-analytic modelling, comparing preoperative CGA and optimisation with standard preoperative care, was undertaken in older patients undergoing elective arterial surgery. The incremental net health benefit of CGA, expressed in terms of quality-adjusted life-years (QALYs), was used to evaluate cost-effectiveness. RESULTS: CGA is a cost-effective substitute for standard preoperative care in elective arterial surgery across a range of cost-effectiveness threshold values. An incremental net benefit of 0.58 QALYs at a cost-effectiveness threshold of £30k, 0.60 QALYs at a threshold of £20k and 0.63 QALYs at a threshold of £13k was observed. Mean total pre- and postoperative health care utilisation costs were estimated to be £1,165 lower for CGA patients largely accounted for by reduced postoperative bed day utilisation. CONCLUSION: this study demonstrates a likely health economic benefit in addition to the previously described clinical benefit of employing CGA methodology in the preoperative setting in older patients undergoing arterial surgery. Further evaluation should examine whether CGA-based perioperative services can be effectively implemented and achieve the same clinical and health economic outcomes at scale.

Early outcomes associated with use of the Zenith TX2 Dissection Endovascular Graft for the treatment of Stanford type B aortic dissection.

OBJECTIVE: To evaluate short term outcomes related to the use of the Zenith TX2 Dissection Endovascular Graft (ZDEG) and the Zenith Dissection Bare stent (ZDES) for the treatment of Stanford type B aortic dissections. METHODS: This retrospective multicenter case cohort study collated data from 10 European institutions for patients with both complicated and uncomplicated type B aortic dissection treated with ZDEG and ZDES between 2011 and 2018. The primary end point was mortality at 30 and 90 days. Secondary end points included complications related to TEVAR, such as, type Ia endoleak, stroke, paraparesis, paraplegia, and retrograde type A dissection (RTAD). Statistical analysis was carried out using the t test, or one-way analysis of variance and the χ2 or Fisher exact tests. RESULTS: We treated 120 patients (87 male; mean age, 62.7 ± 12.2years) either in the acute 76 (63.3%), subacute 16 (13.3%), or chronic 28 (23.3%) phase. Seven patients (5.8%) died within 30 days after the index procedure and two (1.7%) between 30 and 90 days. There was one instance of postoperative RTAD in a patient treated for rupture. Stroke and paraplegia occurred in three (2.5%) and five (4.2%), patients, respectively. Eight patients (6.7%) had a type Ia endoleak in the perioperative period. There were no instances of paraplegia, no permanent dialysis, and no requirement for adjunctive superior mesenteric or celiac artery stenting in the 33 patients (27.5%) who were treated by concurrent placement of ZDES distal to the ZDEG. The length and distal oversizing of ZDEG components used was less in this group. CONCLUSIONS: The present series demonstrates a low (<1%) RTAD rate and favorable morbidity and mortality. The lower rate of paraplegia, dialysis, and visceral artery stenting in the cohort that had adjunctive use of ZDES is compelling and merits further assessment.

Endovascular Treatment of Post Type A Chronic Aortic Arch Dissection With a Branched Endograft: Early Results From a Retrospective International Multicenter Study.

OBJECTIVE: The objective of this study was to evaluate the outcome of endovascular aortic arch repair for chronic dissection with a custom-made branched endograft. BACKGROUND: Acute type A aortic dissections are often treated with prosthetic replacement of the ascending aorta. During follow-up, repair of an aneurysmal evolution of the false lumen distal to the ascending prosthesis can be a challenge both for the surgeon and the patient. METHODS: We conducted a multicenter, retrospective study of consecutive patients from 14 vascular units treated with a custom-made, inner-branched device (Cook Medical, Bloomington, IN) for chronic aortic arch dissection. Rates of in-hospital mortality and stroke, technical success, early and late complications, reinterventions, and mortality during follow-up were evaluated. RESULTS: Seventy consecutive patients were treated between 2011 and 2018. All patients were considered unfit for conventional surgery. In-hospital combined mortality and stroke rate was 4% (n = 3), including 1 minor stroke, 1 major stroke causing death, and 1 death following multiorgan failure. Technical success rate was 94.3%. Twelve (17.1%) patients required early reinterventions: 8 for vascular access complication, 2 for endoleak correction, and 2 for pericardial effusion drainage. Median follow-up was 301 (138-642) days. During follow-up, 20 (29%) patients underwent secondary interventions: 9 endoleak corrections, 1 open repair for prosthetic kink, and 10 distal extensions of the graft to the thoracic or thoracoabdominal aorta. Eight patients (11%) died during follow-up because of nonaortic-related cause in 7 cases. CONCLUSIONS: Endovascular treatment of aortic arch chronic dissections with a branched endograft is associated with low mortality and stroke rates but has a high reintervention rate. Further follow-up is required to confirm the benefits of this novel approach.

Patient radiation dose from x-ray guided endovascular aneurysm repair: a Monte Carlo approach using voxel phantoms and detailed exposure information.

Endovascular aneurysm repair (EVAR) is a well-established minimally invasive technique that relies on x-ray guidance to introduce a stent through the femoral artery and manipulate it into place. The aim of this study was to estimate patient organ and effective doses from EVAR procedures using anatomically realistic computational phantoms and detailed exposure information from radiation dose structured reports (RDSR). Methods: Lookup tables of conversion factors relating kerma area product (PKA) to organ doses for 49 different beam angles were produced using Monte Carlo simulations (MCNPX2.7) with International Commission on Radiological Protection (ICRP) adult male and female voxel phantoms for EVAR procedures of varying complexity (infra-renal, fenestrated/branched and thoracic EVAR). Beam angle specific correction factors were calculated to adjust doses according to x-ray energy. A MATLAB function was written to find the appropriate conversion factor in the lookup table for each exposure described in the RDSR, perform energy corrections and multiply by the respective exposure PKA. Using this approach, organ doses were estimated for 183 EVAR procedures in which RDSRs were available. A number of simplified dose estimation methodologies were also investigated for situations in which RDSR data are not available. Results: Mean estimated bone marrow doses were 57 (range: 2-247), 86 (2-328) and 54 (8-250) mGy for infra-renal, fenestrated/branched and thoracic EVAR, respectively. Respective effective doses were 27 (1-208), 54 (1-180) and 37 (5-167) mSv. Dose estimates using non-individualised, average conversion factors, along with those produced using the alternative Monte Carlo code PCXMC, yielded reasonably similar results overall, though variation for individual procedures could exceed 100% for some organs. In conclusion, radiation doses from x-ray guided endovascular aneurysm repairs are potentially high, though this must be placed in the context of the life sparing nature and high success rate for this procedure.

Streptococcus pneumoniae as a Cause of Mycotic and Infected Aneurysms in Patients without Respiratory Features: Challenging Diagnoses Aided by 16S PCR.

BACKGROUND: Streptococcus pneumoniae is considered a rare cause of mycotic aneurysms. The microbiological diagnosis of mycotic aneurysms can be difficult, and many patients have negative blood culture results. METHODS: We describe a series of four consecutive cases of mycotic aneurysms caused by S. pneumoniae with no respiratory features or extravascular septic foci. In two patients with negative blood culture results, 16S PCR was used for the diagnosis of S. pneumoniae infection. RESULTS: Four men with mycotic aneurysms affecting the aorta, axillary, and popliteal arteries caused by S. pneumoniae presented to our center between 2015 and 2016. All were treated with at least one month of intravenous antibiotics, followed by at least 4 weeks of oral antibiotics. Two were additionally managed using endovascular surgical techniques, and one underwent an open surgical repair. The fourth patient presented with bilateral popliteal aneurysms, one of which ruptured and was managed using surgical ligation and bypass, whereas the other side subsequently ruptured and was repaired endovascularly. Three of the four patients are currently off antibiotics and considered cured, while one died of an unrelated cause. CONCLUSIONS: S. pneumoniae should be considered a potential causative agent of mycotic aneurysms. Diagnosis can be confirmed using 16S PCR, especially in patients where peripheral blood cultures are uninformative.