Author + information
- Received January 17, 2014
- Revision received April 17, 2014
- Accepted April 24, 2014
- Published online October 1, 2014.
- Daniel Wendt, MD, PhD∗∗ (, )
- Philipp Kahlert, MD, PhD†,
- Susanne Pasa, MD∗,
- Karim El-Chilali, MD†,
- Fadi Al-Rashid, MD†,
- Konstantinos Tsagakis, MD∗,
- Daniel Sebastian Dohle, MD∗,
- Raimund Erbel, MD, PhD†,
- Heinz Jakob, MD, PhD∗ and
- Matthias Thielmann, MD, PhD∗
- ∗Department of Thoracic and Cardiovascular Surgery, West-German Heart Center Essen, University Hospital Essen, Germany
- †Department of Cardiology, West-German Heart Center Essen, University Hospital Essen, Essen, Germany
- ↵∗Reprint requests and correspondence:
Dr. Daniel Wendt, West-German Heart Department of Thoracic and Cardiovascular Surgery Center Essen, University Hospital Essen, Hufelandstraße 55, 45122 Essen, Germany.
Objectives This study sought to evaluate the self-expandable ACURATE TA device (Symetis SA, Ecublens, Switzerland) in a cohort of patients with pure aortic regurgitation (AR).
Background Transcatheter aortic valve replacement (TAVR) has been initially considered as an alternative for high-risk patients with aortic stenosis. Although the current experience is limited, TAVR might be also an alternative to treat patients with pure, severe AR.
Methods Between April 2012 and December 2013, a total of 8 high-risk patients with pure, severe AR were enrolled (grade III+). Clinical and hemodynamic data as well as data on device and procedure parameters and outcomes were collected.
Results Patient mean was 72.5 ± 8.4 years, and 37.5% of patients were female. Logistic EuroSCORE was 34.0 ± 7.9% and the Society of Thoracic Surgeons score was 7.3 ± 3.3% on average. Two patients had undergone emergency aortic operation before due to acute type A aortic dissection, and both were treated by replacement of the ascending aorta (including root reconstruction) and the aortic arch combined with or without E-vita Open stent graft (Jotec GmbH, Hechingen, Germany) (January 2011 and March 2012), whereas the other patients experienced primary AR. All patients underwent successful transapical TAVR with the transapical ACURATE TA device (size small, n = 1, size medium, n = 3, size large, n = 4) without any intraprocedural complications according to the Valve Academic Research Consortium 2 criteria. Post-procedure AR grade I+ or lower, as revealed by transoesophageal echocardiography and angiography, was present in all 8 patients. At 30 days, the stroke incidence and all-cause mortality rate were 0%.
Conclusions This small single-center series demonstrates the feasibility of transapical TAVR with the self-expandable ACURATE TA device in high-risk patients with severe AR.
Transcatheter aortic valve replacement (TAVR) has been well established in the treatment of high-risk patients presenting with aortic valve stenosis and has changed the paradigms in the treatment of aortic valve stenosis (1,2). The original concept of this technique is based in principle on implanting an oversized balloon- or self-expandable transcatheter heart valve (THV) into the calcified native aortic annulus (3). As a result, aortic calcification is presumably essential for stable fixation of the stent frame. This follows from the fact that pure, severe aortic regurgitation (AR) has been considered a relative contraindication to TAVR due to the absence of aortic calcification.
The purpose of the present study was therefore to evaluate the feasibility and early results of off-label transapical TAVR by the use of the self-expandable and self-positioning ACURATE TA (Symetis SA, Ecublens, Switzerland) THV in a cohort of high-risk patients with pure AR.
The present study was a prospective, nonrandomized, single center feasibility study including eight consecutive patients, who underwent transapical TAVR with the ACCURATE TA device at the West-German Heart Center Essen between April 2012 and December 2013. The present study obtained institutional review board approval according to the Declaration of Helsinki. Only high-risk patients with a logistic EuroSCORE >20% were enrolled in the present study. The indication for TAVR in the individual patient was discussed for each patient in an interdisciplinary consensus conference (heart team) of cardiologists and cardiac surgeons, and the patient’s or physician’s preference alone was not considered adequate for decision making. In addition, all patients were informed in detail about the TAVR procedure and the off-label use of the ACURATE TA device, and all patients gave written informed consent.
The primary study endpoint was in-hospital mortality, defined as all causes of death within 30 days, including all enrolled patients. Follow-up was also performed. Patient and operative demographic characteristics were recorded in a prospective institutional database and retrospectively extracted and evaluated. Echocardiographic data were stored in an institutional parallel workflow platform (Horizon Cardiology, Medcon/McKESSON, San Francisco, California). Chronic obstructive pulmonary disease was defined according to the EuroSCORE definition. Survival was obtained by active follow-up. All outcomes were reported according to the standardized Valve Academic Research Consortium (VARC 2) criteria.
Preoperative echocardiographic assessment
Preoperative transthoracic 2-dimensional echocardiographic standard views were obtained with patients in the left lateral supine position using a standard ultrasound system with a 1- to 5-MHz (S5-1) probe (iE33, Philips Medical Systems, Andover, Massachusetts). Left ventricular dimensions were measured according to the recommendations of the American Society of Echocardiography. Standard gray-scale images were obtained in the standard parasternal (long and short axis) and apical views (2- and 4-chamber and apical long-axis views). Doppler flow data were acquired from the left ventricular outflow tract region in the pulsed-wave mode and from the aortic valve in the continuous-wave mode in the apical 5-chamber view. In case of atrial fibrillation, a representative heartbeat was taken.
Detailed transesophageal echocardiography (TEE) was performed before TAVR. Two-dimensional TEE was performed with the use of a standard Philips i33 ultrasound system with a multiplane (X7-2t) matrix-array probe (Philips Medical Systems). The probe consists of a transducer that provides high-resolution images and operates at broadband frequencies ranging between 2 and 7 MHz. Pre-procedural TEE was performed after administration of topical anesthesia of the pharynx and application of intravenous sedation (midazolam), after which the probe was introduced into the esophagus. Using the short-axis view, the opening of the insufficient aortic valve was captured, and the highest quality loops were viewed and evaluated after acquisition as described in the following. The aortic annulus diameter was measured by using the 3-chamber long-axis view at an ∼120° angle. The diameter was measured as the largest possible diameter during systole using the inner edge to inner edge as recommended (4,5).
Follow-up echocardiographic examinations
All patients underwent a detailed pre-procedural transthoracic echocardiography (TTE) and TEE examination as described previously. Intraoperative TEE was performed with all patients under general anesthesia. Post-procedural TTE was performed during follow-up (3 to 6 months) in all patients. An experienced echocardiographer who did not attend the TAVR procedure performed all transthoracic follow-up evaluations. During follow-up TTE, color Doppler echocardiography was performed after optimizing the Nyquist limit to evaluate the presence of regurgitant valve disease. AR was evaluated according to the current recommendations. The degree of AR was classified according to the VARC-2 criteria (6). Briefly, AR severity was assessed by the grading of an experienced echocardiographer by integrating VARC-2 criteria.
All TAVRs were performed with patients under general anesthesia in a dedicated hybrid operating room offering full functionality for cardiac catheterization, anesthesiology, and cardiac surgery; a cardiopulmonary bypass circuit and clinical perfusion team was kept on stand-by. Competences of the interdisciplinary heart team, consisting of cardiac surgeons, cardiologists, anesthesiologists, and perfusionists, provided optimal support during the TAVR procedure. Transapical access was performed as previously described by our group (7) using 4 pledged-armed U-stitches (Prolene 3-0, MH needle). However, in contrast to our standard TAVR protocol, intraprocedural preparatory balloon aortic valvuloplasty was not performed due to the absence of aortic calcification, and, moreover, all valve implantations were done without rapid pacing.
The ACURATE TA device (Symetis SA, Ecublens, Switzerland) consists of a self-expandable nitinol stent, available in 3 sizes of 23 (small), 25 (medium), and 27 (large) mm, covering an aortic annulus diameter of between 21 and 27 mm (small, 21 to 23 mm; medium, 23 to 25 mm; large, 25 to 27 mm). This self-expandable nitinol stent acts as an anchoring structure within the native aortic annulus, consisting of upper and lower crowns, enabling correct valve fixation in a subcoronary and supra-annular position. Three additional stabilization arches within the outflow tract are used to orient the bioprosthesis in the ascending aorta during deployment. This unique implantation method facilitates the self-positioning of the device within the aortic annulus. A 3-leaflet porcine valve composed of 3 independent porcine noncoronary leaflets is fixed within the lower part of the nitinol stent. A double polyethylene terephthalate skirt covers the inner and outer surface of the stent body and lower crown to reinforce the biological porcine valve and thereby avoid any direct contact between the biologic tissue and the metal stent struts. The valve is depicted in Figure 1. This additional polyethylene terephthalate skirt seals the cells of the nitinol stent frame and guarantees impermeability of the stent at the aortic annular level to prevent leakage. The whole system enables a sheathless implantation (28-French equivalent) via the apex of the left ventricle. The valve prosthesis is contained within the distal section of the delivery device. The valve is released by an unsheathing process initiated by rotating a knob on the proximal end of the delivery system (8). The sequence of delivery is shown in Figure 2.
Continuous and normally distributed data were reported as mean ± SD. All statistical analyses were performed using the SPSS software package, version 19.0 (IBM Corp., Armonk, New York).
Eight consecutive patients (3 female and 5 male) with severe AR were enrolled in the study. Mean age was 72.5 ± 8.4 years (range, 55 to 81 years). The mean aortic valve area was 2.1 ± 0.4 cm2. The mean B-type natriuretic peptide level before intervention was 760 ± 866 pg/ml. Baseline patient characteristics are listed in Table 1. Four patients had undergone previous cardiac surgery. Two patients underwent previous coronary artery bypass graft surgery, and 2 patients underwent surgery because of an acute type A aortic dissection (AAD). Patient #1 underwent emergency cardiac surgery due to acute AAD on March 9, 2012, at the West-German Heart Center Essen. In this particular patient, the aortic root was reconstructed by partial sinus replacement according to the method of Yacoub, and the ascending aorta and the aortic arch were replaced by a 28-mm Dacron graft under selective cerebral perfusion. In addition, 12-mm and 8-mm Dacron prostheses replaced the brachiocephalic trunk and left carotid artery, respectively. Patient #3 also underwent emergency aortic surgery at the West-German Heart Center Essen due to complex aortic disease with AAD on the January 13, 2011. In this patient, the ascending aorta was replaced by a 28-mm Dacron graft, and the aortic arch and descending aorta were treated under selective cerebral perfusion by a 28-mm E-vita Open stent graft prosthesis (Jotec GmbH, Hechingen, Germany). Moreover, due to severe AR, the aortic root was reconstructed by using gelatin-resorcinol-formaldehyde glue, and the noncoronary sinus was reconstructed by the ascending Dacron graft without any additional reinforcement. Both patients showed only grade 0-I° AR after aortic reconstruction. The other 2 patients had elective and uneventful coronary artery bypass graft surgery in 2006 and 2001. Mean calculated logistic EuroSCORE of the study population (n = 8) was 34.0 ± 7.9% (range, 24.2% to 47.9%), and all patients were in New York Heart Association (NYHA) functional class III or IV. Figure 3 illustrates AR of patients 1 and 2 as diagnosed by pre-procedural TEE.
Patient 7 underwent an elective cardiac catheterization in a referring hospital, resulting in cardiac perforation with cardiac tamponade, which was treated by echocardiography-guided percutaneous pericardial puncture and pigtail catheter placement. He was transferred for emergency treatment to our department, presenting with cardiac tamponade requiring inotropic support.
TAVR was technically successful in all patients with no intraprocedural complications. No proximal or distal valve embolization occurred. The small size device was used in 1 patient, the medium size device in 3 patients, and the large size device in the remaining patients. Using rapid pacing, post-dilation was performed in 2 patients. The final angiographic examination showed no signs of AR or coronary obstruction by the stent frame itself. Figure 4 illustrates the intraoperative angiographic results of patients 1 and 2.
The 30-day all-cause mortality rate was 0%, and no major stroke occurred in any patient. At 3 to 6 months follow-up, all patients were alive without any major adverse events. No permanent pacemaker implantation was needed. One patient experienced gastrointestinal bleeding due to dual-antiplatelet therapy, which was treated conservatively. As of January 10, 2014, all patients were contacted by active telephone follow-up with no adverse events reported. Procedural and postoperative characteristics are shown in Table 2, and clinical and safety outcomes according to VARC-2 in Table 3. No myocardial infarction occurred with maximal cardiac troponin I levels of 6.26 ± 2.74 ng/ml 24 h postoperatively. At 3- to 6-month follow-up, only Patient #1 showed trace paravalvular leakage. Figure 5 illustrates follow-up TTE of Patients 1 and 2. Mean transvalvular pressure gradients were 10.5 ± 2.7 mm Hg with an aortic valve area of 2.0 ± 0.7 cm². Patients #1, #2, #4, #6, and #7 were in NYHA functional class I, and Patients 3, 5, and 8 in NYHA functional class II. Left ventricular ejection fraction did not differ between the preoperative and 3- to 6-month follow-up echocardiography (46.1 ± 9.5% vs. 45.6 ± 9.1%, p = 0.91). Table 4 shows the 3- to 6-month echocardiographic follow-up.
The present study demonstrates the first clinical experience and proves the feasibility of TAVR with the ACURATE TA device in high-risk patients presenting with severe AR. At present, the ACURATE TA device is only available for implantation via the transapical approach and has obtained the CE Mark approval in 2011 for the treatment of stenosed and calcified aortic valve disease. A transfemoral version, the ACURATE TF is currently in clinical trials (9).
To date, TAVR has been suggested as an alternative treatment option to conventional aortic valve replacement in selected patients and has become a more widely practiced and accepted therapeutic option (1,2). TAVR was primarily developed for patients presenting with aortic valve stenosis; however, although aortic stenosis is more prevalent, high-risk patients presenting with AR may benefit from such new catheter-based techniques. Therefore, we sought to evaluate the self-expandable Symetis ACURATE TA device in a cohort of high-risk patients with AR. Moreover, the decision to evaluate the Symetis ACURATE TA device in AR was mainly driven by the fact that 2 patients presented with severe AR after complex aortic surgery due to previous AAD. Hence, a persisting dissection in the descending aorta prohibited a transfemoral approach with the use of the CoreValve prosthesis (Medtronic, Minneapolis, Minnesota). In addition, according to our initial animal experiments, we provided evidence for safely anchoring the Symetis ACURATE TA device in noncalcified aortic annuli (8).
The concept of TAVR was originally based on the concept of valve fixation by displacing the native calcified valve by an oversized THV. Absence of aortic calcification may result in prosthesis dislodgement. There are currently 2 types of transcatheter valve available: self-expandable and balloon-expandable THVs. The original concept of TAVR was based on balloon-expandable valves, which depend on aortic calcification. In contrast, self-expandable valves offer high and permanent recoil forces, and, therefore, this concept is better suited for treating AR. As a result, during the past 12 months, the first reports treating AR only by self-expandable THVs have been published (10–12). In addition to some single case reports, 2 larger series were reported: Roy et al. (13) presented their results of a voluntary multi-institutional registry using the self-expandable CoreValve prosthesis (Medtronic) in a total of 43 patients with AR. In this series, final implantation was performed in 42 patients (1 conversion to open heart surgery) with a VARC-defined procedure success for TAVR of 74.4% when grade II or higher AR and the need for a second valve were taken into account. In their series, a total of 8 patients (18.6%) required a second valve during the index procedure due to residual AR. Another study by Seiffert et al. (14) evaluated a second-generation TAVR device in a series of 5 patients (mean age, 66.6 ± 7.0 years) with noncalcific AR. The authors selected the JenaValve prosthesis (JenaValve Technology GmbH, Munich, Germany) because it features a unique clip fixation mechanism of the native aortic valve leaflets that may even offer secure anchorage even in the absence of calcifications. They reported successful implantation of the device in all cases without any major device- or procedure-related adverse events. All patients were reported to be alive at 3-month follow-up without any significant AR (14). Meanwhile, as of September 2013, JenaValve technology has received extended CE mark approval for AR. The JenaValve is now the only TAVR device approved for the treatment of high-risk or inoperable patients with severe AR. The concepts of valve fixation of the JenaValve and Symetis ACURATE TA device are different because the JenaValve device features 3 nitinol feelers. These feelers aim to embrace the native leaflets of the aortic valve, irrespective whether the leaflets are calcified. In contrast to the JenaValve, the Symetis ACURATE TA device offers the difference that the 3 leaflets are not clipped between feelers. The self-expandable Symetis ACURATE TA device is fixed in a waistlike manner, thereby covering the aortic annulus (hourglass design).
The decision to evaluate the ACURATE TA device to treat AR was based on the fact that the ACURATE TA system offers tactile feedback and comes with the unique feature of self-positioning at a supra-annular level (15). According to the delivery sequence of the ACURATE TA device, the upper crown of the stent is released and the whole prosthesis is pulled back to reach the annular level. The lower part of the stent crown is released only when the upper crown is in the proper position. The tactile feedback (movement of the whole delivery device once the aortic annulus level is reached) guides the operator for optimal deployment. We did not observe any valve dislodgments or malpositioning. In addition, the ACURATE TA device offers a partial resheathing of the valve until the safety knob is released. We oversized the valve by at least 1 to 2 mm. In the present study, we implanted mainly large valves (50%) and 3 medium-size valves. Moreover, the patients who received a medium-size valve showed an aortic annulus of 21 to 22 mm. This is in contrast to the manufacturer’s recommendation in aortic stenosis that the medium size valve cover an aortic annulus diameter of 23 to 25 mm. On the other hand, based on the unique mechanism of valve fixation (waistlike shape) of the Symetis device, slightly larger aortic annuli might be treated. We were able to implant a large device in an aortic annulus of 27 to 28 mm. VARC-2 defined procedure success rate of 100%. The mean pressure gradient (12.4 ± 6.4 mm Hg) and aortic valve area (2.0 ± 0.3 cm²) were found at 6-month follow-up.
Study strengths and limitations
Our study is the first to evaluate the self-expandable and self-positioning ACURATE TA prosthesis in a series of patients with AR. Despite the small number of patients and the off-label use of the ACURATE TA device, we observed favorable hemodynamic outcomes and no significant paravalvular leakages. Nevertheless, our analysis should be viewed in the light of its limitations. This single-center descriptive study is limited by the small study numbers and therefore needs to be confirmed in a larger patient population.
This initial trial with the self-expandable and self-positioning ACURATE TA device demonstrated the feasibility of the treatment of AR. The valve hemodynamic findings were satisfactory and comparable to conventional heart valves. Furthermore, the specific architecture of the bioprosthesis lends itself to secure annular placement and alignment in the native anatomy of the noncalcified aortic valve.
Drs. Kahlert and Wendt are proctors for Edwards Lifesciences. Dr. Thielmann is a proctor for Symetis SA. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- acute aortic dissection
- aortic regurgitation
- New York Heart Association
- transcatheter aortic valve replacement
- transcatheter heart valve
- transesophageal echocardiography
- transthoracic echocardiography
- Valve Academic Research Consortium
- Received January 17, 2014.
- Revision received April 17, 2014.
- Accepted April 24, 2014.
- American College of Cardiology Foundation
- Cribier A.,
- Eltchaninoff H.,
- Bash A.,
- et al.
- Zamorano J.L.,
- Badano L.P.,
- Bruce C.,
- et al.
- Leon M.B.,
- Piazza N.,
- Nikolsky E.,
- et al.
- Roy D.A.,
- Schaefer U.,
- Guetta V.,
- et al.
- Seiffert M.,
- Diemert P.,
- Koschyk D.,
- et al.
- Kempfert J.,
- Rastan A.J.,
- Beyersdorf F.,
- et al.