Author + information
- Received August 8, 2012
- Revision received January 4, 2013
- Accepted January 15, 2013
- Published online March 1, 2013.
- Ronald K. Binder, MD⁎,
- Ulrich Schäfer, MD†,
- Karl-Heinz Kuck, MD†,
- David A. Wood, MD⁎,
- Robert Moss, MD⁎,
- Jonathon Leipsic, MD⁎,
- Stefan Toggweiler, MD⁎,
- Melanie Freeman, MBBS⁎,
- Avi J. Ostry, MD⁎,
- Christian Frerker, MD†,
- Alexander B. Willson, MBBS⁎ and
- John G. Webb, MD⁎,⁎ ()
- ↵⁎Reprint requests and correspondence
: Dr. John Webb, University of British Columbia, St Paul's Hospital, 1081 Burrard Street, Room 476A, Vancouver, British Columbia, V6Z 1Y6, Canada
Objectives The aim of this study was to demonstrate feasibility and short- and midterm clinical outcomes with a new self-expanding transcatheter heart valve and motorized delivery system.
Background Refining transcatheter aortic valve replacement with newly designed bioprostheses and delivery systems is anticipated to facilitate the procedure, reduce the risk of complications, improve outcomes, and widen applicability.
Methods The CENTERA valve (Edwards Lifesciences, Irvine, California) was implanted in 15 patients with symptomatic severe aortic stenosis via femoral or axillary arterial percutaneous access. Patients underwent transesophageal echocardiography during and transthoracic echocardiography and multidetector computed tomography before and after valve implantation. Clinical and echocardiographic follow-up was obtained at 30 days and for the initial 10 patients after 1 year.
Results All 15 device implants were successful. Aortic valve area increased from 0.7 ± 0.1 cm2 to 1.6 ± 0.4 cm2 post-procedure (p < 0.01) and 1.8 ± 0.3 cm2 at 1 year. Mean transaortic gradient decreased from 36.3 ± 14.2 mm Hg to 10.6 ± 5.4 mm Hg post-procedure (p < 0.001) and 10.8 ± 4.1 mm Hg at 1 year. Paravalvular aortic regurgitation at 30-day follow-up was none/trivial in 3 (23%), mild in 9 (69%), and moderate in 1 (8%) patient. Four patients (27%) received a new permanent pacemaker. Survival was 87% at 30 days and 80% at 1 year. All surviving patients were in New York Heart Association functional class I (25%) or II (75%) at 1 year.
Conclusions Transcatheter aortic valve replacement with the CENTERA transcatheter heart valve and motorized delivery system is feasible and can lead to good short- and midterm clinical and hemodynamic outcomes.
- paravalvular regurgitation
- self-expanding transcatheter heart valve
- severe aortic stenosis
- transcatheter aortic valve replacement
Transcatheter aortic valve replacement (TAVR) has been shown to reduce mortality in a randomized comparison with medical treatment (1) and to be noninferior to surgical aortic valve replacement in “high-risk operable” patients (2). Further refinement of the procedure and current developments focus on minimizing access site complications, reducing stroke risk, improving paravalvular sealing, avoiding heart block, and facilitating easy and accurate prosthesis implantation. Some of these issues might be addressed by new delivery systems and transcatheter heart valves (THV). We report early experience with the CENTERA self-expanding valve and a unique motorized delivery system (Edwards Lifesciences, Irvine, California).
The TAVR with the CENTERA THV was performed in 15 patients with symptomatic, severe aortic stenosis at 2 centers (St. Paul's Hospital, Vancouver, Canada, and the Asklepios Klinik St. Georg, Hamburg, Germany) between 2010 and 2012. All patients were considered at increased risk for surgery by a multidisciplinary team including cardiac surgeons and cardiologists, due to age, frailty, comorbidities, or technical issues (e.g., adherent coronary artery bypass grafts). All patients gave written informed consent for prospective data acquisition approved by the local ethics committee. Outcomes were reported according to the Valve Academic Research Consortium guidelines (3) and the Risk, Injury, Failure, Loss, and End-stage Kidney classification criteria (4). Patients underwent pre-procedural aortic root, coronary and iliofemoral angiography, transthoracic echocardiography (TTE), and multidetector computed tomography (MDCT). Before discharge post-procedural TTE and MDCT were performed. The MDCTs were read by a single radiologist (J.L.) at St. Paul's Hospital. The TTEs were read at the local site. Clinical and echocardiographic follow-up was obtained at 30 days and 1 year. All data were prospectively collected in a dedicated database.
Valve and delivery system
The CENTERA THV (Fig. 1) is composed of a self-expandable, radiopaque, nitinol stent; trileaflet bovine pericardial tissue valve (at annular level); and polyethylene terephthalate fabric. The delivery catheter is composed of an inner tubing assembly that contains the guidewire lumen, a torque shaft and delivery cylinder assembly, and an outer shaft (Fig. 2). These are attached to a control handle (Fig. 3). The guidewire lumen accommodates a 0.035-inch guidewire. The self-expanding THV is constrained in a metallic delivery cylinder. The catheter incorporates a deflection mechanism to assist in traversing the aortic arch and facilitate coaxial positioning within the native valve. The 26-mm CENTERA was indicated, according to the first-in-human protocol, if the aortic annulus measured 20 to 23 mm by transesophageal echocardiography (TEE) and the minimal internal lumen diameter of the access vessel was ≥5.5 mm.
The detachable handle (Fig. 3) is a battery-powered, motorized unit designed to provide sufficient torque to advance or retract the delivery cylinder when loading and deploying the THV. The handle has 2 buttons, allowing for either valve deployment (big button) or valve loading (small button).
The TAVR with the 26-mm CENTERA was performed under general anesthesia (10 patients) or local anesthesia (n=5) and fluoroscopy as well as TEE guidance. Patients were pre-medicated with aspirin and clopidogrel. An 18-F (initial 11 patients) or 16-F (last 4 transfemoral patients) sheath was introduced into the common femoral (n=11) or axillary artery (n=4) after pre-closure sutures were inserted percutaneously (ProStar for transaxillary patients or Perclose ProGlide for transfemoral patients, Abbott, Inc., Abbott Park, Illinois). The preferred access was transfemoral in Vancouver and trans-axillary in Hamburg. Pre-implant balloon aortic valvuloplasty was performed under rapid ventricular pacing in all cases. The delivery catheter was advanced over an Amplatz extra stiff 0.035-inch guidewire (Cook, Inc., Bloomington, Indiana) into the left ventricle. Accurate positioning of the THV was ascertained by aortic root angiograms with a pigtail catheter and by TEE. Release of the THV was automatically performed by motorized retraction of the deployment cylinder. After the inflow and midportion of the THV were released and accurate positioning was confirmed, rapid ventricular pacing was initiated to facilitate final deployment of the THV (Fig. 4). The valve position was documented by aortic root angiograms and TEE. The femoral or axillary access site was closed percutaneously. Patients were monitored for at least 72 h and discharged to continue on a regimen of low-dose aspirin and 3 months of daily clopidogrel (75 mg) unless oral anticoagulation was indicated.
All analyses were performed with the SPSS software (version 17, SPSS, Inc., Chicago, Illinois). Continuous variables are expressed as mean values ± SD. Categorical variables are described by frequencies and percentages. Comparisons of continuous variables were performed by a paired t test. All statistical tests were 2-tailed, and a value of p < 0.05 was considered statistically significant.
Baseline clinical characteristics are outlined in Table 1.
The CENTERA THV was successfully deployed in all 15 patients with a fully percutaneous approach. No patient required implantation of a second THV, and there were no cases of valve migration or embolization. In 1 patient the deployment was started too high above the annulus, and after partial deployment the THV was recaptured and immediately redeployed in the correct position. Five patients (33%) underwent intra-procedural post-dilation to address significant paravavular regurgitation (PAR). This reduced PAR to trace in 2 patients and mild in the remainder. One patient developed hemo-pericardium caused by pacing wire perforation, which was percutaneously drained. Complete heart block directly after valve deployment occurred in 4 patients (27%) and necessitated permanent pacemaker implantation. Moderate-to-severe PAR was seen in 1 patient at discharge. He underwent post-dilation with a 25-mm balloon 30 days post-procedure, which reduced PAR to mild. Short- and midterm clinical outcomes are shown in Table 2.
Survival was 87% (13 of 15) at 30 days and 80% (8 of 10) at 1-year follow-up. There were 2 in-hospital deaths, 1 due to a cardiac arrest complicating renal failure (hyperkalemia and volume overload) on Day 8, and a second due to in-hospital acquired pneumonia with respiratory failure on Day 23. A third later death occurred on Day 49 in a patient who was initially doing well and was urgently readmitted with sepsis. Autopsies were performed on all 3 patients. The deaths were found not to be valve-related (Fig. 5). However, the 2 in-hospital deaths might be attributed to post-procedural complications. All patients, who were treated in 2010, were in New York Heart Association functional class I (2 patients, 25%) or II (6 patients, 75%) at 1-year follow-up (8 of 10 patients alive after 12 months).
Mean transaortic gradient was reduced from 36.3 ± 14.2 mm Hg to 10.6 ± 5.4 mm Hg post-procedure (p < 0.001) and 10.8 ± 4.1 mm Hg at 1 year. The aortic valve area increased from 0.7 ± 0.1 cm2 to 1.6 ± 0.4 cm2 post-procedure (p < 0.01) and 1.8 ± 0.3 cm2 at 1-year. The PAR as assessed by TTE at 30-day follow-up was none/trivial in 3 (23%) patients, mild in 9 (69%) patients, and moderate in 1 (8%) patient. At 1-year follow-up PAR was none/trivial in 2 (29%), mild in 4 (57%), and moderate in 1 (14%) patient (TTE at 1-year follow-up completed in 7 patients).
Three-dimensional evaluation of the aortic valve was performed before TAVR. The diameter of the native aortic annulus was 23.0 ± 1.3 mm (mean of short and long axis), with a diameter in the long axis of 25.4 ± 1.8 mm and in the short axis of 20.7 ± 2.0 mm. Mean annular area was 4.1 ± 0.5 cm2. The MDCT was performed in 6 patients post-TAVR (DynaCT, Siemens, Inc., Erlangen, Germany) (Fig. 6). The MDCT is shown in Figure 7. The area of the stent frame was 4.2 ± 0.5 cm2 at the inflow, 4.7 ± 0.7 cm2 in the midportion, and 5.2 ± 0.6 cm2 at the outflow. The THV eccentricity (1-short axis/long axis) at the inflow level was 18.7 ± 10.9% and did not differ from annular eccentricity pre-TAVR 19.4 ± 11.5% (p = 0.903) (Fig. 7).
We report the first-in-human experience with a new self-expanding THV and motorized delivery system. A TAVR with the CENTERA THV and motorized delivery system was performed successfully in 15 patients with good hemodynamic and clinical short- and midterm outcomes.
The CENTERA THV design shares some similarities with current balloon-expandable THVs (SAPIEN and SAPIEN XT, Edwards Lifesciences). All incorporate bovine pericardial tissue leaflets and an internal polyethylene terephthalate paravalvular seal and use relatively “short” stent frames. The salient difference is the self-expanding nitinol frame, with a flared inflow, narrower annular segment, and a larger-diameter outflow. This shape is designed to facilitate self-seating in the aortic annulus. In comparison with most other self-expanding nitinol valves the CENTERA THV does not extend into the ascending aorta for anchoring or self-alignment.
The CENTERA fixation and alignment is dependent on the self-seating stent frame but also on a radically different delivery system. The motorized system is designed to improve the accuracy of deployment, without the high forces and uncertainty of manual unsheathing. Unlike other currently available systems, the THV does not tend to move axially during deployment, because it is fixed to the rigid inner catheter. The ability to flex the catheter contributes to accurate positioning. Although these design elements seem functional, the ability to position the THV coaxial to the annulus was markedly limited by the prototypic catheter system with a relatively long rigid distal segment. This might have resulted in suboptimal positioning, expansion, and sealing in the early experience.
Ideally a transcatheter valve would be optimally positioned on initial deployment; however, if positioning is suboptimal then the ability to recapture and reposition or retrieve would be a valuable option. The CENTERA valve incorporates features intended to assure correct positioning with the first attempt. However, it is apparent that further modification of the delivery catheter will be necessary to fully achieve this goal. Despite this, if initial valve deployment was suboptimal due to noncoaxial deployment, the CENTERA THV has a feature to allow easy recapture with the single hand operated motorized delivery system. This will be a possibility as long as the aortic end of the stent frame remains within the delivery cylinder. We used rapid ventricular pacing during final deployment. Whether this is necessary for stable THV release will be further studied.
Stent frame geometry
Currently available balloon expandable stainless steel (SAPIEN) and cobalt chromium (SAPIEN XT) frames generate a relatively high radial force and are generally circular despite the generally oval shape of the native aortic annulus (5). Self-expanding nitinol frames tend to generate a lower radial force and the inflow segment is more likely to be asymmetrical (6–8). In vitro testing has documented the potential for impaired hemodynamic performance and reduced durability with asymmetrical, noncircular valves (9). It has been suggested that THV designs that incorporate supra-annular leaflets might mitigate against these concerns (7). Most THVs are required to undergo accelerated wear testing simulating an asymmetrical deployment and have been found to function relatively well within a certain range of under-expansion. To what extent this assures clinical durability is unknown.
Atrioventricular conduction delays after TAVR have been more common with the self-expanding CoreValve device (Medtronic, Minneapolis, Minnesota) than the balloon-expandable SAPIEN THV (10). Although no second- or third-degree heart block was observed in the first-in-human experience (8) with the self-expanding Portico valve (St. Jude Medical, Inc., St. Paul, Minnesota), the rate of new permanent pacemaker implantation in the early experience with the Lotus valve (Boston Scientific, Inc., Natick, Massachusetts) was 36% (REPRISE I [REpositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus Valve SystEm] trial, presented PCR London Valves 2012). In the current trial with the CENTERA THV the rate of permanent pacemaker insertion was 27%. Whether this is a general characteristic of self-expanding valves is unknown. Specific device-related and procedure-related factors might determine the likelihood of mechanical injury to the interventricular septum. Whether ongoing expansion of self-expanding valves is a factor in the development of delayed block is speculative. It does seem that procedural factors can be mitigated by avoiding ventricular outflow tract positioning and excessive oversizing. However, specific designs that favor outflow tract position place excess pressure on the interventricular septum or require more oversizing might predispose to atrioventricular block.
Study limitations and future directions
These results represent the initial learning curve with very novel approaches to THV design and implantation. Modifications of the delivery system are planned to assure more reliable coaxial engagement of the native annulus, a limitation of this first-generation system. A reduced inflow diameter will be incorporated into the next-generation CENTERA THV with the goal, in part, to reduce mechanical stresses applied to the interventricular septum and conduction system (planed THV sizes 23, 26, and 29 mm). Further evaluation of the enhanced system is anticipated with a possible CE mark trial being completed by 2013.
Transcatheter aortic valve replacement with the CENTERA THV and motorized delivery system is feasible and can lead to good short- and midterm hemodynamic and clinical outcomes.
Drs. Binder, Leipsic, Webb, and Wood are consultants to Edwards Lifesciences. Dr. Schäfer has served as proctor for Edwards Lifesciences and Medtronic. Dr. Moss has received educational honoraria from Edwards Lifesciences. Drs. Binder and Toggweiler received unrestricted research grants from the Swiss National Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- multidetector computed tomography
- paravalvular regurgitation
- transcatheter aortic valve replacement
- transesophageal echocardiography
- transcatheter heart valve
- transthoracic echocardiography
- Valve Academic Research Consortium
- Received August 8, 2012.
- Revision received January 4, 2013.
- Accepted January 15, 2013.
- American College of Cardiology Foundation
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