Hemodynamic performance of the Medtronic Mosaic and Perimount Magna aortic bioprostheses: five-year results of a prospectively randomized study.

Abstract

Clinical outcomes of patients undergoing aortic valve replacement may be influenced by the presence of residual gradients and patient-prosthesis mismatch. The aim of this study was to compare hemodynamic performance and clinical outcomes at 5 years after prospectively randomized porcine versus bovine aortic valve replacement. We also aimed to determine the effects of valve hemodynamics on left ventricular (LV) mass regression.
A total of 108 patients undergoing aortic valve replacement were randomized to receive either the Medtronic Mosaic (MM) porcine (n=54) or the Edwards Perimount Magna (EPM) bovine pericardial prosthesis (n=54). Clinical outcomes, mean gradients, effective orifice area and LV mass regression were evaluated at 1 and 5 years after surgery. Follow-up echocardiograms were performed on 106 (98%) and 87 (92%) patients, respectively.
Preoperative characteristics were similar between groups. Mean aortic annulus diameter and mean implant size were comparable in both groups. At 1 and 5 years, mean transprosthetic gradients were lower in the EPM group: EPM 10.3±3.4mmHg versus MM 16.3 ± 7.6 mmHg (p<0.0001) and EPM 9.6 ± 3.5 mmHg versus MM 16.8 ± 8.7 mmHg (p<0.0001), respectively. Similarly, indexed effective orifice areas (IEOA) at 1 and 5 years were significantly greater in the EPM group: EPM 1.10 ± 0.22 cm(2)m(-2) versus MM 0.96 ± 0.22 cm(2)m(-2) (p<0.004) and EPM 1.02 ± 0.25 cm(2)m(-2) versus MM 0.76 ± 0.19 cm(2)m(-2) (p<0.0001), respectively. At 5 years, the incidence of patient-prosthesis mismatch (IEOA ≤0.85 cm(2)m(-2)) was significantly lower in the EPM group: EPM 22.9% vs MM 73.9% (p<0.0001). Such differences were similar when analysis was stratified by surgically measured annular size and implant valve size. During the first year after surgery, both groups demonstrated similar regression of LV mass index (MM -26.3 ± 43 gm(2) vs EPM -30.1 ± 36 gm(-2); p=0.8); however, at 5 years, regression of LV mass index was significantly greater in the EPM group: (EPM -47.4 ± 35 gm(-2) vs -4.4 ± 36 gm(-2); p<0.0001). Five-year survival was 79.6 ± 4.1% in the MM group and 94.4 ± 2.2% in the EPM group (p=0.03). Conclusions: At 5 years, the EPM valve was significantly superior to the MM prosthesis with regard to hemodynamic performance, incidence of patient-prosthesis mismatch and regression of LV mass index. The hemodynamic superiority of the EPM prostheses in comparison to MM-prostheses demonstrated at 1 year, increased significantly over time.

Full text

Page 1

DOI: 10.1016/j.ejcts.2010.11.015
2011;39:844-852
Eur J Cardiothorac Surg
Sastre, Javier López-Rodríguez, María Bueno, Mario Castaño and Antonio Arribas
María José Dalmau, José María González-Santos, José Antonio Blázquez, José Alfonso

bioprostheses: five-year results of a prospectively randomized study
Hemodynamic performance of the Medtronic Mosaic and Perimount Magna aortic
This information is current as of May 25, 2011
http://ejcts.ctsnetjournals.org/cgi/content/full/39/6/844
located on the World Wide Web at:
The online version of this article, along with updated information and services, is
ISSN: 1010-7940.
European Association for Cardio-Thoracic Surgery. Published by Elsevier. All rights reserved. Print
for Cardio-thoracic Surgery and the European Society of Thoracic Surgeons. Copyright © 2011 by
The European Journal of Cardio-thoracic Surgery is the official Journal of the European Association
by Maria Jos? Dalmau Sorli on May 25, 2011 ejcts.ctsnetjournals.orgDownloaded from

Page 2

Hemodynamic performance of the Medtronic Mosaic and Perimount Magna
aortic bioprostheses: five-year results of a prospectively randomized study§
Marı ´a Jose ´ Dalmau*, Jose ´ Marı ´a Gonza ´lez-Santos, Jose ´ Antonio Bla ´zquez,
Jose ´ Alfonso Sastre, Javier Lo ´pez-Rodrı ´guez, Marı ´a Bueno, Mario Castan ˜o, Antonio Arribas
Department of Cardiac Surgery, Salamanca University Hospital, Paseo de San Vicente, N8 58—182, 37007 Salamanca, Spain
Received 1 September 2010; received in revised form 30 October 2010; accepted 4 November 2010; Available online 28 December 2010
Abstract
Objective: Clinical outcomes of patients undergoing aortic valve replacement may be influenced by the presence of residual gradients and
patient—prosthesis mismatch. The aim of this study was to compare hemodynamic performance and clinical outcomes at 5 years after
prospectively randomized porcine versus bovine aortic valve replacement. We also aimed to determine the effects of valve hemodynamics
on left ventricular(LV) mass regression.Methods: A total of 108 patientsundergoing aortic valve replacement were randomizedto receive either
theMedtronicMosaic(MM)porcine(n = 54)ortheEdwardsPerimountMagna(EPM)bovinepericardialprosthesis(n = 54).Clinicaloutcomes,mean
gradients,effectiveorificeareaandLVmassregressionwereevaluatedat1and5yearsaftersurgery.Follow-upechocardiogramswereperformed
on 106 (98%) and 87 (92%) patients, respectively. Results: Preoperative characteristics were similar between groups. Mean aortic annulus
diameter and mean implant size were comparable in both groups. At 1 and 5 years, mean transprosthetic gradients were lower in the EPM group:
EPM 10.3 ? 3.4 mmHg versus MM 16.3 ? 7.6 mmHg (p < 0.0001) and EPM 9.6 ? 3.5 mmHg versus MM 16.8 ? 8.7 mmHg (p < 0.0001), respec-
tively. Similarly, indexed effective orifice areas (IEOA) at 1 and 5 years were significantly greater in the EPM group: EPM 1.10 ? 0.22 cm2m?2
versus MM 0.96 ? 0.22 cm2m?2(p < 0.004) and EPM 1.02 ? 0.25 cm2m?2versus MM 0.76 ? 0.19 cm2m?2(p < 0.0001), respectively. At 5 years,
the incidence of patient—prosthesis mismatch (IEOA ? 0.85 cm2m?2) was significantly lower in the EPM group: EPM 22.9% vs MM 73.9%
(p < 0.0001). Such differences were similar when analysis was stratified by surgically measured annular size and implant valve size. During
thefirst yearaftersurgery,bothgroupsdemonstratedsimilarregressionofLVmassindex(MM?26.3 ? 43 g m2vsEPM?30.1 ? 36 g m?2;p = 0.8);
however, at 5 years, regression of LV mass index was significantly greater in the EPM group: (EPM ?47.4 ? 35 g m?2vs ?4.4 ? 36 g m?2;
p < 0.0001). Five-year survival was 79.6 ? 4.1% in the MM group and 94.4 ? 2.2% in the EPM group (p = 0.03). Conclusions: At 5 years, the EPM
valve was significantly superior to the MM prosthesis with regard to hemodynamic performance, incidence of patient—prosthesis mismatch and
regression of LV mass index. The hemodynamic superiority of the EPM prostheses in comparison to MM-prostheses demonstrated at 1 year,
increased significantly over time.
# 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
Keywords: Aortic valve replacement; Biological prosthesis; Hemodynamic performance; Left ventricular mass index
1. Introduction
Contemporary practices in aortic valve replacement (AVR)
have seen an increasing use of biological valve substitutes
because of the growing number of elderly patients requiring
surgery and the anticoagulant-related complications asso-
ciated with the use of mechanical prostheses. Although aortic
biologic prostheses, both porcine and bovine, have proven to
be clinically reliable over time, they have undergone
modifications in design during the past decades to optimize
hemodynamic performance and prolong durability.
The hemodynamic performance of aortic substitutes has
been the focus of many investigations due to the influence of
patient—prosthesis mismatch (PPM) on left ventricular (LV)
mass regression and clinical outcome after AVR [1,2].
Compelling evidence suggests that patients with PPM or
high residual transprosthetic gradients have lesser sympto-
matic improvement and experience poorer LV mass regres-
sion at intermediate and long-term follow-up [3—5]. Despite
continuous improvement in design and manufacturing of
aortic valve biological substitutes, all of them produce a
certain degree of LV outflow obstruction. The variability in
residual gradients between different aortic bioprostheses
may be clinically relevant, whereas the surgical objective
sought is to minimize gradients for a given annular size.
We conducted a prospective randomized study comparing
two biological and last-generation supra-annular aortic valve
substitutes, the Edwards Perimount Magna (EPM) pericardial
www.elsevier.com/locate/ejcts
European Journal of Cardio-thoracic Surgery 39 (2011) 844—852
§Presented at the 24th Annual Meeting of the European Association for
Cardio-thoracic Surgery, Geneva, Switzerland, September 11—15, 2010.
* Corresponding author. Tel.: +34 923291263; fax: +34 923291263.
E-mail address: dalmau_mjo@gva.es (M.J. Dalmau).
1010-7940/$ — see front matter # 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.ejcts.2010.11.015
by Maria Jos? Dalmau Sorli on May 25, 2011 ejcts.ctsnetjournals.orgDownloaded from

Page 3

xenograft and the Medtronic Mosaic porcine bioprosthesis
(MM). With the aim to provide more objective data, both
devices were compared taking the diameter of the patient’s
aortic annulus as a reference rather than the less reliable
manufacturer’s labeled valve size [6]. The objective of this
study was to compare survival and hemodynamic perfor-
mance at 1 and 5 years after AVR, and to determine the
effects of valve hemodynamics on regression of LV hyper-
trophy.
2. Patients and methods
2.1. Patients
Between February 2004 and February 2006, a total of 116
consecutive patients scheduled to have bioprosthetic valve
replacement in the aortic position were randomized to
receive either an EPM valve or an MM bioprosthesis. Patients
undergoing an isolated AVR and those requiring associated
aortocoronary bypass grafting, ascending aortic surgery, or
tricuspid annuloplasty were included in the study. Exclusion
criteria were the replacement of more than one valve or a
pre-existing prosthetic valve in another position.
Appropriate institutional research ethics board approval
was obtained. Patients were informed of the study and
provided written consent.
Preoperative, postoperative 12-month and 5-year patient
characteristics were extracted from databases constructed
during follow-up phases of this randomized trial. The medical
records and the echocardiographic outcomes at 1 and 5 years
were analyzed. We compared demographics, preoperative
clinical data, operative data, hemodynamic profiles, and
clinical outcomes at 1 and 5 years. Primary outcomes
included transvalvular gradients, effective orifice areas
(EOAs), and the regression of LV mass index (LVMI) measured
with two-dimensional (2D) echocardiography at 1 and 5
years. Survival and clinical outcomes were secondary end
points in this follow-up study.
2.2. Sample size
Based on earlier studies on LVMI regression after AVR with
the Carpentier—Edwards Perimount prosthesis [7], an
incidence of 41% patients having any residual LV hypertrophy
1 year after surgery was assumed and, therefore, was chosen
to determine the sample size of our study. Our objective was
to demonstrate that the incidence of successful LV hyper-
trophy regression with the MM valve would be <20% than that
with the EPM prosthesis. A total of 86 patients in two
randomized groups was required to declare a significant
difference with a b = 0.8 and a = 0.05.
2.3. Randomization
The randomization was computer generated and incorpo-
rated into sealed envelopes to allow for consecutive intra-
operative allocation. Randomization was performed in the
operating theater using the sealed envelope technique after
patient eligibility was confirmed. Patients were randomized
to receive either the EPM valve or the MM valve. After
randomization and because of procedural difficulties, two
patients randomized to receive a Magna valve received a
Mosaic valve, and two randomized to receive a Mosaic valve
received a Magna, instead. A total of 108 hospital survivors
were finally included in the study and comprised 54 patients
with a Mosaic and 54 with a Magna valve.
2.4. Operative technique
Operations were performed using standard cardiopulmon-
ary bypass techniques, including mild systemic hypothermia
and both antegrade and retrograde cold blood cardioplegia.
Thenativeaorticvalvewasexcisedandtheexactinneraortic
annular diameter was assessed based on manual measure-
ments using standardized metric sizers (graduated in
millimeters). Thereafter, sizing for both valve types was
undertaken in each patient using the appropriate original
sizer provided by each manufacturer before the randomiza-
tion envelope was opened.
Surgeons were extremely consistent in selecting similar
valve sizes for a given annular diameter, regardless of
prosthesis type and avoided any oversizing. As such, each
surgeon was required to commit to a specific valve size
before valve selection. This protocol was designed to prevent
surgeon-specific selection bias. All valves were implanted in
the supra-annular position using interrupted, pledget-
supported, non-everting mattress sutures. No patients
underwent annular enlargement procedures.
For the purpose of the study and further comparisons,
patients were stratified for annulus size in three categories:
<22 mm, 22—23 mm, and >23 mm.
2.5. Bioprostheses
The third-generation MM bioprosthesis (Medtronic, Inc,
Minneapolis,MN,USA)isastentedporcineheartvalve,whichis
fixed with glutaraldehyde by using a combination of the zero-
pressure and root-pressure methods to preserve the natural
morphology of the fibers in the leaflets. The Mosaic tissue is
treated with alpha-amino-oleic acid to reduce the buildup of
calcium.Ithasbeeninclinicalusesince1994(Europe)and2000
(United States), respectively, and its hemodynamic perfor-
manceandfreedomratesfromadverseeventshavebeenfound
to be highly satisfactory [8]. Introduced in 2002, the
Carpentier—EdwardsPerimount
(Edwards Lifesciences LLC, Irvine, CA, USA) is a modification
ofthestandardPerimountvalve.TheEPMprosthesisconsistsof
bovinepericardiummountedonanElgiloyframe.Thecuspsare
fixedwithglutaraldehydeatlowpressureandaretreatedwith
surfactant combined with thermal treatment (XenoLogiX and
ThermaFix processes) to retard calcification. The EPM is
characterized by a design specifically intended for supra-
annular positioning that is claimed to have better hemody-
namic and flow characteristics. Although its short-term
hemodynamic performance was proved to be superior to that
of the Perimount standard model [9], up until now, the long-
termhemodynamicresultsofEPMprosthesesarenotavailable.
Nevertheless, the Perimount standard bioprosthesis has been
in clinical use since 1981 and its long-term clinical and
hemodynamic results have previously been reported to be
excellent [10].
Magnaaorticxenograft
M.J. Dalmau et al./European Journal of Cardio-thoracic Surgery 39 (2011) 844—852
845
by Maria Jos? Dalmau Sorli on May 25, 2011 ejcts.ctsnetjournals.orgDownloaded from

Page 4

Comparison of valve performance requires uniform
measurements of valve size; and manufacturer’s labeled
valve size has no standard and can be misleading [11].
Labeled valve size is related to different features of the
externaldiameteroftheprostheses;thus,theinternalorifice
for a given valve size may vary widely among types of
prostheses. In general, the inner diameter of the MM
prosthesis is smaller across all sizes than the inner diameter
of the EPM prosthesis, whereas the external sewing ring
diameter of the MM valve is 1 mm larger in sizes 19 and 21;
2 mm larger in size 23; and 3 mm larger in sizes 27 and 29 in
comparison to the EPM valve.
2.6. Echocardiographic assessment
Patients were followed up by transthoracic Doppler
echocardiography at 1 year (median 12 ? 1.5 months) and
5 years postoperatively (median 4.9 ? 0.8 years). The
modified Bernoulli equation was used to calculate peak
and meanpressure gradients acrosstheprosthetic valve. EOA
was calculated by the continuity equation and indexed to
bodysurfaceareatoassessthepresence ofPPM.Accordingto
previous investigations [4,5], PPM was considered as not
significant (i.e., mild or no PPM), if the indexed EOA was
>0.85 cm2m?2; significant PPM was defined by indexed
EOA ? 0.85 cm2m?2; and severe mismatch if indexed EOA
was 0.65 cm2m?2or less. LV dimensions were measured
according to the recommendations of the American Society
ofEchocardiography(ASE).LVmass(LVM)wascalculatedwith
the corrected ASE formula as follows [12]: LVM = 0.8 1.04
(IVSd+ LVIDd+ PWTd)3 ? LVIDd3 + 0.6, where IVSdis the end-
diastolic interventricular septum thickness, LVIDdis the LV
end-diastolic internal diameter, and PWTd is the LV end-
diastolic posterior wall thickness. Residual LV hypertrophy
was defined as an LVM index >131 g m?2in males and
>100 g m?2in females. LVM regression was calculated by
subtracting the mass index at follow-up from the mass index
preoperatively.
2.7. Statistical analysis
Thestatistical analysiswasperformed usingtheStatistical
Package for Social Sciences (SPSS) 17.0 statistical software
for Windows (SPSS Inc., Chicago, IL, USA). Continuous
variables were expressed as mean values ? standard devia-
tion (SD) and time variables as median values ? SD.
Comparisons were performed using a t-test in case of normal
data distribution and the Mann—Whitney U test in case of not
normally distributed data. For measurements within groups
over time, paired t-test or Wilcoxon test were applied.
Categorical variables were presented as frequencies and
percentages. Associations among categorical variables were
compared by Pearson’s x2test or Fisher’s exact test as
appropriate. Statistical analysis of the association of
variables was performed with the Pearson (r) or Spearman
(rs) correlation coefficients. After univariate analysis, we
include significative variables in a multivariate logistic
regression model. A stepwise backward elimination using
the likelihood ratio test with elimination defined by a p-value
of 0.1 or greater was performed. For each of the explanatory
variables, we calculated the coefficient, the odds ratio (OR)
and the confidence interval (CI). Survival curves were
determined by means of Kaplan—Meier method, and
comparisons were made using a log-rank test. Statistical
significance was defined as a p value of <0.05.
3. Results
A total of 112 consecutive patients selected for elective
bioprosthetic AVR were prospectively assigned to receive
either an EPM valve or an MM bioprosthesis. There were four
perioperative deaths, none related to the implanted
prosthesis. Thus, a total of 108 hospital survivors (EPM
n = 54, MM n = 54) were finally included in the study. Patient
preoperative characteristics and operative data were similar
for both groups (Table 1).
Based on manufacturer’s labeled size, there was a
difference of borderline statistical significance in mean
implanted valve size between groups (EPM 22.7 ? 1.9 mm vs
MM 23.4 ? 2.1 mm, p = 0.051). However, actual internal
annular diameters were not significantly different in both
groups (EPM 23.8 ? 2.1 mm vs MM 23.4 ? 2.3 mm; p = 0.8).
Patients were grouped by intra-operatively measured aortic
annulus diameter (AAD) as follows: <22 mm (n = 16), 22—
23 mm (n = 39) and >23 mm (n = 53).
3.1. Hemodynamic measurements
Among 108 patients participating in this trial, a total of
106 patients were echocardiographically evaluated at a
median follow-up of 12 months, with a complete follow-up in
98% of the patients. Five-year echocardiograms were
performed on 87 of 94 eligible patients (92%).
Comparisons of hemodynamic data for both valve types at
1- and 5-year follow-up are listed in Table 2. The EPM
prosthesis showed significantly lower mean transvalvular
M.J. Dalmau et al./European Journal of Cardio-thoracic Surgery 39 (2011) 844—852
846
Table 1. Preoperative patient characteristics and surgical data.
EPM (n = 54)MM (n = 54)p value
Gender (male/female)
Age
Body surface area (m2)
EuroSCORE (additive)
NYHA functional class
NYHA I—II
NYHA III—IV
Aortic valve lesion
Stenosis
Insufficiency
Mixed
Etiology
Rheumatic
Calcific
Additional procedures
CABG
TA
AAS
CPB time (min)
Aortic cross-clamp time (min)
Isolated procedures
Combined procedures
34/20
75.6 ? 4.5
1.75 ? 0.16
6.54 ? 1.6
32/22
75.4 ? 4.2
1.73 ? 0.14
6.54 ? 1.8
0.69
0.77
0.32
1.00
0.31
32 (59%)
22 (41%)
34 (62%)
20 (37%)
0.09
29 (54%)
9 (17%)
16 (29%)
26 (48%)
4 (8%)
24 (44%)
0.15
5 (9%)
49 (91%)
1 (2%)
53 (98%)
0.87
17 (31%)
3 (5%)
4 (7%)
108 ? 33
16 (30%)
2 (4%)
5 (9%)
103 ? 320.44
67 ? 14
96 ? 27
62 ? 13
94 ? 20
0.14
0.77
EPM: Edwards Perimount Magna; MM: Medtronic Mosaic; CABG: coronary artery
bypass graft; TA: tricuspid annuloplasty; AAS: ascending aorta surgery; CPB:
cardiopulmonary bypass. Variables are presented as mean ? SD values or as
number of patients (%).
by Maria Jos? Dalmau Sorli on May 25, 2011 ejcts.ctsnetjournals.orgDownloaded from

Page 5

gradients at 1 and 5 years than did MM valves (EPM
10.3 ? 3.4 mmHg vs MM 16.3 ? 7.6 mmHg, p < 0.0001; EPM
9.6 ? 3.5 mmHg
Further, average EOAs were significantly larger at these
time points (p = 0.001, p < 0.0001). Similarly, 1 and 5 years
echocardiographic studies revealed significantly greater
indexed effective orifice areas (IEOAs) in the EPM group:
EPM 1.10 ? 0.22 cm2m?2versus MM 0.96 ? 0.22 cm2m?2
(p = 0.004);EPM 1.02 ? 0.25 cm2m?2
0.76 ? 0.19 cm2m?2(p < 0.0001).
Similar hemodynamic performance of both prosthesis
types was observed when patients were grouped according to
AAD (Table 3). Further, for each AAD group, mean pressure
gradients at 1 and 5 years were slightly lower for the EPM
valves. This difference was statistically significant in patients
with an AAD of 22—23 mm and >23 mm. Accordingly,
significantly larger EOAs were obtained for each AAD group
vsMM16.8 ? 8.7 mmHg,p < 0.0001).
versus MM
at 1 and 5 years, especially in AAD of 22—23 mm (p < 0.01).
Similarly, in each AAD group, the EPM prosthesis showed
slightly higher IEOA, reaching statistical significance in AAD
of 22—23 mm and >23 mm. No hemodynamic differences
were demonstrated in patients with an AAD of <22 mm,
although an obvious trend toward better hemodynamics was
also seen in this group.
These differences were also apparent between groups
when compared by industry-labeled valve size (Table 4).
When comparing individual prosthesis sizes, EPM prostheses
showed significantly lower mean transvalvular gradients and
larger IEOAs at 1 and 5 years, reaching statistical significance
when comparing the 21-mm, 23-mm and 25-mm labeled
valves.
Hemodynamic data for both prosthesis types revealed
significant changes over time (Table 2). The mean changes in
peak transprosthetic gradients between 1- and 5-year
M.J. Dalmau et al./European Journal of Cardio-thoracic Surgery 39 (2011) 844—852
847
Table 2. Echocardiograms 1 and 5 years postoperatively.
1 year 5 yearsDifferences 1 year
vs 5 years
p value 1 year
vs 5 years
Peak gradient (mmHg)
Magna
Mosaic
p value
Mean gradient (mmHg)
Magna
Mosaic
p value
EOA (cm2)
Magna
Mosaic
p value
Indexed EOA (cm2m?2)
Magna
Mosaic
p value
PPMa
Magna
Mosaic
p value
19.7 ? 6.1
30.4 ? 4.6
<0.0001
20.8 ? 6.3
36.2 ? 16.6
<0.0001
+ 1.3 ? 6.0
+ 4.8 ? 9.7
0.04
0.11
0.001
10.3 ? 3.4
16.3 ? 7.6
<0.0001
9.6 ? 3.5
16.8 ? 8.7
<0.0001
? 0.5 ? 3.6
+ 0.2 ? 6.1
0.6
0.3
0.9
1.94 ? 0.44
1.66 ? 0.40
0.001
1.81 ? 0.51
1.31 ? 0.32
<0.0001
? 0.13 ? 0.34
? 0.35 ? 0.21
0.02
0.1
<0.0001
1.10 ? 0.22
0.96 ? 0.22
0.004
1.02 ? 0.25
0.76 ? 0.19
<0.0001
? 0.09 ? 0.21
? 0.19 ? 0.11
0.02
0.009
<0.0001
9.2%
30.1%
0.006
22.9%
73.9%
<0.0001
+13.6%
+43.8%
0.01
0.007
<0.0001
EOA: effective orifice area; PPM: patient—prosthesis mismatch.
aIndexed EOA < 0.85 cm2m?2.
Table 3. Hemodynamic performance at 1 and 5 years postoperatively according to aortic annulus diameter.
Size1 year follow-up (98%)5 years follow-up (92%)
Magna Mosaicp value MagnaMosaicp value
AAD <22 (n = 16)
Mean gradient (mmHg)
EOA (cm2)
IEOA (cm2m?2)
PPM
AAD 22—23 mm (n = 39)
Mean gradient (mmHg)
EOA (cm2)
IEOA (cm2m?2)
PPM
AAD >23 mm (n = 53)
Mean gradient (mmHg)
EOA (cm2)
IEOA (cm2m?2)
PPM
11.4 ? 4.6
1.60 ? 0.29
0.98 ? 0.19
16.6%
18.6 ? 9.9
1.44 ? 0.30
0.90 ? 0.23
30%
0.07
0.3
0.5
0.5
14.4 ? 2.7
1.27 ? 0.25
0.79 ? 0.17
30%
15.8 ? 4.3
1.23 ? 0.28
0.77 ? 0.20
71%
0.4
0.7
0.8
0.5
10.1 ? 3.3
1.77 ? 0.41
1.03 ? 0.23
11.7%
17.7 ? 7.9
1.50 ? 0.18
0.88 ? 0.08
33.3%
<0.001
<0.01
<0.01
<0.05
10.58 ? 4.4
1.72 ? 0.50
1.00 ? 0.24
21.4%
18.8 ? 12
1.22 ? 0.22
0.72 ? 0.13
84%
<0.02
<0.01
<0.001
<0.0001
10.2 ? 3.3
2.11 ? 0.42
1.14 ? 0.20
6.4%
13.8 ? 5.3
1.90 ? 0.47
1.06 ? 0.27
27.3%
<0.003
0.1
0.2
<0.04
8.3 ? 2.1
1.95 ? 0.49
1.07 ? 0.25
17.2%
15.1 ? 5.6
1.46 ? 0.38
0.80 ? 0.22
64.7%
<0.0001
<0.001
<0.001
<0.002
AAD: aortic annulus diameter; EOA: effective orifice area; IEOA: indexed effective orifice area; PPM: patient—prosthesis mismatch.
by Maria Jos? Dalmau Sorli on May 25, 2011 ejcts.ctsnetjournals.org Downloaded from

Page 6

echocardiograms were +1.39 mmHg for EPM prostheses
(p = 0.1)and+4.81 mmHgforMMvalves(p = 0.001).Changes
after 5 years in peak transvalvular gradients between EPM
and MM prostheses were statistically significant (p = 0.04).
Similarly, changes over time with respect to EOA and IEOA
were relevant between both bioprostheses (p < 0.02), the
mean change in IEOA being ?0.09 cm2m?2
prostheses (p = 0.009) and ?0.19 cm2m?2for MM valves
(p < 0.0001, Fig. 1).
A significant correlation between IEOAs and mean
transvalvular gradients weredemonstrated inboth subgroups
at 1 year (EPM group r = ?0.366, p < 0.006; MM group,
r = ?0.365, p < 0.007) and 5 years (EPM group, r = ?0.634,
p < 0.0001; MM group, r = ?0.325, p = 0.02).
The prevalence of significant PPM was different according
to the type of the implanted bioprosthesis (Table 2). At first
year, 30.1% of patients with an MM valve had an
IEOA ? 0.85 cm2m?2, whereas this occurred only in 9.2%
of those with an EPM valve (p = 0.006). This difference
increasedovertimeand,after5years,differenceswereeven
more distinctive (EPM 22.9% vs MM 73.9%, p < 0.0001). At 1
[()TD$FIG]
for EPM
year, severe mismatch occurred in 7.5% of MM valves
compared with 1.8% EPM valves (p < 0.005) and, at 5 years,
the prevalence of severe PPM was 32.5% in the MM group and
4% in the EPM group (p < 0.0001). The presence of PPM was
different according to the valve type and the AAD (Table 3). A
significant percentage of patients with small AAD (<22 mm)
showed a mismatch in both groups at 1 years (MM 30.1% vs
EPM 16.6%) and 5 years (MM 71% vs EPM 30%). In the EPM
group, the incidence of significant PPM decreased with
increasing AAD; however, in the MM group, PPM was present
constantly in all AAD.
Changes in LVM and LVMI between preoperative echocar-
diographicmeasurementsandfollow-upareshowninTable5.
There was no difference between groups in baseline values of
LVM (p = 0.5) or LVMI (p = 0.6). During the first year after
implantation, LVM and LVMI significantly decreased in both
groups. At this time point, there were no significant
differences between both valve types regarding absolute
LVM regression (EPM ?49.2 ? 59.3 vs MM ?51.5 ? 77.0) and
absoluteLVMI reduction(EPM
?26.3 ? 43.8). Neither valve had a significant early size-
related advantage when patients were stratified by AAD.
Mass regression continued up to 5 years in the EPM group,
although most of the effects occurred during the first
postoperative year. Between the first and fifth year post-
operatively, ventricular mass remained relatively stable and
did not experience further regression in patients with MM
valves while decreasing in patients with EPM prostheses to a
significant degree. Therefore, the absolute LVM regression at
5 years’ follow-up was significantly greater in patients with
EPM prosthesis (EMP ?82.6 ? 61.1 vs MM ?10.4 ? 63.4;
p < 0.0001). A similar trend was demonstrated with respect
to LVMI, which decreased significantly over time in the EPM
group (Fig. 2). At 5 years, differences in LVMI reduction were
statistically significant in favor of the EPM prostheses (EPM
?47.4 ? 35.1 vs ?4.3 ? 36.1; p < 0.0001).
By means of simple linear regression analysis, relation-
ships between absolute LVM index regression were correlated
to the 5-year IEOA with r = ?0.484 (p < 0.001); to the mean
transprosthetic gradientat5yearswithr = 0.310(p = 0.002);
and to the presence of patient prosthesis mismatch with
rs= 0.475 (p < 0.0001).
?30.0 ? 36.2 vsMM
M.J. Dalmau et al./European Journal of Cardio-thoracic Surgery 39 (2011) 844—852
848
Table 4. Hemodynamic performance at 1 and 5 years postoperatively according to labeled valve size.
Size1 year follow-up (98%)5 years follow-up (92%)
MagnaMosaicp valueMagnaMosaicp value
19 mm (n = 3)
MG (mmHg)
IEOA (cm2m?2)
21 mm (n = 34)
MG (mmHg)
IEOA (cm2m?2)
23 mm (n = 41)
MG (mmHg)
IEOA (cm2m?2)
25 mm (n = 17)
MG (mmHg)
IEOA (cm2m?2)
27 mm (n = 13)
MG (mmHg)
IEOA (cm2m?2)
15.2 ? 4.3
0.87 ? 0.21
13.9
0.95
0.8
0.8
15.5 ? 4.9
0.69 ? 0.14
16.0
0.69
0.9
0.9
11.2 ? 3.2
0.99 ? 0.21
22.3 ? 10.7
0.83 ? 0.14
<0.0001
<0.01
11.3 ? 3.8
0.90 ? 0.15
22.9 ? 14
0.67 ? 0.15
<0.003
<0.001
0.98 ? 3.4
1.16 ? 0.21
15.2 ? 5.5
0.98 ? 0.17
<0.001
<0.005
8.6 ? 2.5
1.12 ? 0.28
14.3 ? 3.3
0.77 ? 0.14
<0.0001
<0.0001
8.1 ? 2.2
1.22 ? 0.18
11.1 ? 3.5
1.00 ? 0.24
<0.05
<0.05
7.5 ? 2.3
1.18 ? 0.23
10.1 ? 5.6
0.77 ? 0.20
<0.05
<0.007
10.6 ? 3.2
1.04 ? 0.01
14.5 ? 4.3
1.06 ? 0.34
0.1
0.9
8.6 ? 1.4
0.87 ? 0.06
17.6 ? 4.8
0.85 ? 0.2
<0.01
0.9
MG: mean gradient; IEOA: indexed effective orifice area.
Fig. 1. Mean indexed effective orifice areas (95% confidence intervals) of
Mosaic and Magna prosthesis at 1 and 5 years after aortic valve replacement.
IEOA: indexed effective orifice area.
by Maria Jos? Dalmau Sorli on May 25, 2011 ejcts.ctsnetjournals.orgDownloaded from

Page 7

Although there was an LVMI reduction in both groups, the
average LVMI at 5 years forthe entire series remained greater
than normal in 42.8% of the patients; 60.5% of MM patients
and 27.1% of EPM patients had LV hypertrophy 5 years after
surgery (x2, p = 0.002). A multivariate logistic regression
analysis revealed the MM valve to be strongly associated with
residual LV hypertrophy (OR 10.7, 95% CI 2.6—44.1,
p = 0.001). IEOA at 5 years was also identified as a predictor
of residual LV hypertrophy (OR 12.6, 95% IC 1.7—21.8,
p = 0.005). Neither mean gradients nor the IEOA and PPM at 1
year were statistically significant when using multivariate
modeling.
At 5-year follow-up, overall survival (freedom from all-
cause mortality) was 79.6% ? 4.1% in the MM group (11
patients) and 94.4 ? 2.2% (three patients) in the EPM group
(p = 0.039,Fig.3).Simplelinearregressionanalysisshoweda
correlation, between time of survival and the absolute LVMI
regression at 5 years (r = ?0.23, r2= 5%, p = 0.03).
Duringfollow-up,threepatientsinEPMgroup(5.6 ? 0.1%)
and 11 patients in MM-group (20.4 ? 0.2%) died. Death
occurredinthefirstyearin1.8%ofMMpatientsversusnoneof
the EPM patients; and, between the first and fifth year, three
patients in the EPM group (5.6 ? 0.1%) versus 10 patients in
the MM group (18.5 ? 0.2%) died. All deaths were not related
to the valve. Causes of death were malignancies in one EPM
[()TD$FIG]
and three MM patients. One EPM patient and three MM
patients died of infections. Three MM patients died of multi-
organ failure after abdominal or urologic surgery. Neurolo-
gical events were the cause of death in one patient of each
group. There was no endocarditis or valve thrombosis. One
patient in the MM group underwent re-operation for new
onset mitral regurgitation and did not survive due to
perioperative complications.
Good hemodynamic function was documented in the
majority of patients on follow-up echocardiographic mea-
surements. Four patients in the MM group presented
significant transvalvular stenosis with reduced prosthetic
areas and transvalvular flow velocities >4 m s?1, all four
patients being less symptomatic.
4. Discussion
The aims of AVR include a reduction of transvalvular
gradients to minimal levels, an increase in EOA to allow
maximal forward flow and a complete regression of LV
hypertrophy. Maximization of EOA area and minimization of
[()TD$FIG]
M.J. Dalmau et al./European Journal of Cardio-thoracic Surgery 39 (2011) 844—852
849
Table 5. Echocardiograms 1 and 5 years postoperatively.
Preoperative1 year5 yearsp value (preop vs 1 y)p value (preop vs 5 y)
LV mass (g)
Magna
Mosaic
p value
LVM index (g m?2)
Magna
Mosaic
p value
Regr. LVM (g)
Magna
Mosaic
p value
Regr.LVMI (g m?2)
Magna
Mosaic
p value
259.5 ? 71.0
271.4 ? 87.1
0.5
222.5 ? 59.5
220.7 ? 74.8
0.8
175.1 ? 38.5
226.9 ? 82.1
<0.0001
<0.0001
0.008
<0.0001
0.3
149.3 ? 40.9
152.7 ? 43.7
0.6
125.6 ? 30.4
125.8 ? 42.6
0.4
99.7 ? 20.4
129.6 ? 42.1
<0.0001
<0.0001
0.01
<0.0001
0.5
? 49.2 ? 59.3
? 51.5 ? 77.0
0.8
? 82.6 ? 61.1
? 10.4 ? 63.4
<0.0001
<0.0001
0.1
? 30.0 ? 36.2
? 26.3 ? 43.8
0.8
? 47.4 ? 35.1
? 4.3 ? 36.1
<0.0001
<0.0001
0.08
LVM: left ventricular mass; LVMI: left ventricular mass index; Regr.: regression.
Fig. 2. Regression of left ventricular mass index (LVMI) over time in patients
with Magna (broken line) and Mosaic (solid line) aortic valve prosthesis.
Fig.3. Actuarialoverallsurvivalafterstentedbovineaorticvalvereplacement
(broken line), and stented porcine aortic valve replacement (solid line).
by Maria Jos? Dalmau Sorli on May 25, 2011 ejcts.ctsnetjournals.orgDownloaded from

Page 8

transprosthetic gradient are seen as the hemodynamic
objectives for an aortic prosthesis. Compelling evidence
suggests that persistently elevated transvalvular gradients
negatively affect the optimal regression of LV hypertrophy
[1,13]. Stented biologic aortic substitutes, both porcine and
bovine, are prone to generate some postoperatively
transvalvular gradients due to suboptimal leaflet opening
and obstruction by sewing rings and stents. The ratio of flow
orificediametertoexternalvalvemountingdimensionsisone
of the most important determinants of a heart valve’s
hemodynamic potential; therefore, changes in design of new
aortic prostheses seek to maximize the ratio between EOA
and the tissue annulus, to minimize pressure gradients.
Significant variability between the manufacturer’s pro-
videdactualdimensionsoftheprosthesisleadtoquestionthe
scientific value of comparisons based only on the industry
labeled valve size [11]. However, comparisons performed in
relation to the actual dimensions of the native aortic
annulus, an independent parameter of valve size, appear
to offer more objective data [6]. The hemodynamic results of
the current study are depicted according to the AAD, which
was measured intra-operatively with a standardized metric
sizer, as well as referring to the industry labeled valve size.
When labeled valve sizes were compared, 1 and 5 years’
data clearly showed the hemodynamic advantage of the EPM
prosthesis, especially in valve sizes 21, 23, and 25 mm. This
can be explained because the size-matched internal
diameter of the EPM prosthesis is between 1.5 and 2.0 mm
larger than the respective manufacturer-reported internal
diameter of the MM valve [14]. Upon implanting valves with
larger internal diameters, the current study demonstrated
the resultant hemodynamic advantages of the EPM prosthe-
sis: lower mean pressure gradients and larger EOA. These
findings correlated closely with previously published studies
comparing the Mosaic and Perimount standard valves
[6,15,16] and confirm the observed hemodynamic superiority
of the new Magna prosthesis compared with Mosaic valves
observed in short-term follow-up studies [17,18] and
differences being more distinctive under stress conditions
[19].
Similarly, the results of our study indicated that the
overall hemodynamic performance of the Magna valve was
superior to the Mosaic prosthesis even when their perfor-
mance was related to the inner diameter of the aortic
annulus. In patients with an AAD < 22 mm, the implanted
valve did not influence the hemodynamic outcome after AVR,
although the number of patients in this group (EPM n = 7 and
MM n = 9) was too small to permit meaningful analyses. By
contrast, in AAD of 22—23 mm and >23 mm, the EPM
prosthesis was significantly superior regarding mean pressure
gradient, EOA and IEOA at 1 and 5 years. These differences
definitively demonstratethehemodynamic advantage ofEPM
valves: upon maximizing the ratio EOA/tissue annulus, the
third-generation Magna prosthesis achieved a reduction of
transvalvular pressure gradients and increased EOAs in
comparison to MM valves.
In the current study, echocardiographic quantification of
IEOA, the only valid parameter that identifies PPM [20], has
been employed to define PPM. The hemodynamic conse-
quence ofmismatchistogenerate highresidualtransvalvular
gradients, which are responsible for an incomplete LVM
regression [7], a phenomenon associated with a negative
effect on intermediate and long-term survival [4]. The
incidence of PPM was statistically different between groups.
In the first year, PPM was present in 30.1% of patients with an
MM valve and in 9.2% of those with an EPM valve. This
difference increased over time and, after 5 years, the
differences were more distinctive (EPM 22.9% vs MM 73.9%).
At 1 and 5 years, the prevalence of severe mismatch was
significantly higher in the MM group. Our data confirm the
outcomes reported in other studies [17—19,21] and showed
that the use of an EPM valve may contribute to reduce the
incidence of PPM, even in patients with a small AAD.
When analyzing the effect of PPM on the hemodynamic
results, the transprosthetic pressure gradient is expected to
decrease with increasing IEOA, a correlation that could be
demonstrated in both groups at 1 and 5 years. Nevertheless,
at 1 year, the effect of PPM magnitude on LVM regression was
less evident. At this time point, our patients showed a
significant regression in LVM and LVMI, irrespective of
prosthesis type or AAD, the LVMI reduction being similar
for both groups. The absence of differences in early LVM
regression seen in our series confirm findings of other studies
showing equivalent LVM regression after 1 year with Mosaic
and pericardial Edwards Perimount valves [15,16]. Never-
theless, it is assumed that mass regression is a continuing
process and further reductions in LVM may occur up to 5 years
postoperatively [22]. Accordingly, a longer follow-up of our
patients has been necessary to determine whether the
difference between these prostheses increases over years.
Our study demonstrated that small differences at 1 year
increased over time and became statistically significant after
5 years. Between the first and fifth year postoperatively, LVMI
remained relatively stable in patients with MM valves, while
it decreased in patients with EPM prostheses to a significant
degree (EPM ?47.4 ? 35.1 vs ?4.3 ? 36.1; p < 0.0001)
(Fig. 2). The reduction of LVMIs observed in patients with
Magna prostheses are of special interest, with possible
clinical implications, which could only be elucidated with
future studies designed and powered to detect differences in
clinical event rates.
A large amount of literature is available on the effect of
AVR on LV hypertrophy regression. However, there are very
few studies directly addressing this issue in relation to PPM.
In a study including 1103 patients with a porcine biopros-
theticvalve,DelRizzoandco-workers[13]foundastrongand
independent relationship between IEOA and the extent of
LVM regression following AVR. There was a mean decrease in
LVM of 23% in patients with an IEOA > 0.8 cm2m?2compared
with only 4.5% in those with an IEOA ? 0.8 cm2m?2
(p = 0.0001). In contrast to these results, Hanayama and
co-workers [23] found no significant relationship between
PPM and regression of LV hypertrophy in a retrospective
study.ThemajorfindingofourstudywasthatIEOA(i.e.,PPM)
was associated with lesser regression of LVM after AVR. This
finding was consistent with the pressure gradient—IEOA
relation, whereby the pressure gradient and, thus, the LV
workload increase markedly when the IEOA falls below 0.8—
0.9 cm2m?2[20,24]. In the current study, absolute LVMI
regression was correlated with the 5-year IEOA, to the mean
transprosthetic gradient at 5 years and to the presence of
PPM at 5 years. Our study demonstrated that patients with
M.J. Dalmau et al./European Journal of Cardio-thoracic Surgery 39 (2011) 844—852
850
by Maria Jos? Dalmau Sorli on May 25, 2011 ejcts.ctsnetjournals.org Downloaded from

Page 9

MM prostheses showed over time a progressive rise of
transprostheticgradients
p = 0.001),whiledecreasing
p < 0.0001). Consequently, an increase in prevalence of
PPM was observed, the presence of mismatch being greater
than 70% at 5 years. These factors may have been responsible
for the poorer extent of LVMI regression seen in this group of
patients.
Although the reduction in LVM was evident in our patients,
theaveragepostoperativeLVMIfortheentireseriesremained
greater than normal in 42.8% of the patients, and 60.5% MM
versus 27.1% EPM patients had LV hypertrophy 5 years after
surgery (p = 0.002). Furthermore, when multivariate model-
ing was used, the MM valve and the IEOA at 5 years have been
identified as independent predictors of residual LV hyper-
trophy. The reasons for incomplete hypertrophy regression
aremainlyduetoresidualaorticgradientsandPPM;however,
other hemodynamic and non-hemodynamic factors such
suboptimal hypertension treatment, physical activity, geno-
type (angiotensin phenotype expression), and the environ-
ment can also affect the degree of mass regression [25].
Previous studies have reported that PPM after AVR is
associated with inferior hemodynamics, incomplete LVM
regression, more cardiac events and higher mortality rates,
all these factors affecting negatively intermediate and long-
term survival [1,2,4,5]. The results of the present study
suggest that the persistence of LV hypertrophy associated
with PPM may be one of the factors contributing to worse
clinical outcomes. Accordingly, our study showed that there
was a significant difference in survival between groups (79%
MM vs 94% EPM) (Fig. 3), and simple linear regression analysis
demonstrated a correlation between the LVMI regression at 5
years and time survival.
Although, the overall mortality was acceptable when
considering patient age, during the follow-up period of 5
years, 20.4% ofthe patients after MM and 5.4% of thepatients
after EPM died of different, mostly non-valve-related,
causes. Nonetheless, in the majority of patients surviving
follow-up, a good hemodynamic functionwas documented on
echocardiographic measurements and both the porcine and
pericardial aortic valve types provided good clinical out-
comes with acceptable survival at medium-term follow-up.
Additional advantages of the Magna prostheses, if any, will
only be determined through long-term follow-up to assess
late patient outcome and valvular durability.
The study has a number of limitations. First, although our
original study was randomized in nature, patient numbers
were too small to enable any definitive conclusions regarding
group-related differences in midterm mortality or clinical
outcome. The study was primarily concerned with hemody-
namic function and was not powered to detect small
differences in clinical event rates. Second, operations were
performed in a group practice with multiple surgeons;
although all of them used a similar surgical implantation
technique, we cannot exclude the fact that small differences
in sizing tendencies exist, leading to this issue becoming a
possible confounding factor. Third, although 5-year echo-
cardiograms were performed on 87 of 94 eligible patients
(92%), seven surviving subjects could not have echocardio-
graphy at 5 years due to co-morbidities. Fourth, this study
reports information up to only 5 years, and it is possible that
(peakgradient + 4.8 mmHg,
IEOAs(?0.19 cm2m?2;
late event rates or durability may differ between groups.
Finally, the regression of LVM is indeed a complex phenom-
enon that is influenced by several patient-related and
prosthesis-related factors. Furthermore, non-hemodynamic
factors may also be involved in the process of LVM regression.
These factors were not measured in this study.
In conclusion, both porcine and pericardial aortic valves
were found to be suitable options for AVR. Our study clearly
demonstrates a favorable hemodynamic function of the
bovine pericardial Edwards Perimount Magna compared with
the porcine Medtronic Mosaic aortic valve prosthesis up to 5
years after implantation, thus achieving lower gradients and
larger IEOA. Although short-term follow-up did not show any
differences in LVM regression between both prostheses, with
longer-term follow-up, Magna valves were found to hemo-
dynamically outperform the Mosaic valves; and such
improvements positively affected LV hypertrophy regression.
In view of the above findings, we believe that patients clearly
benefit from the implantation of the EPM prosthesis, thus
resulting in a significantly superior hemodynamic perfor-
mance, a minimized risk of PPM, and a greater regression of
LV mass.
References
[1] Pibarot P, Dumesnil JG. Hemodynamic and clinical impact of prosthesis—
patientmismatch intheaortic valveposition anditsprevention.JAmColl
Cardiol 2000;36:1131—41.
[2] Rao V, Jamieson WR, Ivanov J, Armstrong S, David TE. Prosthesis—patient
mismatch affects survival after aortic valve replacement. Circulation
2000;102(19 Suppl. 13):III-5—9.
[3] Pibarot P,DumesnilJG, Lemieux M, Cartier P, Metras J, Durand LG. Impact
of prosthesis—patient mismatch on hemodynamic and symptomatic sta-
tus, morbidity and mortality after aortic valve replacement with a
bioprosthetic heart valve. J Heart Valve Dis 1998;7:211—8.
[4] Blais C, Dumesnil JG, Baillot R, Simard S, Doyle D, Pibarot P. Impact of
valve prosthesis—patient mismatch on short-term mortality after aortic
valve replacement. Circulation 2003;108:983—8.
[5] Fuster RG, Montero Argudo JA, Albarova OG, Sos FH, Lopez SC, Codoner
MB, Buendia Minano JA, Albarran IR. Patient—prosthesis mismatch in
aortic valve replacement: really tolerable? Eur J Cardiothorac Surg
2005;27:441—9.
[6] Seitelberger R, Bialy J, Gottardi R, Seebacher G, Moidl R, Mittelbock M,
SimonP,WolnerE.Relation betweensizeofprosthesisandvalvegradient:
comparison of two aortic bioprosthesis. Eur J Cardiothorac Surg
2004;25:358—63.
[7] Tasca G, Brunelli F, Cirillo M, DallaTomba M, Mhagna Z, Troise G, Quaini E.
Impact of valve prosthesis—patient mismatch on left ventricular mass
regression following aortic valve replacement. Ann Thorac Surg
2005;79:505—10.
[8] Riess FC, Cramer E, Hansen L, Schiffelers S, Wahl G, Wallrath J, Winkel S,
KremerP.ClinicalresultsoftheMedtronicMosaicporcinebioprosthesisup
to 13 years. Eur J Cardiothorac Surg 2010;37(1):145—53.
[9] Dalmau MJ, Marı ´agonza ´lez-Santos J, Lo ´pez-Rodrı ´guez J, Bueno M, Arribas
A. The Carpentier—Edwards Perimount Magna aortic xenograft: a new
design with an improved hemodynamic performance. Interact Cardiovasc
Thorac Surg 2006;5(3):263—7.
[10] Banbury MK, Cosgrove DM, Thomas JD, Blackstone EH, Rajeswaran J,
Okies E, Frater RM. Hemodynamic stability during 17 years of the
Carpentier—Edwards aortic pericardial bioprosthesis. Ann Thorac Surg
2002;73:1460—5.
[11] Christakis GT, Buth KJ, Goldman BS, Fremes SE, Rao V, Cohen G, Borger
MA, Weisel RD. Inaccurate and misleading valve sizing: a proposed
standard for valvesize nomenclature.
1998;66(4):1198—203.
[12] Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA,
Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT,
Sutton MS, Stewart WJ. Recommendations for chamber quantification: a
report from the American Society of Echocardiography’s Guidelines and
AnnThoracSurg
M.J. Dalmau et al./European Journal of Cardio-thoracic Surgery 39 (2011) 844—852
851
by Maria Jos? Dalmau Sorli on May 25, 2011 ejcts.ctsnetjournals.orgDownloaded from

Page 10

Standards Committee and the Chamber Quantification Writing Group,
developed in conjunction with the European Association of Echocardiog-
raphy, a branch of the European Society of Cardiology. J Am Soc Echo-
cardiogr 2005;18:1440—63.
[13] DelRizzoDF,AbdohA,CartierP,DotyDB,WestabyS.Factorsaffectingleft
ventricular mass regression after aortic valve replacement with stentless
valves. Semin Thorac Cardiovasc Surg 1999;11:114—20.
[14] Jamieson WER, Janusz MT, MacNab J, Henderson C. Hemodynamic com-
parison of second- and third-generation stented bioprostheses in aortic
valve replacement. Ann Thorac Surg 2001;71:S282—4.
[15] Suri RM, Zehr KJ, Sundt 3rd TM, Dearani JA, Daly RC, Oh JK, Schaff HV.
Left ventricular mass regression after porcine versus bovine aortic valve
replacement:arandomized
2009;88(4):1232—7.
[16] ChambersJB,RajaniR,ParkinD,RimingtonHM,BlauthCI,VennGE,Young
CP, Roxburgh JC. Bovine pericardial versus porcine stented replacement
aortic valves: early results of a randomized comparison of the Perimount
and the Mosaic valves. J Thorac Cardiovasc Surg 2008;136(5):1142—8.
[17] Ruzicka DJ, Hettich I, Hutter A, Bleiziffer S, Badiu CC, Bauernschmitt R,
Lange R, Eichinger WB. The complete supraannular concept: in vivo
hemodynamics of bovine and porcine aortic bioprostheses. Circulation
2009;120(September (11 Suppl.)):S139—45.
[18] Dalmau MJ, Marı ´a Gonza ´lez-Santos J, Lo ´pez-Rodrı ´guez J, Bueno M,
Arribas A, Nieto F. One year hemodynamic performance of the Perimount
Magna pericardial xenograft and the Medtronic Mosaic bioprosthesis in
the aortic position: a prospective randomized study. Interact Cardiovasc
Thorac Surg 2007;6(3):345—9.
[19] Wagner IM, Eichinger WB, Bleiziffer S, Botzenhardt F, Gebauer I, Guen-
zinger R, Bauernschmitt R, Lange R. Influence of completely supra-
annular placement of bioprostheses on exercise hemodynamics in
patients with a small aortic annulus. J Thorac Cardiovasc Surg
2007;133(5):1234—41.
[20] Pibarot P, Dumesnil JG, Cartier PC, Me ´tras J, Lemieux MD. Patient—
prosthesis mismatch can be predicted at the time of operation. Ann
Thorac Surg 2001;71:S265—8.
[21] Flameng W, Meuris B, Herijgers P, Herregods MC. Prosthesis—patient mis-
match is not clinically relevant in aortic valve replacement using the
Carpertier—Edwards Perimount valve. Ann Thorac Surg 2006;82:530—6.
[22] Krayenbuehl H, Hess OM, Monrad S, Schneider J, Mall G, Turina M. Left
ventricular myocardial structure in aortic valve disease before, interme-
diate, and later after aortic
1989;79:744—55.
[23] Hanayama N, Christakis GT, Mallidi HR, Joyner CD, Fremes SE, Morgan CD,
Mitoff PR, Goldman BS. Patient prosthesis mismatch is rare after aortic
valve replacement: valve size may be irrelevant. Ann Thorac Surg
2002;73:1822—9.
[24] Dumesnil JG, Yoganathan AP. Valve prosthesis hemodynamics and the
problem of high transprosthetic pressure gradients. Eur J Cardiothorac
Surg 1992;6:S34—8.
[25] Dellgren G, Eriksson MJ, Blange I, Brodin LA, Radegran K, Sylven C.
Aongiotensin-converting enzyme gene polymorphism influences degree
of left ventricular hypertrophy and its regression in patient undergoing
operation for aortic stenosis. Am J Cardiol 1999;84:909—13.
comparison.AnnThoracSurg
valvereplacement.Circulation
Appendix A. Conference discussion
Dr R. Dion (Genk, Belgium): This is a very detailed analysis from the
Salamanca group of the function of two bioprostheses in the aortic position.
The authors present overwhelming evidence of the superior hemodynamic
characteristics of the Edwards Perimount Magna. This leads to significantly
greater left ventricular mass regression, and even survival, at five years.
However, although the multivariate analysis identified the indexed orifice area
atoneandfiveyearsasindependentpredictors ofdeath,thecauses ofdeathin
this report are not all cardiac-related and therefore the statement must be
taken with caution.
Ialsoregrettheabsenceofstresstestsinthecomparisonoftheprostheses.
It might be that, in view of the presence of a muscular band in one of the
leaflets of the Mosaic prosthesis, the gradient during the stress test would rise
proportionately less than that of the pericardial prosthesis, because the
increased flow would force this leaflet open.
In the Mosaic group, the fact that the PPM, the mean gradient, and the
indexed effective orifice area are worst in the 22—23 aortic annulus diameter,
is certainly a matter of concern. It is not only in the small diameters but also in
the middle cohort of patients. Even in the greater than 23 aortic annulus
diameter group, the Mosaic yields a PPM at five years in 65% of the patients.
However, recently Jamieson has questioned the influence of a moderate
PPM on the postoperative evolution and underlined that only severe PPM,
<0.65 cm2m?2, is a problem. This leads to my first question. Why did the
authors choose not to follow only what happens in the patient with a severe
PPM? In the manuscript the authors only mention in the discussion that severe
PPM was present at one year in 7.5% of the Mosaic patients versus 1.8% in the
Perimount patients, and at five years, 32.5% versus 4%.
My second question would be, how do the authors explain the less evident
effect of PPM magnitude on the left ventricular mass regression at one year
compared to five years?
Dr Dalmau: In the manuscript we described the incidence of severe PPM in
our patients. Unfortunately an analysis of the effect of severe PPM on clinical
or hemodynamic outcomes has not been performed.
The second question, in the Magna group the prevalence of mismatch
increased over time, but we observed a greater increase in the Mosaic group.
This is explained because the achieved indexed effective orifice area in the
Mosaic group decreased significantly over time. As PPM is reflected, or is
defined by the indexed effective orifice area, when orifice areas decreased
over time, the prevalence of mismatching increased.
Dr Dion: So you believe you explain the difference in decrease of left
ventricular mass by the fact that the indexed orifice area is constantly
decreasing with time?
Dr Dalmau: Yes.
Dr F.C. Riess (Hamburg, Germany): I am very astonished, because our
results with long-term follow-up are in contrast to your findings. We had a
chance to take part in the FDA trial, and for the 300 cases we operated in our
center,wenowhave15years’follow-upavailable.Wefoundthatthegradients
are higher compared to other valves described in the literature, which is in
contrast to your results. By the way, we looked at each patient each year with
echocardiography, and we found very stable gradients, a very slight increase,
and a very small reduction of orifice area. So this is in contrast.
My questiontoyouis,howisthemeasurement oftheaorticrootperformed
by your surgeons? Do you use the original sizers or do you use metal devices?
Dr Dalmau: Before randomization, the aortic valve was excised, and the
aortic annulus diameter was assessed using standardized metric sizers. We
routinely don’t perform any oversizing and all valves were implanted in the
supra-annular position. Surgeons used the same surgical implantation
technique.
Dr Riess: My second question is, we found that for porcine valves, they
have very good closure compared with the pericardial valves. So my question
to you is, did you investigate with echocardiography and do you have some
details about how high the degree of regurgitation was after five years?
Dr Dalmau: Can you repeat the question.
Dr Riess: Concerning regurgitation: pericardial valves always have a small
amount of regurgitation because their closure is not so rapid as compared with
porcine valves. Did you look at the degree of regurgitation? How many patients
had regurgitation at the follow-up?
Dr Dalmau: All surviving patients were echocardiographically followed up
at five years, and we found no difference with respect to aortic valve
regurgitation between both prosthesis types.
Dr P. Myken (Gothenburg, Sweden): I agree with Professor Dion that there
mightbeotherreasonsthattheleftventricular massdecreasediffersafterfive
years. You have just 87 patients to follow-up at five years, and we don’t even
know how many in each group. Did you look at hypertension, which is more
relevant than the valves? It might even be that the valves are not that
important.
Dr Dalmau: Left ventricular mass regression is a complex phenomenon in
which several patient-related and prosthesis-related factors are involved.
Also, non-hemodynamic factors could affect LV mass regression. In our study,
the most important factor was the existence of residual transvalvular gradient
and the presence of patient—prosthesis mismatch. However, other factors,
such ashypertension, physical activity and genetic factors, were notmeasured
in this study, but they can also affect left ventricular mass regression. I agree
with you.
M.J. Dalmau et al./European Journal of Cardio-thoracic Surgery 39 (2011) 844—852
852
by Maria Jos? Dalmau Sorli on May 25, 2011 ejcts.ctsnetjournals.orgDownloaded from

Page 11

DOI: 10.1016/j.ejcts.2010.11.015
2011;39:844-852
Eur J Cardiothorac Surg
Sastre, Javier López-Rodríguez, María Bueno, Mario Castaño and Antonio Arribas
María José Dalmau, José María González-Santos, José Antonio Blázquez, José Alfonso

bioprostheses: five-year results of a prospectively randomized study
Hemodynamic performance of the Medtronic Mosaic and Perimount Magna aortic
This information is current as of May 25, 2011

& Services
Updated Information
http://ejcts.ctsnetjournals.org/cgi/content/full/39/6/844
including high-resolution figures, can be found at:

References
http://ejcts.ctsnetjournals.org/cgi/content/full/39/6/844#BIBL
This article cites 25 articles, 21 of which you can access for free at:

Subspecialty Collections
http://ejcts.ctsnetjournals.org/cgi/collection/valve_disease

Valve disease
following collection(s):
This article, along with others on similar topics, appears in the

Permissions & Licensing
http://ejcts.ctsnetjournals.org/misc/Permissions.shtml
or in its entirety can be found online at:
Information about reproducing this article in parts (figures, tables)

Reprints
http://ejcts.ctsnetjournals.org/misc/reprints.shtml
Information about ordering reprints can be found online:
by Maria Jos? Dalmau Sorli on May 25, 2011 ejcts.ctsnetjournals.org Downloaded from