Abstract
Background
The location and severity of vascular calcification may influence closure device success in transfemoral transcatheter aortic valve implantation. The aim of this study was to analyze effects of vascular access-site calcification on vascular and bleeding outcomes post-transcatheter aortic valve implantation.
Methods
The Randomized Comparison of CatHeter-based Strategies fOr Interventional ACcess SitE CLOSURE during Transfemoral Transcatheter Aortic Valve Implantation (CHOICE-CLOSURE) trial assigned 516 patients to access site closure using a pure plug-based technique (MANTA, Teleflex) or a primary suture-based technique (ProGlide, Abbott Vascular). The principal finding of the overall study was that access-site or access-related complications were more common after the plug-based strategy compared to percutaneous closure with a suture-based strategy. In this predefined subgroup analysis, the overall cohort was split into patients with and without anterior calcification at the access site and divided by degree of calcification severity using the classification system developed in the MANTA vs. suture-based vascular closure after transcatHeter aortic valve replacement (MASH) trial. Differences in bleeding and vascular complications were compared. The primary endpoint consisted of access-site- or access-related major and minor vascular complications.
Results
There were more access-site-related major and minor vascular complications for patients with anterior wall vascular calcification and MASH severe calcification. No significant interaction with choice of closure technique in terms of access-site-related major and minor vascular complications was observed (odds ratio 1.70, 95% CI 0.77-3.78, p = 0.19 for the primary endpoint in plug- vs. suture-based strategy in patients with anterior calcification, odds ratio 1.78, 95% CI 0.56-5.65, p = 0.33 for primary endpoint in plug- vs. suture-based strategy with MASH severe calcification, pint = 0.97 for anterior calcification, pint = 0.95 for MASH severe calcification).
Conclusions
The total number of vascular complications was found to be greater in the presence of anterior and MASH severe calcification. Overall, the presence of anterior or severe calcification does not significantly modify the efficacy of the suture-based strategy compared to the plug-based strategy.
Keywords: Access site, Aortic stenosis, Bleeding, Femoral, Transcatheter aortic valve implantation (TAVI), Vascular access closure device
Introduction
Vascular complications are not as frequent as in the early days of transcatheter aortic valve implantation (TAVI), with significant incremental improvements as a consequence of multiple device iterations and the development of minimally invasive closure techniques. Nonetheless, particularly given the age and frailty of patients in whom TAVI is most frequently the treatment of choice, vascular complications still occur in a significant proportion of patients and, when they do occur, are associated with poorer outcomes.1, 2, 3
Clinical experience and prior analysis suggest that the degree of vascular calcification may influence closure device success post-TAVI.3 In particular, anterior vessel wall (ventral) calcification has been correlated with major access-site complications, even when overall calcification volume was nonpredictive.4 This may be due to the fact that closure device failure is more likely to occur when calcification is located geographically near the area of planned device deployment.
Generally, a suture-based vascular closure device strategy (ProGlide, Abbott Vascular, Abbott Park, Illinois) has been the lynchpin of percutaneous access-site closure.5, 6, 7 In recent years, however, alternative plug-based devices have become available, with the most common being the collagen-based MANTA device (Teleflex, Wayne, Pennsylvania).8 Although a recent meta-analysis identified some factors that were likely to lead to plug-based closure device failure, calcification specifically was not considered.9 Furthermore, given the difference in mechanism between the plug- and suture-based closure strategies, it may be that one or the other strategy is more favorable for a given set of circumstances or a particular patient cohort.
The ease of use and lack of a steep learning curve associated with the plug-based strategy, as well as the reassurance of a safety wire in the suture-based strategy, mean identification of the strategy that is best employed for a given patient’s situation is paramount. We, therefore, analyzed the specific effects of vascular access-site calcification on vascular and bleeding outcomes in a population in which both devices were utilized.
Methods
Study Design
The present analysis is based on data from the recently published investigator-initiated, open-label, multicenter, randomized, controlled Randomized Comparison of CatHeter-based Strategies fOr Interventional ACcess SitE CLOSURE during Transfemoral Transcatheter Aortic Valve Implantation (CHOICE-CLOSURE) trial (https://www.clinicaltrials.gov; Unique identifier: NCT04459208), which compared a pure plug-based closure device strategy to a primary suture-based technique, potentially complemented by a small plug.10 The study was approved by the ethics committee at each participating center, and all patients signed written informed consent. Data management and analysis were carried out by an independent data coordinating center, with oversight from a steering committee. The data that supports the findings of this study are available from the corresponding author on reasonable request.
The individual study design, definitions, and endpoints, including inclusion and exclusion criteria, used within the trial have been previously described.10 In brief, the primary endpoint consisted of access-site-related major and minor vascular complications during index hospitalization, defined according to the Valve Academic Research Consortium-2 (VARC-2) criteria.11 Major and minor bleeding were also defined according to VARC-2 criteria. The principal finding of the overall study was that access-site or access-related complications were more common after the plug-based strategy compared to percutaneous closure with a suture-based strategy.
Assessment of Access Site Calcification
Patients were assessed with transthoracic echocardiography and multidetector computer tomography. On three-dimensional multidetector computer tomography, the minimal diameter of the iliofemoral arteries, the location of the femoral artery bifurcation, the location and severity of calcification, and the presence and severity of tortuosity were assessed. Severity of calcification was assessed according to the MANTA vs. suture-based vascular closure after transcatHeter aortic valve replacement (MASH) trial classification (none, mild [longitudinal extent of calcium ≤1 cm, circumferential extent ≤180°], moderate [>1 cm, ≤180°] and severe [>1 cm, >180°]) (Figure 1).12 The authors chose the MASH classification because it takes into account both the longitudinal and circumferential extent of femoral artery calcification. Tortuosity of the iliofemoral arteries was defined as mild (30° to 60°), moderate (60° to 90°) or severe (>90°). Anterior calcification was defined as the presence of calcification at the level of the common femoral artery from the 9-o’clock to 3-o’clock position, while nonanterior calcification was defined as the presence of calcification in the trans-axial plane outside of this segment.
Figure 1.
MASH classification. Classification of coronary calcium according to the MASH (MANTA vs. suture-based vascular closure after transcatheter aortic valve replacement) trial criteria. Created with BioRender.com.
Endpoints and Definitions
In this subgroup study, two independent analyses were carried out. The first split the overall cohort into those patients with anterior (ventral) and no anterior calcification, and the second divided the cohort by degree of calcification severity. In addition to the primary endpoint, we also assessed (as secondary endpoints) the rate of vascular closure device failure, defined as failure of a closure device strategy to achieve hemostasis without the need for an alternative treatment (other than manual compression or adjunctive endovascular ballooning); unplanned vascular surgery and/or use of endovascular stent or stent-graft or other endovascular interventions at the puncture site; bleeding as a composite of minor/major/life-threatening events; and access site stenosis. All endpoints were assessed during index hospitalization and adjudicated by a clinical events committee blinded to treatment assignment. Of note, a vascular ultrasound was performed at least once after the procedure and before discharge to exclude silent vascular injury or underestimated vascular stenoses.
Statistical Analysis
The primary analysis was carried out on an intention-to-treat basis. Continuous data are presented as mean ± SD. Categorical data are presented as counts and proportions (%). Differences between groups were checked for significance with the independent samples Student t test or Wilcoxon rank-sum test (continuous data) or the chi-square or Fisher exact test as required. The chi-square or Fisher-Freeman-Halton test was used to make comparisons in contingency tables with more than two possible outcomes. Results of subgroup analyses are presented as odds ratios (ORs) and 95% CIs and were adjusted for clinically relevant baseline parameters that were significantly different between treatment groups, specifically sex, presence of peripheral vascular disease, and baseline hemoglobin. These parameters were chosen on the basis that they were most likely to represent a source of bias for the analysis, and given the number of primary endpoint events overall, we chose to limit our adjusted analysis to these variables. As per the recommendation of McNamee et al., an automatic selection algorithm was not used to assess confounders.13 ORs, CIs, and formal tests for interaction were assessed by logistic regression. No adjustment was made for the primary and secondary endpoint comparisons. All tests were two-sided, and a p-value < 0.05 was considered statistically significant. All statistical analysis was carried out in SPSS (IBM SPSS Statistics Subscription, Build 1.0.0.1508, IBM Corp., Armonk, N.Y., USA).
Results
Baseline Characteristics
Overall, 516 patients were included in the CHOICE-CLOSURE study, with n = 258 patients randomized to the suture-based and plug-based groups, respectively. Twenty-five patients were excluded from this subanalysis as computed tomography scan images were not available to assess calcification in more detail, leaving 491 patients for analysis, of which n = 247 were in the suture-based and n = 244 in the plug-based groups, respectively.
Anterior wall calcification was noted in 33.2% (163/491) of patients (34.0% of plug-based [83/244] and 32.4% [80/247] of suture-based patients, p = 0.77) (Figure 2a). In terms of baseline characteristics (Table 1), fewer women had anterior calcification (37.4% with vs. 47.6% without, p = 0.042). Those patients with anterior calcification had a higher EuroScore II (5.4 ± 5.0 vs. 3.9 ± 3.4, p < 0.001) and Society of Thoracic Surgery score (4.7 ± 3.3 vs. 3.8 ± 2.6, p < 0.001), as well as higher prevalence of coronary artery disease (63.2 vs. 43.0%, p < 0.001) and peripheral vascular disease (11.7 vs. 5.5%, p = 0.024). In terms of laboratory parameters, baseline creatinine, hemoglobin, and N-terminal prohormone of brain natriuretic peptide were higher in the anterior calcification subgroup (Table 1). Left ventricular ejection fraction was lower in the anterior calcification group (Supplemental Table 1, 52.9% ± 13.6% vs. 55.4% ± 12.1%, p = 0.034), and on preprocedure computed tomography, the diameter of both the right and left femoral artery was smaller in those patients with anterior calcification (Supplemental Table 1).
Figure 2.
(a) Anterior calcification. Flowchart for anterior calcification subgroup analysis. (b) Severe calcification. Flowchart for MASH (MANTA vs. suture-based vascular closure after transcatheter aortic valve replacement) severe calcification subgroup analysis.
Abbreviation: CT, computed tomography.
Table 1.
Baseline clinical and procedural characteristics for patients with anterior calcification vs. no anterior calcification
| Characteristic | Anterior calcification (n = 163) | No anterior calcification (n = 328) | p-value |
|---|---|---|---|
| Age (y) | 80.8 ± 6.3 | 80.3 ± 6.5 | 0.204 |
| Female sex no/total no. (%) | 61/163 (37.4%) | 156/328 (47.6%) | 0.042 |
| Weight (kg) | 81.0 ± 18.2 | 78.9 ± 15.2 | 0.391 |
| Height (m) | 167.3 ± 9.2 | 166.4 ± 8.7 | 0.234 |
| Body mass index (kg/m2) | 28.9 ± 5.7 | 28.5 ± 5.0 | 0.595 |
| EuroSCORE II | 5.4 ± 5.0 | 3.9 ± 3.4 | <0.001 |
| Society of Thoracic Surgeons Score | 4.7 ± 3.3 | 3.8 ± 2.6 | <0.001 |
| NYHA class – no/total no. (%) | 0.225 | ||
| I | 8/163 (4.9%) | 32/328 (9.8%) | |
| II | 40/163 (24.5%) | 79/328 (24.1%) | |
| III | 100/163 (61.3%) | 196/328 (59.8%) | |
| IV | 15/163 (9.2%) | 21/328 (6.4%) | |
| Diabetes mellitus – no/total no. (%) | 71/163 (43.6%) | 119/328 (36.3%) | 0.144 |
| Hyperlipidemia – no/total no. (%) | 123/163 (75.5%) | 213/328 (64.9%) | 0.024 |
| Coronary artery disease – no/total no. (%) | 103/163 (63.2%) | 141/328 (43.0%) | <0.001 |
| Previous MI – no/total no. (%) | 20/163 (12.3%) | 39/328 (11.9%) | 1.000 |
| Previous CABG – no/total no. (%) | 20/163 (12.3%) | 23/328 (7.0%) | 0.076 |
| Previous PCI – no/total no. | 44/163 (27.0%) | 65/328 (19.8%) | 0.092 |
| Previous valve surgery – no/total no. (%) | 21/163 (12.9%) | 25/328 (7.6%) | 0.085 |
| Cerebral vascular disease – no/total no. (%) | 16/163 (9.8%) | 34/328 (10.4%) | 0.975 |
| Previous stroke – no/total no. (%) | 20/163 (12.3%) | 43/328 (13.1%) | 0.905 |
| Peripheral vascular disease – no/total no. (%) | 19/163 (11.7%) | 18/328 (5.5%) | 0.024 |
| Previous peripheral intervention – no/total no. (%) | 7/163 (4.3%) | 4/328 (1.2%) | 0.065 |
| Pulmonary disease – no/total no. (%) | 27/163 (16.6%) | 56/328 (17.1%) | 0.989 |
| Permanent pacemaker – no/total no. (%) | 23/163 (14.1%) | 41/328 (12.5%) | 0.721 |
| Atrial fibrillation – no/total no. (%) | 50/163 (30.7%) | 100/328 (30.5%) | 1.000 |
| Severe chronic renal failure∗ - no/total no. (%) | 20/163 (12.3%) | 24/328 (7.3%) | 0.101 |
| Baseline creatinine (μmol/L) | 125.7 ± 104.6 | 105.7 ± 59.6 | 0.003 |
| Baseline Hb (mmol/L) | 7.5 ± 1.2 | 8.0 ± 4.6 | 0.011 |
| Baseline INR | 1.2 ± 0.4 | 1.4 ± 5.4 | 0.477 |
| Baseline NT-pro BNP – median (Q1, Q3) | 2194 (756, 6086) | 1350 (525, 2795) | 0.001 |
| Procedure fluoroscopy time – median (Q1, Q3) (mins) | 15.3 (11.0, 22.6) | 13.25 (10.0, 18.0) | 0.002 |
Notes. Plus-minus values are means ± SD.
Abbreviations: CABG, coronary artery bypass graft; INR, International Normalized Ratio; IQR, interquartile range; MI, myocardial infarction; NT-pro BNP, N-terminal prohormone of brain natriuretic peptide; NYHA, New York Heart Association Class; PCI, percutaneous coronary intervention.
Defined as a glomerular filtration rate <30 ml/min/1.73 m2.
Similarly, MASH severe vascular access-site calcification was present in 13.9% (68/491) of patients (12.7% [31/244] of the plug-based and 15.0% [37/247] of the suture-based patients, p = 0.55), (Figure 2b). In terms of baseline characteristics (Table 2), the majority parallel what we see for the case of anterior vs. no anterior calcification, with the addition that a higher proportion of those patients with MASH severe calcification were diabetic (51.5 vs. 36.6%, p = 0.028) or had prior coronary artery disease treatment (coronary artery bypass graft 16.2 vs. 7.6%, p = 0.036 and percutaneous coronary intervention 32.4 vs. 20.6%, p = 0.044).
Table 2.
Baseline clinical and procedural characteristics for patients with MASH severe vs. nonsevere calcification
| Variable | Severe calcification (n = 68) | No severe calcification (n = 423) | p-Value |
|---|---|---|---|
| Age (y) | 81.2 ± 5.8 | 80.3 ± 6.2 | 0.201 |
| Female sex no/total no. (%) | 21/68 (30.9%) | 196/423 (46.3%) | 0.024 |
| Weight (kg) | 81.8 ± 18.5 | 79.2 ± 15.9 | 0.416 |
| Height (m) | 168.4 ± 8.5 | 166.4 ± 8.9 | 0.058 |
| Body mass index (kg/m2) | 28.7 ± 5.8 | 28.6 ± 5.2 | 0.996 |
| Euroscore II | 6.5 ± 6.0 | 4.1 ± 3.6 | <0.001 |
| Society of Thoracic Surgeons Score | 4.9 ± 3.7 | 4.0 ± 2.7 | 0.011 |
| NYHA class – no/total no. (%) | 0.143 | ||
| I | 3/68 (4.4%) | 37/423 (8.7%) | |
| II | 11/68 (16.2%) | 108/423 (25.5%) | |
| III | 47/68 (69.1%) | 249/423 (58.9%) | |
| IV | 7/68 (10.3%) | 29/423 (6.9%) | |
| Diabetes mellitus – no/total no. (%) | 35/68 (51.5%) | 155/423 (36.6%) | 0.028 |
| Hyperlipidemia – no/total no. (%) | 52/68 (76.5%) | 284/423 (67.1%) | 0.163 |
| Coronary artery disease – no/total no. (%) | 50/68 (73.5%) | 194/423 (45.9%) | <0.001 |
| Previous MI – no/total no. (%) | 8/68 (11.8%) | 51/423 (12.1%) | 1.000 |
| Previous CABG – no/total no. (%) | 11/68 (16.2%) | 32/423 (7.6%) | 0.036 |
| Previous PCI – no/total no. | 22/68 (32.4%) | 87/423 (20.6%) | 0.044 |
| Previous valve surgery – no/total no. (%) | 10/68 (14.7%) | 36/423 (8.5%) | 0.161 |
| Cerebral vascular disease – no/total no. (%) | 10/68 (14.7%) | 40/423 (9.5%) | 0.266 |
| Previous stroke – no/total no. (%) | 6/68 (8.8%) | 57/423 (13.5%) | 0.385 |
| Peripheral vascular disease – no/total no. (%) | 14/68 (20.6%) | 23/423 (5.4%) | <0.001 |
| Previous peripheral intervention – no/total no. (%) | 4/68 (5.9%) | 7/423 (1.7%) | 0.081 |
| Pulmonary disease – no/total no. (%) | 13/68 (19.1%) | 70/423 (16.5%) | 0.726 |
| Permanent pacemaker – no/total no. (%) | 9/68 (13.2%) | 55/423 (13.0%) | 1.000 |
| Atrial fibrillation – no/total no. (%) | 24/68 (35.3%) | 126/423 (29.8%) | 0.439 |
| Severe chronic renal failure∗ – no/total no. (%) | 9/68 (13.2%) | 35/423 (8.3%) | 0.271 |
| Baseline creatinine (μmol/L) | 132.2 ± 106.2 | 109.1 ± 72.1 | 0.048 |
| Baseline Hb (mmol/L) | 7.5 ± 1.3 | 7.9 ± 4.1 | 0.097 |
| Baseline INR | 1.2 ± 0.3 | 1.4 ± 4.7 | 0.306 |
| Baseline NT-pro BNP – median (IQR) | 2865 [759, 6845] | 1444 [563, 3183] | 0.017 |
| Procedure fluoroscopy time – median (IQR) (mins) | 15.1 [12.1, 22.6] | 13.7 [10.1, 18.8] | 0.012 |
Notes. Plus-minus values are means ± SD.
Abbreviations: CABG, coronary artery bypass graft; INR, International Normalized Ratio; IQR, interquartile range; MASH, MANTA vs. suture-based vascular closure after transcatheter aortic valve replacement; MI, myocardial infarction; NT-pro BNP, N-terminal prohormone of brain natriuretic peptide; NYHA, New York Heart Association Class; PCI, percutaneous coronary intervention.
Defined as a glomerular filtration rate <30 ml/min/1.73 m2.
Procedural Details
Details of vascular closure for patients with anterior calcification vs. no anterior calcification are shown in Supplemental Table 3, while details for those with MASH severe calcification vs. no severe calcification are shown in Supplemental Table 4. In summary, there were no significant differences between parameters in both cases.
In-Hospital Outcomes
Outcomes for patients with and without anterior calcification, and separately, with and without MASH severe calcification, are highlighted in Table 3. For the anterior calcification subgroup overall, the primary endpoint occurred in 20.2% (33/163) of cases, in comparison to 13.7% (45/328) of cases without anterior calcification, adjusted OR 1.60, 95% CI 0.96-2.65, p = 0.07. Similarly, for the MASH severe calcification subgroup overall, the primary endpoint occurred in 23.5% (16/68) of cases, in comparison to 14.7% (62/423) of cases without severe calcification, adjusted OR 1.87, 95% CI 0.98-3.55, p = 0.06 (Figure 3). Thus, although not statistically significant, there was a trend towards both a greater incidence of the primary endpoint (and more bleeding) in the presence of anterior and MASH severe calcification, respectively. Indeed, the difference in bleeding rates was statistically significant in the comparison between patients with and without MASH severe calcification (16.2 vs. 8.5%, adjusted OR 2.39, 95% CI 1.13-5.08, p = 0.02).
Table 3.
Procedural outcomes as odds ratios by multivariate regression analysis, adjusted vs. unadjusted
| Anterior calcification | Present (n = 163) | Absent (n = 328) | Unadjusted OR | 95% CI | p-Value | Adjusted OR | 95% CI | p-Value | Pint |
|---|---|---|---|---|---|---|---|---|---|
| Primary endpoint (overall) | 20.2% | 13.7% | 1.60 | 0.97-2.62 | 0.06 | 1.60 | 0.96-2.65 | 0.07 | 0.97 |
| Plug-based | 24.1% (20/83) | 16.8% (27/161) | 1.58 | 0.82-3.02 | 0.17 | 1.54 | 0.79-3.02 | 0.21 | |
| Suture-based | 16.3% (13/80) | 10.8% (18/167) | 1.61 | 0.74-3.47 | 0.23 | 1.69 | 0.77-3.70 | 0.19 | |
| Bleeding | 12.9% | 8.0% | 1.72 | 0.94-3.16 | 0.08 | 1.79 | 0.96-3.32 | 0.07 | |
| Life threatening | 0.6% | 0.3% | 2.02 | 0.13-32.48 | 0.62 | 1.86 | 0.11-30.37 | 0.66 | |
| Major | 0.6% | 0.6% | 1.15 | 0.33-4.00 | 0.82 | 1.17 | 0.33-4.09 | 0.81 | |
| Minor | 9.8% | 5.5% | 1.88 | 0.93-3.78 | 0.08 | 1.93 | 0.94-3.93 | 0.07 | |
| Closure device failure | 5.5% | 4.9% | 1.14 | 0.49-2.63 | 0.76 | 1.17 | 0.50-2.75 | 0.71 | |
| Unplanned endovascular treatment | 10.4% | 7.3% | 1.48 | 0.77-2.83 | 0.24 | 1.53 | 0.78-2.97 | 0.21 | |
| Access site stenosis | 10.4% | 3.7% | 3.07 | 1.43-6.59 | 0.004 | 3.38 | 1.52-7.50 | 0.003 |
| MASH severe calcification | Present (n = 68) | Absent (n = 423) | Unadjusted OR | 95% CI | p-Value | Adjusted OR | 95% CI | p-Value | Pint |
|---|---|---|---|---|---|---|---|---|---|
| Primary endpoint (overall) | 23.5% | 14.7% | 1.79 | 0.96-3.34 | 0.07 | 1.87 | 0.98-3.55 | 0.06 | 0.95 |
| Plug-based | 29.0% (9/31) | 17.8% (38/213) | 1.88 | 0.80-4.41 | 0.15 | 1.85 | 0.77-4.46 | 0.17 | |
| Suture-based | 18.9% (7/37) | 11.4% (24/210) | 1.81 | 0.72-4.57 | 0.21 | 2.03 | 0.78-5.32 | 0.15 | |
| Bleeding, access site related | 16.2% | 8.5% | 2.08 | 1.00-4.31 | 0.05 | 2.39 | 1.13-5.08 | 0.02 | |
| Life threatening | 1.5% | 0.2% | 6.30 | 0.39-101.91 | 0.20 | 6.06 | 0.37-100.15 | 0.21 | |
| Major | 1.5% | 0.5% | 2.39 | 0.62-9.26 | 0.21 | 2.66 | 0.67-10.47 | 0.16 | |
| Minor | 10.3% | 6.4% | 1.68 | 0.70-4.03 | 0.24 | 1.89 | 0.77-4.64 | 0.17 | |
| Closure device failure | 7.4% | 4.7% | 1.60 | 0.58-4.41 | 0.37 | 1.85 | 0.66-5.22 | 0.24 | |
| Unplanned endovascular treatment | 8.8% | 8.3% | 1.07 | 0.43-2.66 | 0.88 | 1.13 | 0.44-2.87 | 0.80 | |
| Access site stenosis | 10.3% | 5.2% | 2.09 | 0.86-5.10 | 0.11 | 2.29 | 0.88-5.93 | 0.09 |
Notes. Adjusted covariates are sex, presence of peripheral arterial disease and baseline hemoglobin. The values in bold are those where the p-value is less than <0.05, suggesting statistical significance.
Abbreviations: CI, confidence interval; MASH, MANTA vs. suture-based vascular closure after transcatheter aortic valve replacement; OR, odds ratio.
Figure 3.
Vascular complications by the presence of absence of anterior and MASH severe calcification. The percentage of access-site or access-related vascular complications are highlighted for those patients with and without anterior calcification and with and without MASH severe calcification, respectively. In both cases, there is a greater incidence of complications in the presence of calcification.
Abbreviation: MASH, MANTA vs. suture-based vascular closure after transcatheter aortic valve replacement.
The primary endpoint occurred in the presence of anterior calcification at a frequency of 24.1% in the plug-based strategy, compared to 16.3% in the suture-based strategy, adjusted OR 1.70, 95% CI 0.77-3.78, p = 0.19. In the absence of anterior calcification, the primary endpoint occurred at a frequency of 16.8% in the plug-based strategy, compared to 10.8% in the suture-based strategy, adjusted OR 1.72, 95% CI 0.90-3.27, p = 0.10, p for interaction = 0.97 (Figure 4, Supplemental Table 5).
Figure 4.
Odds ratios for the primary endpoint. Odds ratios and interaction p-values for the primary endpoint.
Abbreviations: CI, confidence interval; Pint, interaction p-value for choice of closure device and presence of anterior or MASH (MANTA vs. suture-based vascular closure after transcatheter aortic valve replacement) severe calcification, respectively.
The primary endpoint occurred in the presence of MASH severe calcification at a frequency of 29.0% in the plug-based strategy, compared to 18.9% in the suture-based strategy, adjusted OR 1.78, 95% CI 0.56-5.65, p = 0.33. In the absence of MASH severe calcification, the primary endpoint occurred at a frequency of 17.8% in the plug-based strategy, compared to 11.4% in the suture-based strategy, adjusted OR 1.69, 95% CI 0.97-2.94, p = 0.06, p for interaction = 0.95 (Figure 4, Supplemental Table 6).
Although a secondary endpoint, minor access-site bleeding appeared more common in the suture-based strategy when anterior calcification was present (4.8 vs. 15.0%), while without anterior calcification, it appeared more minor bleeding occurred in the plug-based cohort (9.3 vs. 1.8%). Similarly, there was a trend towards minor access-site bleeding being more common in the suture-based group when MASH severe calcification was present (3.2 vs. 16.2%) and in the plug-based cohort in the absence of MASH severe calcification (8.5 vs. 4.3%). Of note, when those patients in the suture-based strategy were stratified according to who received an additional small plug-based device, no differences in minor bleeding between those who did and did not were noted (Supplemental Table 7).
Discussion
This subanalysis of the CHOICE-CLOSURE trial assessing the impact of anterior and MASH severe femoral artery calcification on TAVI outcomes in a total population of 516 randomized patients can be summarized as follows:
Firstly, we note a trend towards more access-site-related vascular and bleeding complications in patients with both anterior and MASH severe calcification undergoing transfemoral TAVI, and specifically, a significant difference in bleeding rates in between those with and without MASH severe calcification. Secondly, in terms of the primary endpoint, no significant interaction between the presence of anterior or MASH severe calcification and the closure strategy was detected.
This study is advantageous in that it uses data from the largest randomized, controlled trial comparing a suture-based strategy posttransfemoral TAVI to a plug-based one and thus provides more robust data than that obtained from single-arm prospective registries. We observed a noteworthy trend in terms of the primary outcome when assessed in those patients with and without both anterior and MASH severe calcification, in that the presence of both is associated with a numerically higher incidence of access-site or access-related major and minor vascular complications, which, while not in itself statistically significant, certainly merits discussion and further dedicated study. This is in agreement with the work of prior studies, which suggest calcification as a predictive factor for VARC major complications.3,4
Although the classification of femoral arterial access-site calcification here was originally set out in the MASH trial, in that trial only a comparison between no-mild and moderate-severe femoral calcium groups was made. Specifically, those patients with no or mild femoral artery access-site calcification were compared to those with moderate or severe calcification, and no significant interaction between these groups, and a suture- vs. plug-based closure strategy was detected in terms of access-site-related major and minor vascular complications.12 Of note, this trial did not allow the use of additional closure devices in the suture-based arm without considering this to be a “modified vascular closure device failure” and this should be borne in mind when interpreting its results. Thus, our study is the first to compare MASH severe calcification to all other groups, clarifying the association between MASH severe calcification and access-site-related complications and, in effect, clinically validating this classification.
In this study, it is important to point out that vascular access was most commonly obtained using digital subtraction angiography and road mapping, in fact in 72.8% of all cases (70.5% in the plug-based and 75.2% in the suture-based cohort), whereas ultrasound-guided puncture was used in 18.2% (19.8% of plug-based and 16.7% of suture-based) patients. In brief, a fluoroscopic sequence of the target femoral artery was acquired during contrast injection from a contralaterally inserted pigtail catheter positioned at the aortic bifurcation. This allowed the puncture to be performed by means of visual guidance, with a real-time fluoroscopic image overlaid on a static image of the iliofemoral vessels. Previously, it has been shown that, in comparison to integration of angiographic data, bony iliofemoral landmarks, and a radio-opaque object, both major vascular complications and major bleeding at 30 days were significantly reduced by a road-mapping approach.14 However, one retrospective review that compared both ultrasound-guided and road-mapping access in TAVI suggested that there were fewer vascular access-site complications with ultrasound (OR 0.51, 95% CI 0.29-0.88, p = 0.02). It should be born in mind that road mapping was the predominant method of ensuring a safe femoral arterial puncture when interpreting the results of this study, although no significant interaction overall between plug- and suture-based groups and choice of access technique was detected.10
Furthermore, according to a secondary analysis within this study, there appeared to be more minor access-site bleeding in the presence of anterior calcification in the suture-based strategy, which is in keeping with the fact that for the suture-based device to work correctly, the walls of the artery at the puncture site need to be well-apposed, and the presence of access-site calcification serves to hinder this.15 Conversely, there appeared to be more minor access-site bleeding with the plug-based strategy in the absence of anterior calcification. This may be the case, as suggested in the overall CHOICE-CLOSURE population, as a consequence of the plug-based device suggesting early complete hemostasis, while in fact there is clinically and angiographically inapparent micro-bleeding occurring around the puncture site, possibly due to incomplete apposition of the plug.10 It must be emphasized, however, that this hypothesis is based purely on a secondary analysis, and further dedicated study is needed to clarify this.
Limitations
This study is a subgroup analysis, although prespecified, and thus not powered to definitively find a significant difference between the subgroups of interest. It should thus be viewed as hypothesis-generating. In particular, due to the relatively low number of patients with MASH severe calcification, there is a risk that population effects related to severe calcification are not detected in this sample due to the limited size. In addition, as this is a subgroup analysis, there is no mechanism to ensure that patient characteristics will be evenly balanced in respective subgroups. However, the only difference in baseline characteristics that does not have either a causal or consequential relationship with calcification was a decreased proportion of females with both anterior and MASH severe calcification. This should be noted, particularly as some studies have reported female sex as an independent risk factor for TAVI-related complications. Furthermore, the limitations of the original CHOICE-CLOSURE study hold, in particular that the routine use of vascular ultrasound may have unmasked vascular complications with questionable clinical significance.
Conclusions
In a subgroup analysis of the CHOICE-CLOSURE trial, access-site-related major and minor vascular complications after transfemoral TAVI were numerically more frequent for both patients with anterior wall vessel calcification and MASH severe calcification. However, there was no significant interaction with the choice of closure technique, and either anterior or MASH severe calcification was detected.
Ethics Statement
The research carried out in this study was approved by the local ethics committees of all participating centers, and each patient provided written informed consent for inclusion in the trial.
Funding
This CLOSURE-CHOICE trial was supported by Helios Kliniken GmbH, Grant-ID: 2020_0191. The sponsor had no role in the design and conduct of the study; the collection, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript.
Disclosure Statement
M. Abdel-Wahab declares that his hospital receives speakers’ honoraria and/or consulting fees on his behalf from Medtronic and Boston Scientific. S. Desch declares that his hospital receives speakers’ honoraria and/or consulting fees on his behalf from Medtronic. All other authors report no disclosures relevant to this work.
Footnotes
Supplemental data for this article can be accessed on the publisher’s website.
Supplementary Material
References
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