Computed tomography derived anatomical predictors of vascular access complications following transfemoral transcatheter aortic valve implantation: A systematic review

Abstract Background Vascular complications after percutaneous transfemoral transcatheter aortic valve implantation (TAVI) are associated with adverse clinical outcomes and remain a significant challenge. Aims The purpose of this review is to synthesize the existing evidence regarding the iliofemoral artery features predictive of vascular complications after TAVI on pre‐procedural contrast‐enhanced multidetector computed tomography (MDCT). Methods A systematic search was performed in Embase and Medline (Pubmed) databases. Studies of patients undergoing transfemoral TAVI with MDCT were included. Studies with only valve‐in‐valve TAVI, planned surgical intervention and those using fluoroscopic assessment were excluded. Data on study cohort, procedural characteristics and significant predictors of vascular complications were extracted. Results We identified 23 original studies involving 8697 patients who underwent TAVI between 2006 and 2020. Of all patients, 8514 (97.9%) underwent percutaneous transfemoral‐TAVI, of which 8068 (94.8%) had contrast‐enhanced MDCT. The incidence of major vascular complications was 6.7 ± 4.1% and minor vascular complications 26.1 ± 7.8%. Significant independent predictors of major and minor complications related to vessel dimensions were common femoral artery depth (>54 mm), sheath‐to‐iliofemoral artery diameter ratio (>0.91–1.19), sheath‐to‐femoral artery diameter ratio (>1.03–1.45) and sheath‐to‐femoral artery area ratio (>1.35). Substantial iliofemoral vessel tortuosity predicted 2–5‐fold higher vascular risk. Significant iliofemoral calcification predicted 2–5‐fold higher risk. The iliac morphology score was the only hybrid scoring system with predictive value. Conclusions Independent iliofemoral predictors of access‐site complications in TAVI were related to vessel size, depth, calcification and tortuosity. These should be considered when planning transfemoral TAVI and in the design of future risk prediction models.


| INTRODUCTION
[3] Technological advances have enabled most TAVI procedures to be performed via percutaneous transfemoral (TF) access, using suturebased vascular closure devices and progressively reduced delivery system sizes.As a result, major vascular complications, as defined by the Valve Academic Research Consortium (VARC), have decreased over time, now in the region of 7%-8%. 4,57][8][9] The vast majority of vascular complications in TF-TAVI occur within the iliofemoral arterial segment. 10As we expand into lower risk, younger patients, there is increased focus on the ability to reliably predict and prevent these complications.
Meticulous pre-procedural imaging and iliofemoral vasculature risk assessment are of paramount importance.
Contrast-enhanced multidetector computed tomography (MDCT) is considered the gold standard for pre-TAVI assessment. 11 offers high spatial resolution and 3-dimensional assessment of iliofemoral morphology to assist in TF access assessment.Numerous studies have examined the predictive value of iliofemoral vessel size, tortuosity and calcification in determining the risk of periprocedural complications.We, therefore, sought to perform a systematic review of evidence to assimilate all reported iliofemoral predictors of vascular complications (Table 1) 12 derived from contrast-enhanced MDCT in patients undergoing percutaneous TF-TAVI.

| METHODS
This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRIS-MA) statement (Table S1). 13A broad systematic search was performed to identify all relevant studies from Embase and Medline ).We reviewed the reference lists of included studies to find additional studies.This study did not require an ethical approval.
T A B L E 1 Valve Academic Research Consortium-3 definition of major and minor access-related vascular complications (adapted from Généreux et al., 2021). 12
-Distal embolization (non-cerebral) from a vascular source resulting in death, amputation, limb or visceral ischaemia, or irreversible endorgan damage.
-Distal embolization treated with embolectomy and/or thrombectomy, not resulting in death, amputation, limb or visceral ischaemia, or irreversible end-organ damage.
-Unplanned endovascular or surgical intervention resulting in death, VARC type ≥2 bleeding, limb or visceral ischaemia, or irreversible neurologic impairment.
-Any unplanned endovascular or surgical intervention, ultra-sound guided compression, or thrombin injection, not resulting in death, VARC type ≥2 bleeding, limb or visceral ischaemia, or irreversible neurologic impairment.
-Closure device failure resulting in death, VARC type ≥2 bleeding, limb or visceral ischaemia, or irreversible neurologic impairment.
-Closure device failure not resulting in death, VARC type ≥2 bleeding, limb or visceral ischaemia, or irreversible neurologic impairment.
Two independent reviewers (VA and OC) screened the titles and abstracts of the retrieved citations after removing duplications based on pre-defined criteria.Potential discrepancies between reviewers were resolved through consensus.The inclusion criteria were (1) any original study published in English language and accompanied by full-text peerreviewed article, (2) evaluating patients undergoing percutaneous TF-TAVI, (3) reporting anatomical predictors or features associated with vascular or access-related complications derived from contrast-enhanced MDCT.Studies investigating risk prediction in valve-in-valve TAVI, non-TF access, planned vascular cut-down/closure and those using fluoroscopic angiography were excluded, as were case reports and conference abstracts.The full texts of relevant manuscripts were reviewed and data extracted into predefined tables.The quality of eligible studies was evaluated using the Newcastle-Ottawa assessment scale (0-9 points). 14dpoints of interest were significant predictors of vascular complications identified through univariate tests and independent predictors in multivariable analyses.Reported risk ratios or odds ratios

| Study selection
Figure 1 shows the PRISMA flow diagram.After removal of 1096 duplicates, a total of 3809 reports were initially identified, of which 3698 were excluded on the basis of screening at the title and abstract level (Figure S1).Of the remaining 111 reports, 64 studies were retrieved in full text and examined for eligibility.Of these, 23 studies involving 8697 patients fulfilled the pre-specified selection criteria and were deemed eligible for the analysis.

| Characteristics of included studies
The key characteristics, design features and predictors of vascular complications of the included studies are summarized in

| Iliac morphology score
Two (8.7%) studies assessed the iliac morphology score (IMS) for predicting vascular complications. 21,26The IMS consists of subjectively assessed IA calcification severity and minimum IA diameter.
Each attribute was graded semi-quantitatively (0-3), with higher scores representing increasingly less favorable morphology.The IMS was a strong independent predictor of major complications (OR: 4 (CI: 1.14-14.0),p = 0.03), with score ≥5 achieving good discrimination (AUC: 0.82, Sensitivity: 83%, Specificity: 73%). 26However, this finding was not reproducible, with another study showing that IMS can predict all but not major vascular complications (OR: 1.25 (CI: 1.08-1.46),p = 0.003) with AUC of 0.58 (Sensitivity, Specificity unknown) suggesting relatively poor discrimination. 17his is the first systematic review to describe all iliofemoral predictors of vascular complications after percutaneous TF-TAVI from preprocedural contrast-enhanced MDCT.A total of 23 unique studies involving 8697 patients were included, with key independent iliofemoral risk factors summarized in Figure 2.
Percutaneous TF approach is the preferred access strategy for TAVI, with >90% of procedures performed using this route. 38wever, TF access involves manipulation of large bore sheaths and TAVI delivery systems in the often diseased iliofemoral vasculature, exposing patients to a risk of vascular complications.
Despite technological improvements with lower sheath profiles and increased operator experience, the rate of vascular complications remains substantial. 39These are associated with increased mortality, poor quality of life, prolonged hospital admissions and increased healthcare costs. 10Therefore, there is a clear need for a continuous effort to identify patient and procedural factors associated with increased risk of vascular complications to prevent them during procedure planning.
Contrast-enhanced MDCT is the gold standard for preprocedural iliofemoral vasculature evaluation, TAVI planning and patient selection.MDCT can accurately evaluate iliofemoral vessel dimensions, calcification load and distribution, tortuosity and depth, all of which can assist in selecting the optimal vessel entry site for TAVI. 11To this date, there are no specific recommendations on how to summarize a broad range of iliofemoral measurements on MDCT to stratify TAVI recipients into distinct risk categories of vascular complications.Additionally, it is unknown if there is a threshold at which a combination of adverse iliofemoral features should warrant an upfront consideration of alternative non-TF access.Most of the studies included in this review reported on individual predictors of vascular complications but have not integrated these into a scoring system.The IMS was the only identified semi-quantitative scoring system for grading the risk of vascular complications in TAVI.
However, the strength of this tool has not been consistently demonstrated, 21,26 with further work required to built on this model.complications. 40,41However, low-profile systems have enabled TAVI deliverability to patients with smaller iliofemoral vessels.Therefore, further work is needed to evaluate the relationship between minimum vessel/sheath diameter and vascular complications in the era of new generation TAVI devices.
Some studies have suggested that female gender is a strong predictor of TAVI-related vascular complications and an important consideration for procedural planning. 17,23,25,33Gender-related differences in iliofemoral morphology on MDCT among TAVI patients remain poorly characterized in the context of other patient-specific factors.However, the increased risk may be due to the smaller calibre of iliofemoral vessels in females compared to males, resulting is less favorable sheath-to-artery ratios. 33,42 minimize potential complications associated with significant Amongst the included studies we demonstrated inconsistency between the severity of iliofemoral tortuosity and vascular complications.This may support wider anecdotal beliefs that even in cases of significant tortuosity, iliofemoral vessels can straighten to allow safe passage of TAVI systems. 11However, this approach may further exacerbate the issues of increased sheath manipulation, with additional exertional force which could contribute to vascular complications.Of the available tools, objective assessment of tortuosity with iliofemoral tortuosity score and maximal vessel angulation has demonstrable utility in identifying patients at higher risk of vascular and bleeding complications. 34,35Applying these quantitative tools to larger cohorts is needed to validate their utility and to improve our understanding of the role that iliofemoral tortuosity plays in predisposing to vascular complications in TF-TAVI.
Iliofemoral calcification is an important factor for predicting vascular complications in TF-TAVI, but this has not been supported consistently across the studies in our review.This heterogeneity may arise because the morphology and protrusion of bulky calcification at specific points within the iliofemoral vessel, such as the puncture site and areas of bifurcation, may be more relevant rather than simply the overall calcification.Further studies are needed to elucidate this by performing detailed segmental iliofemoral plaque analysis.
Overall, some but not all of the studies evaluated in this review found consistent iliofemoral predictors of vascular complications after TAVI.This may be attributed to insufficient power of smaller studies due to the low numbers of vascular complication events.
Another confounder that could influence the ability of adverse MDCT-derived features to predict vascular complications is the technique for percutaneous TF puncture.This was largely unknown and inconsistently reported between studies.Ultrasound-guided micro-puncture can localize femoral bifurcation and calcium-free areas, allowing precise arterial puncture for vascular closure device deployment and TAVI sheath insertion.In a recent meta-analysis, ultrasound-guided TF access in TAVI reduced the risk of access-site vascular and bleeding complications by 50% and ~40%, respectively. 43Increased operator experience is another important factor linked with fewer vascular complications and this could be considered alongside anatomical predictors in future models. 44Different largebore vascular closure methods could have an impact on access-site complications after TAVI but these were heterogeneous and frequently not reported in the included studies.Vascular closure device failure is not uncommon, occurring in up to 8% of patients, 45 and linked with adverse iliofemoral characteristics, including small CFA diameter, 46 SFAR, 47 and calcification. 48This could limit the routine upfront use of "one fits all" closure device strategy, instead warranting pre-emptive use of specific devices in adverse iliofemoral morphology.

| LIMITATIONS
We reviewed the literature to provide a systematic summary of all available iliofemoral predictors of access-related complications after TF-TAVI from contrast-enhanced MDCT.However, there are several notable limitations.Most selected studies were retrospective and some were relatively small, making them prone to bias regarding valid ascertainment of risk predictors.There was considerable heterogeneity of iliofemoral calcification and tortuosity assessment methodologies, which prohibited performing a comprehensive meta-analysis.
Included studies were published over a wide time frame, which may | 183 assist in the creation of this important systematic decision tool for the Heart Team pre-procedural TAVI planning.

(
Pubmed) databases on 26.11.2022 using the following keywords and phrases: (transcatheter aortic valve implantation [All Fields] OR transcatheter aortic valve replacement [All Fields] OR TAVI[All Fields] OR TAVR [All Fields]) AND (access-site complications [All Fields] OR vascular complications [All Fields] OR access-related complications [All Fields]

( 2 (
Sensitivity 63.3%, Specificity 40.9%), with area under curve (AUC) of 0.61 suggesting relatively poor predictive accuracy.Six (26.1%) studies demonstrated higher sheath to iliofemoral artery ratio (SIFAR) to be an independent predictor of access site complications [All complications-HR: 14.5 (CI: 1.75-120.12),p = 0.013; 31 OR: 6.52 (CI: 1.19-21.34),p = 0.002; 21 Major complications-OR: 280 (CI: 0.9-90150), p = 0.049; 19 OR: 32.CI: 7.44-139.6),p < 0.001; 18 OR: 1.91 (CI: 1.27-2.87),p = 0.001; 20 OR: 7.51 (CI: 1.61-34.95),p = 0.010; 32 OR: 31.02(CI: 4.03-238.6),p = 0.001. 21] ( Most of the included studies investigated the predictors of vascular complications across the whole spectrum of TAVI valves, including older generation devices with larger delivery systems compared with those currently in routine clinical use.The ratio between minimal iliofemoral diameter and sheath outer diameter has been consistently predictive of vascular complications, although with poor/modest predictive accuracy.Furthermore, variable cut-offs have been reported, making identification of patients at higher risk challenging.This is possibly reflective of TAVI developments over time and transition to smaller sheath sizes with newer generation devices, which are associated with reduced vascular and bleeding F I G U R E 2 Independent iliofemoral predictors of access site vascular complications in TAVI.CFA, common femoral artery; IFA, iliofemoral artery; SFAAR: sheath to femoral artery area ratio; SFAR, sheath to femoral artery diameter ratio; SIFAR, sheath to iliofemoral artery diameter ratio.[Color figure can be viewed at wileyonlinelibrary.com] introduce temporal bias related to technical advances in TAVI and patient care.Some studies included early generation devices using larger delivery sheaths, which are no longer in routine clinical use, that could affect the applicability of predictors derived from these studies to latest generation systems.Predictors of vascular complications related to secondary access site have not been examined in the included studies.This study focussed on identifying key iliofemoral risk predictors and anatomical features associated with other major vascular complications related to aortic dissection and aortic/annular rapture is beyond the scope of this review.6| CONCLUSIONThis is the first systematic review to describe all known iliofemoral predictors of vascular complications in percutaneous TF-TAVI on contrast-enhanced MDCT.Future studies are needed to devise and validate a simple, objective and reproducible risk score of vascular complications after TF-TAVI in a contemporary cohort of patients across the spectrum of operative risk.We suggest integrating a combination of quantitative and qualitative measurements to assess iliofemoral dimensions, arterial depth, calcification and tortuosity to ANDROSHCHUK ET AL.