ORIGINAL ARTICLE
Single-Center Experience and Short-term Outcome With the JenaValve A Second-Generation Transapical Transcatheter Aortic Valve Implantation Device Oliver Reuthebuch, MD,* Devdas Thomas Inderbitzin, MD,* Florian Ru¨ter, MD,* Raban Jeger, MD,Þ Christoph Kaiser, MD,Þ Peter Buser, MD,Þ Jens Fassl, MD,þ and Friedrich S. Eckstein, MD* Objective: We present the post-CE(Conformite´ Europe´enne)-mark single-center implantation experience and short-term outcome with the second-generation transapical JenaValve transcatheter aortic valve implantation system. Methods: Patients [N = 27; 9 women; mean (SD) age, 80.3 (5.5) years] were operated on between November 2011 and August 2012. Via a transapical approach, the valve was positioned, in some cases, repositioned, and finally implanted. All data were collected during the hospital stay. Results: The implantation success rate was 100%; the mean (SD) operation time was 124.7 (43.2) minutes; and the size of the implanted prosthesis was 23 mm (n = 6), 25 mm (n = 14), and 27 mm (n = 7). The in-hospital major adverse cardiac and cerebrovascular events were as follows: intraoperative resuscitation with subsequent aortic rupture (n = 1), postoperative hemorrhage needing revision (n = 1), myocardial infarction (n = 1), atrioventricular block needing a definitive pacemaker (n = 1), new-onset renal failure needing hemodialysis (n = 1), and stroke (n = 1). The 30-day mortality was 11.1% (n = 3). The mean (SD) intensive care unit/total stay was 2.2 (1.7)/11.7 (7.9) days. Postoperative echocardiography [day 6.7 (4.8)] revealed residual paravalvular leakage of trace to grade 1 in 12 patients (44.5%) and no leakage in 15 patients, with a mean (SD) transvalvular pressure gradient of 11.6 (5.6) mm Hg with significant reduction by 36.0 (17.7) mm Hg (P = 0.0001, Wilcoxon signed rank test).
Conclusions: This second-generation repositionable transcatheter aortic valve implantation device could safely and successfully be implanted with a fast learning curve, significant reduction in pressure gradients, overall clinical improvement at discharge, as well as an acceptable morbidity and mortality rate in this highestrisk patient cohort. Key Words: Transapical transcatheter valve implanation, Aortic stenosis, Second-generation self-expanding aortic valve prosthesis, JenaValve. (Innovations 2014;9:368Y374)
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Address correspondence and reprint requests to Oliver Reuthebuch, MD, Department of Cardiac Surgery, University Hospital Basel, Spitalstrasse 21, CH-4031 Basel, Switzerland. E-mail: [email protected]. Copyright * 2014 by the International Society for Minimally Invasive Cardiothoracic Surgery ISSN: 1556-9845/14/0905-0368
ranscatheter aortic valve implantation (TAVI) has become a valuable alternative to open aortic valve replacement, with a lower perioperative risk, particularly in elderly and comorbid patients.1Y3 Aortic valve replacement was shown to be the most effective therapy for symptomatic aortic valve stenosis even in the presence of left ventricular dysfunction.3,4 Considering a demographic tendency toward an aging population in western countries and the increasing prevalence of severe symptomatic aortic stenosis in the elderly,3 TAVI offers a promising therapeutic option for such patients. Since the first description of TAVI in a human in 2002,5 multiple access routes have been established, including the retrograde transfemoral, subclavian, direct aortic, and antegrade transapical cardiac access. Kinking or limited vessel diameter of the aorta and peripheral arterial axis favor a transapical approach. Currently, several TAVI systems have been CE(Conformite Europe´enne)-mark approved for commercial implantation in Europe: the Edwards original SAPIEN System (Edwards Lifesciences Inc, Irvine, CA USA); the Medtronic CoreValve (Medtronic Inc, St Paul, MN USA); as well as the second-generation JenaValve (JenaValve Technology GmbH, Munich, Germany), Acurate TA (Symetis, Ecublens, Switzerland), and Engager (Medtronic Inc, St Paul, MN USA). Edwards SAPIEN, JenaValve, Acurate TA, and Engager can be placed by transapical access. In contrast to the first-generation prostheses, JenaValve, Acurate, and Engager provide the option of repetitive repositioning before final release. The JenaValve and Engager can be placed and released without the need for rapid pacing, thus with less compromised hemodynamic flow as well as lower risk for ventricular dilation and subsequent cardiac failure.
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Accepted for publication February 17, 2014. From the Departments of *Cardiac Surgery, †Cardiology, and ‡Anesthesiology, University Hospital Basel, Basel, Switzerland. Oliver Reuthebuch, MD, and Devdas Thomas Inderbitzin, MD, contributed equally to this study. Presented at the Annual Scientific Meeting of the International Society for Minimally Invasive Cardiothoracic Surgery, June 12Y15, 2013, Prague, Czech Republic. Disclosures: Oliver Reuthebuch, MD, is a proctor for JenaValve (JenaValve Technology GmbH, Munich, Germany), and Florian Ru¨ter, MD, was the principal investigator of the multicenter JUPITER trial. Devdas Thomas Inderbitzin, MD; Raban Jeger, MD; Christoph Kaiser, MD; Peter Buser, MD; Jens Fassl, MD; and Friedrich S. Eckstein, MD, declare no conflicts of interest.
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Innovations & Volume 9, Number 5, September/October 2014
Second-Generation Transapical TAVI: Early Results
We present the first Swiss postYCE-mark single-center implantation experience and short-term outcome with this second-generation self-expanding transapical TAVI device.
diameter e 6 mm, aneurysm, severe calcifications) were selected for a transapical instead of transfemoral access. Thus, approximately one third of the patient cohort was treated transapically; and two thirds, transfemorally. The transapical cohort group received the JenaValve if the aortic valve was tricuspid, the aortic annulus diameter ranged from 21 to 27 mm, the length of the ascending aorta from the annulus to the beginning of the arch measured 65 mm or greater, and the minimal distance of the annulus to the coronary ostia was 8 mm. In the absence of these specific selection criteria, the patient would have been implanted with the alternative SAPIEN XT prosthesis, which was not the case in the present cohort. Particular considerations such as porcelain aorta, previous chest radiation, and liver cirrhosis were not applicable. Baseline preoperative characteristics, preoperative transthoracic and esophageal echocardiographic findings, as well as angiographic computed tomography (angio-CT) findings are summarized in Table 1.
METHODS Patients and Baseline Characteristics From November 2011 to June 2012, a total of 27 consecutive patients receiving transapical TAVI using the JenaValve (JenaValve Technology GmbH, Munich, Germany) were enrolled. No patient was excluded. Data of all patients were prospectively collected and analyzed post hoc. Indication for aortic valve replacement was evaluated by our ‘‘heart team’’ according to international guidelines.6 Surgical risk was assessed by the European System for Cardiac Operative Risk Evaluation I (EuroSCORE I).6 Patients with a logistic EuroSCORE I of greater than 20 and/or 80 years or older were considered to be best treated by the TAVI program. Patients with improper iliofemoral arterial axis (kinking,
TABLE 1. Patients’ Characteristics (Number, Clinical, Cardiovascular Risk Factors, Echocardiographic, and Angiographic Computed Tomography Data) Patients’ Characteristics Total no. patients Age, mean (SD), y Male sex, n (%) Body weight, mean (SD), kg Body mass index, mean (SD), kg/m2 Logistic EuroSCORE I, mean (SD) NYHA classification, median (range) Coronary artery disease, n (%) Prior PCI with stenting, n (%) Prior cardiac surgery, n (%) Arterial hypertension, n (%) Cerebrovascular disease, n (%) Peripheral vascular disease, n (%) Fontaine stadium I Fontaine stadium II a Fontaine stadium II b COPD, n (%) Chronic renal insufficiency, serum creatinine 9 150 mmol/L, n (%) Hyperlipidemia, n (%) Smoker, n (%) Active Previous Diabetes, n (%) Positive family disposition, ‘‘cardiac event of a relative of first grade,’’ n (%) LVEF, mean (SD), % Transvalvular pressure gradient, mean (SD), mm Hg Aortic valve orifice, mean (SD), cm2 Grade of aortic stenosis: mild, moderate, severe,7 n (%) Leaflet calcification by echocardiography, n (%) Concomitant native valve disease, n (%) CT aortic annular diameter (3mensio program), mean (SD), mm Distance of the annulus to the left coronary artery ostium by angio-CT, mean (SD), mm
27 80.3 (5.5) 19 (70.4) 73.5 (17.8) 28.8 (5.1) 28.5 (7.7) III (IIYIV) 24 (88.9) 9 (33.3) (all 9 24 h before surgery) 10 (37) (9 CABG/1 aortic valvuloplasty) 26 (96.3) 2 (7.4) 13 (48.1) 6 (22.2) 3 (11.1) 4 (14.8) 3 (1.1) (all COPD GOLD II) 10 (37) (1 patient on long-term dialysis) 21 (77.8) 22 (81.5) 5 (18.5) 17 (63) 10 (37) (2 insulin-dependent diabetes) 18 (66.7) 50.5 (13.3) 47.5 (16.2) 0.82 (0.21) 0/0/27 (100) 27 (100%) 0 (0) 24.9 (1.5) 13.9 (2.2)
Angio-CT indicates angiographic computed tomography; CABG, coronary artery bypass graft; COPD, chronic obstructive pulmonary disease; GOLD, Global Initiative for Chronic Obstructive Lung Disease; CT, computed tomography; EuroSCORE, European System for Cardiac Operative Risk Evaluation; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; PCI, percutaneous coronary intervention.
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The Device: The JenaValve System The JenaValve system is a transapical TAVI device. A trileaflet porcine aortic native valve is mounted on a low-profile nitinol self-expanding stent with supporting flexible stent posts. Three positioning feelers allow correct placement into the corresponding annuli, and a clipping system fixes the stent to the diseased native valve leaflets. The available sizes are 23, 25, and 27 mm, encompassing annuli from 21 to 27 mm. The device is applied by a sheathless 32F delivery catheter. Optimal prosthesis size was calculated preoperatively by analyzing angio-CT images using the three-dimensional planning and sizing software 3mensio (3mensio Medical Imaging BV, Bilthoven, The Netherlands).
Anesthesia, Surgery, and Procedural Characteristics All patients received general anesthesia and continuous monitoring by two-lead electrocardiography (II, V5), pulse oximetry, as well as invasive measurement of arterial blood and central venous pressure. Transesophageal echocardiography
FIGURE 1. The JenaValve and its three basic steps of prosthesis delivery and implantation. A, The prosthesis is folded and mounted on the delivery system. B, Step 1: The catheter positions the sheathed prosthesis above the diseased native valve, and positioning feelers are released by partial retraction of the catheter sheath, allowing location of the feelers in the native sinus (‘‘landing zone’’) between the aortic wall and the diseased leaflets under beating heart conditions, permitting repositioning or retrieving. C, Step 2: Partial release of the prosthesis at its proximal end after correct positioning of the feelers. The nitinol stent self-expands, securely anchoring the prosthesis in the native annulus. The prosthesis immediately functions. D, Step 3: Complete expansion of the prosthesis at its distal end and separation from the catheter. The JenaClip mechanism clips the stent on the diseased native leaflets, and the prosthesis attaches firmly to the aortic wall. Safe retraction of the delivery system.
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FIGURE 2. Intraoperative radiographic image of a deployed JenaValve prosthesis.
was performed throughout the procedure. Implantation was performed as previously described.2 Briefly, the apex was exposed via left anterolateral thoracotomy, and two felt-pledgeted purse-string sutures and an epimyocardial ventricular pacing wire were placed. After heparinization (activated clotting time 9 250 seconds), a pigtail catheter was introduced via the femoral artery and placed in the aortic sinus. A ‘‘super stiff’’ guide wire was transapically inserted into the descending aorta. Balloon aortic valvuloplasty (BAV) using a transapical 14F sheath was performed under rapid pacing for no longer than 5 seconds. The crimped and mounted valve prosthesis was inserted with the Cathlete (JenaValve Technology GmbH, Munich, Germany) delivery catheter under fluoroscopic control. The corresponding steps are detailed in Figure 1. Correct placement was controlled (Fig. 2). Eventual paravalvular leakage was addressed by repeated BAV. After removal of the guide wire, purse strings were tied, heparin was reversed, and the chest was closed after placement of a chest tube. The patient was transferred to the intensive care unit. Anticoagulation management consisted of 100 mg of aspirin daily for life and 75 mg of clopidogrel daily for 6 months postoperatively. The mean operation time, implanted valve sizes, as well as sizes of balloons for predelivery and postdelivery valvuloplasty were noted. Prosthetic valve performance8 was described by the rate of successful implantations, number of necessary intraoperative postdelivery balloon dilations under rapid pacing, transesophageal echocardiographic assessment, conversion rate to open cardiac surgery, and apical bleeding requiring reoperation. ‘‘Valve’’-associated complications8 were conduction disturbances/cardiac arrhythmia, coronary obstruction, and other prosthesis-related implant-associated adverse events, for example, new-onset mitral valve dysfunction, ventricular septal defects, and aortic root rupture/perforation/dissection, respectively.
Clinical and Echocardiographic Short-term Follow-up and Major Adverse Cerebral and Cardiac Events Patient follow-up was provided until discharge for cardiac rehabilitation including clinical (mobilization from bed)
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Innovations & Volume 9, Number 5, September/October 2014
Second-Generation Transapical TAVI: Early Results
and transthoracic echocardiographic data: valve function and positioning, left ventricular ejection fraction (LVEF; in percentage), mean transvalvular pressure gradients (in millimeters of mercury), presence of paravalvular regurgitation, as well as valvular thrombosis. Major adverse cardiac and cerebrovascular events (MACCEs) were defined according to the Valve Academic Research Consortium criteria.8 Briefly, mortality (cardiac, noncardiac), myocardial infarction, stroke, major bleeding requiring surgical revision, new-onset kidney injury, and major vascular complication were considered.
of the introducer was self-explanatory and smooth. Immediate conduction disturbances or myocardial ischemia due to secondary coronary occlusion after final release of the device did not occur. Preimplantation BAV of the native valve was restricted to a maximal duration of 5 seconds and was uneventful in all patients. Positioning and final release of the prosthesis were performed without rapid pacing. There was no paravalvular leakage greater than grade 2 after primary release. Secondary balloon dilation was performed in 17 patients (63%) and was omitted in 3 patients (11.1%) despite paravalvular leakage (all grade 1) because of massive aortic annular calcification with a potential risk for cerebral embolization. Two of 17 patients needed repeated valvuloplasty. Successful paravalvular leakage downgrading was achieved in 12 of 17 patients, ensuing a success rate of 70.6%. Grade 2 leakages were completely eliminated. Procedural characteristics such as prosthetic valve performance and ‘‘valve’’-associated complications are shown in Table 2.
Data Management and Statistical Analysis Data were prospectively collected and analyzed post hoc by an independent statistician. Continuous variables are given as mean and standard deviation (SD). Categorical variables are expressed as numbers and proportions (percentage). New York Heart Association class is given as median, minimum, and maximum. Changes in continuous and categorical variables between baseline and discharge were compared with the Wilcoxon rank test, considering the small number. A two-sided P G 0.05 was considered statistically significant.
Ethical Considerations The study was approved by the local ethical committee in accordance with the principles of the Declaration of Helsinki. All participating investigators and statisticians have signed a declaration of confidentiality. All authors had unlimited access to the complete data set and take responsibility for its integrity. All authors have read and agreed to the manuscript as written.
RESULTS Patients and Baseline Characteristics From November 2011 to August 2012, a total of 27 patients [70.4% men; mean (SD) age, 80.3 (5.5) years; mean (SD) logistic EuroSCORE I, 28.5 (7.7)] received transapical TAVI using the JenaValve system. All patients had a severe aortic valvular stenosis. The median preoperative New York Heart Association class was III, ranging from II to IV. Preoperative transthoracic echocardiography revealed a mean (SD) aortic valve orifice area of 0.82 (0.21) cm2 as well as a mean (SD) transvalvular pressure gradient of 47.5 (16.2) mm Hg and a mean (SD) LVEF of 50.5% (13.3%). All native valves were tricuspid and severely calcified. The patients’ demographics and baseline characteristics as well as preoperative echocardiographic and angio-CT scan findings are summarized in Table 1.
Procedural Characteristics The JenaValve was implanted successfully and uneventfully in all patients (100%). The mean (SD) operation time was 124.7 (43.2) minutes. Technical problems or failure and directly device-related intraoperative complications were not observed. During placing and release of the valve, the implanting surgeon had constant control of the anatomically correct positioning. Handling
Clinical and Echocardiographic Short-term Follow-up and MACCEs Postoperative clinical follow-up showed excellent prosthesis-related clinical and echocardiographic results. All patients (excluding three patients who died in the intensive care unit; n = 24) were successfully mobilized out of bed until discharge. Echocardiographic follow-up at postoperative day 6.7 (4.8) showed an overall mean (SD) transvalvular pressure gradient of 11.6 (5.6) mm Hg, with a significant reduction by 36.0 (17.7) mm Hg (P = 0.0001, two-sided Wilcoxon signed rank test). The transvalvular pressure gradient was higher in the smallest prosthesis size, 23 mm [17.0 (4.8) mm Hg], compared with the sizes 25 and 27 mm [10.3 (4.8) mm Hg and 9.4 (3.2) mm Hg]. Paravalvular leakages of grade 2 were completely prevented by BAV. Twelve patients (44.5%) of the
TABLE 2. Procedural Characteristics: Prosthetic Valve Performance and ‘‘Valve’’-Associated Complications Procedural Characteristic Overall operation time, mean (SD), min 124.7 (43.2) Implanted valve sizes, n (%) 23-mm valve 6 (22.2) 25-mm valve 14 (51.9) 27-mm valve 7 (25.9) Successful implantations, n (%) 27 (100) Intraoperative balloon dilation, n (%) 17 (63) 1 attempt 15 (55.5) 2 attempts 2 (7.4) Omitted balloon dilation due to massive calcification 3 (11.1) with risk for cerebral embolization, n (%) Success rate: dilation with downgrading, n (%) 12 (70.6) Conduction disturbances and arrhythmia, n (%) 1 (3.7) (pacemaker for AV block grade III) Coronary obstruction, n (%) 0 (0) Other implant-related complications, n (%) 0 (0) AV indicates atrioventricular.
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cohort revealed residual paravalvular leakage of trace to grade 1, and 15 patients (55.5%) were free of leakage. There was no significant change of LVEF compared with preoperative assessment (P = 0.769, two-sided Wilcoxon signed rank test). Overall all-cause 30-day mortality was 11.1% (n = 3). One patient died in the operating room: the patient developed hemodynamic instability after Protamine (MEDA Pharmaceuticals, Wangen-Bru¨ttisellen, Switzerland) injection and needed mechanical resuscitation. Because of subsequent massive intrathoracic bleeding, a median sternotomy was performed and revealed a laceration of the aortic sinus near the prosthetic strut. There was no evidence of a mechanical perforation by the guide wire. Initial hemodynamic instability was interpreted as an anaphylactic reaction to Protamine. All further attempts to save the patient failed. The second patient died of low output and cardiogenic shock due to severe postoperative nonYST-elevated myocardial infarction on postoperative day 3. The patient had undergone aortocoronary bypass surgery 16 years ago and received multiple percutaneous transluminal coronary angioplasties 3 months before TAVI. The third patient died of severe acute-onchronic renal failure, needing hemofiltration, due to aggravating low cardiac output. Preoperative LVEF was already reduced to 25%. The predicted logistic EuroSCORE I in these patients was 42.9%, 25.1%, and 25.9%. Postoperative MACCE according to the Valve Academic Research Consortium criteria9 were one postoperative relevant hemorrhage (n = 1), one myocardial infarction without TAVI-associated coronary occlusion (n = 1), one atrioventricular (AV) bundle block grade III needing a permanent pacemaker (n = 1), and one stroke (n = 1). The bleeding at the apex of the heart despite double purse-string suture was controlled by immediate surgical revision. The AV bundle block grade III showed no postoperative recovery. A definitive pacemaker was implanted at day 5 after TAVI. The low and one-sided hemiparesis after stroke showed almost full recovery at discharge. Clinical and echocardiographic outcome as well as MACCEs are displayed in Table 3.
DISCUSSION Transcatheter aortic valve implantation has become an accepted alternative treatment to open aortic valve replacement, with comparable outcome10 in elderly patients with an increased risk for open surgery. Developmental effort has been invested in various TAVI systems,2,9,11 addressing the needs of a constantly aging population in the western world. The JenaValve is a CEmarkYcertified second-generation transapical self-expanding TAVI device allowing repetitive positioning before final release without rapid pacing. The device is merely clipped onto the native valve leaflets, thus avoiding coronary occlusion and conduction disturbances. Both the new-generation Acurate and Engager devices are designed with similar intentions. The definition of a ‘‘successful’’ implantation varies in the current state of TAVI literature. Although some studies2,9Y12 concentrate on intraoperative complications, abortion, or conversion to open surgery, others13,14 include the echocardiographic outcome. The absence of device-related intraoperative complications, abortions, or conversions and residual paravalvular leakage of higher than grade I implies a successful implantation in the present study, comparable with other devices: the
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TABLE 3. Clinical and Echocardiographic Outcome and Major Cardiac and Cerebrovascular Events Follow-up Characteristic/MACCE Days on intensive care unit, mean (SD) 2.2 (1.7) In-hospital days, mean (SD) 11.7 (7.9) Time on respirator 9 24 h, n (%) 3 (11.1) (up to 48 h) LVEF, mean (SD), % 49.0 (13.1) Transvalvular pressure gradient, mean (SD), mm Hg 11.6 (5.6) 23-mm valve 17.0 (4.8) 25-mm valve 10.3 (4.8) 27-mm valve 9.4 (3.2) Difference of transvalvular pressure gradient, 36.0 (17.7) mean (SD), mm Hg Paravalvular regurgitation, n (%) None 15 (55.5) Grade G 2 (grade 1 or lower) 12 (44.5) Valvular thrombosis, n (%) 0 (0) Overall mortality at 30 d, n (%) 3 (11.1) Perioperative myocardial infarction, n (%) 1 (3.7) Perioperative stroke, n (%) 1 (3.7) (complete in-hospital recovery) Major bleeding requiring surgical revision, n (%) 1 (3.7) Postoperative new-onset dialysis or hemofiltration, n (%) 1 (3.7) Major vascular complication, n (%) 0 (0) LVEF indicates left ventricular ejection fraction; MACCE, major adverse cardiac and cerebrovascular event.
success rates given for the first-generation TAVI range from 92.4% to 95.9%,10,12Y14 with abortion and subsequent conversion to open surgery in 0.7%13,14 to 5.8%10,12 or to valvein-valve deployment in 2.2% to 2.9%.11,13,14 The success rate was 89% for the JenaValve (CE mark),2 95% for the Acurate,11 and 100% for the Engager.9 The relatively high conversion rates of 6% to open surgery in the JenaValve CE-mark study2 and of 2.5% with the Acurate11 need careful interpretation when compared with the first-generation devices because they are biased by first-implantation experiences and lower patient numbers. Although complications such as coronary obstruction and annular dissection were successfully addressed by lower stent profiles, alternative anchoring mechanisms and device deployment without rapid pacing as well as the need for valve-in-valve conversion in 5% with the Acurate11 and in 3% in the JenaValve CE-mark study2 still indicate a persistent amount of transvalvular or paravalvular leakage that could not be corrected by BAV. Paravalvular leakage is a known complication in TAVI,2,9,11,12,15 and a moderate-to-severe paravalvular leakage was associated with an increase in late mortality in the 2-year follow-up of the PARTNER (Placement of AoRtic TraNscathetER Valves) trial.10 Although paravalvular leakage can be addressed by balloon redilation of the implanted device, none of the relevant studies illuminate the numbers of redilation needed with associated success rates. In our series, all patients had severe calcifications of the aortic annulus and leaflets, a known risk factor of paravalvular leakage.16 Of 20 patients (74%) with paravalvular leakage (none 9 grade 2), 17 (63%) were redilated, with a success rate of 70.6%. All moderate leaks were excluded. Before discharge, 12 patients (44.5%) showed residual leakage of trace to
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Innovations & Volume 9, Number 5, September/October 2014
Second-Generation Transapical TAVI: Early Results
grade 1 and 15 patients (55.5%) were free of leakage. This incidence is comparable with the Edwards SAPIEN and the CoreValve,13 reporting 0.8%, 16.3%, and 47.4% for leakages graded 3, 2, and 1, respectively. During the implantation of the Acurate,11 paravalvular leak of higher than grade 2 occurred in two patients, which received valve-in-valve TAVI, of which one patient even had to be converted to open valve replacement because of coronary occlusion. Thirty-day follow-up echocardiography showed absence of leak in 50% and grade 2 leaks in 3.4%. The Engager9 study found no leak higher than grade 1 but does not mention any corrective BAV. The JenaValve CE-mark study2 found paravalvular leakages of grade 2 in 13.6% and of grade 1 in 39%. We are aware that comparing our limited number of patients with larger clinical trials may implement a certain bias. However, our results indicate a tendency for lower leakage rates graded 1 when compared with the SAPIEN and the CoreValve.13 On the other hand, the CE-mark JenaValve study2 with a comparable number of patients showed similar results omitting the leakages graded 2. Furthermore, all our leakages graded higher than 2 could successfully be corrected in contrast to the SAPIEN, CoreValve, Acurate, and JenaValve studies. The JenaValve seems suitable to treat even severely calcified aortic stenosis. The clipping fixation to the leaflets might be less prone to cause residual leakage than a circular intra-annular anchoring, with its inferior adaptability to severely calcified asymmetric annuli. It is surprising that the Engager tends to have similar leakage grades and rates as the JenaValve, despite its subannular skirt designed to avoid this devastating complication. Further directly device-related complications are conduction disturbances needing a permanent pacemaker and coronary occlusion with subsequent myocardial infarction. Conduction blocks are caused by physical pressure of the device on the aortic annulus and the subaortic portion in the region of the AV bundle. Hence, the anchoring mechanism of a device plays a key role in triggering conduction problems. The cited incidence using the CoreValve varies from 20% to 38%,15,17 and that with the SAPIEN, from 3% to 11.5%.12,15,18 The higher incidence of bundle blocks caused by the CoreValve most probably originated from its stent reaching below the aortic annulus. The Engager comprises a similar subvalvular anchoring skirt to avoid paravalvular leakage. Subsequently, the Engager is expected to cause a higher incidence of pacemaker-requiring conduction blocks as the JenaValve, which is free from any subvalvular anchoring. Both the JenaValve CE-mark2 pacemaker requirement of 9.1% and our incidence of 3.7% suggest a lower risk than the rate of 20% in the first Engager implants.9 However, further implantations of both devices are required to confirm this trend. Coronary ostial occlusion occurs because of secondary displacement of a native calcified aortic valve leaflet covering the ostium rather than by the prosthesis itself. Therefore, in first-generation prostheses, the recommended distance between the aortic annulus and the coronary ostium is 12 mm.15 The JenaValve and the Engager with a clipping fixation at the native leaflets and low-profile nitinol stent are less prone to cause coronary obstruction because the sinuses remain free. With both valves, so far, no event of device-related coronary occlusion has been reported. In our cohort, even a minimal distance of 8 mm between the aortic annulus and the ostium was safe for implantation.
The mean (SD) transvalvular pressure gradient of 11.6 (5.6) mm Hg with a significant reduction by 36.0 (17.7) mm Hg indicates a correct choice of prosthesis size and implant. However, the 23-mm valves showed significantly higher pressure gradients of 17 (4.8) mm Hg. Although this differentiation is not given in the Acurate, the Engager, or the JenaValve CE-mark study,2,9,11 the relatively high gradient questions a favorable midterm and long-term outcome for this smallest JenaValve size and has to be observed in the future. Nevertheless, our overall mean (SD) transvalvular gradient was excellent compared with the Acurate11 [12.5 (5) mm Hg] and the Engager9 [15.6 (4.9)]. Further MACCEs in our cohort were one myocardial infarction, one stroke, and one renal failure. The infarction was not associated with coronary occlusion but rather occurred because of a highly limiting coronary situation. Given the incidence of 88.9% of coronary arterial disease within the cohort as well as prior interventional and surgical operation in 33.3% and 37.0%, respectively, the perioperative infarction rate seems quite reasonable. The stroke and kidney failure rates seem comparable with the literature for first-generation transapical TAVI12,14,15,18 (5% respectively 7.2%) and the JenaValve CEmark study2 (3% respectively 4.5%), with similar preoperative risk profiles of patients. The 30-day mortality in first-generation TAVI prostheses is cited from 11.2%14 to 18.8%.12 Although these rates do not interfere with the technical success rate of a TAVI implantation, they express the related highest perioperative risk in the polymorbid elderly patient usually eligible for TAVI. Our mortality was 11.1%, with two postoperative cardiac failures and one intraoperative death. This patient needed sternotomy because of massive bleeding after resuscitation as a result of hemodynamic instability after Protamine administration. An aortic sinus laceration near the device strut was found. The patient died on the table, as all means of resuscitation failed. The initial suspicion of a device-related complication, namely, an aortic guide-wire perforation, was ruled out in situ and by the fact that, after successful device implantation and before Protamine administration, no sign of instability or bleeding had occurred. We suspect an anaphylactic reaction to Protamine despite its rare expected incidence. The Acurate11 (12.5%) and Engager9 (10%; 1 of 10 patients) 30-day mortality was comparable with our results, with similar EuroSCORE I. The mortality in the CE-mark study2 of the JenaValve was slightly lower than our results, with 3% for cardiac and 7.6% for all causes. Our mortality is comparable with the CE-mark data considering the low patient number and shows an acceptable trend when compared with the first-generation devices.12,14,15,18 The present study has certain limitations: our experience is based on a small number of patients, and our results indicate only trends with limited power of interpretation when compared with the large trials of other devices. On the other hand, the present cohort is biased by the selection for transfemoral or transapical TAVI. We report about a selected group of elderly patients with multiple comorbidities who were not eligible for transfemoral TAVI. Although our first implantation experience and short-term outcome were promising, larger prospective studies are required to evaluate the true associated morbidity and mortality or advantages and disadvantages of the JenaValve.
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ACKNOWLEDGMENTS The authors thank statistician Brigitta Gahl for her assistance, data management, and statistical analysis.
REFERENCES 1. Cribier A. Development of transcatheter aortic valve implantation (TAVI): a 20-year odyssey. Arch Cardiovasc Dis. 2012;105:146Y152. 2. Treede H, Mohr FW, Baldus S, et al. Transapical transcatheter aortic valve implantation using the JenaValve system: acute and 30-day results of the multicentre CE-mark study. Eur J Cardiothorac Surg. 2012;41:e131Ye138. 3. Vahanian A, Alfieri O, Al-Attar N, et al. Transcatheter valve implantation for patients with aortic stenosis: a position statement from the European Association of Cardio-Thoracic Surgery (EACTS) and the European Society of Cardiology (ESC), in collaboration with the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2008;29:1463Y1470. 4. Bonow RO, Carabello BA, Kanu C, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and The Society of Thoracic Surgeons. Circulation. 2006;114:e84Ye231. 5. Cribier A, Eltchaninoff H, Bash A, et al. Percutaneous transcatheter implantation of an aortic valve prosthesis for calcific aortic stenosis: first human case description. Circulation. 2002;106:3006Y3008. 6. Nashef SA, Roques F, Michel P, Gauducheau E, Lemeshow S, Salamon R. European System for Cardiac Operative Risk Evaluation (EuroSCORE). Eur J Cardiothorac Surg. 1999;16:9Y13. 7. Vahanian A, Baumgartner H, Bax J, et al. Guidelines on the management of valvular heart disease: The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology. Eur Heart J. 2007;28: 230Y268.
8. Leon MB, Piazza N, Nikolsky E, et al. Standardized endpoint definitions for transcatheter aortic valve implantation clinical trials: a consensus report from the Valve Academic Research Consortium. Eur Heart J. 2011;32:205Y217. 9. Su¨ndermann SH, Gru¨nenfelder J, Corti R, et al. Feasibility of the Engager aortic transcatheter valve system using a flexible over-the-wire design. Eur J Cardiothorac Surg. 2012;42:e48Ye52. 10. Kodali SK, Williams MR, Smith CR, et al. Two-year outcomes after transcatheter or surgical aortic-valve replacement. N Engl J Med. 2012; 366:1686Y1695. 11. Kempfert J, Treede H, Rastan AJ, et al. Transapical aortic valve implantation using a new self-expandable bioprosthesis (ACURATE TA): 6-month outcomes. Eur J Cardiothorac Surg. 2013;43:52Y56. 12. Lefe`vre T, Kappetein AP, Wolner E, et al. One year follow-up of the multicentre European PARTNER transcatheter heart valve study. Eur Heart J. 2011;32:148Y157. 13. Gilard M, Eltchaninoff H, Iung B, et al. Registry of transcatheter aorticvalve implantation in high-risk patients. N Engl J Med. 2012;366: 1705Y1715. 14. Wendler O, Walther T, Schroefel H, et al. Transapical aortic valve implantation: mid-term outcome from the SOURCE registry. Eur J Cardiothorac Surg. 2013;43:505Y511. 15. Willson A, Webb J. Transcatheter treatment approaches for aortic valve disease. Int J Cardiovasc Imaging. 2011;27:1123Y1132. 16. Koos R, Mahnken AH, Dohmen G, et al. Association of aortic valve calcification severity with the degree of aortic regurgitation after transcatheter aortic valve implantation. Int J Cardiol. 2011;150:142Y145. 17. Berry C, Asgar A, Lamarche Y, et al. Novel therapeutic aspects of percutaneous aortic valve replacement with the 21F CoreValve Revalving System. Catheter Cardiovasc Interv. 2007;70:610Y616. 18. Thomas M, Schymik G, Walther T, et al. Thirty-day results of the SAPIEN aortic Bioprosthesis European Outcome (SOURCE) Registry: a European registry of transcatheter aortic valve implantation using the Edwards SAPIEN valve. Circulation. 2010;122:62Y69.
CLINICAL PERSPECTIVE This is a small single-center experience looking at short-term outcomes with the second-generation transapical JenaValve transcatheter aortic valve replacement (TAVR) system. The study included 27 patients with a mean age of older than 80 years operated on between November, 2011, and August, 2012. They had 100% implantation success. The 30-day mortality was greater than 11%. They had acceptable postoperative transvalvular pressure gradients and a low incidence of significant perivalvular leak. Although the results from this center with the JenaValve are promising, larger, prospective studies will be needed to truly evaluate the morbidity and morbidity associated with this valve.
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Copyright © 2014 by the International Society for Minimally Invasive Cardiothoracic Surgery. Unauthorized reproduction of this article is prohibited.
Single-Center Experience and Short-term Outcome With the JenaValve A Second-Generation Transapical Transcatheter Aortic Valve Implantation Device Oliver Reuthebuch, MD,* Devdas Thomas Inderbitzin, MD,* Florian Ru¨ter, MD,* Raban Jeger, MD,Þ Christoph Kaiser, MD,Þ Peter Buser, MD,Þ Jens Fassl, MD,þ and Friedrich S. Eckstein, MD* Objective: We present the post-CE(Conformite´ Europe´enne)-mark single-center implantation experience and short-term outcome with the second-generation transapical JenaValve transcatheter aortic valve implantation system. Methods: Patients [N = 27; 9 women; mean (SD) age, 80.3 (5.5) years] were operated on between November 2011 and August 2012. Via a transapical approach, the valve was positioned, in some cases, repositioned, and finally implanted. All data were collected during the hospital stay. Results: The implantation success rate was 100%; the mean (SD) operation time was 124.7 (43.2) minutes; and the size of the implanted prosthesis was 23 mm (n = 6), 25 mm (n = 14), and 27 mm (n = 7). The in-hospital major adverse cardiac and cerebrovascular events were as follows: intraoperative resuscitation with subsequent aortic rupture (n = 1), postoperative hemorrhage needing revision (n = 1), myocardial infarction (n = 1), atrioventricular block needing a definitive pacemaker (n = 1), new-onset renal failure needing hemodialysis (n = 1), and stroke (n = 1). The 30-day mortality was 11.1% (n = 3). The mean (SD) intensive care unit/total stay was 2.2 (1.7)/11.7 (7.9) days. Postoperative echocardiography [day 6.7 (4.8)] revealed residual paravalvular leakage of trace to grade 1 in 12 patients (44.5%) and no leakage in 15 patients, with a mean (SD) transvalvular pressure gradient of 11.6 (5.6) mm Hg with significant reduction by 36.0 (17.7) mm Hg (P = 0.0001, Wilcoxon signed rank test).
Conclusions: This second-generation repositionable transcatheter aortic valve implantation device could safely and successfully be implanted with a fast learning curve, significant reduction in pressure gradients, overall clinical improvement at discharge, as well as an acceptable morbidity and mortality rate in this highestrisk patient cohort. Key Words: Transapical transcatheter valve implanation, Aortic stenosis, Second-generation self-expanding aortic valve prosthesis, JenaValve. (Innovations 2014;9:368Y374)
T
Address correspondence and reprint requests to Oliver Reuthebuch, MD, Department of Cardiac Surgery, University Hospital Basel, Spitalstrasse 21, CH-4031 Basel, Switzerland. E-mail: [email protected]. Copyright * 2014 by the International Society for Minimally Invasive Cardiothoracic Surgery ISSN: 1556-9845/14/0905-0368
ranscatheter aortic valve implantation (TAVI) has become a valuable alternative to open aortic valve replacement, with a lower perioperative risk, particularly in elderly and comorbid patients.1Y3 Aortic valve replacement was shown to be the most effective therapy for symptomatic aortic valve stenosis even in the presence of left ventricular dysfunction.3,4 Considering a demographic tendency toward an aging population in western countries and the increasing prevalence of severe symptomatic aortic stenosis in the elderly,3 TAVI offers a promising therapeutic option for such patients. Since the first description of TAVI in a human in 2002,5 multiple access routes have been established, including the retrograde transfemoral, subclavian, direct aortic, and antegrade transapical cardiac access. Kinking or limited vessel diameter of the aorta and peripheral arterial axis favor a transapical approach. Currently, several TAVI systems have been CE(Conformite Europe´enne)-mark approved for commercial implantation in Europe: the Edwards original SAPIEN System (Edwards Lifesciences Inc, Irvine, CA USA); the Medtronic CoreValve (Medtronic Inc, St Paul, MN USA); as well as the second-generation JenaValve (JenaValve Technology GmbH, Munich, Germany), Acurate TA (Symetis, Ecublens, Switzerland), and Engager (Medtronic Inc, St Paul, MN USA). Edwards SAPIEN, JenaValve, Acurate TA, and Engager can be placed by transapical access. In contrast to the first-generation prostheses, JenaValve, Acurate, and Engager provide the option of repetitive repositioning before final release. The JenaValve and Engager can be placed and released without the need for rapid pacing, thus with less compromised hemodynamic flow as well as lower risk for ventricular dilation and subsequent cardiac failure.
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Accepted for publication February 17, 2014. From the Departments of *Cardiac Surgery, †Cardiology, and ‡Anesthesiology, University Hospital Basel, Basel, Switzerland. Oliver Reuthebuch, MD, and Devdas Thomas Inderbitzin, MD, contributed equally to this study. Presented at the Annual Scientific Meeting of the International Society for Minimally Invasive Cardiothoracic Surgery, June 12Y15, 2013, Prague, Czech Republic. Disclosures: Oliver Reuthebuch, MD, is a proctor for JenaValve (JenaValve Technology GmbH, Munich, Germany), and Florian Ru¨ter, MD, was the principal investigator of the multicenter JUPITER trial. Devdas Thomas Inderbitzin, MD; Raban Jeger, MD; Christoph Kaiser, MD; Peter Buser, MD; Jens Fassl, MD; and Friedrich S. Eckstein, MD, declare no conflicts of interest.
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Innovations & Volume 9, Number 5, September/October 2014
Second-Generation Transapical TAVI: Early Results
We present the first Swiss postYCE-mark single-center implantation experience and short-term outcome with this second-generation self-expanding transapical TAVI device.
diameter e 6 mm, aneurysm, severe calcifications) were selected for a transapical instead of transfemoral access. Thus, approximately one third of the patient cohort was treated transapically; and two thirds, transfemorally. The transapical cohort group received the JenaValve if the aortic valve was tricuspid, the aortic annulus diameter ranged from 21 to 27 mm, the length of the ascending aorta from the annulus to the beginning of the arch measured 65 mm or greater, and the minimal distance of the annulus to the coronary ostia was 8 mm. In the absence of these specific selection criteria, the patient would have been implanted with the alternative SAPIEN XT prosthesis, which was not the case in the present cohort. Particular considerations such as porcelain aorta, previous chest radiation, and liver cirrhosis were not applicable. Baseline preoperative characteristics, preoperative transthoracic and esophageal echocardiographic findings, as well as angiographic computed tomography (angio-CT) findings are summarized in Table 1.
METHODS Patients and Baseline Characteristics From November 2011 to June 2012, a total of 27 consecutive patients receiving transapical TAVI using the JenaValve (JenaValve Technology GmbH, Munich, Germany) were enrolled. No patient was excluded. Data of all patients were prospectively collected and analyzed post hoc. Indication for aortic valve replacement was evaluated by our ‘‘heart team’’ according to international guidelines.6 Surgical risk was assessed by the European System for Cardiac Operative Risk Evaluation I (EuroSCORE I).6 Patients with a logistic EuroSCORE I of greater than 20 and/or 80 years or older were considered to be best treated by the TAVI program. Patients with improper iliofemoral arterial axis (kinking,
TABLE 1. Patients’ Characteristics (Number, Clinical, Cardiovascular Risk Factors, Echocardiographic, and Angiographic Computed Tomography Data) Patients’ Characteristics Total no. patients Age, mean (SD), y Male sex, n (%) Body weight, mean (SD), kg Body mass index, mean (SD), kg/m2 Logistic EuroSCORE I, mean (SD) NYHA classification, median (range) Coronary artery disease, n (%) Prior PCI with stenting, n (%) Prior cardiac surgery, n (%) Arterial hypertension, n (%) Cerebrovascular disease, n (%) Peripheral vascular disease, n (%) Fontaine stadium I Fontaine stadium II a Fontaine stadium II b COPD, n (%) Chronic renal insufficiency, serum creatinine 9 150 mmol/L, n (%) Hyperlipidemia, n (%) Smoker, n (%) Active Previous Diabetes, n (%) Positive family disposition, ‘‘cardiac event of a relative of first grade,’’ n (%) LVEF, mean (SD), % Transvalvular pressure gradient, mean (SD), mm Hg Aortic valve orifice, mean (SD), cm2 Grade of aortic stenosis: mild, moderate, severe,7 n (%) Leaflet calcification by echocardiography, n (%) Concomitant native valve disease, n (%) CT aortic annular diameter (3mensio program), mean (SD), mm Distance of the annulus to the left coronary artery ostium by angio-CT, mean (SD), mm
27 80.3 (5.5) 19 (70.4) 73.5 (17.8) 28.8 (5.1) 28.5 (7.7) III (IIYIV) 24 (88.9) 9 (33.3) (all 9 24 h before surgery) 10 (37) (9 CABG/1 aortic valvuloplasty) 26 (96.3) 2 (7.4) 13 (48.1) 6 (22.2) 3 (11.1) 4 (14.8) 3 (1.1) (all COPD GOLD II) 10 (37) (1 patient on long-term dialysis) 21 (77.8) 22 (81.5) 5 (18.5) 17 (63) 10 (37) (2 insulin-dependent diabetes) 18 (66.7) 50.5 (13.3) 47.5 (16.2) 0.82 (0.21) 0/0/27 (100) 27 (100%) 0 (0) 24.9 (1.5) 13.9 (2.2)
Angio-CT indicates angiographic computed tomography; CABG, coronary artery bypass graft; COPD, chronic obstructive pulmonary disease; GOLD, Global Initiative for Chronic Obstructive Lung Disease; CT, computed tomography; EuroSCORE, European System for Cardiac Operative Risk Evaluation; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; PCI, percutaneous coronary intervention.
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The Device: The JenaValve System The JenaValve system is a transapical TAVI device. A trileaflet porcine aortic native valve is mounted on a low-profile nitinol self-expanding stent with supporting flexible stent posts. Three positioning feelers allow correct placement into the corresponding annuli, and a clipping system fixes the stent to the diseased native valve leaflets. The available sizes are 23, 25, and 27 mm, encompassing annuli from 21 to 27 mm. The device is applied by a sheathless 32F delivery catheter. Optimal prosthesis size was calculated preoperatively by analyzing angio-CT images using the three-dimensional planning and sizing software 3mensio (3mensio Medical Imaging BV, Bilthoven, The Netherlands).
Anesthesia, Surgery, and Procedural Characteristics All patients received general anesthesia and continuous monitoring by two-lead electrocardiography (II, V5), pulse oximetry, as well as invasive measurement of arterial blood and central venous pressure. Transesophageal echocardiography
FIGURE 1. The JenaValve and its three basic steps of prosthesis delivery and implantation. A, The prosthesis is folded and mounted on the delivery system. B, Step 1: The catheter positions the sheathed prosthesis above the diseased native valve, and positioning feelers are released by partial retraction of the catheter sheath, allowing location of the feelers in the native sinus (‘‘landing zone’’) between the aortic wall and the diseased leaflets under beating heart conditions, permitting repositioning or retrieving. C, Step 2: Partial release of the prosthesis at its proximal end after correct positioning of the feelers. The nitinol stent self-expands, securely anchoring the prosthesis in the native annulus. The prosthesis immediately functions. D, Step 3: Complete expansion of the prosthesis at its distal end and separation from the catheter. The JenaClip mechanism clips the stent on the diseased native leaflets, and the prosthesis attaches firmly to the aortic wall. Safe retraction of the delivery system.
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FIGURE 2. Intraoperative radiographic image of a deployed JenaValve prosthesis.
was performed throughout the procedure. Implantation was performed as previously described.2 Briefly, the apex was exposed via left anterolateral thoracotomy, and two felt-pledgeted purse-string sutures and an epimyocardial ventricular pacing wire were placed. After heparinization (activated clotting time 9 250 seconds), a pigtail catheter was introduced via the femoral artery and placed in the aortic sinus. A ‘‘super stiff’’ guide wire was transapically inserted into the descending aorta. Balloon aortic valvuloplasty (BAV) using a transapical 14F sheath was performed under rapid pacing for no longer than 5 seconds. The crimped and mounted valve prosthesis was inserted with the Cathlete (JenaValve Technology GmbH, Munich, Germany) delivery catheter under fluoroscopic control. The corresponding steps are detailed in Figure 1. Correct placement was controlled (Fig. 2). Eventual paravalvular leakage was addressed by repeated BAV. After removal of the guide wire, purse strings were tied, heparin was reversed, and the chest was closed after placement of a chest tube. The patient was transferred to the intensive care unit. Anticoagulation management consisted of 100 mg of aspirin daily for life and 75 mg of clopidogrel daily for 6 months postoperatively. The mean operation time, implanted valve sizes, as well as sizes of balloons for predelivery and postdelivery valvuloplasty were noted. Prosthetic valve performance8 was described by the rate of successful implantations, number of necessary intraoperative postdelivery balloon dilations under rapid pacing, transesophageal echocardiographic assessment, conversion rate to open cardiac surgery, and apical bleeding requiring reoperation. ‘‘Valve’’-associated complications8 were conduction disturbances/cardiac arrhythmia, coronary obstruction, and other prosthesis-related implant-associated adverse events, for example, new-onset mitral valve dysfunction, ventricular septal defects, and aortic root rupture/perforation/dissection, respectively.
Clinical and Echocardiographic Short-term Follow-up and Major Adverse Cerebral and Cardiac Events Patient follow-up was provided until discharge for cardiac rehabilitation including clinical (mobilization from bed)
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Innovations & Volume 9, Number 5, September/October 2014
Second-Generation Transapical TAVI: Early Results
and transthoracic echocardiographic data: valve function and positioning, left ventricular ejection fraction (LVEF; in percentage), mean transvalvular pressure gradients (in millimeters of mercury), presence of paravalvular regurgitation, as well as valvular thrombosis. Major adverse cardiac and cerebrovascular events (MACCEs) were defined according to the Valve Academic Research Consortium criteria.8 Briefly, mortality (cardiac, noncardiac), myocardial infarction, stroke, major bleeding requiring surgical revision, new-onset kidney injury, and major vascular complication were considered.
of the introducer was self-explanatory and smooth. Immediate conduction disturbances or myocardial ischemia due to secondary coronary occlusion after final release of the device did not occur. Preimplantation BAV of the native valve was restricted to a maximal duration of 5 seconds and was uneventful in all patients. Positioning and final release of the prosthesis were performed without rapid pacing. There was no paravalvular leakage greater than grade 2 after primary release. Secondary balloon dilation was performed in 17 patients (63%) and was omitted in 3 patients (11.1%) despite paravalvular leakage (all grade 1) because of massive aortic annular calcification with a potential risk for cerebral embolization. Two of 17 patients needed repeated valvuloplasty. Successful paravalvular leakage downgrading was achieved in 12 of 17 patients, ensuing a success rate of 70.6%. Grade 2 leakages were completely eliminated. Procedural characteristics such as prosthetic valve performance and ‘‘valve’’-associated complications are shown in Table 2.
Data Management and Statistical Analysis Data were prospectively collected and analyzed post hoc by an independent statistician. Continuous variables are given as mean and standard deviation (SD). Categorical variables are expressed as numbers and proportions (percentage). New York Heart Association class is given as median, minimum, and maximum. Changes in continuous and categorical variables between baseline and discharge were compared with the Wilcoxon rank test, considering the small number. A two-sided P G 0.05 was considered statistically significant.
Ethical Considerations The study was approved by the local ethical committee in accordance with the principles of the Declaration of Helsinki. All participating investigators and statisticians have signed a declaration of confidentiality. All authors had unlimited access to the complete data set and take responsibility for its integrity. All authors have read and agreed to the manuscript as written.
RESULTS Patients and Baseline Characteristics From November 2011 to August 2012, a total of 27 patients [70.4% men; mean (SD) age, 80.3 (5.5) years; mean (SD) logistic EuroSCORE I, 28.5 (7.7)] received transapical TAVI using the JenaValve system. All patients had a severe aortic valvular stenosis. The median preoperative New York Heart Association class was III, ranging from II to IV. Preoperative transthoracic echocardiography revealed a mean (SD) aortic valve orifice area of 0.82 (0.21) cm2 as well as a mean (SD) transvalvular pressure gradient of 47.5 (16.2) mm Hg and a mean (SD) LVEF of 50.5% (13.3%). All native valves were tricuspid and severely calcified. The patients’ demographics and baseline characteristics as well as preoperative echocardiographic and angio-CT scan findings are summarized in Table 1.
Procedural Characteristics The JenaValve was implanted successfully and uneventfully in all patients (100%). The mean (SD) operation time was 124.7 (43.2) minutes. Technical problems or failure and directly device-related intraoperative complications were not observed. During placing and release of the valve, the implanting surgeon had constant control of the anatomically correct positioning. Handling
Clinical and Echocardiographic Short-term Follow-up and MACCEs Postoperative clinical follow-up showed excellent prosthesis-related clinical and echocardiographic results. All patients (excluding three patients who died in the intensive care unit; n = 24) were successfully mobilized out of bed until discharge. Echocardiographic follow-up at postoperative day 6.7 (4.8) showed an overall mean (SD) transvalvular pressure gradient of 11.6 (5.6) mm Hg, with a significant reduction by 36.0 (17.7) mm Hg (P = 0.0001, two-sided Wilcoxon signed rank test). The transvalvular pressure gradient was higher in the smallest prosthesis size, 23 mm [17.0 (4.8) mm Hg], compared with the sizes 25 and 27 mm [10.3 (4.8) mm Hg and 9.4 (3.2) mm Hg]. Paravalvular leakages of grade 2 were completely prevented by BAV. Twelve patients (44.5%) of the
TABLE 2. Procedural Characteristics: Prosthetic Valve Performance and ‘‘Valve’’-Associated Complications Procedural Characteristic Overall operation time, mean (SD), min 124.7 (43.2) Implanted valve sizes, n (%) 23-mm valve 6 (22.2) 25-mm valve 14 (51.9) 27-mm valve 7 (25.9) Successful implantations, n (%) 27 (100) Intraoperative balloon dilation, n (%) 17 (63) 1 attempt 15 (55.5) 2 attempts 2 (7.4) Omitted balloon dilation due to massive calcification 3 (11.1) with risk for cerebral embolization, n (%) Success rate: dilation with downgrading, n (%) 12 (70.6) Conduction disturbances and arrhythmia, n (%) 1 (3.7) (pacemaker for AV block grade III) Coronary obstruction, n (%) 0 (0) Other implant-related complications, n (%) 0 (0) AV indicates atrioventricular.
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cohort revealed residual paravalvular leakage of trace to grade 1, and 15 patients (55.5%) were free of leakage. There was no significant change of LVEF compared with preoperative assessment (P = 0.769, two-sided Wilcoxon signed rank test). Overall all-cause 30-day mortality was 11.1% (n = 3). One patient died in the operating room: the patient developed hemodynamic instability after Protamine (MEDA Pharmaceuticals, Wangen-Bru¨ttisellen, Switzerland) injection and needed mechanical resuscitation. Because of subsequent massive intrathoracic bleeding, a median sternotomy was performed and revealed a laceration of the aortic sinus near the prosthetic strut. There was no evidence of a mechanical perforation by the guide wire. Initial hemodynamic instability was interpreted as an anaphylactic reaction to Protamine. All further attempts to save the patient failed. The second patient died of low output and cardiogenic shock due to severe postoperative nonYST-elevated myocardial infarction on postoperative day 3. The patient had undergone aortocoronary bypass surgery 16 years ago and received multiple percutaneous transluminal coronary angioplasties 3 months before TAVI. The third patient died of severe acute-onchronic renal failure, needing hemofiltration, due to aggravating low cardiac output. Preoperative LVEF was already reduced to 25%. The predicted logistic EuroSCORE I in these patients was 42.9%, 25.1%, and 25.9%. Postoperative MACCE according to the Valve Academic Research Consortium criteria9 were one postoperative relevant hemorrhage (n = 1), one myocardial infarction without TAVI-associated coronary occlusion (n = 1), one atrioventricular (AV) bundle block grade III needing a permanent pacemaker (n = 1), and one stroke (n = 1). The bleeding at the apex of the heart despite double purse-string suture was controlled by immediate surgical revision. The AV bundle block grade III showed no postoperative recovery. A definitive pacemaker was implanted at day 5 after TAVI. The low and one-sided hemiparesis after stroke showed almost full recovery at discharge. Clinical and echocardiographic outcome as well as MACCEs are displayed in Table 3.
DISCUSSION Transcatheter aortic valve implantation has become an accepted alternative treatment to open aortic valve replacement, with comparable outcome10 in elderly patients with an increased risk for open surgery. Developmental effort has been invested in various TAVI systems,2,9,11 addressing the needs of a constantly aging population in the western world. The JenaValve is a CEmarkYcertified second-generation transapical self-expanding TAVI device allowing repetitive positioning before final release without rapid pacing. The device is merely clipped onto the native valve leaflets, thus avoiding coronary occlusion and conduction disturbances. Both the new-generation Acurate and Engager devices are designed with similar intentions. The definition of a ‘‘successful’’ implantation varies in the current state of TAVI literature. Although some studies2,9Y12 concentrate on intraoperative complications, abortion, or conversion to open surgery, others13,14 include the echocardiographic outcome. The absence of device-related intraoperative complications, abortions, or conversions and residual paravalvular leakage of higher than grade I implies a successful implantation in the present study, comparable with other devices: the
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TABLE 3. Clinical and Echocardiographic Outcome and Major Cardiac and Cerebrovascular Events Follow-up Characteristic/MACCE Days on intensive care unit, mean (SD) 2.2 (1.7) In-hospital days, mean (SD) 11.7 (7.9) Time on respirator 9 24 h, n (%) 3 (11.1) (up to 48 h) LVEF, mean (SD), % 49.0 (13.1) Transvalvular pressure gradient, mean (SD), mm Hg 11.6 (5.6) 23-mm valve 17.0 (4.8) 25-mm valve 10.3 (4.8) 27-mm valve 9.4 (3.2) Difference of transvalvular pressure gradient, 36.0 (17.7) mean (SD), mm Hg Paravalvular regurgitation, n (%) None 15 (55.5) Grade G 2 (grade 1 or lower) 12 (44.5) Valvular thrombosis, n (%) 0 (0) Overall mortality at 30 d, n (%) 3 (11.1) Perioperative myocardial infarction, n (%) 1 (3.7) Perioperative stroke, n (%) 1 (3.7) (complete in-hospital recovery) Major bleeding requiring surgical revision, n (%) 1 (3.7) Postoperative new-onset dialysis or hemofiltration, n (%) 1 (3.7) Major vascular complication, n (%) 0 (0) LVEF indicates left ventricular ejection fraction; MACCE, major adverse cardiac and cerebrovascular event.
success rates given for the first-generation TAVI range from 92.4% to 95.9%,10,12Y14 with abortion and subsequent conversion to open surgery in 0.7%13,14 to 5.8%10,12 or to valvein-valve deployment in 2.2% to 2.9%.11,13,14 The success rate was 89% for the JenaValve (CE mark),2 95% for the Acurate,11 and 100% for the Engager.9 The relatively high conversion rates of 6% to open surgery in the JenaValve CE-mark study2 and of 2.5% with the Acurate11 need careful interpretation when compared with the first-generation devices because they are biased by first-implantation experiences and lower patient numbers. Although complications such as coronary obstruction and annular dissection were successfully addressed by lower stent profiles, alternative anchoring mechanisms and device deployment without rapid pacing as well as the need for valve-in-valve conversion in 5% with the Acurate11 and in 3% in the JenaValve CE-mark study2 still indicate a persistent amount of transvalvular or paravalvular leakage that could not be corrected by BAV. Paravalvular leakage is a known complication in TAVI,2,9,11,12,15 and a moderate-to-severe paravalvular leakage was associated with an increase in late mortality in the 2-year follow-up of the PARTNER (Placement of AoRtic TraNscathetER Valves) trial.10 Although paravalvular leakage can be addressed by balloon redilation of the implanted device, none of the relevant studies illuminate the numbers of redilation needed with associated success rates. In our series, all patients had severe calcifications of the aortic annulus and leaflets, a known risk factor of paravalvular leakage.16 Of 20 patients (74%) with paravalvular leakage (none 9 grade 2), 17 (63%) were redilated, with a success rate of 70.6%. All moderate leaks were excluded. Before discharge, 12 patients (44.5%) showed residual leakage of trace to
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Innovations & Volume 9, Number 5, September/October 2014
Second-Generation Transapical TAVI: Early Results
grade 1 and 15 patients (55.5%) were free of leakage. This incidence is comparable with the Edwards SAPIEN and the CoreValve,13 reporting 0.8%, 16.3%, and 47.4% for leakages graded 3, 2, and 1, respectively. During the implantation of the Acurate,11 paravalvular leak of higher than grade 2 occurred in two patients, which received valve-in-valve TAVI, of which one patient even had to be converted to open valve replacement because of coronary occlusion. Thirty-day follow-up echocardiography showed absence of leak in 50% and grade 2 leaks in 3.4%. The Engager9 study found no leak higher than grade 1 but does not mention any corrective BAV. The JenaValve CE-mark study2 found paravalvular leakages of grade 2 in 13.6% and of grade 1 in 39%. We are aware that comparing our limited number of patients with larger clinical trials may implement a certain bias. However, our results indicate a tendency for lower leakage rates graded 1 when compared with the SAPIEN and the CoreValve.13 On the other hand, the CE-mark JenaValve study2 with a comparable number of patients showed similar results omitting the leakages graded 2. Furthermore, all our leakages graded higher than 2 could successfully be corrected in contrast to the SAPIEN, CoreValve, Acurate, and JenaValve studies. The JenaValve seems suitable to treat even severely calcified aortic stenosis. The clipping fixation to the leaflets might be less prone to cause residual leakage than a circular intra-annular anchoring, with its inferior adaptability to severely calcified asymmetric annuli. It is surprising that the Engager tends to have similar leakage grades and rates as the JenaValve, despite its subannular skirt designed to avoid this devastating complication. Further directly device-related complications are conduction disturbances needing a permanent pacemaker and coronary occlusion with subsequent myocardial infarction. Conduction blocks are caused by physical pressure of the device on the aortic annulus and the subaortic portion in the region of the AV bundle. Hence, the anchoring mechanism of a device plays a key role in triggering conduction problems. The cited incidence using the CoreValve varies from 20% to 38%,15,17 and that with the SAPIEN, from 3% to 11.5%.12,15,18 The higher incidence of bundle blocks caused by the CoreValve most probably originated from its stent reaching below the aortic annulus. The Engager comprises a similar subvalvular anchoring skirt to avoid paravalvular leakage. Subsequently, the Engager is expected to cause a higher incidence of pacemaker-requiring conduction blocks as the JenaValve, which is free from any subvalvular anchoring. Both the JenaValve CE-mark2 pacemaker requirement of 9.1% and our incidence of 3.7% suggest a lower risk than the rate of 20% in the first Engager implants.9 However, further implantations of both devices are required to confirm this trend. Coronary ostial occlusion occurs because of secondary displacement of a native calcified aortic valve leaflet covering the ostium rather than by the prosthesis itself. Therefore, in first-generation prostheses, the recommended distance between the aortic annulus and the coronary ostium is 12 mm.15 The JenaValve and the Engager with a clipping fixation at the native leaflets and low-profile nitinol stent are less prone to cause coronary obstruction because the sinuses remain free. With both valves, so far, no event of device-related coronary occlusion has been reported. In our cohort, even a minimal distance of 8 mm between the aortic annulus and the ostium was safe for implantation.
The mean (SD) transvalvular pressure gradient of 11.6 (5.6) mm Hg with a significant reduction by 36.0 (17.7) mm Hg indicates a correct choice of prosthesis size and implant. However, the 23-mm valves showed significantly higher pressure gradients of 17 (4.8) mm Hg. Although this differentiation is not given in the Acurate, the Engager, or the JenaValve CE-mark study,2,9,11 the relatively high gradient questions a favorable midterm and long-term outcome for this smallest JenaValve size and has to be observed in the future. Nevertheless, our overall mean (SD) transvalvular gradient was excellent compared with the Acurate11 [12.5 (5) mm Hg] and the Engager9 [15.6 (4.9)]. Further MACCEs in our cohort were one myocardial infarction, one stroke, and one renal failure. The infarction was not associated with coronary occlusion but rather occurred because of a highly limiting coronary situation. Given the incidence of 88.9% of coronary arterial disease within the cohort as well as prior interventional and surgical operation in 33.3% and 37.0%, respectively, the perioperative infarction rate seems quite reasonable. The stroke and kidney failure rates seem comparable with the literature for first-generation transapical TAVI12,14,15,18 (5% respectively 7.2%) and the JenaValve CEmark study2 (3% respectively 4.5%), with similar preoperative risk profiles of patients. The 30-day mortality in first-generation TAVI prostheses is cited from 11.2%14 to 18.8%.12 Although these rates do not interfere with the technical success rate of a TAVI implantation, they express the related highest perioperative risk in the polymorbid elderly patient usually eligible for TAVI. Our mortality was 11.1%, with two postoperative cardiac failures and one intraoperative death. This patient needed sternotomy because of massive bleeding after resuscitation as a result of hemodynamic instability after Protamine administration. An aortic sinus laceration near the device strut was found. The patient died on the table, as all means of resuscitation failed. The initial suspicion of a device-related complication, namely, an aortic guide-wire perforation, was ruled out in situ and by the fact that, after successful device implantation and before Protamine administration, no sign of instability or bleeding had occurred. We suspect an anaphylactic reaction to Protamine despite its rare expected incidence. The Acurate11 (12.5%) and Engager9 (10%; 1 of 10 patients) 30-day mortality was comparable with our results, with similar EuroSCORE I. The mortality in the CE-mark study2 of the JenaValve was slightly lower than our results, with 3% for cardiac and 7.6% for all causes. Our mortality is comparable with the CE-mark data considering the low patient number and shows an acceptable trend when compared with the first-generation devices.12,14,15,18 The present study has certain limitations: our experience is based on a small number of patients, and our results indicate only trends with limited power of interpretation when compared with the large trials of other devices. On the other hand, the present cohort is biased by the selection for transfemoral or transapical TAVI. We report about a selected group of elderly patients with multiple comorbidities who were not eligible for transfemoral TAVI. Although our first implantation experience and short-term outcome were promising, larger prospective studies are required to evaluate the true associated morbidity and mortality or advantages and disadvantages of the JenaValve.
Copyright * 2014 by the International Society for Minimally Invasive Cardiothoracic Surgery
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Copyright © 2014 by the International Society for Minimally Invasive Cardiothoracic Surgery. Unauthorized reproduction of this article is prohibited.
Innovations & Volume 9, Number 5, September/October 2014
Reuthebuch et al
ACKNOWLEDGMENTS The authors thank statistician Brigitta Gahl for her assistance, data management, and statistical analysis.
REFERENCES 1. Cribier A. Development of transcatheter aortic valve implantation (TAVI): a 20-year odyssey. Arch Cardiovasc Dis. 2012;105:146Y152. 2. Treede H, Mohr FW, Baldus S, et al. Transapical transcatheter aortic valve implantation using the JenaValve system: acute and 30-day results of the multicentre CE-mark study. Eur J Cardiothorac Surg. 2012;41:e131Ye138. 3. Vahanian A, Alfieri O, Al-Attar N, et al. Transcatheter valve implantation for patients with aortic stenosis: a position statement from the European Association of Cardio-Thoracic Surgery (EACTS) and the European Society of Cardiology (ESC), in collaboration with the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2008;29:1463Y1470. 4. Bonow RO, Carabello BA, Kanu C, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and The Society of Thoracic Surgeons. Circulation. 2006;114:e84Ye231. 5. Cribier A, Eltchaninoff H, Bash A, et al. Percutaneous transcatheter implantation of an aortic valve prosthesis for calcific aortic stenosis: first human case description. Circulation. 2002;106:3006Y3008. 6. Nashef SA, Roques F, Michel P, Gauducheau E, Lemeshow S, Salamon R. European System for Cardiac Operative Risk Evaluation (EuroSCORE). Eur J Cardiothorac Surg. 1999;16:9Y13. 7. Vahanian A, Baumgartner H, Bax J, et al. Guidelines on the management of valvular heart disease: The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology. Eur Heart J. 2007;28: 230Y268.
8. Leon MB, Piazza N, Nikolsky E, et al. Standardized endpoint definitions for transcatheter aortic valve implantation clinical trials: a consensus report from the Valve Academic Research Consortium. Eur Heart J. 2011;32:205Y217. 9. Su¨ndermann SH, Gru¨nenfelder J, Corti R, et al. Feasibility of the Engager aortic transcatheter valve system using a flexible over-the-wire design. Eur J Cardiothorac Surg. 2012;42:e48Ye52. 10. Kodali SK, Williams MR, Smith CR, et al. Two-year outcomes after transcatheter or surgical aortic-valve replacement. N Engl J Med. 2012; 366:1686Y1695. 11. Kempfert J, Treede H, Rastan AJ, et al. Transapical aortic valve implantation using a new self-expandable bioprosthesis (ACURATE TA): 6-month outcomes. Eur J Cardiothorac Surg. 2013;43:52Y56. 12. Lefe`vre T, Kappetein AP, Wolner E, et al. One year follow-up of the multicentre European PARTNER transcatheter heart valve study. Eur Heart J. 2011;32:148Y157. 13. Gilard M, Eltchaninoff H, Iung B, et al. Registry of transcatheter aorticvalve implantation in high-risk patients. N Engl J Med. 2012;366: 1705Y1715. 14. Wendler O, Walther T, Schroefel H, et al. Transapical aortic valve implantation: mid-term outcome from the SOURCE registry. Eur J Cardiothorac Surg. 2013;43:505Y511. 15. Willson A, Webb J. Transcatheter treatment approaches for aortic valve disease. Int J Cardiovasc Imaging. 2011;27:1123Y1132. 16. Koos R, Mahnken AH, Dohmen G, et al. Association of aortic valve calcification severity with the degree of aortic regurgitation after transcatheter aortic valve implantation. Int J Cardiol. 2011;150:142Y145. 17. Berry C, Asgar A, Lamarche Y, et al. Novel therapeutic aspects of percutaneous aortic valve replacement with the 21F CoreValve Revalving System. Catheter Cardiovasc Interv. 2007;70:610Y616. 18. Thomas M, Schymik G, Walther T, et al. Thirty-day results of the SAPIEN aortic Bioprosthesis European Outcome (SOURCE) Registry: a European registry of transcatheter aortic valve implantation using the Edwards SAPIEN valve. Circulation. 2010;122:62Y69.
CLINICAL PERSPECTIVE This is a small single-center experience looking at short-term outcomes with the second-generation transapical JenaValve transcatheter aortic valve replacement (TAVR) system. The study included 27 patients with a mean age of older than 80 years operated on between November, 2011, and August, 2012. They had 100% implantation success. The 30-day mortality was greater than 11%. They had acceptable postoperative transvalvular pressure gradients and a low incidence of significant perivalvular leak. Although the results from this center with the JenaValve are promising, larger, prospective studies will be needed to truly evaluate the morbidity and morbidity associated with this valve.
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Copyright * 2014 by the International Society for Minimally Invasive Cardiothoracic Surgery
Copyright © 2014 by the International Society for Minimally Invasive Cardiothoracic Surgery. Unauthorized reproduction of this article is prohibited.
