Journal of the American College of Cardiology
`© 2005 by the American College of Cardiology Foundation
`Published by Elsevier Inc.
`
`Vol. 46, No. 2, 2005
`ISSN 0735-1097/05/$30.00
`doi:10.1016/j.jacc.2005.04.028
`
`Direct-Access Valve Replacement
`A Novel Approach for Off-Pump Valve Implantation Using Valved Stents
`Christoph H. Huber, MD,* Lawrence H. Cohn, MD,* Ludwig K. von Segesser, MD†
`Boston, Massachusetts; and Lausanne, Switzerland
`OBJECTIVES
`
`METHODS
`
`RESULTS
`
`This study validates the off-pump antegrade transventricular route for ultrasound-guided
`direct-access aortic valved stent implantation.
`BACKGROUND Direct-access aortic valved stent implantation offers numerous advantages over the remote-
`access percutaneous approach and may one day provide an alternative to surgical aortic valve
`replacement.
`Valved stents were implanted off-pump in 12 pigs (68.5.0 ⫾ 7.3 kg) via direct-access
`transapical approach using a left-sided mini-thoracotomy and continuous ultrasonic and
`fluoroscopic guidance. Acute valved stent function was studied with intravascular and
`intracardiac ultrasound. All valved stents were tested in vitro before insertion. Macroscopic
`analysis was performed at necropsy.
`In 8 of 12 pigs, valved stents were delivered to the target site over the native aortic valve
`leaflets without interference of coronary blood flow and with good acute valve function. Two
`valved stents were deployed and supra-annularly occluded the coronary orifice, leading to fatal
`outcome. Two valved stents dislodged into the left ventricle, one because of size mismatch
`and one that failed to unfold correctly.
`CONCLUSIONS Twelve pigs underwent deployment of a valved stent in the aortic position. Six valves observed
`for an average 4.5-h period showed satisfactory postimplantation valve function.
`(J Am Coll
`Cardiol 2005;46:366–70) © 2005 by the American College of Cardiology Foundation
`
`The clinical feasibility of percutaneous off-pump implanta-
`tion of valved stents in the right and left heart has been
`demonstrated (1). The remote access technique, however, is
`not suited to off-pump surgical aortic valve replacement
`(AVR) because the diseased aortic valve cannot removed by
`this route, and it is preferable to remove heavily calcified
`native leaflets before implanting valved stents. More than a
`decade has passed since Andersen (2) published the princi-
`ple of valved stent implantation for transluminal aortic
`placement. Yet introducing valved stents into the aorta
`remains a major experimental challenge without consensus
`as to design, expansion method, access, direction of delivery,
`or optimal deployment and positioning. We present a new
`concept for valved stent design and implantation using a
`left-sided mini-thoracotomy and direct-access–transapical
`approach, with the goal of developing an off-pump surgical
`AVR technique that might one day substitute for on-pump
`AVR.
`
`PATIENTS AND METHODS
`
`Valved stent design and in vitro testing. The valved stent
`custom designed for this study (Fig. 1) is based on a
`previously described prototype (3). The outer scaffold is
`constructed of three linked nitinol Z-stents that form a
`cylindrical structure with minimal surface coverage. The
`self-expanding characteristics of this valved stent eliminate
`the need for balloon expansion. A low-profile tissue valve is
`
`From the *Division of Cardiac Surgery, Brigham and Women’s Hospital, Harvard
`Medical School, Boston, Massachusetts; and the †Service de Chirurgie Cardiovas-
`culaire, Centre Hospitalier Universitaire Vaudois, CHUV, Lausanne, Switzerland.
`Manuscript received November 14, 2004; revised manuscript received March 25,
`2005, accepted April 5, 2005.
`
`sutured into the stent scaffold. Before implantation in vivo,
`all valved stents undergo static and dynamic (30 min)
`performance testing inside a pulsatile hydrodynamic mock
`loop circuit equipped with a high-fidelity tip-mounted
`Millar pressure transducer. Acute valve function is moni-
`tored in vivo with real-time intravascular ultrasound (IVUS)
`(12.5 MHz, 6-F) (Clearview, Boston Scientific Corpora-
`tion, Sunnyvale, California). Criteria determining suitability
`for implantation include transvalvular gradient ⬍8 mm Hg
`and regurgitation value ⱕ1°.
`Animal studies. Direct-access valved stent implantation
`was performed in 12 pigs (68.5.0 ⫾ 7.3 kg). All animals
`received humane care in compliance with the “Principles of
`Laboratory Animals” formulated by the National Society of
`Medical Research and the “Guide for the Care and Use of
`Laboratory Animals” prepared by the Institute of Labora-
`tory Animal Resources and published by the National
`Institutes of Health. All data are expressed as mean ⫾ SD.
`Direct-access implantation technique. The jugular veins
`and carotid arteries are mobilized and animals fully
`equipped for complete invasive monitoring. An 11-F intro-
`ducer (B-Braun, Medical Inc., Bethlehem, Pennsylvania) is
`inserted into the right femoral vein to provide intracardiac
`ultrasound (AcuNav) access.
`A 5- to 10-cm incision is made. The sixth intercostal
`space is entered. A xylocaine (1.5 mg/kg) drip is started to
`minimize arrhythmias. Two purse-string sutures (Prolene
`4-0) are placed on the left ventricular (LV) apex using the
`native pericardial sac for reinforcement. After hepariniza-
`tion (300 IU/kg), the 10-F AcuNav probe (Sequoia, oper-
`ating frequencies 4.0 to 10.0 MHz, 90 cm insertion length,
`Acuson Corporation, Mountain View, California) is in-
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`JACC Vol. 46, No. 2, 2005
`July 19, 2005:366–70
`
`Huber et al.
`Direct-Access Percutaneous Valve Replacement
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`
`Abbreviations and Acronyms
`AcuNav⫽ intracardiac ultrasound
`AVR ⫽ aortic valve replacement
`CBF ⫽ coronary blood flow
`IVUS ⫽ intravascular ultrasound
`LCA ⫽ left coronary artery
`⫽ left ventricle/ventricular
`LV
`RCA ⫽ right coronary artery
`RCSSI ⫽ residual coronary sinus stent index
`
`serted into the right atrium (Fig. 2). Predeployment mea-
`surements of the aortic valve, root, and coronary ostia
`configuration are made with intracardiac ultrasound to avoid
`postdeployment interference caused by the echo-dense stent
`struts, a major disadvantage of transesophageal echocardi-
`ography.
`LV valved stent implantation. The implant is hand-
`crimped to the delivery device (Fig. 3). The LV apex is
`punctured and a guide wire is inserted under fluoroscopic
`guidance. An 8-F introducer (Arrows, Reading, Pennsylva-
`nia) is advanced over the guide wire, which is placed
`through the aortic valve into the descending aorta. Catheter
`location is confirmed by AcuNav. The monorail wire-
`guided disposable IVUS 6-F catheter transducer (Sonicath
`Ultra 6, 12.5MHz Imaging Catheter, Medi-tech, Water-
`town, Massachusetts) is advanced for aortic road mapping.
`The location of the IVUS probe is monitored with AcuNav
`and fluoroscopy for target site identification. Three to four
`radiopaque markers are placed on the skin to provide
`additional fluoroscopic reference points at the level of the
`aortic annulus, end of the native leaflet in systole, sinotu-
`bular junction, and beginning of the brachiocephalic trunk.
`The fluoroscopic C-arm and operating table are locked into
`position to avoid parallaxes.
`AcuNav and fluoroscopy for real-time valved stent de-
`ployment monitoring. After removing the IVUS and 8-F
`introducer, the valved stent delivery system is advanced over
`the guide wire under fluoroscopic and AcuNav guidance.
`When fluoroscopic and sonographic target sites reach con-
`gruency, the valved stent is deployed orthotopically over the
`native valve leaflets, releasing the distal end first. If the
`location remains unchanged, the proximal end is released.
`
`Figure 2. Navigating the valved stent through the heart with intracardiac
`ultrasound (AcuNav) and intravascular ultrasound (IVUS) guidance.
`
`The valved stent is targeted to land slightly above the
`optimal site to ensure that the entire device can be pulled
`back if needed after opening the first line of the Z-stent.
`The self-expanding nitinol stent has a low metal-to-stent
`ratio with minimal contact area between the interface of the
`stent and aortic wall. These features increase the expansion
`force at the interface, creating a firm attachment to the
`aortic root without injuring the aortic wall. This stent
`design is being used clinically for aortic endovascular
`procedures.
`The residual coronary sinus stent index. We used the
`residual coronary sinus stent index (RCSSI) to evaluate
`coronary blood flow (CBF) impairment. This index com-
`pares the flow ratio between the native coronary flow and
`the blood flow required to pass through the valved stent
`after implantation. More specifically, the RCSSI is a com-
`parison between the coronary cross-sectional surface area
`and the plane defined by the valved stent and the native
`aortic wall (Fig. 4). Coronary diameter was measured at the
`termination of the sinus portion. The residual stent aortic
`wall plane was measured at the level of the coronary orifice.
`All measurements were made using intracardiac ultrasound.
`To calculate the index value, the distance of the stent from
`the aortic wall (residual gap at the level of the aortic sinus
`portion) is divided by the coronary diameter. Coronary
`
`Figure 1. Valved stent used for off-pump direct-access antegrade implantation.
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`JACC Vol. 46, No. 2, 2005
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`rate of 4.7 ⫾ 1.5 l/min. Intravascular ultrasound imaging
`exhibited full opening and closing of the pericardial leaflets
`in all valves. Mild paravalvular leakage was observed in 2 of
`12 valved stents. No valved stent migration occurred inside
`the silicon valved stent chamber.
`In vivo study. AcuNav measurements revealed aortic di-
`ameter 23.0 ⫾ 2.2 mm, valve area 3.76 ⫾ 1.3 cm2, height of
`the native leaflets 11.4 ⫾ 2.4 mm, depth of the coronary
`sinuses of Valsalva 4.2 ⫾ 1.3 mm, height of the sinus
`portion 14.6 ⫾ 1.7 mm, and diameter at the sinotubular
`junction 25.2 ⫾ 2.8 mm.
`Eight of 12 implanted valved stents were delivered
`accurately. Two were deployed supra-annularly and oc-
`cluded the right coronary artery (RCA). Another two
`dislodged into the LV, one because of size mismatch, the
`other because of failure to fully deploy.
`AcuNav demonstrated good leaflet motion, with full
`valvular opening and closing in all correctly delivered,
`deployed, and sized valved stents. The overall planimetric
`valve orifice area was 2.6 ⫾ 0.8 cm2. Of the eight correctly
`deployed valved stents, one had mild-to-moderate paraval-
`vular leakage due to size mismatch and one exhibited mild
`regurgitation. All eight valved stents had a low transvalvular
`gradient of 5.3 ⫾ 3.9 mm Hg (mean, peak-to-peak) on
`invasive measurement and 5.6 ⫾ 4.7 mm Hg on noninvasive
`measurement.
`Continuous cardiac output remained stable (5.2 ⫾ 0.6
`l/min valved stent. 4.7 ⫾ 0.4 l/min) for the eight correctly
`delivered valved stents. Intracardiac color Doppler imaging
`revealed laminar blood flow.
`Procedure time was typically 120 min (range 90 to 180
`min), and duration of delivery and deployment was 4 to 6
`min. The postimplantation CBF pattern using AcuNav
`color Doppler and M-mode (Fig. 5) indicated no signs of
`CBF impairment in the valved stents deployed exactly on
`target. Residual coronary sinus stent index was obtained to
`evaluate potential flow impairment in the LCA (Fig. 5).
`Mean distance between the coronary orifice and aortic wall
`was 8.1 ⫾ 2.4 mm. Mean diameter of the LCA was 5.7 ⫾
`1.2 mm, yielding an RCSSI value of 1.6 ⫾ 0.5. The
`postimplantation observation period was 4.5 ⫾ 1.8 h.
`Postmortem examination (Fig. 6) confirmed that 8 of 12
`valved stents were correctly positioned and firmly anchored
`to the aortic wall. No implants showed signs of coronary
`obstruction. Necropsy confirmed that the two supra-annular
`deployments occluded the RCA. The two dislodged valved
`stents were found in the LV. Macroscopic analysis provided
`no evidence of damage to the aortic wall, signs of dissection,
`or hematoma. Eight valved stents were structurally sound.
`All were thrombus-free.
`
`DISCUSSION
`
`This acute animal study confirms that antegrade direct-
`access orthotopic aortic valve implantation via the LV apex
`is feasible. Recent reports show promising results with
`
`Figure 3. Valved stent and delivery system: the off-pump valved stent was
`collapsed radially and then manually loaded into a standard endoprosthetic
`delivery device with a maximum diameter of 9.2 mm.
`
`blood flow impairment was not observed for index values
`⬎1.
`Outcome assessment. In vivo assessment included leaflet
`motion, planimetric valve orifice, RCSSI, CBF, character-
`istics of the left coronary artery (LCA), transvalvular gradi-
`ent, regurgitation, and paravalvular leaking. After the ex-
`periments, animals were sacrificed and a macroscopic
`analysis was performed at necropsy.
`
`RESULTS
`
`In vitro study. All valved stents demonstrated good func-
`tion, with a pressure gradient of 5.2 ⫾ 2.6 and mean flow
`
`Figure 4. Intracardiac ultrasound after orthotopic valved stent implanta-
`tion. LCA ⫽ left coronary artery.
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`JACC Vol. 46, No. 2, 2005
`July 19, 2005:366–70
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`Huber et al.
`Direct-Access Percutaneous Valve Replacement
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`369
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`Figure 5. M-mode recordings showing stable left anterior descending flow before (top) and after (bottom) valved stent implantation.
`
`remote access percutaneous antegrade and retrograde valved
`stent implantation in the pulmonary or aortic position in
`selected patients (1,4,5). However, the remote access tech-
`nique is not a viable alternative to surgical AVR. Innovative
`surgical techniques are becoming increasingly less invasive
`(6). These innovations are likely to improve measurable
`parameters such as patient outcome, length of hospital stay,
`and perioperative mortality and morbidity, but more data
`are needed to establish their true benefits.
`Development of an off-pump surgical AVR technique
`began in our laboratory in 1999 (3,7,8). Early experience
`with direct right ventricular access for antegrade pulmonary
`valved stent implantation encouraged us to develop an
`analog for the left heart. The advantages of direct-access via
`the LV apex include avoidance of the cardiopulmonary
`circulation, decreased distance to the target site, and ability
`to deliver larger devices for valve removal.
`
`Cribier et al. (1,4) demonstrated that the antegrade
`approach to aortic valved stent implantation was feasible.
`However, mitral valve function was compromised by the
`transvalvular guidewire, resulting in severe mitral regurgita-
`tion in one-third of reported patients (1).
`Design features for optimal implantation or replace-
`ment of the aortic valve include: 1) antegrade access
`through the LV apex; 2) a delivery system with direc-
`tional guidance to eliminate the risk of coronary orifice
`obstruction; and 3) a mechanism for reloading malposi-
`tioned valved stents.
`AcuNav in combination with fluoroscopy can locate the
`level of deployment with precision, but is not sufficient to
`monitor rotation of the device within the aorta before
`deployment. Currently, we are developing a radiopaque
`marker for the delivery envelope that contains the collapsed
`valved stent.
`
`Figure 6. A valved stent in situ after antegrade off-pump implantation at necropsy. The light blue catheter is inside the left coronary artery orifice; the dark
`blue catheter in the right coronary artery.
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`Four of 12 valved stents were incorrectly placed at
`necropsy. Two were dislodged, one because of failure to
`fully expand, attributed to difficulties in collapsing and
`loading the device into the delivery system, and the other
`because an undersized valved stent was used in a larger than
`anticipated aortic root. Both animals remained stable during
`the operation, but all attempts to recover or reposition the
`device without going on pump failed. Only one valved stent
`dislodged after it was initially correctly placed. Similar
`difficulties have been described (9). Two valved stents were
`deployed supra-anularly and occluded the RCA.
`No interference with CBF was found in correctly placed
`and deployed devices. Previous studies lack data on postim-
`plantation CBF secondary to interference from echo-dense
`stent struts. AcuNav eliminated much of this interference in
`the present study, permitting reliable postimplantation CBF
`analysis. In line with previous reports (8), RCSSI was a
`useful indicator for absence of CBF flow interference for all
`index values ⬎1. Moreover, leaving the native leaflets in
`place did not cause coronary ostia obstruction. These
`findings conflict with other published data (9), which
`demonstrate a high failure rate with valved stent implants in
`the annular aortic position (orthotopic) consequent to flow
`restriction caused by the native leaflets.
`Further measures to ensure the safety of valved stent
`aortic valve implantation and replacement include the de-
`velopment of embolic devices to protect
`the coronary
`orifices and aortic arch, similar to the devices used for
`percutaneous carotid endarterectomy or the aortic filter
`cannulae used in cardiac surgery. Specialized tools for
`remote decalcification and tissue removal are also needed.
`Several have been proposed, such as laser ablation, ablation
`chambers, or cutting catheters, but experimental data are
`lacking to support their feasibility. A temporary valve to
`support LV function during the removal/replacement inter-
`val and to overcome increased afterload caused by embolic
`filters and intra-aortic tools used for decalcification will also
`be required. Previous publications have proposed valve-
`tipped catheters as a temporary solution. Left ventricular
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`JACC Vol. 46, No. 2, 2005
`July 19, 2005:366–70
`
`assist devices placed in the LV outflow tract, such as the
`Impella VAD catheter, might also work.
`The necessity of placing valved stents in patients with
`heavily calcified aortic valves calls for new strategies and
`techniques such as the proposed direct-access approach.
`Our experimental data demonstrate that direct-access ante-
`grade off-pump aortic valved stent implantation through the
`LV apex is feasible in animals with normal, noncalcified
`leaflets. The absence of CBF impairment or mitral valve
`hindrance in properly placed and sized devices makes the
`direct-access valved stent-based approach a promising new
`technology.
`
`Reprint requests and correspondence: Dr. Christoph H. Huber,
`Division of Cardiac Surgery, Brigham and Women’s Hospital,
`75 Francis Street, Boston, Massachusetts 02115. E-mail:
`huberch@dr.com.
`
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