(Circulation. 1999;100:II-70.)
© 1999 American Heart Association, Inc.
Surgery for Valvular Heart Disease |
Functional Evaluation of the Medtronic Stentless Porcine Xenograft Mitral Valve in Sheep
From the Department of Cardiovascular and Thoracic Surgery (P.D., G.R.G., T.A.T., G.T.D., N.B.I., D.C.M.), Division of Cardiovascular Medicine (T.L.T., A.F.B.), and the Department of Anesthesia (L.E.F.), Stanford University School of Medicine, Stanford, Calif; Cardiology Section (T.L.T., A.F.B.), Department of Veterans Affairs Medical Center, Palo Alto, Calif; and Department of Cardiovascular Physiology and Biophysics (G.T.D., N.B.I.), Research Institute of the Palo Alto Medical Foundation, Palo Alto, Calif.
Correspondence to D. Craig Miller, MD, Department of Cardiovascular and Thoracic Surgery, Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, CA 94305-5247. E-mail dcm{at}leland.stanford.edu
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Abstract |
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Background—Recently, renewed interest in allograft and stentless "freehand" bileaflet xenograft mitral valve replacement has arisen. The variability of human papillary tip anatomy and scarcity of donors limit allograft availability, making xenograft mitral valves an attractive alternative; however, these valves require new surgical implantation techniques, and assessment of their hemodynamics and functional geometry is lacking.
Methods—Seven sheep underwent implantation of a new stentless, glutaraldehyde-preserved porcine mitral valve (Physiological Mitral Valve [PMV], Medtronic) and were studied acutely under open-chest conditions. A new method of retrograde cardioplegia was developed. Hemodynamic valve function was assessed by epicardial Doppler echocardiography. 3D motion of miniature radiopaque markers sutured to the valve leaflets, annulus, and papillary tips was measured. Six other sheep with implanted markers served as controls.
Results—Both papillary muscle tips avulsed in the first animal, leaving 6 other animals. Mitral regurgitation was not observed in any xenograft valve. The peak and mean transvalvular gradients were 4.6±1.8 mm Hg and 2.6±1.5 mm Hg, respectively. The average mitral valve area was 5.7±1.6 cm2. Valve closure in the xenograft group occurred later (30±11 ms, P<0.015) and at higher left-ventricular pressure (61±9 mm Hg, P<0.001) than in the control group; furthermore, leaflet coaptation was displaced more apically (5.6±2.2 mm, P<0.001) and septally (5.8±1.5 mm, P<0.001), and the anterolateral papillary tip underwent greater septal-lateral displacement (2.7±1.5 mm, P<0.001). Annular contraction during the cardiac cycle was similar in the 2 groups (xenograft 9.2±4.5% versus control 10.6±4.5% [mean±SD; 2-factor ANOVA model]).
Conclusions—Successful freehand stentless porcine mitral valve implantation is feasible in sheep and was associated with excellent early postoperative hemodynamics. Physiological mitral valve annular contraction and functional leaflet closure mechanics were preserved. Long-term valve durability, calcification, and hemodynamic performance remain to be determined in models.
Key Words: mitral valve replacement • unstented valve • xenograft valves • cardiac surgery
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Introduction |
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Stentless bioprosthetic valves promise to provide superior hemodynamic performance compared with stented tissue and mechanical valves and perhaps also offer the potential for enhanced durability when compared with stented bioprostheses. These potential advantages have led to an explosion of interest in the use of stentless porcine xenograft and pulmonary autograft (Ross procedure) valves in the aortic position. In contrast to the many options for aortic valve replacement, the only currently available alternatives for mitral valve replacement are mechanical valves and stented tissue bioprostheses (glutaraldehyde-preserved porcine aortic valve or bovine pericardial tissue). In comparison with stented tissue valves, the theoretical advantages of a stentless tissue valve in the mitral position include better hemodynamic performance and reduced mechanical stress on the valvular tissue, which may translate into better valve durability.1 2 3 4 Preservation of valvular-ventricular interaction, or papillary-annular continuity, also confers an additional advantage in terms of left ventricular (LV) systolic pump function.5 6
Allograft mitral valve replacement has a long history,7 8 9 but its use was abandoned early due to the lack of a reproducible implantation technique and difficulties with proper papillary muscle fixation. Subsequent attempts to replace the mitral valve with a xenograft mitral valve10 11 also failed because of papillary muscle avulsion, chordal rupture, and leaflet calcification and disruption.12 The development of improved techniques for mitral valve repair and superior methods of tissue fixation, however, has recently prompted renewed interest in orthotopic, unstented allograft and xenograft mitral valve replacement13 14 and unstented, chordally supported mitral valve bioprostheses.15 16
In contrast to the heterogeneous papillary muscle
anatomy in human mitral valve allografts,17 with
the attendant implantation difficulties, porcine xenografts offer a
consistent anatomic preparation. This consistency
makes them amenable to a well-defined and reproducible implantation
technique with predictable functional outcome. The lack of anatomic
homology across species of the mitral valve, particularly the papillary
muscles, however, complicates xenograft mitral valve implantation. The
anatomic discrepancies include porcine papillary muscles that lie
180° apart and porcine mitral leaflets that are approximately
equal in size.
To define the implications of porcine xenograft anatomic differences for surgical technique and functional outcome, we investigated the surgical feasibility and immediate postoperative hemodynamic function of a new orthotopic, stentless porcine mitral valve in sheep. Transvalvular hemodynamics were assessed by use of epicardial Doppler echocardiography. Miniature radiopaque markers on the valve were visualized with biplane cinefluoroscopy, which allowed precise characterization of 3D dynamic motion of the leaflets and subvalvular structures. We compared the valvular function and LV geometry of this unstented xenograft valve with that of the native mitral valve in sheep controls.
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Methods |
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Seven adult castrated male sheep (73±8 kg) underwent implantation of a stentless porcine xenograft mitral valve and insertion of miniature radiopaque markers on the mitral annulus, xenograft leaflets, papillary muscle tips, and the left ventricle. Both papillary tip implants avulsed in the first animal before data acquisition. The remaining 6 animals were taken to the experimental-animal cardiac catheterization laboratory for immediate study through use of an open-chest preparation. The control group, which consisted of 6 sheep (66±11 kg), underwent marker insertion only but were studied 7 to 10 days postoperatively under closed-chest conditions. The surgical preparation and cardiac catheterization of these animals were similar and have been reported previously.18
Stentless Porcine Xenograft Mitral Valve
The PMV Bioprosthesis, a stentless porcine xenograft
mitral valve, was provided by Medtronic Heart Valve Division. The
valves were removed from pig hearts with the annulus, leaflets, chordae
tendineae, and papillary heads intact and fixed in
glutaraldehyde. Dacron sewing tubes were sutured to
each papillary head, and a thin Dacron sewing ring was sutured to the
annulus.
Surgical Preparation
The animals were intubated and ventilated mechanically (Servo
Anesthesia Ventilator, Siemens-Elema AB). General
anesthesia was maintained with inhalational isofluorane
(1.0% to 2.2%). The mediastinum was exposed through a left
thoracotomy at the fifth intercostal space. Pneumatic occluders (In
Vivo Metric Systems) were placed around the superior and
inferior vena cavae. The heart was suspended in a
pericardial cradle, and 9 miniature radiopaque tantalum markers (ID
0.8 mm, OD 1.3 mm, length 1.5 to 3.0 mm) were inserted
in the LV epicardium and septum for calculation of LV volume and
load-independent measures of ventricular
contractility. Markers were placed circumferentially on
the anterior, lateral, posterior, and septal walls at 2 levels: LV
apical and LV equatorial. An additional marker was placed at the LV
apex.
The animals underwent cardiopulmonary bypass (CPB) with left
carotid artery and right-atrial cannulation. The hemiazygos vein
("persistent left superior vena cava"), which consistently
drains into the coronary sinus in sheep, was cannulated, and
the heart was arrested by use of retrograde cold crystalloid
cardioplegia solution; external finger pressure on the coronary
sinus ostium was used to keep the cardioplegia from flowing into the
right atrium. Through a left atriotomy, the mitral valve was sized,
based on the intertrigonal distance and size of the anterior leaflet,
by use of a Duran annuloplasty ring sizer. The native valve was
completely excised; the chordae were sharply transected at papillary
muscle insertion. Eight tantalum radiopaque markers were sutured
circumferentially to the native mitral annulus in addition to the 10
markers that were sutured to the xenograft valve before implantation (4
markers along the central meridian of the anterior leaflet, 4 markers
along the central meridian of the posterior leaflet, and 2 markers on
each papillary tip, Figure 1
).
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The valve was oriented so that the xenograft anterior leaflet matched the orientation of the native anterior mitral valve leaflet. The resultant appropriate direction and position of the xenograft papillary tips were noted. Two or 3 Ethibond mattress sutures (2-0) with polytetrafluoroethylene pledgets were used to affix the papillary tips to the LV endocardial surface with deep mural sutures. The xenograft anterolateral papillary muscle sewing tube was implanted toward the septal side of the native anterolateral papillary muscle, and the posteromedial papillary sewing tube was secured near the native posteromedial papillary muscle. The increased length of xenograft chordae and papillary muscle tips, compared with the native valve, required careful implantation of the papillary muscle sewing tubes apically far. Poor exposure deep inside the ventricle made this somewhat difficult in these normal-sized, naturally hypertrophic sheep hearts. The xenograft sewing ring was then sutured to the native mitral annulus with a continuous 5-0 polypropylene suture. Coaptation of the mitral leaflets was assessed by injecting saline into the ventricle. The atriotomy was closed, the heart de-aired, the cross clamp removed, and the heart defibrillated into sinus rhythm. A micromanometer-tipped catheter (Millar MPC-500, Millar Instruments [previously zeroed in a 37°C water bath]) was positioned in the LV chamber through the apex.
Experimental Design
After 1 to 2 hours of recovery and stabilization, the
isofluorane was stopped and sedation maintained with
intravenous ketamine and diazepam. The animals were
transported to the experimental-animal cardiac
catheterization laboratory and ventilated mechanically
(Veterinary Anesthesia Ventilator 2000, Hallowell EMC) with
100% oxygen. Simultaneous biplane videofluoroscopic and
hemodynamic data were acquired with the animal in the
right lateral decubitus position. The animals were studied in normal
sinus rhythm after autonomic blockade and with ventilation arrested at
end expiration during data acquisition runs to minimize the effects of
respiratory variation. Data were acquired during control conditions
after an intravenous bolus infusion of
CaCl2 (15 mg/kg) to augment
contractility and during a slow infusion of sodium
nitroprusside to reduce maximum LV pressure by 25%.
All animals received humane care in compliance with the Principles of Laboratory Animal Care formulated by the National Society for Medical Research and the Guide for Care and Use of Laboratory Animals prepared by the National Academy of Sciences and published by the National Institutes of Health (DHEW[NIH] publication 85-23, revised 1985). This study was approved by the Stanford Medical Center Laboratory Research Animal Review Committee and conducted according to Stanford University policy.
Data Acquisition
A Philips Optimus 2000 biplane Lateral ARC 2/poly DIAGNOST C2
system (Philips Medical Systems, North America Company) was used to
collect videofluoroscopic data at 60 Hz with the image intensifiers in
the 9-inch mode. 2D images from each of the 2 x-ray views (45° right
anterior oblique and 45° left anterior oblique) were digitized and
merged to yield 3D coordinates for each radiopaque marker every 16.7
ms. Analog LV and left atrial pressures and ECG voltage were
recorded on the video images during data acquisition and were
digitized simultaneously. A Hewlett-Packard SONOS 1500
system was used for epicardial echocardiography.
System software was used to calculate the velocity-time integral of
Doppler signals across the implanted valves.
Data Analysis
End systole was defined as the videofluoroscopic frame preceding
the maximum negative dP/dt (-dP/dtmax); end
diastole was defined as the videofluoroscopic frame
containing the peak of the ECG R wave.
Echocardiography
Epicardial echocardiography was used to
study valve leaflet morphology and function. Pulse-wave (PW)
Doppler was used to calculate flow velocities across the valve. The
peak transvalvular pressure gradient, 
P, was
computed from the peak flow velocity V by using the modified Bernoulli
equation P=4V2. The mean
transvalvular pressure gradient was calculated from the
velocity-time integral of the mitral valve Doppler signal by use of
integrated Hewlett-Packard software. Mitral valve area (MVA) was
estimated from the pressure half-time Pt1/2, the
time required for velocity to drop to one half of peak velocity, using
the empirically derived equation MVA=220/Pt1/2.
Satisfactory PW Doppler signals could not be acquired for the
seventh animal.
LV Volume
An instantaneous estimate of LV volume was calculated every 16.7
ms from the epicardial LV markers by use of a multiple tetrahedral
model reconstructed from the marker coordinates and corrected for LV
convexity. The details of this method have been reported
previously.19
LV Systolic Function
Preload recruitable stroke work (PRSW), calculated from stroke
work and end-diastolic volume (EDV), was used to
assess global LV systolic function.
Mitral Valve Leaflets
The height of each mitral valve leaflet was calculated from the
sum of the distances between adjacent leaflet markers at end
diastole (ED), the distance extended from the annular
marker to the respective leaflet edge marker. The leaflet heights were
computed at ED to minimize error introduced by possible leaflet folding
at other times in the cardiac cycle. The time of mitral leaflet closure
was defined as the first videofluoroscopic frame that showed a change
of <10% between successive frames in the distance between the leaflet
edge markers. The point of leaflet coaptation was defined as the
midpoint of the 2 leaflet edge markers at the time of leaflet
closure.
Mitral Valve Annulus
The area of the mitral valve annulus was computed from the 8
annular markers together with the geometric centroid of these 8
markers. Eight triangular regions were defined; the base of each
triangle consisted of the annular length between adjacent pairs of
markers, and the annular centroid was the apex of each triangle. The
annular area was approximated by the sum of the areas of the 8
triangular components. The mitral annular area was computed for each
videofluoroscopic frame during the cardiac cycle. The area reported for
each frame was the average area for 3 consecutive steady-state cardiac
cycles.
Coordinate System
Marker laboratory coordinates were transformed into a coordinate
system fixed within the heart, with the origin being the midpoint of
the septal and lateral annular markers (markers 1 and 5, respectively,
Figure 1
). The y axis was directed through the LV
apex from the origin, the x axis was directed orthogonally
to the y axis (in the plane of the apical-septal markers),
and the z axis was directed orthogonally to both the
x and y axes, toward the posterior commissure.
Septal displacement was defined as displacement along the x
axis toward the septal marker, apical displacement as motion along the
y axis away from the origin and toward the apical marker,
and commissural displacement as displacement along the z
axis toward the posterior commissure. All distances, angles, and
displacements were calculated relative to this internal coordinate
system. Because the coordinate system is fixed in the heart, changes in
these measurements during the cardiac cycle are not affected by rigid
body rotation and translation artifacts that occur in the external
fixed laboratory coordinate reference system.
Statistical Analysis
All data are reported as mean±1 SD. For each animal, data
represent the average of 3 consecutive steady-state cardiac
cycles. Comparisons between the control and the xenograft mitral valve
groups were made by use of a 2-factor ANOVA model. Comparisons within
each group were made with repeated-measures ANOVA. The level of
significance for all statistical comparisons was
P<0.05.
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Results |
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Both papillary tips avulsed (1 completely and 1 partially) in the first sheep soon after it was weaned from CPB. A 27-mm xenograft PMV valve was implanted in that animal. The remaining 6 animals received 29-mm valves; all the remaining surgical valve implantations were successful, and data acquisition in those 6 animals was completed in the catheterization suite.
Hemodynamics
The hemodynamics of the 6 animals with PMV
xenograft valves and the 6 animals in the control group are shown in
Table 1. No significant difference
was observed in PRSW, which suggests that the LV systolic
contractile state between the 2 groups was similar. Loading conditions,
however, were significantly different: in the control group, LV preload
(LV EDV) was higher, and in the PMV xenograft group, LV afterload
(estimated as maximum systolic LVP) was lower. This difference
in LV loading conditions may account for the higher stroke volume
observed in the PMV animals.
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Echocardiography of the Xenograft PMV
Epicardial 2D echocardiography of the
implanted xenograft mitral valves revealed good leaflet-edge apposition
during diastole, with no evidence of mitral incompetence
(Figure 2a). During systole, the valve
leaflets opened wide, allowing unimpeded LV filling (Figure 2b).
Xenograft leaflet morphology during valve opening and closing, however,
differed markedly from that of native valve leaflets. The xenograft
mitral valve leaflets were markedly larger than the native leaflets.
That increased leaflet redundancy may account for the increased leaflet
coaptation noted during valve closure compared with the native valves.
In addition, the glutaraldehyde-treated porcine
xenograft leaflets appeared less compliant and relatively inflexible.
In spite of the increased leaflet height, no evidence of
systolic anterior leaflet motion or LV outflow tract (LVOT)
obstruction, was observed in any animal. This finding may be due to the
stiffer nature of the xenograft leaflets.
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A short-axis view at the level of the native papillary muscle tips
confirmed that the tips were oriented 120° from each other
relative to an axis through the centroid of the mitral annulus (Figure 3a). In contrast, the xenograft papillary
tips were 180° from each other, where they were sutured to the LV
endocardium (Figure 3b).
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Doppler echocardiography (PW Doppler)
revealed relatively normal physiological flow
patterns across the implanted xenograft mitral valves (Figure 4A). Early rapid ventricular
filling across the valve was present, corresponding to the E wave
in the PW Doppler tracing (Figure 4B). The A wave, or
transvalvular flow generated by atrial contraction, was fused
with the E wave on the PW tracing at these fast heart rates or
significantly dampened in comparison with a normal A wave. The average
peak and mean transvalvular pressure gradients across the PMV
valves were 4.6±1.8 mm Hg and 2.6±1.5 mm Hg (Table 2). The average mitral valve area was
5.7±1.6 cm2.
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Leaflet Motion During Mitral Valve Closure
The closure mechanics of the mitral valve leaflets were studied in
both groups of sheep under steady-state conditions. In the control
group, examination of the septal-lateral leaflet profile revealed that
both leaflets began to move rapidly toward the closed configuration 17
ms before ED and had completed closure by 34 ms after ED (Figure 5A). The precise time of valve closure
estimated from the distance between the leaflet-edge markers was 25±17
ms after ED. The LV pressure gradient during that time interval rose
from 10±12 mm Hg at ED to 29±17 mm Hg at the time of
valve closure. During valve closure, inspection of the motion of the
markers along the central meridian showed that the leaflet was
predominantly concave toward the atrium. Apposition of the leaflet-edge
markers when closed indicated no leaflet redundancy at the point of
leaflet coaptation.
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Conversely, the mitral valve xenograft leaflets showed markedly
different closing mechanics. In the PMV group, both leaflets began to
move rapidly toward a closed configuration 17 ms after ED and completed
closure by 67 ms after ED (Figure 5B). The time of valve closure
was 55±14 ms after ED, which was significantly later than in the
control group (P=0.015). In addition, a higher pressure
gradient (P<0.001) was required to close the xenograft
valve: the LV pressure gradient rose from 15±6 mm Hg at ED to
90±18 mm Hg at valve closure.
The septal-lateral leaflet profiles of the xenograft PMV leaflets
during valve closure differed markedly from those of the control group.
The leaflets were convex toward the atrium throughout valve closure and
demonstrated increased convexity with increased leaflet apposition
(Figure 5b).
The height of the anterior and posterior xenograft leaflets was 27.4±2.9 mm and 23.9±2.1 mm, respectively, versus 20.4±2.6 mm and 11.9±2.3 mm, respectively, for the native leaflets in the control group, based on the implanted leaflet markers. The heights of the xenograft leaflets were significantly greater than those of the native leaflets (anterior P=0.002; posterior P<0.001). During xenograft valve closure, this redundant tissue led to substantial leaflet overlap at the margin of coaptation, which extended to the markers adjacent to the leaflet-edge markers. Leaflet coaptation was also displaced more apically (xenograft 16.1±4.2 mm versus control 10.5±1.2 mm, P<0.001) and septally toward the LVOT (xenograft -4.8±2.6 mm versus control 1.0±1.5 mm, P<0.001), but clinical or echocardiographic signs of LVOT obstruction were not evident. Leaflet coaptation of the xenograft valve after a bolus of CaCl2 that increased maximum dP/dt (3027±532 mm Hg/s, P=0.025 versus steady state) and maximum LVP (127±16 mm Hg, P<0.005 versus steady state) did not change the position of the leaflet coaptation in the septal-lateral or apical direction (-4.9±2.8 mm and 15.2±4.3 mm, respectively). The position of leaflet coaptation in the xenograft valve was also unchanged in the septal-lateral and apical directions (-5.0±2.3 mm and 16.6±5.4 mm, respectively) after infusion of sodium nitroprusside, which decreased maximum LVP (80±18 mm Hg, P=0.028 versus control). Despite the convex shape, redundant leaflet tissue, and smaller LV chamber volumes, leaflet billowing was not observed.
Papillary Motion During Mitral Valve Closure
The position and motion of the implanted xenograft papillary tips
were compared with the native papillary muscle tips in the control
group during valve closure (Figures 5 and 6). The apical position of the implanted
and control papillary tips did not differ significantly. At ED, the
apical coordinates of the xenograft and control papillary tips were
22.0±3.0 mm and 22.2±1.6 mm for the anterolateral papillary
tip and 28.4±4.8 mm and 30.3±1.0 mm for the posteromedial
papillary tips, respectively. Similarly, the commissure-commissure
position did not differ significantly between the 2 groups. At ED, the
commissure-commissure coordinates of xenograft and control papillary
tips were -18.7±2.6 mm and -19.1±1.0 mm for the
anterolateral papillary tip and 4.2±5.1 mm and 7.1±1.1 mm
for the posteromedial papillary tip, respectively. Along the
septal-lateral dimension, however, the 2 groups differed significantly
(P<0.001): at ED, the septal-lateral coordinates of
implanted and control papillary tips were, respectively,
-8.9±3.8 mm and 0.9±1.9 mm for the anterolateral papillary
tip and -3.4±5.2 mm and 3.3±1.1 mm for the posteromedial
papillary tip. During mitral valve closure, the control papillary tips
did not move significantly from the ED positions. Similarly, the
implanted papillary tips did not have significant motion in either the
apical or commissure directions. Along the septal-lateral direction,
however, the xenograft anterolateral papillary tip underwent a
2.7±1.5 mm displacement from its ED position during valve closure
(P<0.001).
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Mitral Annular Area
The stentless design of the xenograft PMV valve allowed the mitral
annulus to change dimensions and shape normally during the cardiac
cycle after valve implantation. The annuli in the animals with
xenograft valves achieved a maximum area of 6.8±1.1
cm2 during diastole. Similar to the
control group, the xenograft valves demonstrated presystolic
annular contraction, with a minimum area of 6.2±1.0
cm2 noted 11.7±14.0 ms after ED. The annular
contraction was 9.2±4.5% (P=0.017) in the xenograft
valves. In the control group, the maximum annular area was 7.8±0.8
cm2 and the minimum area was 7.0±0.8
cm2, with minimum area occurring 22.3±13.6 ms
after ED. The relative fractional mitral annular area reduction was
10.6±4.5% (P<0.001). The maximum annular area in that
group was larger than that in the xenograft PMV group, but the
difference did not achieve statistical significance
(P=0.095). Neither the degree of annular area reduction nor
the time of minimum annular area after ED differed significantly
between the 2 groups (P>0.2).
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Discussion |
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The resurgence of mitral valve allografts and unstented xenografts as a viable alternative to mechanical or stented bioprosthetic mitral valve replacement has prompted increased interest in the physiological and hemodynamic behavior of those valves, their durability, and mode of eventual failure. Mitral valve allografts or xenografts have several advantages over conventional rigid-tissue valve replacement alternatives. By preserving valvular-ventricular continuity, those valves help enhance LV systolic function.5 6 Furthermore, unstented mitral valves possibly offer superior hemodynamics1 2 and diminished risk of thromboembolism, endocarditis, and complications associated with anticoagulation.
The limited availability of suitable donors, the competing needs for the aortic valve, the larger sizes required for allograft implantation,13 and the heterogeneity of human papillary muscle anatomy17 limit the widespread availability of mitral valve allografts. Porcine xenograft mitral valves offer a solution to this shortage, and their relatively consistent configuration favors a standardized and reproducible surgical implantation technique. Although allograft mitral valve implantation has been repeatedly investigated in humans,13 14 20 21 22 sheep,1 23 24 and dogs,7 25 few clinical studies have been conducted on xenograft mitral valve implantation,10 11 12 and no animal studies have been performed. Because the ovine mitral anatomy shares substantial anatomic homology with human anatomy, sheep provide a suitable animal model for developing porcine xenograft implantation methods and investigating the effect of those techniques on stentless xenograft valve function.
The porcine mitral valve differs from the ovine (and human)
mitral valve in several key anatomic features. The 2 porcine mitral
valve leaflets are approximately equal in height and area; in contrast,
the anterior leaflet in sheep (and humans) is approximately twice the
size of the posterior leaflet. That geometric difference in leaflet
size leads to geometric divergence in the subvalvular
structures. To balance chordal load distribution and ensure symmetric
leaflet closure, the papillary muscle tips assume a position
approximately equidistant from the center of both leaflets. Thus, the
equally sized porcine valve leaflets position the papillary tips
diametrically opposite each other, subtending an angle of 180°. To
preserve the porcine papillary muscle configuration, the papillary tips
were sutured directly to the ventricular endocardium and
not the native (ovine) papillary muscles. Implantation of the papillary
tips onto the ventricular wall, however, subjects them to
the dynamic motion of the ventricle during the cardiac cycle. Thus, the
site of papillary tip implantation balanced the risk of leaflet
prolapse with the potential risk of papillary tip avulsion. The
position of the implanted xenograft papillary tips did not differ
significantly from the control group in the apical or commissural
directions. Attachment of the xenograft papillary tips adjacent to the
native papillary muscles, however, resulted in significant septal
displacement of the xenograft papillary tips compared with the control
group.
The greatest stress on the mitral subvalvular structures occurs during valve closure and isovolumic contraction, when the mitral valve undergoes a rapid increase in load. During that period, the implanted xenograft PMV papillary tips do not move in the apical or commissural directions, which is similar to the stability exhibited by the native papillary tips during the same period. The implanted anterolateral papillary tip, however, moved significantly along the septal-lateral direction during valve closure. That displacement was likely caused by the effect of ventricular contraction and wall thickening on the endocardially fixed anterolateral papillary tip. Although the increased motion of this papillary tip did not appear to affect valve competency (and, perhaps, even assisted in leaflet closure), the long-term implications of the dynamic stresses caused by this motion on subvalvular integrity need further study. The papillary-ventricular fixation site may remodel favorably over time to minimize motion and dissipate subvalvular stresses during valve closure.
The leaflet-closing mechanics of the xenograft valve differed markedly from the native valve. Leaflet closure in the xenograft valve occurred later and at higher LV pressures than did the native valve. The mechanism for this increased dependence on transvalvular pressure gradient to close the xenograft valve is probably related to the thicker, less compliant glutaraldehyde-treated xenograft leaflets, the denervated nature of this bioprosthesis, possible chordal restriction caused by the septally displaced papillary muscle tips, and, in this experimental preparation, higher left atrial pressures. In addition to closing later and over a longer period, the xenograft leaflets were convex toward the atrium during closure, whereas the native mitral leaflets are concave toward the atrium.26 The natural "sigmoid" or concave shape of the native leaflets is probably maintained by tension on the second-order chordae tendineae, which are inserted on the mid-portion of the leaflet at the junction of the rough and smooth zones.26 If that mechanistic hypothesis is operant, it would suggest that inadequate tension on the second-order chordae tendineae of the xenograft valve may explain the convex shape of the leaflets.
In comparison with the control group, the leaflet coaptation region in the xenograft valves was displaced septally and toward the LVOT. The most obvious explanation for that displacement is septal displacement of the implanted papillary tips relative to native papillary tip locations. In addition, the larger xenograft leaflets created an increased zone of coaptation. Despite the septal displacement and increased zone of coaptation, LVOT obstruction was not observed under control conditions nor after interventions that increased contractility or decreased afterload.
In summary, this study established the feasibility of a reproducible, albeit technically complex, surgical technique for mitral valve replacement with the Medtronic stentless porcine xenograft mitral valve. The implanted valves had excellent transvalvular hemodynamics. The larger and stiffer glutaraldehyde-treated xenograft leaflets did not compromise LV filling, and there was no appreciable regurgitation. The leaflets opened widely throughout diastole, allowing unimpeded filling of the ventricle with acceptable peak and mean transvalvular pressure gradients. In addition, the stentless design of the xenograft valve allowed the annulus to undergo normal physiological annular motion during the cardiac cycle. The ability of the xenograft annulus to respond in a physiological fashion may reduce peak loading and shearing stresses that are known to occur in stented bioprosthetic valves.3 4 Clearly, long-term studies are needed to establish the fate of the papillary-ventricular fixation site and the effect of leaflet shape reversal on PMV valve durability.
Study Limitations
The closing and opening mechanics of the unstented PMV porcine
xenograft valve were compared with those of native ovine mitral valves
in the control sheep. Because of substantial anatomic differences in
valve structure between the species, it is conceivable that the closing
mechanics of a native in situ porcine mitral valve differ from those of
the ovine mitral valve. Furthermore, in contrast to the open-chest
preparation used to investigate the implanted PMV xenograft valves, the
control group of animals was studied under closed-chest conditions 7 to
10 days after surgery. Hemodynamic differences between
the 2 groups may also be attributed to the different postoperative
times of investigation (immediate versus 7 to 10 days) and study
conditions (immediate, anesthetized, open-chest
preparation versus conscious-sedated, closed chest). Because CPB
required the addition of 2 L of crystalloid volume, the intravascular
volume status of the PMV xenograft valve animals was enhanced in the
immediate post-CPB period compared with the recovered control animals,
which had undergone diuresis. Varied levels of core rewarming
and endogenous adrenergic stimulation may also have
potentially accounted for the observed differences between the 2
groups. The extent to which those differences affected PMV valve
function or masked potential systolic anterior motion of the
valve leaflets is unknown; future long-term, closed-chest studies of
the PMV valve are needed to resolve those questions. Finally, because
markers were placed only along the central meridian of the xenograft
leaflets, the convexity of the PMV leaflets observed during closure
might represent bending of the leaflets along that line.
Leaflet shape and mechanics on either side of the central meridian and
closer to the sites of first- and second-order chordal insertion cannot
be reliably inferred from the motion of the limited leaflet marker
array.
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Acknowledgments |
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We appreciate the technical assistance provided by Mary K. Zasio, BA; Carol W. Mead, BA; and Erin K. Schultz, BS.
This work was supported in part by grants HL-29589 and HL-48837 from the National Heart, Lung, and Blood Institute and a grant from Medtronic Heart Valve Division, Medtronic, Inc, Irvine, Calif. Drs Dagum and Green were supported by the National Heart, Lung, and Blood Institute Individual Research Service Awards HL10000-01 and HL-09569, respectively. Dr Timek is a recipient of a Thoracic Surgery Foundation Research Fellowship Award. Drs Dagum, Green, and Timek are Carl and Leah McConnell Cardiovascular Surgical Research Fellows.
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