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`STRUCTURAL
`
`Comparison of Self-Expanding and
`Mechanically Expanded Transcatheter
`Aortic Valve Prostheses
`Robert P. Gooley, MD,*y Andrew H. Talman, MD,*y James D. Cameron, MD,*y Siobhan M. Lockwood, MD,*y
`Ian T. Meredith, AM, MD*y
`
`ABSTRACT
`
`OBJECTIVES The aim of this study was to determine whether transcatheter aortic valve replacement (TAVR) with the
`mechanically expanded Lotus valve (Boston Scientific, Natick Massachusetts) offers potential benefits over treatment
`with the self-expanding CoreValve (Medtronic, Minneapolis, Minnesota).
`
`BACKGROUND New-generation transcatheter aortic valve systems are emerging in clinical trials and practice with
`design features aimed at improving safety and efficacy. To date, these devices have not been compared systematically
`with current-generation devices.
`
`METHODS A total of 100 patients (83.4  4.8 years of age, 44% male, Society of Thoracic Surgeons Predicted Risk
`of Mortality score of 5.5  2.4) were assessed. Fifty consecutive patients undergoing a Lotus transcatheter aortic
`valve replacement were enrolled and compared with 50 matched patients treated with a CoreValve. An independent core
`laboratory reviewed all echocardiographic data, and an independent clinical events committee adjudicated all events.
`
`RESULTS Valve Academic Research Consortium 2–defined device success was 84% and 64% in the Lotus and CoreValve
`cohorts, respectively (p ¼ 0.02). This difference was driven by lower rates of moderate or greater aortic regurgitation
`(4% vs. 16.7%, respectively; p ¼ 0.04) and higher rates of successfully implanting a single device in the correct anatomic
`position (100% vs. 86%, respectively; p ¼ 0.06). Cardiovascular mortality rate (0% vs. 4%, respectively; p ¼ 0.32),
`major stroke rate (4% vs. 2%, respectively; p ¼ 0.56), and permanent pacemaker insertion rate (28% vs. 18%,
`respectively; p ¼ 0.23) were not different at 30 days in the Lotus and CoreValve cohorts.
`
`CONCLUSIONS In this matched comparison of high surgical risk patients undergoing transcatheter aortic valve
`replacement, the use of the Lotus device was associated with higher rates of Valve Academic Research Consortium
`2–defined device success compared with the CoreValve. This was driven by higher rates of correct anatomic positioning
`and lower incidences of moderate paraprosthetic regurgitation. The clinical significance of these differences needs to be
`tested in a large randomized, controlled trial. (J Am Coll Cardiol Intv 2015;8:962–71) © 2015 by the American College of
`Cardiology Foundation.
`
`From *MonashHeart, Monash Health, Clayton, Victoria, Australia; and the yMonash Cardiovascular Research Centre, Monash
`University, Clayton, Victoria, Australia. Dr. Gooley, Dr. Lockwood, and Prof. Meredith receive modest consulting fees from Boston
`Scientific. Prof. Meredith serves on the Strategic Advisory Boards of Boston Scientific and Medtronic. Dr. Gooley receives a
`research scholarship from the National Health and Medical Research Council of Australia. All other authors have reported that
`they have no relationships relevant to the contents of this paper to disclose.
`
`Manuscript received February 23, 2015; revised manuscript received March 20, 2015, accepted March 26, 2015.
`
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`
`Gooley et al.
`Comparison of Self-Expanding and Mechanically Expanding TAVR Devices
`
`963
`
`T ranscatheter aortic valve replacement (TAVR)
`
`has proved to be a safe and effective treatment
`for severe aortic stenosis in appropriately
`selected high and extremely high surgical risk pa-
`tients (1,2). Since its inception in 2002 (3), TAVR
`has gained wide acceptance and clinical approval in
`many countries on the basis of a rapidly growing
`body of evidence. As a result, adoption of the technol-
`ogy and implant rates have grown nearly exponen-
`tially (4,5).
`Most global TAVR experience has been obtained
`with either
`the Edwards SAPIEN or SAPIEN XT
`(Edwards Lifesciences, Irvine, California) or the Med-
`tronic CoreValve device, (Minneapolis, Minnesota);
`however, a growing number of next-generation pros-
`theses are now entering clinical trials and routine
`practice (6–9). Most of these devices incorporate novel
`features designed to reduce the modest yet impor-
`tant complications identified with current-generation
`devices. Data supporting enhanced safety and effi-
`cacy of new-generation devices, however, are modest
`and derived from single-arm studies.
`The CoreValve Revalving System (Medtronic) is a
`self-expanding device fashioned from nitinol wire.
`The distinctive frame has a flared inflow portion to
`anchor in the native annulus, a constrained midseg-
`ment to avoid coronary obstruction, and a flared
`outflow portion to improve coaxial alignment to the
`aortic flow plane. In a U.S. pivotal trial, the CoreValve
`was found to have a significantly higher survival rate
`at 1 year than surgical valve replacement in a high-
`risk cohort
`(10). These results mirror
`favorable
`safety and efficacy data from large single-center
`(11,12), national
`(13–15), and multinational
`(16)
`registries.
`The Lotus device (Boston Scientific, Natick, Mas-
`sachusetts) is a new TAVR device that uses a unique
`mechanical expansion mechanism. It is made of a
`single braided nitinol wire and 3 bovine pericardial
`leaflets. The outer surface of the lower half of the
`frame is covered with an adaptive seal, essentially
`a polymer membrane that concertinas as the device
`is expanded and,
`in doing so, occupies any small
`residual
`interstices, sealing the frame against the
`native aortoventricular interface (8,17). This has been
`reported to reduce the rate of paraprosthetic aortic
`regurgitation (PAR). The device is fully repositionable
`and resheathable, even in the completely expanded
`position, allowing for fine control and the potential
`for removal should the device position or size be
`deemed suboptimal. The Lotus device was studied
`in the REPRISE I (Repositionable Percutaneous Re-
`placement of Stenotic Aortic Valve Through Implan-
`tation of LotusÔ Valve System) (18), the REPRISE II
`
`(Repositionable Percutaneous Replacement
`of Stenotic Aortic Valve Through Implanta-
`tion of LotusÔ Valve System—Evaluation of
`Safety and Performance) (19), and REPRISE II
`Extension single-arm trials.
`Although there has been an adoption of
`new devices such as the Lotus at some cen-
`ters, to date, there have been no systematic
`head-to-head comparisons, with indepen-
`dent core laboratory assessments, of devices
`to accurately determine their relative safety
`and efficacy.
`
`METHODS
`
`A B B R E V I A T I O N S
`
`A N D A C R O N Y M S
`
`EOA = effective orifice area
`
`MDCT = multidetector
`computed tomography
`
`PAR = paraprosthetic aortic
`regurgitation
`
`TAVR = transcatheter aortic
`valve replacement
`
`TTE = transthoracic
`echocardiography
`
`VARC2 = Valve Academic
`Research Consortium 2
`
`STUDY POPULATION. A total of 100 patients (mean
`age, 83.4  4.8 years, 44% male) with symptomatic
`severe aortic stenosis were included in this study.
`Fifty consecutive and prospectively enrolled patients
`receiving a Lotus transcatheter device were compared
`with 50 matched patients who had undergone TAVR
`with the CoreValve device during the same period.
`All patients were treated at a single Australian
`center. All patients were deemed to be at high or
`extremely high surgical risk because of an increased
`Society of Thoracic Surgeons Predicted Risk of
`Mortality score (higher than 8) and/or the collective
`opinion of
`the institution’s Heart Team after a
`comprehensive history, examination, and frailty
`assessment (dominant hand-grip strength, 5-m gait
`speed, and serum albumin). Patients were eligible
`for inclusion if they had severe aortic stenosis based
`on echocardiographic
`criteria
`(mean transaortic
`gradient $40 mm Hg or aortic velocity $4 m/s and an
`aortic valve area #1 cm2 or indexed aortic valve
`area #0.7 cm2/m2) and reported symptoms attribut-
`able to severe aortic stenosis (Table 1).
`All patients were assessed in a systematic and
`standardized manner beginning with their atten-
`dance and clinical evaluation at our Structural Heart
`Disease Clinic. All patients underwent multidetector
`computed tomography (MDCT), transthoracic echo-
`cardiography (TTE), invasive angiography, and right
`heart catheterization before inclusion. Only patients
`who had MDCT annular sizing that allowed for
`treatment with either device (according to the
`respective instructions for use) and were treated
`via the femoral access route were considered suitable
`for
`the study. Patients were matched on age,
`sex, Society of Thoracic Surgeons score, and frailty
`indexes.
`
`PRE-PROCEDURAL MDCT ASSESSMENT. All patients
`underwent prospectively electrocardiography-gated,
`
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`Gooley et al.
`Comparison of Self-Expanding and Mechanically Expanding TAVR Devices
`
`J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 8 , N O . 7 , 2 0 1 5
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`J U N E 2 0 1 5 : 9 6 2 – 7 1
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`TABLE 1
`
`Inclusion and Exclusion Criteria
`
`Inclusion criteria
`1. Severe aortic stenosis
`Mean aortic gradient $40 mm Hg or aortic velocity $4 m/s
`AVA #1 cm2 or indexed AVA #0.7 cm2/m2
`2. Symptoms consistent with aortic stenosis
`NYHA functional class II–IV dyspnea
`Exertional angina
`Exertional syncope or pre-syncope
`3. High or extreme surgical risk
`STS PROM $8 or heart team agreement that patient
`is at high surgical risk
`4. Suitable aortic root anatomy for placement of either a Lotus*
`or CoreValve† prosthesis
`MDCT-derived annular dimension $19 mm and #27 mm
`5. Suitable peripheral vasculature for passage of an
`18-/20-F sheath
`Exclusion criteria
`1. Inability to consent
`
`*Boston Scientific, Natick, Massachusetts. †Medtronic, Minneapolis, Minnesota.
`AVA ¼ aortic valve area; NYHA ¼ New York Heart Association; STS PROM ¼
`Society of Thoracic Surgeons Predicted Risk of Mortality; MDCT ¼ multidetector
`computed tomography.
`
`320-MDCT imaging of the aortic root at baseline. All
`scans were performed on a Toshiba Aquilion One
`320-detector row scanner (Toshiba Medical Systems,
`Otawara, Japan). No heart rate control was used.
`Collimation was individualized to achieve a z-axis
`that encompassed the entire aortic
`root. Slice
`thickness was 0.5 mm. Gantry rotation speed was
`275 ms per rotation, tube voltage was 100 to 120
`kV, and the tube current was individualized to
`body habitus. Intravenous contrast (Omnipaque 350,
`GE Healthcare, Little Chalfont, Buckinghamshire,
`United Kingdom) was administered via an 18-gauge
`antecubital vein as a 70-ml bolus followed by a
`50-ml saline solution bolus at a rate of 6 ml/s.
`Systolic phase images (20) were acquired after
`manual triggering by monitoring for contrast den-
`sity in the descending aorta to ensure adequate
`contrast opacification.
`All MDCT scans were analyzed by an experienced
`computed tomography cardiologist using the 3Mensio
`valve analysis program (3Mensio Medical Imaging,
`Bilthoven, the Netherlands). The annular plane was
`identified as the short axis through the nadir of
`each coronary cusp, and diameters, perimeter, and
`area were measured. The eccentricity was calculated
`using the eccentricity index (eccentricity index ¼ 1
`minimal diameter/maximal diameter). Further mea-
`surements were taken in the left ventricular outflow
`tract 4 mm below the annular plane, sinus of Val-
`salva, ascending aorta, and height of the coronary
`arteries.
`
`Sizing of TAVR devices was guided by the
`3-dimensional MDCT measurements and strictly con-
`formed with the respective manufacturer’s
`in-
`structions for use. The degree of oversizing for each
`device was calculated based on annular plane perim-
`eter (perimeter oversizing ¼ (device perimeter
`annular perimeter)/annular perimeter  100) and
`annular plane area (area oversizing ¼ (device area
`annular area)/annular area  100).
`PRE-PROCEDURAL TTE ASSESSMENT. TTE was per-
`formed using an iE33 machine (Philips, Best, the
`Netherlands) before enrollment. All
`scans were
`assessed by an experienced echocardiologist with
`severity of aortic stenosis graded based on European
`Association of Echocardiography and American Soci-
`ety of Echocardiography joint guidelines (21). An
`independent echocardiography core laboratory sub-
`sequently reviewed these studies with these results
`used for study analysis.
`
`PRE-PROCEDURAL
`INVASIVE
`ANGIOGRAPHIC
`ASSESSMENT. All patients underwent invasive coro-
`nary and peripheral angiography to confirm access
`site suitability and to identify significant coronary
`artery disease warranting treatment before TAVR.
`Treatment of concomitant coronary artery disease
`was at the discretion of the implanting cardiologist.
`Right heart catheterization was performed to ex-
`clude significant primary pulmonary hypertension
`and corroborate ultrasound-based hemodynamic
`measurements.
`
`TREATMENT. All TAVR procedures were performed
`in the cardiac catheterization laboratory with patients
`under general anesthesia or conscious sedation.
`Three experienced TAVR cardiologists performed all
`procedures with 2 operators present at each proce-
`dure. The femoral artery was used for device access in
`all cases with an 18-F Cook sheath (Cook Medical,
`Bloomington, Indiana) used for all CoreValve pro-
`cedures, whereas an 18-F Lotus Introducer (Boston
`Scientific) was used for 23-mm Lotus cases and 20-F
`Lotus Introducer for those receiving a 27-mm Lotus
`valve. The femoral access site was managed uni-
`formly in all patients. The designated femoral access
`was routinely “pre-closed” with either a single Pros-
`tar or 2 Proglide devices (Abbott Vascular, Abbott
`Park,
`Illinois), and final access site closure was
`performed using a crossover balloon occlusion tech-
`nique (22).
`Balloon valvuloplasty was performed in all pa-
`tients under
`rapid ventricular pacing to enable
`maximal balloon stability. Valvuloplasty balloons
`were sized so as to not exceed the minimal diameter
`of the left ventricular outflow tract.
`
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`Gooley et al.
`Comparison of Self-Expanding and Mechanically Expanding TAVR Devices
`
`965
`
`Deployment of the respective devices was per-
`formed in strict accordance with manufacturer’s
`guidelines and current best practices (8,16,17).
`Aortic regurgitation was assessed by aortography
`after final deployment using 20 ml of
`iodinated
`contrast delivered at 20 ml/s and 800 psi by auto-
`mated injector through a 5-F pigtail catheter posi-
`tioned above the prosthesis leaflets. Moderate or
`greater aortic regurgitation, identified at the time of
`deployment by either
`imaging modality and/or
`haemodynamic assessment, was treated by post-
`dilation in the CoreValve cohort and repositioning
`in the Lotus cohort. Aortography was repeated after
`final device manipulation to reassess final degree
`of PAR and to exclude the need for
`further
`manipulation.
`
`INDEPENDENT CORE LABORATORY ECHOCARDIO-
`GRAPHIC ASSESSMENT. All patients had a TTE study
`performed on day 7 to 10 or on the day of discharge,
`if this occurred earlier, and again at 30 days after
`TAVR. The independent core laboratory assessed
`prosthesis function, degree, and location of aortic
`regurgitation, severity of mitral regurgitation,
`left
`ventricular function, and pulmonary artery pressure.
`Prosthetic regurgitation was assessed in accordance
`with Valve Academic Research Consortium 2 (VARC2)
`(23) recommendations.
`
`CLINICAL REVIEW. A study investigator reviewed
`patients at the time of each echocardiogram, and a
`detailed history was taken and an examination per-
`formed. New York Heart Association functional class
`was determined on the basis of the patient’s self-
`reporting of symptoms.
`
`ENDPOINTS. The primary endpoint of the trial was
`VARC2-defined device success (23). This is a com-
`posite endpoint that includes the absence of proce-
`dural mortality, correct positioning of a single
`prosthesis in the correct anatomic position, and
`intended prosthesis function (no prosthesis-patient
`mismatch, mean aortic valve gradient <20 mm Hg,
`peak velocity <3 m/s, and no moderate or greater
`aortic regurgitation on TTE at time of discharge).
`Prosthesis function was determined by core labora-
`tory assessment of the discharge echocardiogram.
`Secondary endpoints were all-cause and cardio-
`vascular mortality at 30 days, minor and major
`bleeding, minor and major vascular
`injury, new
`pacemaker insertion, and disabling and nondisabling
`stroke.
`
`STATISTICAL ANALYSIS. Categorical variables were
`expressed as frequencies and percentages, whereas
`continuous variables were expressed as means and
`
`SDs. Categorical variables were compared using a chi-
`square test, whereas nonparametric continuous vari-
`ables were compared using the Mann-Whitney or
`independent-sample t test. A 2-sided p value <0.05
`was considered statistically significant. Statistical
`analysis was performed using IBM SPSS Statistics
`version 22.0 (IBM Corporation, Armonk, New York).
`
`RESULTS
`
`BASELINE CHARACTERISTICS. The baseline de-
`mographic and clinical characteristics are described
`in Table 2. In brief, there were no clinically significant
`differences between the 2 study populations other
`than a higher proportion of patients with NYHA
`functional class IV symptoms in the Lotus cohort and
`more patients with pre-existing atrial fibrillation in
`the CoreValve cohort. Baseline Society of Thoracic
`Surgeon scores, Charlson Comorbidity Index, and
`frailty index were similar.
`Baseline echocardiographic parameters of aortic
`stenosis severity were not significantly different
`between the Lotus and CoreValve cohorts, with
`average mean gradients of 44.9  12.9 mm Hg and
`47.3  12.5 mm Hg, respectively (p ¼ 0.34). There
`
`TABLE 2 Baseline Characteristics
`
`Age, yrs
`Male
`Height, cm
`Weight, kg
`Body mass index, kg/m2
`STS PROM, %
`STS M&M
`Charlson Comorbidity Index
`Hand grip strength
`5-m gait speed
`Serum albumin
`NYHA functional class
`II
`III
`IV
`Creatinine, mmol/l
`Type 2 diabetes mellitus
`Existing coronary artery disease
`Previous coronary bypass surgery
`Peripheral vascular disease
`Chronic pulmonary disease
`Atrial fibrillation
`Existing permanent pacemaker
`
`Lotus*
`(n ¼ 50)
`84.0  5.2
`18 (36)
`161.4  10.0
`72.9  17.2
`28.1  6.6
`5.80  2.40
`26.21  7.44
`2.7  2.0
`16.6  7.0
`9.9  3.0
`33.9  5.6
`
`7 (14)
`36 (72)
`7 (14)
`97.6  57.3
`10 (20)
`29 (58)
`7 (14)
`3 (6)
`14 (28)
`5 (10)
`5 (10)
`
`CoreValve†
`(n ¼ 50)
`82.7  4.5
`26 (52)
`163.8  8.9
`73.9  14.6
`27.5  4.8
`5.21  2.47
`23.97  6.08
`2.6  1.4
`16.0  6.3
`9.5  2.9
`32.1  5.8
`
`13 (26)
`36 (72)
`1 (2)
`103.2  28.4
`12 (24)
`33 (66)
`15 (30)
`6 (12)
`16 (32)
`14 (28)
`7 (14)
`
`p Value
`
`0.19
`0.11
`0.20
`0.75
`0.62
`0.23
`0.10
`0.65
`0.73
`0.55
`0.12
`
`0.05
`0.54
`0.63
`0.41
`0.05
`0.30
`0.66
`0.02
`0.54
`
`Values are mean  SD or n (%). *Boston Scientific, Natick, Massachusetts. †Medtronic,
`Minneapolis, Minnesota.
`STS M&M ¼ Society of Thoracic Surgeons Morbidity and Mortality; other abbreviations
`as in Table 1.
`
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`Comparison of Self-Expanding and Mechanically Expanding TAVR Devices
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`J U N E 2 0 1 5 : 9 6 2 – 7 1
`
`were no differences in the proportion of patients
`with mild, moderate, or severe aortic regurgitation
`at baseline. MDCT annular dimensions, whether
`diameter, perimeter, or perimeter-derived metrics,
`were well matched. The basal plane was slightly
`more eccentric among the CoreValve cohort (eccen-
`tricity index: 0.20  0.06 vs. 0.23  0.06, p ¼ 0.02).
`Left ventricular outflow tract, sinus dimensions, and
`height of the coronary arteries above the basal plane
`were similar. Full baseline anatomic dimensions are
`shown in Table 3.
`
`PROCEDURAL DETAILS. Twenty-six patients (52%)
`in the Lotus cohort were treated with the smaller
`
`TABLE 3 Pre-procedural Echocardiographic and Computed Tomographic
`Imaging Assessment
`
`Lotus*
`(n ¼ 50)
`
`CoreValve†
`(n ¼ 50)
`
`p Value
`
`Transthoracic echocardiography
`Mean gradient
`AVA
`AVA indexed
`Dimensionless index
`Pulmonary artery pressure
`Left ventricular ejection fraction
`Mitral regurgitation
`None/trivial
`Mild
`Moderate
`Tricuspid regurgitation
`None/trivial
`Mild
`Moderate
`Moderate/severe
`Severe
`Aortic regurgitation
`None/trivial
`Mild
`Moderate
`Multidetector computed tomography
`Basal plane
`Minimal diameter
`Maximal diameter
`Eccentricity index
`Perimeter
`Area
`Left ventricular outflow tract
`Minimal diameter
`Maximal diameter
`Eccentricity index
`Perimeter
`Area
`Sinus of Valsalva
`Area
`
`44.9  12.9
`0.70  0.17
`0.41  0.10
`0.23  0.05
`41.3  11.4
`56.4  9.1
`
`47.3  12.5
`0.67  0.16
`0.39  0.07
`0.22  0.05
`39.1  9.8
`54.9  9.2
`
`29 (58)
`14 (28)
`7 (14)
`
`22 (44)
`23 (46)
`5 (10)
`0
`0
`
`21 (42)
`23 (46)
`6 (12)
`
`25 (50)
`25 (50)
`0
`
`30 (60)
`17 (34)
`2 (4)
`0
`1 (2)
`
`20 (40)
`28 (56)
`2 (4)
`
`21.2  1.9
`26.5  2.1
`0.20  0.06
`75.6  5.5
`435.7  63.4
`
`19.2  2.6
`27.4  2.7
`0.30  0.09
`74.6  6.8
`405.8  80.5
`
`21.0  2.0
`27.3  2.2
`0.23  0.06
`76.5  5.8
`447.1  68.9
`
`19.5  2.4
`27.7  2.8
`0.30  0.07
`75.8  6.8
`424.9  77.3
`
`776.8  122.2
`
`831.3  136.2
`
`Values are mean  SD or n (%). *Boston Scientific, Natick, Massachusetts. †Medtronic,
`Minneapolis, Minnesota.
`AVA ¼ aortic valve area.
`
`0.34
`0.35
`0.41
`0.39
`0.34
`0.51
`
`0.01
`
`0.22
`
`0.28
`
`0.68
`0.09
`0.02
`0.42
`0.40
`
`0.59
`0.54
`0.99
`0.36
`0.23
`
`0.04
`
`Lotus device (23 mm), whereas 22 patients (44%) in
`the CoreValve group received the smaller CoreValve
`prosthesis (26 mm) (p < 0.001). There was greater
`perimeter oversizing (3.6  5.7% vs. 14.0  6.2%, p <
`0.001) and area oversizing (13.0  12.3% vs. 36.6 
`15.4%, p < 0.001) in the CoreValve cohort. All patients
`left the catheterization laboratory with a functioning
`TAVR prosthesis. There were no differences in pro-
`cedure duration (Table 4).
`The primary outcome measure of VARC2-defined
`device success was achieved in 84% of the Lotus
`cohort and 64% of the CoreValve cohort (p ¼ 0.02).
`The components of
`this outcome measure were
`the absence of procedural mortality (100% vs. 96%;
`p ¼ 0.15), correct positioning of a single prosthesis
`(100% vs. 86%; p ¼ 0.06), mean gradient across the
`prosthesis <20 mm Hg (96% vs. 100%; p ¼ 0.16),
`absence of prosthesis-patient mismatch (92% vs.
`86%; p ¼ 0.68), and no more than mild aortic regur-
`gitation (96% vs. 83.3%; p ¼ 0.04) in the Lotus and
`CoreValve cohorts, respectively (Figure 1).
`All-cause death was 0% in the Lotus cohort and 4%
`in the CoreValve cohort at 7 days. At 7 days, 1 death
`in the CoreValve cohort was due to ischemic colitis
`after a partially deployed prosthesis was retrieved
`through the aorta, whereas the other death was due
`to progressive congestive cardiac failure in the setting
`of severe PAR that was refractory to post-dilation.
`There was 1 additional death in the Lotus cohort at
`30 days due to a hemorrhagic stroke, and 1 additional
`death in the CoreValve cohort due to pneumonia and
`respiratory failure.
`There was no significant difference in the rates of
`acute kidney injury, minor or major vascular injury,
`disabling or nondisabling stroke, or periprocedural
`myocardial
`infarction. The rate of new pacemaker
`insertion was greater in the Lotus cohort (28% vs.
`18%), although not statistically different (p ¼ 0.23)
`(Figure 2).
`
`CORE LABORATORY DISCHARGE ASSESSMENT. The
`mean transprosthetic gradients were 12.4  4.2 mm Hg
`and 8.5  2.9 mm Hg (p < 0.001) for the Lotus and
`CoreValve cohorts, respectively. The mean effective
`orifice areas (EOAs) were similar in both cohorts
`(1.6  0.3 cm2 vs. 1.7  0.4 cm2, p ¼ 0.07). There were
`no differences in the severity of mitral regurgita-
`tion, pulmonary artery pressure, or left ventricular
`function (Table 5).
`Core laboratory–adjudicated PAR was mild in
`14% and 56.2% (p < 0.001) and moderate in 4%
`and 16.7% (p ¼ 0.04) of the Lotus and CoreValve
`cohorts,
`respectively. Although 1 patient
`in the
`CoreValve cohort died of complications of severe
`
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`Gooley et al.
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`
`967
`
`there
`PAR before the discharge TTE time point,
`were no further cases of severe PAR in those
`patients alive at 7 days.
`
`CORE LABORATORY 30-DAY ASSESSMENT. There
`was no deterioration in valve function as assessed by
`TTE at 30 days by mean transprosthetic gradient or
`EOA. The mean transprosthetic gradient remained
`significantly higher in the Lotus cohort than the
`CoreValve cohort (12.6  6.5 mm Hg and 8.2  2.6
`mm Hg, respectively; p < 0.001), with no difference in
`the prosthesis EOA (1.7  0.4 cm2 vs. 1.8  0.4 cm2,
`respectively; p ¼ 0.17).
`Moderate PAR occurred in 0% and 10.6% (p ¼ 0.02)
`of patients in the Lotus and CoreValve cohorts,
`respectively, with no cases of severe PAR at 30 days.
`The percentage of patients with mild AR was similar
`to that at discharge: 14.3% and 66% (p < 0.001),
`respectively (Table 5).
`
`FUNCTIONAL ASSESSMENT. There was a significant
`improvement in New York Heart Association score in
`both cohorts with 79.2% of patients in the Lotus
`group and 82.9% in the CoreValve group, improving
`by 1 class or more (Figure 3).
`
`DISCUSSION
`
`There is a substantial body of evidence supporting
`the efficacy and safety of TAVR as an alternate
`treatment to surgical valve replacement in high-risk
`patients (1,10) and its superiority to medical therapy
`in patients denied surgery due to extreme risk (2).
`Despite improvements in patient selection, the utility
`of 3-dimensional computed tomography image-based
`sizing algorithms and deployment
`techniques, a
`number of limitations remain with the current tech-
`nologies. These include vascular access complica-
`tions (24,25), need for permanent pacemaker after
`implantation (26,27), PAR (28), and stroke (29,30).
`Although second-generation devices, designed to
`address some of these limitations, are emerging in
`both clinical trials and clinical practice, the evidence
`supporting their safety and efficacy is limited. This
`study was designed to systematically compare a
`widely accepted and well-studied current-generation
`device,
`the CoreValve, with an emerging new-
`generation device, the Lotus valve.
`In this nonrandomized, single-center study, we
`observed that both the Lotus and CoreValve devices
`were associated with high rates of procedural suc-
`cess, although the VARC2-defined primary compos-
`ite outcome of device success was higher in the
`Lotus cohort. Device success was 84% and 64% in
`the Lotus and CoreValve arms, respectively, driven
`
`TABLE 4 Procedural Characteristics
`
`Lotus* (n ¼ 50)
`
`CoreValve† (n ¼ 50)
`
`Device size
`Small (23-mm Lotus, 26-mm CoreValve)
`Large (27-mm Lotus, 29-mm CoreValve)
`Sheath size, Fr
`18
`20
`Prosthesis oversizing
`Perimeter
`Area
`No. of devices used
`Post-dilation
`Procedure duration, min
`
`26 (52)
`24 (48)
`
`26 (52)
`24 (48)
`
`3.6  5.7
`14.0  6.2
`1.12  0.32
`0 (0)
`118.0  39.2
`
`22 (44)
`28 (56)
`
`50 (100)
`0 (0)
`
`13.0  12.3
`36.6  15.4
`1.14  0.40
`13 (26)
`114.2  35.8
`
`*Boston Scientific, Natick, Massachusetts. †Medtronic, Minneapolis, Minnesota.
`
`p Value
`
`<0.001
`
`<0.001
`
`<0.001
`<0.001
`0.79
`<0.001
`0.62
`
`by higher rates of correct positioning of a single
`device and lower rates of moderate PAR in the
`Lotus group. Importantly, the rates of procedural
`mortality and transprosthesis gradient greater than
`20 mm Hg and prosthesis patient mismatch were
`not different.
`It could be argued that the difference we observed
`was due to a lower than expected VARC2 device
`success
`rate in the CoreValve group; however,
`the rate was comparable to that observed in the
`CoreValve arm of
`the CHOICE trial
`(Comparison
`of balloon-expandable vs. self-expandable valves
`in patients undergoing transcatheter aortic valve
`replacement) —77.5% (31)—if the same VARC defini-
`tion is used. The CHOICE trial used the first VARC
`
`F I G U R E 1 Device Success and Composites
`
`Primary outcome measure of Valve Academic Research Consortium 2–defined device
`success and its composites. AR ¼ aortic regurgitation.
`
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`Comparison of Self-Expanding and Mechanically Expanding TAVR Devices
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`J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S V O L . 8 , N O . 7 , 2 0 1 5
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`J U N E 2 0 1 5 : 9 6 2 – 7 1
`
`F I G U R E 2 Secondary Outcome Measures
`
`Comparison of Valve Academic Research Consortium 2 defined outcome measures between the valve types. MI ¼ myocardial infarction; PPM ¼
`permanent pacemaker.
`
`definition of device success, which, unlike VARC2,
`does not
`include prosthesis-patient mismatch in
`the composite endpoint.
`If the prosthesis-patient
`mismatch is not included in the composite, the rates of
`
`device success in our study are 92% and 74% in the
`Lotus and CoreValve cohorts, respectively. Moreover,
`the rate of moderate PAR observed in this study
`was comparable, if not lower, than that observed in
`
`TABLE 5 Core Laboratory–Adjudicated Echocardiographic Assessment
`
`Paraprosthetic aortic regurgitation
`None/trivial
`Mild
`Moderate
`Moderate/severe
`Severe
`Valvular aortic regurgitation
`None/trivial
`Mild
`Moderate
`Moderate/severe
`Severe
`Mean transprosthetic gradient
`Effective orifice area
`Pulmonary artery pressure
`Left ventricular ejection fraction
`Mitral regurgitation
`None/trivial
`Mild
`Moderate
`Moderate/severe
`Severe
`
`Lotus*
`(n ¼ 50)
`
`41 (82)
`7 (14)
`2 (4)
`0
`0
`
`46 (92)
`3 (6)
`1 (2)
`0
`0
`12.4  4.2
`1.6  0.3
`41.4  10.8
`55.3  10.1
`
`25 (50)
`22 (44)
`3 (6)
`0
`0
`
`Discharge
`
`CoreValve†
`(n ¼ 48)
`
`13 (27.1)
`27 (56.2)
`8 (16.7)
`0
`0
`
`44 (91.7)
`4 (8.3)
`0
`0
`0
`8.5  2.9
`1.7  0.4
`34.8  8.9
`54.5  8.7
`
`16 (33.3)
`29 (60.4)
`3 (6.3)
`0
`0
`
`p Value
`
`<0.001
`
`<0.001
`
`0.04
`
`0.95
`0.65
`0.33
`
`<0.001
`0.07
`0.03
`0.70
`
`0.24
`
`Lotus
`(n ¼ 49)
`
`42 (85.7)
`7 (14.3)
`0
`0
`0
`
`44 (89.8)
`5 (10.2)
`0
`0
`0
`12.6  6.5
`1.7  0.4
`40.4  10.1
`56.0  8.9
`
`27 (55.1)
`18 (36.7)
`4 (8.2)
`0
`0
`
`1 Month
`
`CoreValve
`(n ¼ 47)
`
`11 (23.4)
`31 (66)
`5 (10.6)
`0
`0
`
`45 (95.7)
`2 (4.3)
`0
`0
`0
`8.2  2.6
`1.8  0.4
`37.0  8.8
`55.3  6.0
`
`20 (42.6)
`22 (46.8)
`5 (10.6)
`0
`0
`
`p Value
`
`<0.001
`
`<0.001
`
`0.02
`
`0.26
`0.26
`
`<0.001
`0.17
`0.11
`0.68
`
`0.68
`
`Values are n (%) or mean  SD. *Boston Scientific, Natick, Massachusetts. †Medtronic, Minneapolis, Minnesota.
`
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`
`J U N E 2 0 1 5 : 9 6 2 – 7 1
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`Gooley et al.
`Comparison of Self-Expanding and Mechanically Expanding TAVR Devices
`
`969
`
`other core laboratory–adjudicated trials (10,16). The
`rate of post-dilation in the CoreValve cohort (26%)
`was also comparable to the rate reported in the
`CoreValve United States Investigational Device Ex-
`emption trial (20.3%) (10). Importantly, the apparent
`difference in device success in the current study was
`not reflected in differences in mortality nor clinical
`efficacy to 30 days.
`Significant PAR after TAVR deployment has been
`shown to correlate with increased morbidity and
`mortality (32,33). Factors contributing to regurgita-
`tion include baseline annular eccentricity (34), the
`depth of device implantation (35), and the degree of
`prosthesis oversizing (36), whereas the degree of
`calcification has been an inconsistent predictor in
`various studies (37–39). In this study, the native basal
`plane was slightly more eccentric in the CoreValve
`cohort, although whether this contributed to the
`device success differences is unclear. The degree
`of prosthesis oversizing was greater in the Core-
`Valve cohort, although this reflected differences in
`the manufacturer sizing recommendations for the 2
`devices.
`the Lotus valve may
`features of
`The novel
`potentially explain the differences observed in de-
`vice success. The Lotus is totally repositionable,
`even when fully expanded in the final position by
`virtue of its deployment and coupling mechanism.
`This enables detailed interrogation of the device
`function, degree of PAR, and device stability before
`uncoupling and release. In addition, the presence of
`an adaptive seal around the outer aspect of the
`lower valve frame appears to reduce PAR by occu-
`pying residual
`interstices between the frame and
`native annulus (17–19). Placement of the CoreValve,
`on the other hand, relies on accurate initial posi-
`tioning and oversizing of
`the device to increase
`device/annular interaction.
`A nonsignificant reduction in the degree of PAR
`was noted between the discharge and 30-day time
`points.
`In the CoreValve cohort, 3 patients with
`moderate PAR at discharge had only mild PAR at
`30 days. Similarly, 2 patients in the Lotus cohort
`had a reduction from moderate to mild PAR.
`Detailed interpretatio