European Journal of Cardio-thoracic Surgery 31 (2007) 9—15
`
`www.elsevier.com/locate/ejcts
`
`Minimally invasive transapical beating heart aortic valve
`implantation — proof of concept
`
`Thomas Walther a,*, Volkmar Falk a, Michael A. Borger a, Todd Dewey b,
`Gerhard Wimmer-Greinecker c, Gerhard Schuler d, Michael Mack b, Friedrich W. Mohr a
`
`a Department of Cardiac Surgery, Heartcenter, University Leipzig, Leipzig, Germany
`b Department of Cardiac Surgery, Cardiopulmonary Research Science and Technology Institute, Dallas, TX, USA
`c Department of Thoracic and Cardiovascular Surgery, JW-Goethe University, Frankfurt, Germany
`d Department of Cardiology, Heartcenter, University Leipzig, Leipzig, Germany
`
`Received 13 October 2006; received in revised form 29 October 2006; accepted 30 October 2006; Available online 9 November 2006
`
`Abstract
`
`Objective: To evaluate the feasibility of minimally invasive transapical beating heart aortic valve implantation (TAP-AVI) for high-risk patients
`with aortic stenosis. Methods: TAP-AVI was performed via a small anterolateral minithoracotomy with or without femoral extracorporeal
`circulation (ECC) on the beating heart. A pericardial xenograft fixed within a stainless steel, balloon expandable stent (Cribier-Edwards, Edwards
`Lifesciences, Irvine, CA, USA) was used. Thirty consecutive patients (82  5.1 years, 21 (70%) female) were operated from 02/06 until 09/06 at
`one center using fluoroscopic and echocardiographic visualization. Average EuroSCORE predicted risk for mortality was 27  12%. Results: Valve
`positioning was successful in 29 patients and one required early conversion to full sternotomy. Implantation (8 mm  23 mm and 22 mm  26 mm
`valves) was performed on the beating heart during brief periods of rapid ventricular pacing. ECC was applied in 13 patients. Neither coronary
`artery obstruction nor migration of the prosthesis was observed and all valves displayed good hemodynamic function. Echocardiography revealed
`minor paravalvular leakage in 14 patients (trace in three, mild in nine and moderate in two). Three patients (10%) died, one on postoperative day
`(POD) three secondary to preoperative global myocardial failure and two on POD 18 and 86 due to abdominal complications. Conclusions:
`Minimally invasive beating heart TAP-AVI is feasible. Initial results are encouraging in view of the high-risk profile of the patients. Long-term
`studies as well as randomized protocols are required.
`# 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
`
`Keywords: Aortic valve replacement; Transapical aortic valve implantation; Minimally invasive cardiac surgery; Beating heart cardiac surgery; Transcatheter valve
`implantation
`
`1. Introduction
`
`is a standard procedure
`Aortic valve replacement
`performed for more than five decades with excellent short
`and long-term outcomes. More than 50,000 patients are
`being operated in the USA and more than 11,000 patients in
`Germany annually [1,2]. Surgical valve replacement is the
`only definitive therapeutic strategy, indicated in presence of
`severe symptomatic disease with a valve orifice area of
`1 cm2 [3]. Current conventional surgical techniques consist
`of partial or complete sternotomy with extracorporeal
`circulation (ECC) and cardioplegic cardiac arrest.
`In parallel with an overall increasing life expectancy more
`and more elderly patients are being diagnosed with AS.
`Besides older age additional perioperative risk factors may be
`
`present such as low ejection fraction, pulmonary hyperten-
`sion, respiratory dysfunction, renal failure or peripheral
`arterial occlusive disease. Such co-morbidities are associated
`with an increased perioperative risk, particularly for
`mortality. Truly minimally invasive strategies may be an
`important treatment option for such high-risk patients.
`Important areas of development include minimizing the
`overall surgical trauma by potentially avoiding a sternotomy,
`avoiding the use of ECC and implanting the prostheses on the
`beating heart thereby avoiding cardiac arrest.
`The aim of our study was to evaluate the feasibility of
`minimally invasive transapical aortic valve implantation
`(TAP-AVI) on the beating heart in high-risk patients.
`
`2. Methods
`
`* Corresponding author. Address: Universita¨t Leipzig, Herzzentrum, Klinik
`fu¨r Herzchirurgie, Stru¨mpellstr. 39, 04289 Leipzig, Germany.
`Tel.: +49 341 865 1424; fax: +49 341 865 1452.
`E-mail address: walt@medizin.uni-leipzig.de (T. Walther).
`
`Before performing a clinical study, extensive experimen-
`tal evaluation of the transapical approach as well as
`transcatheter valve implantation techniques was performed
`
`1010-7940/$ — see front matter # 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
`doi:10.1016/j.ejcts.2006.10.034
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`[4,5]. The clinical study protocol was approved by the local
`ethical committee and the study was registered at the
`federal governmental offices.
`
`2.1. Patient selection
`
`Patient selection was performed on the basis of an
`increased perioperative risk profile according to the Euro-
`SCORE scale [6]. Patients with 9 points indicating a risk for
`mortality of >11% according to the logistic EuroSCORE were
`considered suitable for inclusion into the study. Detailed
`echocardiographic analysis was then performed in order to
`delineate the diameter of the aortic annulus as well as the
`distribution of cusp calcification, presence of fused com-
`missures, tricuspid or biscuspid pathology as well as presence
`of severe eccentric calcification. Patients with an aortic
`annulus 24 mm and equally distributed calcification were
`considered suitable for inclusion in the study. The ther-
`apeutic option of TAP-AVI was discussed extensively with the
`patients and family members. This discussion focused on the
`overall
`risk profile of the individual patient, on the
`preoperative activities of daily living and the motivation of
`the individual patient, and on the ongoing results of the new
`technique. All patients considered suitable for inclusion into
`the study gave informed consent; no one opted for a
`conventional surgical approach.
`
`2.2. Cribier-Edwards prosthesis
`
`The Cribier-Edwards prosthesis is a pericardial xenograft
`mounted on a stainless steel stent and is available in two
`sizes—23 mm and 26 mm (Edwards Lifesciences, Irvine, CA,
`USA). Comparable to other pericardial xenografts, the valve
`has three cusps and three commissures. The stainless steel
`stent has a very low profile when fully expanded. The lower
`inflow portion of the valve is covered with polyethylene
`terephthalate (PET) cloth. The prosthesis is the same device
`as used in recent clinical percutaneous approaches [7—9]
`(see Fig. 1). The sutureless stent-fixed aortic valve was
`prepared for transapical antegrade delivery under sterile
`conditions in the operating room by a technician just prior to
`implantation. The delivery catheter was flushed with a
`heparinized saline solution. The deployment balloon was
`primed with a mixture of saline and contrast that was free of
`air. The valve was crimped onto the deployment balloon so
`that it was equidistant between two radiopaque markers and
`was able to be passed through the 33F transapical delivery
`sheath. All valve deployments were performed using
`standard volumetric inflation of the balloon.
`
`2.3. Technical equipment: operating theatre
`
`All operations were performed in a hybrid operation
`theatre. This is a standard operating room with an additional
`angiography system equivalent to any standard catheteriza-
`tion laboratory. A monoplane fluoroscopic angiography system
`(Axiom Sensis, Siemens, Munich, Germany) was used. Fluoro-
`scopy is important for providing a perpendicular view of the
`aortic root. This allows for optimal delineation of the level of
`the aortic annulus in relation to the aortic sinuses, along with
`imaging of the coronary ostia. Optimal visualization of the
`
`Fig. 1. Cribier-Edwards prosthesis: Balloon expandable pericardial xenograft
`fixed on a low-profile steel stent for transcatheter delivery.
`
`aortic root was usually achieved at a left anterior oblique 258
`and cranial 108 position. Besides standard hemodynamic
`monitoring, transesophageal echocardiography and extracor-
`poreal circulation (ECC) were routinely available. Transeso-
`phageal
`echocardiography was
`used
`for
`repeated
`measurements of aortic annular diameters. We chose a calve
`
`Fig. 2. Schematic illustration of transapical aortic valve implantation. The
`prosthesis is being dilated at the annular level within the native aortic valve
`cusps. Transapical sheath insertion is secured with a puse-string suture.
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`
`size that was 2—3 mm larger than the echocardiographic
`annular measurements in order to achieve good contact with
`the aortic annulus and to minimize the risk of paravalvular
`leaks (oversizing technique).
`
`2.4. Transapical aortic valve implantation (TAP-AVI):
`operative technique
`
`The patients were placed in a supine position with the
`left chest slightly elevated. The left sided femoral vessels
`were dissected, either for cannulation for ECC (on pump
`procedure) or to place a venous guidewire (off pump
`procedure) for safety reasons in order to be prepared for
`fast cannulation. In addition a femoral arterial sheath (6F)
`was inserted and an aortic root pigtail catheter for
`angiographic visualization was placed. High dose heparin
`(300 IU/kg) was given for on-pump cases, and low dose
`heparin (5000 IU) was used for off-pump procedures with a
`target activated clotting time of 180—200 s. An anterolat-
`eral minithoracotomy (5—7 cm) was then performed in the
`fifth intercostal space to access the apex of the heart. The
`pericardium was incised longitudinally and fixed with stay
`sutures allowing persistent ventilation of the lungs. A
`bipolar epicardial pacing wire was placed and tested. Two
`apical purse-string sutures with Teflon felt pledgets were
`placed with an inner diameter of approximately 2—3 cm.
`The left ventricular apex was punctured and a soft
`guidewire passed antegradely across the stenotic aortic
`valve under fluoroscopic and echocardiographic monitoring.
`A 14F soft sheath was introduced and positioned across the
`aortic valve. A 03500 super-stiff guide-wire (Amplatz super-
`stiff; 260 cm, Boston Scientific) was then positioned across
`the aortic arch and ‘anchored’ into the descending aorta.
`The sheath was partially withdrawn and a 20 mm balloon
`valvuloplasty catheter positioned under fluoroscopic and
`echocardiographic guidance. Balloon valvuloplasty was
`performed once during a brief episode of rapid ventricular
`pacing (150/min.). The balloon catheter and apical sheath
`were withdrawn and a 33F transapical delivery sheath
`inserted bluntly. The valve was then inserted using the
`specific application system. After careful de-airing of the
`sheath the valve was positioned so that the annulus bisects
`the stent. Fluoroscopic and echocardiographic imaging was
`used to position the valve and single shot aortic root
`angiography was used to confirm the intraannular position
`below the coronary ostia. During a second brief episode of
`rapid ventricular pacing, the valve was near instantaneously
`implanted using rapid balloon inflation. Rapid pacing was
`then stopped and hemodynamic function allowed to
`recover. Repeat dilatation was indicated in the presence
`of moderate paravalvular leakage. Valve function was
`immediately assessed by using angiographic and echocar-
`diographic visualization. The transapical
`sheath was
`removed and the apex securely closed with the purse-string
`sutures. ECC was weaned, if necessary, and the cannulas
`removed and protamine administered. Intercostal blockade
`was performed using Ropivacaine. The pericardium was
`partially closed over the apex and a left lateral chest tube
`inserted. The incision was closed in a standard fashion. A
`schematic illustration of TAP-AVI is displayed in Fig. 2,
`and perioperative images are displayed in Fig. 3a—c.
`
`Postoperative device specific medical therapy consisted
`only of aspirin 100 mg daily.
`
`2.5. Statistical evaluation
`
`Results are given in a standard fashion throughout the
`manuscript. Continuous variables are expressed as mean
` SEM or as median when appropriate, and caregorical
`variables are expressed as proportions.
`
`3. Results
`
`3.1. Patient characteristics
`
`Thirty consecutive patients underwent TAP-AVI between
`February and September 2006, and all patients are included
`in this study. All patients suffered severe symptomatic aortic
`stenosis (aortic valve area < 0.9 cm2) and their preoperative
`characteristics are displayed in Table 1. Additional co-
`morbidities that were not reflected in the EuroSCORE risk
`assessment are displayed in Table 2.
`
`3.2. Perioperative results
`
`All patients were operated on using an anterolateral
`minithoracotomy. Exposure of the left ventricular apex was
`good in all patients, even in re-operations. For proper valve
`
`Table 1
`Preoperative patient characteristics
`
`Patient number (n)
`Age (years)
`Female gender (n)
`NYHA
`Body weight (kg)
`EuroSCORE (points)
`Logistic EuroSCOREa (%)
`Previous cardiac surgeryb (n)
`Cardiac index (l/min/m2)
`LVEDP (mmHg)
`AOA (cm2)
`
`30
`82  5
`21
`3.5  0.6
`70  14
`11.3  1,7
`27.1  12.2
`5
`1.8  0.4
`20  9
`0.5  0.2 (range 0.3—0.9)
`
`NYHA: New York Heart Association; LVEDP: left ventricular enddiastolic pres-
`sure; AOA: aortic valve opening area.
`a Predicted risk for mortality.
`b All re-operative patients had previous coronary bypass graft surgery with
`patent grafts.
`
`Table 2
`Presence of additional comorbidities not necessarily reflected in the
`EuroSCORE risk assessment (n = 30 total)
`
`Coronary artery disease
`Recent myocardial infarction
`Mild to moderate mitral valve incompetence
`Recent cardiac decompensation
`Previous stroke
`Pulmonary disease/COPD
`Hypertension
`Diabetes
`Leukemia
`Renal failure
`On dialysis
`
`COPD: Chronic obstructive pulmonary disease.
`
`7
`4
`6
`4
`5
`7
`23
`12
`3
`13
`3
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`Fig. 3. Stepwise illustration of transapical aortic valve implantation: (a) valve positioning at the annulus. (b) Dilated valve in situ. (c) Aortic root angiography
`displaying good valve function and patent coronary arteries.
`
`positioning, fluoroscopic and angiographic visualization was
`most reliable. Transesophageal echocardiography was useful
`for valvular morphologic and hemodynamic assessment, but
`was not adequate for precise valve positioning during
`deployment due to shadowing caused by the crimped steel
`stent and balloon catheter. Rapid ventricular pacing at 150/
`min was sufficient in all patients to unload the left ventricle
`during valve deployment. Regular cardiac rhythm was
`recaptured after cessation of pacing in all patients. Valve
`implantation was performed using ECC in 13 patients and
`without ECC support in 17 patients. Nine patients underwent
`femoral cannulation for possible ECC support, but ECC was
`subsequently not required. More recently, eight patients
`underwent surgery completely off pump with only a venous
`wire inserted in the femoral vein.
`Valve implantation was successful in 29 of 30 patients
`(96.7%). One patient with severe eccentric calcification of
`
`one of the native aortic valve cusps required early
`conversion to full sternotomy: In this patient balloon
`dilatation was more gradual rather than instantaneous.
`The valve slipped downwards due to the eccentric calcifica-
`tion, resulting in a fixed position in the left ventricular
`outflow tract and subsequent severe mitral valve incompe-
`tence. Conversion to conventional valve replacement was
`successfully performed.
`There was no neurological event and no stroke in any of
`the patients. Perioperative laboratory examination did not
`reveal any relevant increase in myocardial enzymes despite
`performing apical puncture and applying apical purse-string
`sutures. Further perioperative results and early postopera-
`tive outcomes are summarized in Table 3.
`Cardiac rhythm was stable throughout the study in all
`patients. Preoperatively, 18 patients were in sinus rhythm, 10
`in atrial fibrillation and two had a pacemaker. Postoperatively,
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`
`Table 3
`Perioperative results (n = 30)
`
`Aortic valve annulus as measured
`by intraoperative TEE (mm)
`Implanted valve size 23 mm
`Implanted valve size 26 mm
`Oversizing technique
`Contrast given (ml)
`Fluoroscopy (min)
`Additional sutures at the apex
`Requiring ECC support
`
`Median duration of intubation (h)
`Same day extubation (n)
`Median ICU stay (h)
`Median hospital stay (days)
`Mean follow-upa (days)
`
`22.8  1.5
`
`8
`22
`All patients
`79  35 (range 20—150)
`8  4.5
`8
`2
`
`6.5
`25
`20
`14
`127  63
`
`TEE: transesophageal echocardiography; ECC: extracorporeal circulation; ICU:
`intensive care unit.
`a Effective from October 27, 2006.
`
`two additional patients required pacemaker implantation, 17
`were in sinus rhythm and nine in atrial fibrillation.
`
`3.3. Morbidity and mortality
`
`In-hospital morbidity is summarized in Table 4. A total of
`seven patients had a completely uneventful postoperative
`course without any complications. Three patients (10%) died
`in-hospital, all due to non-valvular causes. One patient died on
`postoperative day (POD) 86 and one on POD 18 due to an acute
`abdomen followed by multiorgan failure. The third patient
`suffered severe biventricular myocardial failure preopera-
`tively during induction of anesthesia. Valve implantation was
`performed during resuscitation as salvage procedure. Despite
`good valve function the patient subsequently died on post-
`operative day 3 due to low cardiac output syndrome. Autopsy
`confirmed correct valve positioning and patent coronary
`arteries in all three patients who died.
`Rethoracotomy for diffuse chest wall bleeding was
`performed in one patient who was receiving ClopidogrelTM
`preoperatively. One other patient required surgical removal
`of an intrapleural hematoma several days after a thoracent-
`esis was performed. Postoperative cardiopulmonary resusci-
`tation was performed successfully in two patients due to AV
`block (1) and respiratory dysfunction.
`
`3.4. Echocardiographic results
`
`Echocardiographic results for the 29 patients who success-
`fully underwent valve implantation are shown in Table 5.
`Preoperative and early postoperative (pre-discharge) trans-
`thoracic echocardiographic measurements are displayed.
`
`Table 4
`In-hospital morbidity (n = 30)
`
`None
`Pleural effusion
`Postoperative episode of supraventricular tachyarrhythmia
`Transient hemofiltration
`Tracheostomy for weaning off ventilation
`Cardiopulmonary resuscitation a
`Pericardial effusion (medical therapy)
`Others
`
`a Both successful, no valve dysfunction on echocardiography.
`
`7
`11
`9
`4
`3
`2
`2
`14
`
`Table 5
`Echocardiographic results
`
`n = 29
`
`Vmax (m/s)
`Pmax (mmHg)
`Pmean (mmHg)
`LVPWd (mm)
`EF (%)
`Aortic incompetence
`
`Preoperative
`4.2  0.6
`76  23
`43  14
`15  4
`52  13
`Any
`Trace
`Minimal (18)
`Moderate (18—28)
`
`Postoperative a
`1.9  0.5
`15.8  8.2
`7.5  4.7
`15  3
`55  12
`14
`3
`9
`2
`
`Vmax: maximum transvalvular blood flow velocity; Pmax: maximum transvalv-
`ular pressure gradient; (simplified Bernouilli equation); Pmean: mean trans-
`valvular pressure gradient; LVPWd: left ventricular posterior wall enddiastolic
`diameter; EF: ejection fraction.
`a Transthoracic measurements prior to discharge.
`
`A small amount of aortic incompetence was diagnosed in 14
`patients prior to discharge. Incompetence was transvalvular in
`five (all mild) and paravalvular in nine of these patients,
`respectively. None of these patients had any signs of hemolysis
`or clinically or hemodynamically important insufficiency.
`
`3.5. Follow-up
`
`Patients are being followed on a routine basis at 6 months,
`1 year and annually thereafter. One patient with a porcelain
`aorta was readmitted and required re-operation on post-
`operative day 37 due to new onset severe aortic valve
`incompetence. During successful re-operation, an annuluar
`dehiscence close to the left-right coronary commissure was
`found. As of the beginning of October 2006, transapically
`implanted aortic valve prostheses have been in situ without
`further complication for a mean of 108 days (range 27—230
`days). Due to the relatively short period of experience with
`this technique, meaningful follow-up data are not yet
`available.
`
`4. Discussion
`
`Transapical aortic valve implantation (TAP-AVI) has
`become a clinical reality for selected patients at some
`specialized centers. Recently, results from seven patients
`considered to have an excessive operative risk and treated as
`compassionate use were published [10]. At present research
`groups in Dallas, Frankfurt, Vancouver, Vienna and Leipzig
`are working together on the transapical approach using the
`Cribier-Edwards prosthesis, also known as the AscendraTM
`investigators. Others will soon join these efforts. To the best
`of our knowledge the present series is the first ethically
`approved study on minimally invasive beating heart transa-
`pical aortic valve implantation (TAP-AVI). The initial results
`of this study are excellent, especially in view of the high-risk
`profile of our patient population. Thus the clinical feasibility
`of minimally invasive beating heart TAP-AVI is proven.
`
`4.1. Concept of TAP-AVI
`
`We believe the concept of transapical aortic valve
`implantation (TAP-AVI) is logical and feasible due to several
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`(a) Previous experience of uncomplicated left
`factors:
`ventricular apical deairing after open heart surgery that
`has been safely performed for decades. (b) The relatively
`easy access to the left ventricular apex via a standard
`anterolateral minithoracotomy.
`(c) The relatively short
`distance from to the left ventricular apex to the aortic
`valve, allowing for exact and direct manipulation of any
`device. (d) The antegrade direction employed when traver-
`sing the severely stenosed native valve as well as the
`antegrade introduction of the prosthesis. All these factors
`may result in the transapical procedure being the preferred
`approach when compared to the retrograde transfemoral
`arterial and transseptal femoral venous approaches that have
`been applied [7—9]. Several experimental studies have been
`performed prior to starting clinical studies, also proving the
`feasibility as well as the safety of the transapical techniques
`[4,5,11]. TAP-AVI procedure will be a valuable and promising
`technique in the future.
`
`4.2. Other approaches for transcatheter valve
`implantation/research activities
`
`There may be several other approaches for transcatheter
`heart valve implantation in the future, reflected by multiple
`research efforts in this field [11—16]. One major issue to be
`determined is the optimal stent material. Two options
`currently exist: Nitinol, a self-expanding material that is
`introduced using an application system or steel, which requires
`active balloon dilatation. At present CoreValve, a porcine
`pericardial valve mounted on a nitinol stent with transfemoral
`retrograde delivery, is being studied at several centers. Initial
`single center clinical results in 25 patients have been recently
`presented [17]. The present study compares favorably to those
`results, especially in view of a significantly higher patient risk
`profile and a lower in hospital mortality.
`
`4.3. Patient selection
`
`Patient selection is the most critical factor determining
`the outcome of any clinical study. When performing a study
`on high-risk elderly patients, selection may be even more
`important. The current study is a consecutive series including
`all patients that met the inclusion criteria during the study
`period and that were considered as high risk for conventional
`surgery. Very few moribund patients were not accepted for
`surgical treatment during this time period at our institution.
`We usually do not consider any patient with severe
`symptomatic aortic valve stenosis to be a non-surgical
`candidate. Thus the study population presented reflects the
`upper edge risk profile of patients currently operated on for
`symptomatic aortic stenosis at our institution.
`
`4.4. Clinical and hemodynamic results
`
`This is a clinical series of 30 high-risk patients with severe
`aortic valve stenosis and significant co-morbidities. The high
`surgical risk of these patients is well reflected by a logistic
`EuroSCORE predicted risk for mortality of 27.1  12.2% as
`well as by a significant number of additional morbidities as
`shown in Table 2. In view of these risks, the perioperative
`outcomes are excellent. We believe this can be attributed to
`
`the minimally invasive nature of TAP-AVI including avoidance
`of a sternotomy incision, implantation of the valves on the
`beating heart and thereby avoiding ischemia, and by avoiding
`ECC altogether in a significant proportion of patients.
`Fortunately there were no neurological events in this
`study. This is extremely encouraging as we could prove that
`the rate of neurological events is low even in patients
`undergoing aortic valvotomy in presence of calcified cusps.
`In the early postoperative period, however, there were
`some morbidities as indicated in Table 4. This is not
`unexpected, as we were treating relatively old patients
`(mean age 82 years) with substantial co-morbidities, as
`mentioned before.
`Regarding hemodynamic function, all patients had
`complete and instantaneous relief of aortic stenosis after
`valve implantation. Excellent hemodynamic function of the
`Cribier-Edwards prosthesis was documented by postopera-
`tive echocardiographic examinations, as summarized in
`Table 5. The excellent hemodynamic function can be
`attributed to the valve design with a short and, most
`importantly, relatively low-profile stent. The valve design
`minimizes valve-intrinsic obstruction, which may be present
`with conventional stented xenografts. The very low max-
`imum blood flow velocities compare very well to conven-
`tional stented or even stentless xenografts in the aortic
`position.
`Potential paravalvular leakage is the major concern when
`using transcatheter valve implantation techniques. To
`minimize this risk, we applied an oversizing technique
`whereby the implanted valve size is at least 2 mm larger than
`the native aortic valve annulus. In addition, the distribution
`of annular as well as native aortic valve cusp calcification is
`an important consideration. Patients presenting with equally
`distributed calcification will probably have a lower risk of
`suffering post-implant paravalvular leakage. In this series we
`did not observe any relevant clinical consequences for the
`patients with postoperative paravalvular leakage. In the
`future there may be additional techniques, such as self-
`sealing cuffs for example, to further minimize the risk of
`paravalvular leakage.
`
`4.5. Team approach
`
`is a new technique combining conventional
`TAP-AVI
`surgical knowledge with techniques traditionally applied in
`the catheterization laboratory, usually by cardiologists.
`Availability of a modern angiographic system is of utmost
`importance for good visualization during valve implantation
`and thus a successful outcome. A hybrid operating room is the
`optimal setting for successful implementation of a trans-
`catheter valve implantation program. In addition, good
`cooperation between all disciplines involved — cardiac
`surgeons, cardiologists and anesthesiologists — will lead to
`further establishment of these new techniques and success-
`ful treatment of high-risk patients.
`
`4.6. Minimally invasive transapical aortic valve
`implantation—a clinical reality
`
`Minimally invasive off pump transcatheter aortic valve
`implantation is a clinical reality. The most important
`
`ENDOHEART AG, EX. 2034 Page 6
`EDWARDS LIFESCIENCES CORPORATION (PETITIONER) v. ENDOHEART AG (PATENT OWNER)
`Case No.: IPR2016-00299, U.S Patent No. 8,182,530
`
`

`
`T. Walther et al. / European Journal of Cardio-thoracic Surgery 31 (2007) 9—15
`
`15
`
`difference between conventional and transcatheter aortic
`valve implantation is
`the attitude of
`surgeons and
`cardiologists towards these techniques. Open-mindedness
`together with flexibility will
`lead to further successful
`applications. Some years ago neither surgeons nor cardiol-
`ogists would have foreseen that aortic valve implantation
`would be possible on the beating heart, without ECC and
`without a sternotomy. Thus TAP-AVI has rapidly evolved into
`a truly minimally invasive procedure for the treatment of
`high-risk patients
`suffering symptomatic aortic valve
`disease.
`
`4.7. Future direction
`
`Based on these successful initial results, we believe TAP-
`AVI will be performed by more and more groups at different
`centers. However, some skepticism remains within the
`surgical and cardiological communities. Therefore prospec-
`tive randomized studies should be performed, comparing
`transapical as well as transfemoral transcatheter valve
`implantation techniques, to the gold standard of conven-
`tional aortic valve replacement surgery. Future protocols are
`being developed at present.
`
`Acknowledgment
`
`We are very grateful to Mark Dehdashtian, Teodoro
`Jimenez and Sal Marquez (all Edwards Lifesciences Irvine,
`CA, USA) for their continuous technical support when
`performing this study.
`
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