Author + information
- Received February 14, 2014
- Revision received May 10, 2014
- Accepted May 22, 2014
- Published online October 1, 2014.
- Moritz Seiffert, MD∗∗ (, )
- Ralf Bader, MD†,
- Utz Kappert, MD‡,
- Ardawan Rastan, MD§,
- Stephan Krapf, MD‖,
- Sabine Bleiziffer, MD¶,
- Steffen Hofmann, MD#,
- Martin Arnold, MD∗∗,
- Klaus Kallenbach, MD††,
- Lenard Conradi, MD∗,
- Friederike Schlingloff, MD†,
- Manuel Wilbring, MD‡,
- Ulrich Schäfer, MD†,
- Patrick Diemert, MD∗ and
- Hendrik Treede, MD∗
- ∗Departments of General and Interventional Cardiology and Cardiovascular Surgery, University Heart Center Hamburg, Hamburg, Germany
- †Departments of Cardiac Surgery and Cardiology, Asklepios Klinik St. Georg, Hamburg, Germany
- ‡Department of Cardiac Surgery, University Heart Center Dresden, Dresden, Germany
- §Department of Cardiovascular Surgery, Cardiovascular Center Rotenburg, Rotenburg a.d. Fulda, Germany
- ‖Department of Cardiothoracic Surgery, Klinikum Augsburg, Augsburg, Germany
- ¶Department of Cardiovascular Surgery, German Heart Center Munich, Munich, Germany
- #Department of Cardiac Surgery, Schüchtermann Klinik Bad Rothenfelde, Bad Rothenfelde, Germany
- ∗∗Department of Cardiology, University Hospital Erlangen, Erlangen, Germany
- ††Department of Cardiac Surgery, University Hospital Heidelberg, Heidelberg, Germany
- ↵∗Reprint requests and correspondence:
Dr. Moritz Seiffert, Department of General and Interventional Cardiology, University Heart Center Hamburg, Martinistrasse 52, 20246 Hamburg, Germany.
Objectives This analysis reports on the initial German multicenter experience with the JenaValve (JenaValve Technology GmbH, Munich, Germany) transcatheter heart valve for the treatment of pure aortic regurgitation.
Background Experience with transcatheter aortic valve implantation (TAVI) for severe aortic regurgitation is limited due to the risk of insufficient anchoring of the valve stent within the noncalcified aortic annulus.
Methods Transapical TAVI with a JenaValve for the treatment of severe aortic regurgitation was performed in 31 patients (age 73.8 ± 9.1 years) in 9 German centers. All patients were considered high risk for surgery (logistic EuroSCORE [European System for Cardiac Operative Risk Evaluation] 23.6 ± 14.5%) according to a local heart team consensus. Procedural results and clinical outcomes up to 6 months were analyzed.
Results Implantation was successful in 30 of 31 cases (aortic annulus diameter 24.7 ± 1.5 mm); transcatheter heart valve dislodgement necessitated valve-in-valve implantation in 1 patient. Post-procedural aortic regurgitation was none/trace in 28 of 31 and mild in 3 of 31 patients. During follow-up, 2 patients underwent valvular reinterventions (surgical aortic valve replacement for endocarditis, valve-in-valve implantation for increasing paravalvular regurgitation). All-cause mortality was 12.9% and 19.3% at 30 days and 6 months, respectively. In the remaining patients, a significant improvement in New York Heart Association class was observed and persisted up to 6 months after TAVI.
Conclusions Aortic regurgitation remains a challenging pathology for TAVI. After initial demonstration of feasibility, this multicenter study revealed the JenaValve transcatheter heart valve as a reasonable option in this subset of patients. However, a significant early noncardiac mortality related to the high-risk population emphasizes the need for careful patient selection.
- aortic regurgitation
- transapical aortic valve implantation
- transcatheter aortic valve implantation
After demonstration of efficacy and safety through randomized trials (1,2), transcatheter aortic valve implantation (TAVI) has evolved as the standard of care for the treatment of severe aortic stenosis in patients considered inoperable or as an alternative to surgery in patients at high operative risk (3). However, predominant aortic regurgitation remains a relative contraindication for TAVI according to recent recommendations (3,4) due to the risk of insufficient anchoring of the transcatheter heart valve (THV) within the noncalcified aortic annulus. Surgical valve replacement remains the treatment of choice in these patients (3), but alternatives are required if they are considered to be at high surgical risk. Off-label uses of the self-expanding Medtronic CoreValve (Medtronic, Minneapolis, Minnesota) or the balloon-expandable Edwards Sapien XT (Edwards Lifesciences, Irvine, California) THV have been reported for the treatment of aortic regurgitation (5,6), but limitations have included a high rate of valve-in-valve implantations related to residual aortic regurgitation or the need for significant oversizing and a subsequent risk for annular rupture.
Recently, several strategies have been developed to provide a transcatheter platform for the sufficient treatment of pure aortic regurgitation. This includes the Helio system (Edwards Lifesciences), featuring a pre-placed dock facilitating implantation of a commercially available Sapien XT (7). The native aortic valve cusps are captured between the dock and the THV for sufficient anchoring and the device is currently under clinical investigation. With the CE-mark (Conformité Européenne) approval of the JenaValve (JenaValve Technology GmbH, Munich, Germany) and Medtronic Engager systems for the treatment of aortic stenosis, new devices have become available that, in addition to their intended uses, may facilitate the treatment of diseased noncalcified valves through their unique anchoring mechanisms. The JenaValve prosthesis features a clip fixation of the native aortic valve cusps (8), offering secure anchorage of the THV even in the absence of calcifications. First reports have demonstrated feasibility and successful treatment of aortic regurgitation using the JenaValve (9–11). We now report on the initial German multicenter experience with implantation of a JenaValve THV for the treatment of pure aortic regurgitation in patients at high risk for surgery.
Patient population and diagnostic workup
From April 12, 2012 through October 10, 2013, 31 patients were treated for pure aortic regurgitation using the JenaValve THV in 9 German centers (as listed in Online Table 1); early results on 5 of these patients were published before (9). All patients presented with severe comorbidities precluding them from surgical aortic valve replacement as determined by an interdisciplinary heart team (Table 1). Pre-procedural workup was completed according to institutional standards. Evaluation and grading of aortic regurgitation at baseline was performed by transesophageal echocardiography in all patients (12). Aortic annulus, root, and valve morphology were assessed by contrast-enhanced multislice computed tomography (n = 20), transesophageal echocardiography (n = 11), or the combination of both techniques (Figure 1). Effective aortic annulus diameters for sizing of the THV were derived from multiplanar reconstruction of computed tomography data or from the mid-esophageal long-axis view in transesophageal echocardiography. All patients presented with pure moderate (n = 1) or severe (n = 30) aortic regurgitation. Any patients with mixed valve disease or previous aortic valve replacement were excluded from the study. Aortic valve calcium was assessed by computed tomography or transesophageal echocardiography, as previously described (13).
Transapical implantation of the JenaValve was performed under general anesthesia by an interdisciplinary heart team as previously described (8,9). Balloon valvuloplasty of the native aortic valve was omitted, except in 1 patient with partial commissural fusion. Valve size was selected according to the manufacturer’s recommendations in 27 of 31 patients. Hence, a 23-mm THV was chosen for an aortic annulus up to 22.9 mm, a 25-mm prosthesis for an aortic annulus from 23 to 24.9 mm, and a 27-mm JenaValve for an aortic annulus from 25 to 27 mm. Excessive oversizing was performed in 4 of 31 patients (27-mm THV in 3 patients with annulus diameters 23 to 24 mm, 25-mm THV in 1 patient with an annulus diameter of 22 mm). Of note, only echocardiographic annulus measurements were available in these 4 patients. Anatomically oriented implantation of the JenaValve prosthesis was performed without the use of rapid ventricular pacing in most cases under fluoroscopic control, as detailed in Figure 2. Evaluation of valve function and quantification of residual aortic regurgitation after TAVI was performed by transesophageal echocardiography and angiography in 26 of 31 and by transthoracic echocardiography in 5 of 31 patients according to recent recommendations (14).
Combined procedures were performed in 4 patients, including concomitant MitraClip (Abbott Vascular, Santa Clara, California) implantation for severe mitral regurgitation (n = 2), occlusion of paravalvular regurgitation after previous mechanical mitral valve replacement (n = 1), and implantation of a left ventricular assist device for severe ischemic cardiomyopathy (n = 1) (HeartWare, Framingham, Massachusetts). Transcatheter treatment for moderate aortic regurgitation in this patient was performed in anticipation of deteriorating regurgitation during left ventricular assistance and the presence of a porcelain aorta precluding surgical valve replacement.
Data management and follow-up
This analysis was designed as an independent voluntary multicenter analysis of patients treated for aortic regurgitation using the JenaValve THV. All relevant baseline, procedural, and follow-up variables were collected retrospectively from 9 German centers in a dedicated database. The authors take full responsibility for the data integrity. Median clinical follow-up duration was 235 days (interquartile range 160, 351 days). Outcomes were analyzed in accordance with the updated standardized endpoints defined by the Valve Academic Research Consortium (VARC) (14).
All patients were fully informed about the procedure and this off-label use of the THV (at the time of implantation). All patients signed written consent forms.
Overall, 31 patients (mean age 73.8 ± 9.1 years, 35.5% female) presented with pure aortic regurgitation and high surgical risk, as listed in Table 1. The etiology of regurgitation was degenerative in the majority of patients but also included annular dilation, previous endocarditis, and rheumatic or post-radiation valve disease. No aortic valve calcium was detected in the majority of patients (24 of 31), whereas 7 patients were considered to have mild valve calcification (small isolated spots) without any signs of valve stenosis. All patients were symptomatic with 28 of 31 in New York Heart Association functional class III or IV; 11 patients had undergone previous sternotomy for coronary artery bypass or valve surgery.
TAVI using the JenaValve second-generation THV was performed successfully in 30 of 31 procedures (Table 2). Due to incomplete capture of the native aortic valve cusps, dislodgment, and subsequent relevant regurgitation, immediate valve-in-valve implantation of an Edwards Sapien XT prosthesis was performed in 1 patient with good final results. A horizontal aorta complicated alignment and implantation in another patient; despite post-dilation, mild paravalvular regurgitation remained. Extracorporeal circulatory support or conversion to surgical valve replacement was not required in any of the patients. Final hemodynamic results confirmed none or trace paravalvular regurgitation in 28 of 31 patients. No more than mild regurgitation or signs of aortic stenosis were observed (Figure 3A).
30-day clinical outcomes
According to the VARC-2 criteria (Table 3), major access site complications and subsequent bleeding events occurred in 3 patients, including a retroperitoneal hematoma with hemorrhagic shock, pericardial effusion requiring pericardiocentesis, and hemothorax necessitating surgical revision. Overall, 7 patients suffered from acute kidney injury, with n = 1 (3.2%) classified as stage 3 acute kidney injury. No cerebrovascular events or myocardial infarctions occurred during 30-day follow-up. Two patients underwent permanent pacemaker implantation for persistent sinus bradycardia (n = 1) and complete heart block (n = 1). Thirty-day mortality was noncardiac in 3 patients (acute renal failure [day 10], pneumonia [day 13], sepsis [day 17]) and cardiac in 1 patient (severe mitral regurgitation [day 7]). The VARC-defined composite endpoints device success and early safety endpoint were reached in 96.8% and 19.3% of patients, respectively.
Six-month clinical outcomes
Valve reinterventions were performed in 2 patients. Despite a primarily uneventful post-operative course, 1 patient showed increasing transvalvular gradients and moderate regurgitation at 3-month follow-up. Fluoroscopy suggested incomplete stent expansion due to an isolated calcium spot at the aortic annulus. After unsuccessful post-dilation of the JenaValve, valve-in-valve implantation with an Edwards Sapien XT was performed with a good result and no residual regurgitation. Clinical follow-up was uneventful thereafter. Another patient required surgical aortic valve replacement due to endocarditis with subsequent severe aortic regurgitation 5 months after complicated TAVI with intraprocedural valve-in-valve implantation.
Overall, residual aortic regurgitation remained low throughout follow-up with 78.2% of patients with none or trace aortic regurgitation at 6 months (Figure 3B). New York Heart Association functional classification improved with 73.3% of patients in class I or II at 30 days compared with 6.7% at baseline and persisted up to 6 months (Figure 3C). Mortality at 6 months was 19.3%, including 2 more noncardiac deaths.
According to the Euro Heart Survey (15), 10.4% of patients with native valve disease suffer from isolated aortic regurgitation. In contrast to elderly patients with calcific aortic stenosis, most of these patients are good surgical candidates with a low perioperative morbidity and mortality. Hence, aortic valve surgery is the standard of care in patients with severe aortic regurgitation and subsequent symptoms or impaired left ventricular function (3). However, therapeutic options in high-risk surgical candidates are scarce because noncalcified or predominant aortic regurgitation has been considered a contraindication to TAVI (3,4). This caution is attributed to imminent limitations of self-expanding or balloon-expandable first-generation THV, largely relying on calcification of the native leaflets for sufficient anchoring of the expanded prosthesis. Absent or minimal calcification of native aortic cusps in pure aortic regurgitation result in the risk of insufficient anchoring and valve embolization or residual paravalvular regurgitation. Excessive oversizing carries a subsequent hazard for aortic root rupture or incomplete valve expansion. In a recently published multicenter series, Roy et al. (5) report on the outcome of 43 patients undergoing implantation of a CoreValve THV for pure aortic regurgitation. Residual aortic regurgitation required implantation of a second valve in 8 patients and conversion to open heart surgery in 1. These complications became particularly apparent in patients with noncalcified valve disease, emphasizing the urgent need for alternative treatment options in these patients.
In addition to safety and efficacy in patients with aortic stenosis (16,17), the JenaValve THV has demonstrated promising results regarding the treatment of aortic regurgitation (9–11). Successful implantation and good hemodynamic performance in patients with pure aortic regurgitation has now been confirmed at a larger scale in this multicenter series. Six-month follow-up was promising with regard to valve function. VARC-2 device success was achieved in 30 of 31 patients and reduction of aortic regurgitation to trace or none in 28 of 31 patients. The feeler-guided positioning and secure clip fixation mechanism of the native aortic valve cusps allows for anatomically oriented implantation in noncalcified aortic valves, making it particularly suitable for patients with predominant or pure aortic regurgitation. However, optimal alignment is required and may be complicated by a difficult anatomy (e.g., horizontal aorta) or insufficient imaging that is mandatory for the precise placement of the feelers within all 3 aortic sinuses for secure anchoring of the valve stent. Inadequate alignment and suboptimal positioning of the THV may render relevant residual regurgitation or—at worst—dislodgment of the prosthesis. Although rare in pure aortic regurgitation, inhomogeneous calcification patterns may not be ideal for the JenaValve THV, which carries less radial force than a balloon-expandable THV does. This was observed in 1 patient with incomplete stent expansion yielding valve-in-valve implantation at a later date. Hence, regular follow-up remains essential in this young phase of experience to detect potential shortcomings or complications at an early stage.
Despite uncomplicated procedures and uneventful post-procedural courses in the majority of patients, 30-day and 6-month noncardiac mortality was significant in this series. Adequate function of the implanted prosthesis was confirmed in all of these patients. However, adverse events linked to underlying comorbidities emphasize the importance of adequate patient selection and optimal timing of the procedure in order to improve overall survival.
Several aspects may render patients with aortic regurgitation particularly suitable for the described transcatheter approach. The absence of aortic valve calcium and a rare need for valvuloplasty may potentially lower the risk for thromboembolic events. Although possibly an effect of the small sample size, no cerebrovascular events were detected in this study. In addition, the omission of oversizing, the low radial force of the JenaValve and the rare need for valvuloplasty or post-dilation may alleviate the risk for conduction disturbances and annular dilation or rupture after TAVI in patients with noncalcified aortic annuli. Rapid ventricular pacing is not required for optimal alignment and stabilization during valve deployment and most procedures can be performed with a beating heart. Particularly in patients with poor left ventricular function this may add safety to the procedure.
Limitations of this voluntary multicenter analysis include its retrospective character and the lack of an echocardiography core laboratory or an independent event adjudication committee. Follow-up was limited to 6 months and further follow-up now needs to confirm persistent valve function in these patients with noncalcified aortic valves over the long term, particularly before moving toward younger or intermediate risk patients. After the recent CE-mark approval for this new indication in September 2013, patients with pure aortic regurgitation are being prospectively included in the currently recruiting JUPITER (Longterm Safety and Performance of the JenaValve) registry (NCT01598844).
Pure aortic regurgitation remains a challenging pathology for TAVI. After initial demonstration of feasibility, this multicenter experience provides broader evidence that the JenaValve THV is an adequate option in these specific patients due to its unique stent design and fixation mechanism. The straightforward implantation technique and good acute results have recently established aortic regurgitation as a new indication for this device. Continued observation is now warranted to confirm persistent valve function during long-term follow-up.
Dr. Seiffert has received lecture fees and travel compensation from JenaValve Technology GmbH. Dr. Bader has received lecture fees and travel compensation from and is a proctor for JenaValve Technology GmbH. Dr. Kappert is a proctor for JenaValve Technology GmbH. Dr. Rastan has received lecture fees and travel compensation from and is a proctor for JenaValve Technology GmbH. Dr. Bleiziffer has received lecture fees and travel compensation from and is a proctor for JenaValve Technology GmbH. Dr. Conradi has received travel compensation from JenaValve Technology GmbH. Dr. Schlingloff has received travel compensation from JenaValve Technology GmbH. Dr. Schaefer has received lecture fees and travel compensation from JenaValve Technology GmbH. Dr. Diemert has received lecture fees and travel compensation from JenaValve Technology GmbH. Dr. Treede has received lecture fees and travel compensation from and is proctor and advisor for JenaValve Technology GmbH. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Drs. Seiffert and Bader contributed equally to this manuscript.
- Abbreviations and Acronyms
- transcatheter aortic valve implantation
- transcatheter heart valve
- Valve Academic Research Consortium
- Received February 14, 2014.
- Revision received May 10, 2014.
- Accepted May 22, 2014.
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