Vascular Complications of Transfemoral Edwards SAPIEN Aortic Valve Implantation

Abstract

Background: Transcatheter aortic valve implantation has recently emerged as an alternative treatment for patients with severe aortic stenosis who have been rejected for conventional aortic valve replacement due to high surgical risk. The aim of this study is to describe vascular access site complications observed in a cohort of patients who underwent transfemoral aortic valve implantation using the Edwards SAPIEN device in a single center.Methods: Prospective single-center analysis of vascular complications that occurred during transfemoral implantation of the Edwards SAPIEN aortic valve prosthesis. Results: Between November 2008 and May 2011, 56 patients underwent transfemoral aortic valve implantation. Vascular complications were observed in 13 patients, including major complications in 5 patients (8.9%) and minor complications in 8 patients (14.3%). Major vascular complications were associated with age (87.2±3.5 vs 82.9±4.4 years; P=.038), female sex (100% vs 52.9%; P=.042), left femoral artery access (60% vs 9.8%; P=.017), and body surface area (1.1±0.13 vs 1.2±0.2 m²; P=0.027). Vascular complications were not associated with mortality, although a nonsignificant increase of in-hospital stay was observed in patients who developed vascular complications (8.6±5.9 vs 5.2±2.6 days; P=.254). Conclusions: Vascular complications are common during transfemoral aortic valve implantation, although they are not associated with higher mortality.

VASCULAR DISEASE MANAGEMENT 2012:9(12):E209-E216
Key words: aortic stenosis, transfemoral aortic prosthesis, vascular complications

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Aortic stenosis is a symptomatic valvulopathy with a higher prevalence in Western countries.¹When this condition is associated with cardiovascular symptoms such as angina, heart failure, or syncope of unknown etiology, valve replacement is considered the first-line treatment.² It occurs predominantly in elderly patients in association with other comorbidities³ who, due to the higher surgical risk,⁴ are not good candidates for surgical valve replacement. In recent years, transcatheter aortic prosthesis implantation has emerged as a safe and efficient alternative in patients rejected for cardiac surgery. 

Several series of patients have been recently published showing acceptable results at the short and  long term with either of the two devices approved to date: Edwards SAPIEN aortic valve prosthesis (Edwards Lifesciences) and CoreValve Revalving System (Medtronic).^5-8 

Moreover,  it has been demonstrated that in this group of high-risk patients the use of the Edwards prosthesis is not inferior to conventional surgery.⁹ However, in spite of continuous improvements, the size of these devices remains large, and the development of vascular complications associated to the transfemoral access site and its relation with adverse events remains a matter of concern.¹⁰

The objective of the present study was to determine the incidence of vascular complications and their effect in the short- and long-term prognosis of a cohort of patients who underwent transfemoral implantation of the Edwards SAPIEN prosthesis (ES prosthesis).

Patients and methods

Patients with severe aortic stenosis and high surgical risk were evaluated in a specialized unit. The final decision on treatment was made by a multidisciplinary team of interventional cardiologists, cardiac surgeons, and clinical cardiologists. Transthoracic echocardiogram with aortic annulus measurement, cardiac catheterization with angiography, and computed axial tomography (CT) of the aortic and iliofemoral axes were performed in all patients. 

Angiography

Angiography was performed in the same procedure as coronary angiography and valvular hemodynamic study. Aortograms were performed with an injection of contrast media in the aortic root and in the descending thoracic aorta, with concomitant angiography of the iliofemoral axes up to the femoral bifurcation. Images were stored in a DICOM format and analyzed to determine the extent of arterial tortuosity and minimal diameter of the artery (Philips Xcelera System for vascular analysis). 

Multislice CT

CT was performed with a 64-slice multidetector scan (General Electric Light Speed VCT), with a collimation of 64 x 0.625 mm, a rotation time of 500 ms, a milliamperage between 300 and 600, and a tube current of 120 kVp. Scans were performed from the thoracic entry to the lesser trochanters without cardiac synchronization. Nonionic contrast media (100 mL) was injected through an antecubital vein with a flow of 4 mL/s, followed by an injection of saline (40 mL) with a flow of 4 mL/s. All the studies were performed during arterial phase enhancement using an automated bolus-tracking technique (Smart-Prep), with automated peak enhancement detection in the ascending aorta. Acquired axial data sets were sent to a workstation (Advantage Windows 4.4, GE Healthcare) for analysis and revision. A combination of multiplanar reformatting, maximum intensity projection and volume rendering was used to evaluate the aorto-iliofemoral axis. Evaluation of the aorta, size of the iliofemoral system, arterial plaque, calcification, tortuosity, and patency was performed. Minimal lumen diameter of the common and external iliac and femoral arteries was measured. Window center and level settings were adjusted to reduce the effect of calcium blooming on vessel measurements. 

Device

The ES aortic prosthesis has been presented in two different versions since its appearance. The first version is a biologic valve made of three leaflets of bovine pericardium attached with suture to a stainless steel stent. The second version (SAPIEN XT, used in our center since May 2010) uses a cobalt-chromium stent that allows a smaller profile. The prosthesis is folded on an expandable balloon used for implantation. Currently, it is available at lengths of 23 and 26 mm. A specific delivery system is used for advancing the prosthesis to the deployment site: the RetroFlex and RetroFlex II systems are used for the first generation of the prosthesis (22 or 24 Fr); the NovaFlex catheter is intended for the SAPIEN XT (18 or 19 Fr). 

Implantation technique

All procedures were performed in the cath lab under general anesthesia, with transesophageal echocardiography monitorization. Aspirin (150 mg) and clopidogrel (300 mg) were administered 24 hours preprocedure, and antibiotic prophylaxis (cefazolin 500 mg) was initiated 1 hour before the intervention. After angiography and CT were performed, the femoral artery with a bigger diameter and lesser tortuosity and/or calcification was selected to conduct implantation of the bioprosthesis. Femoral puncture was performed using the Seldinger technique and cannulation was conducted by means of an 8 Fr sheath. Before insertion of the sheath, an angiogram was performed with a small amount of contrast media to confirm adequate access site in the common femoral artery. 

Cannulation of contralateral femoral artery and vein was conducted to advance a pigtail catheter (6 Fr) up to the aortic root and an electrocatheter (6 Fr) to the right ventricle. After vascular access was achieved, heparin was administered (a loading dose of 100 IU/kg and additional doses, when needed, to maintain an activated clotting time >250 seconds). After crossing the aortic valve through the retrograde approach, the angiographic guidewire was exchanged for an extra-stiff guidewire. Over this, gradual and progressive dilatations of the vascular access were made until appropriate size to introduce the intended device was achieved. 

Finally, the introducer designed for prosthesis implantation (RetroFlex system 22 or 24 Fr, NovaFlex system 18 or 19 Fr) was inserted and advanced to the abdominal aorta.  Balloon predilatation of the native aortic valve was performed in all cases. After predilatation, the bioprosthesis was advanced to the aortic annulus and deployed. Both predilatation and bioprosthesis deployment were performed under rapid ventricular stimulation (180-200 beats per minute). Arterial surgical repair was needed in the cases where RetroFlex II system introducers were used (recommended by manufacturer), while percutaneous closure with two Prostar XL devices (Perclose,  Abbott Vascular Devices) was indicated in the cases where the NovaFlex system was used. In both cases selective iliofemoral angiography was performed at the end of the procedure. Closure of the contralateral artery was made with an AngioSeal percutaneous device (St. Jude Medical), and vein access with manual compression. Antibiotic prophylaxis was administered for 48 hours (cefazolin 500 mg intravenously, every 6 hours), clopidogrel (75 mg, daily for 1 month), and aspirin (150 mg, lifelong). When oral anticoagulation was indicated, treatment was initiated in the postoperative period, and antiplatelet aggregation was not added. 

Definition of events

Recorded events were analyzed according to VARC (Valve Academic Research Consortium)¹¹ recommendations and were as follows:

Death:  all cause death during follow up.

Vascular complications

Major vascular complications:

• Any dissection of the thoracic aorta.
• Access site or access-related vascular injury (dissection, stenosis, perforation, rupture, arteriovenous fistula, pseudoaneurysm, hematoma, irreversible nerve injury, compartment syndrome) leading to either death, need for significant blood transfusions (≥4 units), unplanned percutaneous or surgical intervention, or irreversible end-organ damage. 
• Distal embolization from a vascular source requiring surgery or resulting in amputation or irreversible end-organ damage. 

Minor vascular complications:

• Access site or access-related vascular injury (dissection, stenosis, perforation, rupture, arteriovenous fistula or pseudoaneurysm requiring compression or thrombin injection therapy, or hematomas requiring blood transfusion of ≥2 but <4 units) not requiring unplanned percutaneous or surgical intervention and not resulting in irreversible end-organ damage. 
• Distal embolization treated with embolectomy and/or thrombectomy and not resulting in amputation or irreversible end-organ damage. 
• Failure of percutaneous access site closure resulting in interventional (e.g. stent-graft) or surgical correction and not associated with death, need for significant blood transfusions (≥4 units), or irreversible end-organ damage.

Follow-up

Follow-up procedures included patient evaluation before hospital discharge and further visits to a specialized unit at 6 and 12 months.  

Statistical analysis

Results are presented as mean ± standard deviation for continuous variables with normal distribution, as median (interquartile range) for continuous variables without a Gaussian distribution, and categorical variables are presented as percentages. Categorical variables were compared using the Pearson χ² or Fisher exact tests. Quantitative variables were analyzed using the Student t or Mann-Whitney U tests depending on the presence of a normal distribution. All baseline and procedural variables were compared to detect relevant associations between vascular complications and major vascular complications. All statistical analyses were calculated with SPSS 16.0 statistical package for Windows (SPSS Inc.). 

Results

From November 2008 to May 2011, 412 patients with aortic valve stenosis and high surgical risk were evaluated. In 96 of them, treatment with transcatheter aortic prosthesis implantation was decided. In 40 of these patients transfemoral approach was contraindicated and implantation was conducted via transapical approach. A total of 56 patients underwent transfemoral valve implantation; this group constitutes the population of the present study. Patient basal characteristics are shown in Table 1. The advanced age of patients and the high prevalence of cardiovascular risk factors and comorbidities are factors to be highlighted. Results of risk scores are also shown in Table 1. Echocardiographic and procedural characteristics are shown in Tables 2 and 3. Procedure success was achieved in all the cases since the bioprosthesis was advanced to the aortic annulus and deployed in planned position. 

Vascular complications: A total of 13 patients developed vascular complications (23.2% of the series); 5 were classified as major vascular complications (8.9%) and the remaining 8 were classified as minor (14.3%).

Major vascular complications: 4 patients had iliofemoral dissection requiring revascularization (Figures 1A, 1B, 1C). In 3 cases, an occlusive dissection in the external iliac artery was observed in the control angiography after surgical repair. In one of these patients a femorofemoral bypass was performed, and in the other two patients a balloon angioplasty over the external iliac artery was performed. In the fourth patient, a small dissection in the external iliac artery, treated initially with a conservative strategy, progressed to late arterial occlusion and distal ischemia requiring stent implantation. All these cases progressed favourably without adverse consequences. The fifth major vascular complication occurred in a patient treated with a closure device (Prostar XL) that failed to achieve hemostasis and was associated with major bleeding. To seal the bleeding site, implantation of a Wallgraft stent (Boston Scientific/Meditech) was successfully performed (Figures 2A, 2B, 2C). Because this patient required a blood transfusion of 4 units, this event was classified as a major vascular complication. 

Relevant factors associated with a higher incidence of major vascular complications are summarized in Table 4. Of note, a significant association between older age, female sex, left femoral access and low body surface and major vascular complications was observed. With regard to total vascular complications, the only factor with a significant association was the arterial diameter/introducer diameter ratio (1.20±0.2 vs 1.08±0.1, P=0.004). Larger sheath introducer diameter was associated with higher incidence of major vascular complication (12,9% for 24-22Fr vs 4% for 19-18 Fr) although this difference was not significant (P=0.245).

Minor vascular complications: Minor vascular complications occurred in 8 patients.  In 5 patients, dissection of common or external iliac artery occurred without flow obstruction; expectant therapy was decided and clinical evolution was good (Figure 3). In 2 patients inguinal hematoma with favorable clinical evolution was observed. In one patient, failure of the Prostar XL sealing system occurred and it was treated with a Wallgraft stent implantation not requiring blood transfusion.   

Mortality and its association with vascular complications: No death occurred during the procedure. Three patients (5.3%) died within the first 30 days post intervention. One-year mortality was 10.7%. None of the patients with major/minor vascular complications died during follow-up. Patients with vascular complications had longer hospital stays, although this difference was not significant (8.6±5.9 vs 5.2±2.6 days,  P=0.254). 

Discussion

 The use of the ES aortic prosthesis for the treatment of severe symptomatic aortic stenosis in subjects with high risk and conventional surgery contraindications is associated with a significant rate of complications in the vascular access site.  Female sex, older age, low body surface and left femoral access are associated with a higher incidence of major vascular complications. However, in our series, these complications were not associated with an increase in procedural failure or mortality but with a slightly longer hospital stay. Selection of candidates is a key issue to minimize the incidence of adverse events. 

Since the technique was initially described by Cribier et al¹² in 2002, transcatheter aortic valve implantation has experienced major improvements. The two commercially available prostheses (ES and CoreValve) have been tested in large series of patients, demonstrating their safety with acceptable rates of in-hospital and long-term mortality. The recently reported 74% survival rate at 12 month follow-up by Webb et al⁵ using the ES prosthesis is significantly better than previous reports on the outcome of patients that either received medical treatment or rejected surgery.^13,14 More recently, the cohort A of the PARTNER trial showed a 77.8% survival rate, and in the SOURCE registry a 81.1% survival rate at 12 month follow-up was calculated for the group assigned to transfemoral implantation, confirming the efficacy of the procedure.¹⁵ Similarly, Piazza et al, in the analysis of their series of 646 patients who underwent prosthesis implantation (CoreValve), showed a procedural success rate of 97% and a 30-day postintervention mortality rate of 8%, again more than acceptable results considering the high risk of the population for whom such prostheses are intended. 

Given the high profile of the devices, incidence of vascular complications in the access site, and its association to mortality and morbidity, is a matter of concern among interventional cardiologists and cardiac surgeons involved in this type of treatment. To date, however, few trials have specifically addressed this issue.^16-19 With regard to the ES prosthesis, Webb et al⁵ reported a major vascular complication incidence of 8% (9 cases), with 2 deaths for this reason, in the series of 113 patients who underwent transfemoral aortic valve implantation. Ducrocq et al¹⁸ recently published the results of his series of 54 cases in which transfemoral ES bioprosthesis implantation had a major vascular complication rate of 16.7% (9 cases). One patient died after a major vascular complication, and thus vascular complication-related mortality in this series is 2%. The Toulouse group¹⁶ recently reported a vascular complication incidence rate of 8.3% (2 cases); complications were not associated to fatal events. In cohort A of the PARTNER trial⁹ the incidence of major vascular complications was 11%, and recently published results from the British Columbia group, following the VARC recommendations, show a vascular complication rate of 17.4%, of which 10% refers to major vascular complications.²⁰ Lack of agreement with previous publications may be explained by the difference in the definition of events used for each publication. In our series, if we follow the VARC recommendations for event definition and take into account only major complications, our vascular complication incidence rate is similar to that reported by Webb et al and the incidence observed in the PARTNER trial.^15,20 Likewise, we have observed a lower number and different pattern of complications in the group of patients who underwent implantation with a lower profile delivery system (18 or 19 Fr). Although occlusive dissections at the level of the iliac or femoral artery occurred with the use of higher profile devices, the use of lower profile devices was related only with closure complications at the puncture site when using the Prostar XL sealing system. With regard to this issue, it is important to highlight that, although infrequent, sealing device failure can potentially result in severe bleeding. It is important to ensure contralateral access to, in the event of bleeding, seal the bleeding point with balloon occlusion and, eventually, with the implantation of a covered stent. In our series, complications were not associated with mortality and all of them were adequately solved, although they were related to a nonsignificantly longer hospital stay.  

With regard to factors associated with the incidence of access site complications, data in the literature are sparse. Hayashida et al²¹ have recently reported the parameter sheath to femoral artery ratio as one of the relevant predictors of vascular complications following transcatheter aortic valve implantation. However, although statistically significant, the hazard ratio and 95% confidence interval of this variable presents important limitations due to the small sample size and event rate of the cohort where it was obtained. In line with this, our study is limited as well and does not have sufficient statistical power. However, our results suggest that age, female sex, left femoral access, femoral artery size and low body surface are factors with a higher prevalence in the group of patients presenting complications. All these factors should be taken into account when selecting candidates for this type of approach, but studies of larger patient populations are required to elucidate robust predictors of vascular complications.

Limitations

The present study has several limitations. First, the reduced sample size does not allow the identification of prognostic factors associated with the occurrence of the analyzed event. Second, we have applied the definitions of the last consensus, which are not generally applied in literature, and therefore the comparison with other series is difficult.

Conclusion

Vascular complications in percutaneous prosthesis implantation through femoral access are not infrequent and are associated to a longer hospital stay. However, with an adequate candidate selection and good management of the complication, they do not significantly affect patient survival.

References

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Editor’s Note: Disclosure:  The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript received May 20, 2012, provisional acceptance given June 18, 2012, final version accepted June 21, 2012.

Address for correspondence: Dr. Rodrigo Estévez Loureiro, Hospital Juan Canalejo, Cardiology, As Xubias 84, La Coruna, La Coruna 15006, Spain. Email:  roiestevez@hotmail.com