論文ID: CJ-14-1110
Background: Feasibility and early results of transfemoral aortic valve implantation using the ACURATE neo/TFTM self-expanding stent are reported.
Methods and Results: The study group of 15 patients (mean age 83.3±6.0) was enrolled with a mean EuroSCORE and STS score of 21.9±11.6% and 7.5±3.1%, respectively. Clinical and echocardiographic evaluations were performed at baseline, discharge, 30 days and 6 months. The primary endpoint was all-cause mortality at 30 days. Transcatheter aortic valve implantation (TAVI) using the ACURATE neo/TF device was successful in 14 patients; 1 patient underwent valve-in-valve implantation because the prosthetic valve embolized during withdrawal of the delivery system. Conversion to surgery, coronary obstruction, peri-operative stroke, and pacemaker implantation did not occur at 30 days. Mean transvalvular gradients at discharge significantly decreased from 44.2±10.5 mmHg (preprocedural) to 7.7±3.1 mmHg (P<0.0001) and effective orifice area significantly increased from 0.77±0.12 to 1.69±0.25 cm2 (P<0.0001). None or trace paravalvular leak was revealed in 50.0%, and no patient exhibited moderate or higher paravalvular leak. The overall mortality at 30 days and 6 months was 0% and 6.7%, respectively.
Conclusions: A new self-expanding TF TAVI device, ACURATE neo/TF, is safe and effective in the treatment of severe aortic stenosis in elderly patients at high risk for surgery.
Transcatheter aortic valve implantation (TAVI) has been a viable long-term solution for aortic stenosis (AS) patients who are either at high risk for surgery or considered inoperable, because it provides the benefit of aortic valve replacement (AVR) without the associated risks of open-heart surgery.1–4 Recent advances in percutaneous techniques and the evolution of collapsible bioprosthetic aortic valves have led to cautious optimism about this emerging approach.5,6 Although less-invasive percutaneous aortic valve procedures have emerged, Symetis S.A. (Lausanne, Switzerland) has developed the ACURATE neo/TFTM as a second-generation device that comprises 3 porcine pericardial leaflets mounted on a self-expanding nitinol stent. The ACURATE TF delivery system has a flexible shaft and ergonomic design allowing for stable, low-profile 3-step implantation with a unique top-down deployment mechanism. The design of the ACURATE neo/TF allows it to engage the calcified leaflets with the upper crown, capping the native valve and pulling the leaflets down, thus protecting the coronaries. Here, we report on the early results of the ACURATE neo/TF clinical research study in Osaka University hospital.
We enrolled patients with severe AS and cardiac symptoms for whom conventional surgery to replace the aortic valve was considered to be a high-risk procedure. Inclusion criteria in this study were patients with symptomatic AS and an aortic valve area ≤0.8 cm2 or effective orifice area index <0.5 cm2/m2 and/or a mean transvalvular pressure gradient ≥40 mmHg and/or a peak velocity >4.0 m/s, and an aortic annulus diameter between 21 and 27 mm on cross-sectional CT. Patients were required to be in New York Heart Association (NYHA) class ≥III (if not , then agreement was required from at least 1 surgeon and 1 cardiologist), and a logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) of ≥20% (if not, then agreement was required from at least 1 surgeon and 1 cardiologist that the patient was not a suitable candidate for surgery because of comorbidities). Pertinent exclusion criteria were: bicuspid or non-calcified aortic valve; an aortic annulus diameter <21 or >27 mm on cross-sectional CT; aortic dissection or iliofemoral dimensions or disease precluding safe sheath insertion; left ventricular ejection fraction (LVEF) <20%; untreated coronary artery disease requiring revascularization; severe (>3+) mitral or aortic regurgitation or a prosthetic valve; severe renal insufficiency (serum creatinine >3.0 mg/dl) or dialysis dependent; acute myocardial infarction within the previous month; active gastrointestinal bleeding; transient ischemic attack or stroke within the previous month; any cardiac procedure (eg, drug-eluting stent implantation and/or balloon valvuloplasty within the previous month); and hemodynamic instability. The complete list of exclusion criteria is provided in Appendix S1. Preprocedural transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) were used to evaluate cardiac function. Preprocedural CT imaging of the diameters of the aorta, femoral vessels and aortic annulus was performed. As a result, between August 2013 and May 2014, 15 patients were enrolled in this study, which was approved by the Institutional Review Board of Osaka University. All patients provided written informed consent.
Study DeviceSymetis ACURATE neo comprises 3 porcine pericardial leaflets treated with BioFixTM anticalcification process and mounted on a self-expanding nitinol stent with inner and outer anti-paravalvular leak skirts (Figure 1A). The valve prosthesis is manufactured in 3 different sizes (23-, 25- and 27-mm at the waist) for implantation in a native aortic annulus ranging in diameter from 21 to 27 mm. The intuitive, easy to use 18F ACURATE TF delivery system (Figure 1B) uses a stepped approach in the unique top-down implantation procedure.
Symetis ACURATE neo/TFTM device comprises 3 porcine pericardial leaflets mounted on a self-expanding nitinol stent (A). Symetis ACURATE TFTM delivery system (B).
All procedures were performed under general anesthesia in hybrid operating rooms equipped for cardiologic interventions and cardiac operations. TEE was performed throughout the procedure. Transfemoral (TF) or iliac access was gained via the groin or retroperitoneal approach, respectively. A bolus of heparin was administered intravenously in a weight-dependent manner to achieve an activated clotting time >250 s.
All steps described were performed under fluoroscopic control and with additional TEE guidance. After the femoral or the iliac artery puncture, a soft guide wire was advanced into the descending aorta and subsequently exchanged for a stiff guide wire. An 18F standard sheath was carefully introduced into the descending aorta. The pigtail catheter was placed in a native leaflet as reference for positioning. After a soft guide wire (straight) insertion into the left ventricle using an Amplatz diagnostic catheter (AL1), subsequently exchanged for a stiff guide wire, balloon valvuloplasty of the native valve was performed under rapid pacing. Sizing of the balloon was dependent on the size of the aortic annulus and the degree of calcification on preoperative CT assessment. After removal of the balloon, the bioprosthesis loaded onto the delivery system was advanced over the guide wire and crossed over the native aortic valve until it was positioned slightly above the native valve (proximal edge of stent holder 5 mm below at the level of the pigtail catheter) (Figure 2A). Under fluoroscopic control, the 1st rotational knob of the release handle was turned counterclockwise until full stop (deployment of the upper anchoring crown and stabilization arches) (Figure 2B). Holding the delivery system at the level of the positioning sheath allowed more controlled placement of the bioprosthesis. At this stage the stabilization arches were fully deployed, and the upper crown partly deployed as well. The bioprosthesis was still anchored to the delivery system through the 3 fixation loops of the stent. After verifying the axial positioning of the bioprosthesis with respect to the native valve, injection of contrast dye facilitated correct positioning of the bioprosthesis (stent holder within left ventricle) (Figure 2C). After removing the safety button, final bioprosthesis deployment started under rapid ventricular pacing. After retrieving the pigtail catheter into the ascending aorta, under fluoroscopic guidance the 2nd rotational knob of the release handle was turned counterclockwise until full stop (deployment of the lower anchoring crown), while maintaining the forward pressure on the delivery system towards the left ventricle (Figure 2D). Once the bioprosthesis was completely deployed, the distal tip and capsule of the delivery system were retracted carefully through the functioning bioprosthesis, leaving the guide wire in position across the bioprosthesis. TEE and aortography (Figure 2E) were performed to reconfirm coronary perfusion, paravalvular and central regurgitation, transvalvular pressure gradients, and effective valve opening area. In case of residual transvalvular gradient or significant paravalvular leakage, post-dilatation of the prosthetic valve with careful positioning of the balloon catheter was performed under rapid ventricular pacing (the implantation technique is shown in Figure 2). Patients were treated with daily aspirin 100 mg for life and 75 mg clopidogrel if possible for at least 6 months post-procedure.
Implantation of the ACURATE neo/TFTM (patient no. 7). Positioning the bioprosthesis (A). Deployment of the upper anchoring crown and stabilization arches (B). After the stabilization arches are fully deployed and the axial positioning of the bioprosthesis is verified with respect to the native valve, injection of contrast dye facilitates correct positioning of the bioprosthesis (stent holder within the left ventricle) (C). Final deployment of the bioprosthesis under rapid ventricular pacing (deployment of the lower anchoring crown) while maintaining forward pressure on the delivery system towards the left ventricle (D). Final aortography (E).
Patients underwent follow-up examinations, including TTE and NYHA functional class status at the time of procedure, at discharge from hospital and at 30 days. Additional follow-up visits were scheduled for 6 and 12 months. In order to generate accurate baseline and follow-up data comparisons, all echocardiographic data relate to TTE. Adverse events data classified according to VARC 2 criteria7 were collected throughout the study.
Statistical AnalysisContinuous variables are presented as mean±standard deviation and were compared between groups through the use of a 2-sample t-test. Survival analysis was performed by the Kaplan-Meier method, with patients censored as of the last date known alive. Categorical variables are given as frequencies and percentages (%) and compared by Fisher’s exact test. A 2-sided P-value <0.05 was considered statistically significant. Statistical analyses were performed using statistical analysis software (SAS 9.2). All authors had full access to the complete data set and take responsibility for its integrity. All authors have read and agreed to the manuscript as written.
A total of 15 patients (men 4 (26.7%), women 11 (73.3%); mean age 83.3±6.0 years) underwent TAVI with the ACURATE neo prosthesis. All patients suffered from severe symptomatic AS. NYHA functional class was III in 6 patients (40.0%) and II in 9 patients (60.0%). Mean LVEF was 63.7±12.4%. Mean logistic EuroSCORE and STS score were 21.9±10.6% and 7.5±3.1%, respectively. Demographic and baseline characteristics including comorbidities are listed in Table 1.
| Age (years) | 83.3±6.0 |
| Female | 11 (73.3) |
| NYHA classification | |
| Class II | 9 (60.0) |
| Class III | 4 (40.0) |
| STS score (%) | 7.5±3.1 |
| <5 | 1 (6.7) |
| 5–10 | 11 (73.3) |
| >10 | 3 (20.0) |
| Logistic EuroSCORE (%) | 21.9±10.6 |
| Diabetes mellitus | 1 (6.7) |
| Creatinine level >2 mg/dl | 0 (0) |
| History of hypertension | 14 (93.3) |
| Peripheral vascular disease | 1 (6.7) |
| Prior stroke | 3 (20.0) |
| Prior TIA | 2 (13.3) |
| Cardiac history | |
| Coronary artery disease | 4 (26.7) |
| Prior coronary artery bypass surgery | 2 (13.3) |
| Prior percutaneous coronary intervention | 4 (26.7) |
| Prior balloon valvuloplasty | 0 (0) |
| Previous myocardial infarction | 3 (20.0) |
| Preexisting pacemaker | 2 (13.3) |
| Prior atrial fibrillation/atrial flutter | 0 (0) |
| Chronic lung disease/COPD | 4 (26.7) |
| Echocardiographic parameters | |
| Mean pressure gradient, mmHg | 46.9±14.5 |
| Mean EOA, cm2 | 0.76±0.12 |
| Left ventricular ejection fraction, % | 63.7±12.4 |
| Moderate or severe aortic regurgitation | 2 (13.3) |
Data presented as number of patients (%) or mean±SD. COPD, chronic obstructive pulmonary disease; EOA, effective orifice area; NYHA, New York Heart Association; STS, Society of Thoracic Surgeons; TIA, transient ischemic attack.
TF and transiliac implantations of the ACURATE neo bioprosthesis were performed in 10 and 5 patients, respectively (TF: 66.7%). The ACURATE neo bioprosthesis was successfully implanted in 14 of 15 patients (procedural success rate 93.3%). Although there was no conversion to surgical AVR, valve-in-valve implantation was necessary in 1 patient because of valve dislocation to the sino-tubular junction, which occurred while detaching the delivery catheter from the implanted prosthetic valve. The patient was treated with successful valve-in-valve implantation of a 23-mm SAPIEN XTTM prosthesis and was discharged after 13 postoperative days. As per protocol, this patient was withdrawn from the efficacy evaluation after discharge because the patient did not receive the study device at the annulus level. It was possible to deliver the ACURATE neo prosthesis to the correct annular position in every patient even if there was severe aortic arch angulation. Acute cardiac tamponade because of left ventricular perforation caused by a stiff guide wire required percutaneous cardiopulmonary bypass (VA ECMO) in 1 patient (6.7%), who was successfully recovered by pericardial drainage under epigastric small incision and discharged from hospital after 13 postoperative days without any adverse event. In the successfully implanted patients (n=14), post-dilatation was required under rapid ventricular pacing in 6 patients (42.9%) with mild or moderate paravalvular leak. Transvalvular pressure gradients at discharge significantly decreased from a mean of 44.2±10.5 mmHg (preprocedural) to 7.7±3.1 mmHg (P<0.0001). The effective orifice area increased from a mean of 0.77±0.12 to 1.69±0.25 cm2 (P<0.0001) (Figure 3). Post-procedure (at discharge), half of patients showed either none or trace (50.0%) paravalvular leak, and AR of moderate or more severity was not found (Figure 4). Every patient was discharged home. Procedural outcomes and characteristics are shown in Table 2 and echocardiographic outcomes in Figure 3.
Mean transvalvular aortic gradient (mPG) and effective orifice area (EOA) over time in patients implanted with the ACURATE neo/TFTM self-expanding stent.
Paravalvular leak over time – all patients implanted with the ACURATE neo/TFTM self-expanding stent.
| Procedural outcomes | |
| Operating time (min) | 96.3±35.0 |
| Amount of contrast agents (ml) | 132±49 |
| Implanted valve size | |
| 23-mm | 8 (53.3) |
| 25-mm | 5 (33.3) |
| 27-mm | 2 (13.3) |
| Device success | 14 (93.3) |
| Requiring post-dilation | 6 (42.9) |
| Requiring percutaneous cardiopulmonary bypass | 1 (6.7) |
| Conversion to open surgery | 0 (0) |
| Valve-in-valve | 1 (6.7) |
| Coronary obstruction | 0 (0) |
| Extubation in operating room | 15 (100) |
| 30-day outcomes (n=15) | |
| All-cause mortality | 0 (0) |
| Stroke (disabling) | 0 (0) |
| Life-threatening bleeding | 1 (6.7) |
| Acute kidney injury (stage 3) | 1 (6.7) |
| Periprocedural myocardial infarction | 0 (0) |
| Access-related complications | 1 (6.7) |
| Valve dysfunction | 0 (0) |
| Early safety | 13 (86.7) |
Data presented as number of patients (%) or mean±SD.
The overall mortality at 30 days and 6 months was 0% and 6.7%, respectively. The VARC 2 defined 30-day combined freedom from safety event rate was 86.7%, and overall device success was 93.3%. One patient (valve-in-valve case) developed major cardiac and cerebrovascular events (6.7%) at 30 postoperative days. The patient was diagnosed as having cholesterol crystal embolization requiring corticosteroids and temporary hemodialysis. Disabling stroke occurred in 1 patient who suffered from paroxysmal atrial fibrillation (6.7%) on postoperative day 179. During the follow-up period, there was only 1 patient (6.7%) who required permanent pacemaker implantation (on postoperative day 161) because of AV block.
The mean follow-up period was 281±105 days (range 73–405 days). NYHA functional class improved significantly at 30 days and 6 months after valve implantation; the majority of patients were NYHA class I (86.7% at 30 days, 86.7% at 6 months) (Figure 5).
New York Heart Association (NYHA) functional class over time in patients implanted with the ACURATE neo/TFTM self-expanding stent.
TAVI has already become the alternative treatment for high surgical-risk patients with severe AS in many European countries and has achieved satisfactory results. At present, the balloon-expandable device and self-expanding devices are approved in Europe for TAVI and have demonstrated good outcomes, but complications still leave room for improvement (eg, access-related complications, strokes, paravalvular leak, and pacemaker implantation).8 The ACURATE neo/TFTM was designed to provide an alternative for TF implantation. This novel self-expanding TF TAVI device has a low profile and a non-expandable standard 18F sheath is sufficient for insertion of the delivery system (even for a large valve). The delivery system is also compatible with the 15Fr balloon-expandable sheath that is available overseas.
Among the 15 patients in the present study, 10 (66.7%) were treated via the TF approach, despite being very small Japanese patients (mean body surface area: 1.50±0.11 m2). Moreover, it was easy to handle the delivery system, even in cases of moderate tortuosity/angulation of the aorta. The procedural time (iliofemoral series: 96±35 min) was similar to that in previous initial reports of the SAPIEN (iliofemoral series: 109±28 min)9 or CoreValveTM (iliofemoral series: 81±44 min)10 in Japan.
The ACURATE neo/TF has the same features as ACURATE TATM (Symetis S.A.), which is a transcatheter aortic valve designed for transapical implantation and granted CE mark in September 2011.11 A special feature of the ACURATE neo valve is its “self-seating” design, which facilitates accurate implantation: after the upper anchoring crown and stabilization arches are deployed, the ideal position can be achieved by slightly pushing the device towards the left ventricle, which might explain why the contrast volume (132±49 ml) in this series was relatively less than that in the previous report of SAPIEN iliofemoral series (161±75 ml).9 Moreover, the stepped approach and intuitive delivery shortens the learning curve.
The rate of more than mild paravalvular leak reported after SAPIEN or CoreValve implantation is between 7% and 20%;12–14 a recent report describes that even mild paravalvular leak is associated with late deaths.1 Another feature of the ACURATE neo is its “self-sealing” design, which minimizes paravalvular leak following TAVI. This feature is related to the unique hourglass shape of the stent, which is 3 mm larger in diameter at the lower crown than at the waist, as well as the covered section at the annular level with pericardial skirts, in addition to the implantation technique whereby the calcified native valve is captured in the annular plane by the upper crown, thus further facilitating effective sealing. In this present series, more than mild paravalvular leak was not found at either discharge or 30 days (0%). On the other hand, post-dilatation of the prosthetic valve was required in 6 patients (42.9%) with mild or moderate paravalvular leak, which might indicate a relatively low radial force of this valve. Post-dilatation of a self-expanding prosthesis valve seems to be relatively common13 and is a limitation of self-expanding devices. Therefore, patients with extremely severe calcification or inhomogeneous calcification will most likely benefit more from a balloon-expandable rather than self-expanding device, including the ACURATE neo/TF.15
In this trial, there was only 1 patient (6.7%) who had conduction disturbances requiring permanent pacemaker implantation on postoperative day 161. Regarding previous self-expanding devices, the rate of pacemaker implantation after valve implantation has been relatively high compared with balloon-expandable devices (26–43% with CoreValve16–20 vs. 5–22% with SAPIEN1,18–20). The conduction disturbances have several causes; for example, the depth of the prosthetic valve and radial force of the device.18 Accurate implantation (self-seating), a characteristic of this new device, may limit the occurrence of conduction disturbances. Moreover, the relatively low radial force of this valve also seems to decrease the rate of conduction disturbances. There was no case of stroke at 30 days and the rate of stroke with the use of the ACURATE neo/TF seems to be less than with CoreValve, another retrograde self-expanding device (4–10%13,17,19).
Study LimitationsBecause of the limited number of patients, there were no cases of coronary obstruction following TAVI with the ACURATE neo/TF, even in small Japanese patients in whom coronary obstruction may occur frequently because of a small sinus of Valsalva. The native cusps after ACURATE neo implantation were pressed down to the annuli on the postoperative ECG-gated CT. The upper anchoring crown (pressing down the native leaflets) might be an advantage of the ACURATE TF system in patients with high risk for coronary obstruction following TAVI. In addition, the accurate positioning also might reduce the risk for coronary obstruction. Therefore, patients with low coronaries might be better treated with the ACURATE neo device.
A new self-expanding TF TAVI device, ACURATE neo/TF, was safe and effective in the treatment of severe AS in elderly Japanese patients at high risk for surgery in a single-center clinical study. This report provides the first evidence that TAVI using the ACURATE neo/TF may bea feasible treatment for high-risk patients with AS and offers promising early results. The unique features of this novel device and its top-down deployment with “self-seating” and “self-sealing” design achieved satisfactory results despite the limited number of cases. Further investigations are mandatory to elucidate potential benefits in terms of durability and valve performance.
The study was supported by Symetis S.A. (device donation and training/proctoring provision only).
Conflict of Interest: No other conflicts of interest are reported.
Supplementary File 1
Appendix S1. Exclusion criteria
Please find supplementary file(s);
http://dx.doi.org/10.1253/circj.CJ-14-1110
