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8 Pathology ofBiological Prosthetic Cardiac Valves
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145
Fig. 8.45 (a, b) TAVI showing massive thrombotic vegetations block-
ing the valve leaets. On histological examination, the thrombotic
material consists of mixture of brin and platelet aggregates (c).
Coronary artery embolization occurred (d). (c) Hematoxylin-eosin
stain. (d) Azan Mallory stain
146
ab c
de f
G. Thiene et al.
Fig. 8.46 Valve-in-valve transcatheter mitral valve implantation
(TMVI): atrial view of the mitral porcine bioprosthetic valve with cusps
in open position (a) in a 54-year-old woman. High-resolution X-ray
with heavy calcications demonstrated by the bright signal (b).
Histological section of a cusp: note intrinsic calcium deposits (black)
(c). Atrial view of Sapien XT bioprosthesis with heavy nodular calci-
cations of the cusps. Fibrous tissue overgrowth involves the metallic
stent (d). High-resolution X-ray showing heavy calcications demonstrated by the bright signal (e). Histological section of the sampling of
(d). Intrinsic nodular calcium deposits (black) are detected (f) (c, g von
Kossa staining). From Tessari C etal., Card Surg. 2021
ab
Fig. 8.47 Mitral clips in mitral incompetence by acute myocardial infarction with partial papillary muscle rupture. (a) atrial view; (b) ventricular
view
8 Pathology ofBiological Prosthetic Cardiac Valves
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147
a
b
Fig. 8.48 Mitral clip in chronic ischemic heart disease with congestive
heart failure. (a) atrial view; (b) ventricular view
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Anticalcification Strategies toIncrease
PR
•T
•
•T
CONS
•
•
cells
Glutataraldheyde Fixation
Bioprosthetic Valve Durability
MarialuisaValente, MiladellaBarbera, UbertoBortolotti,
andGaetanoThiene
9
Mineralization is the main cause of structural valve deterioration of xenograft bioprosthetic valves. In the time interval
1975–2000, 411 valve xenografts were explanted at surgical
redo at the University of Padua because of failure. Calcic
structural deterioration was detected in 368 (89.5%) (Table9.1).
Glutaraldehyde xation is certainly needful and at present
still unique for achieving stabilization by collagen crosslinking, prevention of immune reaction, and tissue sterilization
(Fig.9.1). After more than 50years of its employment, no
suitable alternative was found.
Free aldehyde residuals with toxic effect on the recipient
cells are considered the culprits.
Moreover, after glutaraldehyde xation and valve bioprosthesis implantation, a cascade of events occurs leading
to cusp stiffness by mineralization. First, phosphorus of cell
membrane links with calcium present in the interstitium and
recipient blood, giving origin to calcication by apatite crystals formation and prosthetic valve failure (Fig.9.2).
The phenomenon has been observed by both spectroscopy and transmission electron microscopy. Energy dispersion analysis demonstrated a Ca++/Ph ratio correspondent to
apatite (calcium phosphate). Transmission electron microscopy showed that origin of calcication starts upon cell
membrane debris (Fig.9.3).
Lipid extraction by solvents is believed to be the best anticalcication treatment.
For this reason, sodium dodecyl sulfate was employed in
the second-generation porcine Hancock valve, ethanol in
Table 9.1 Calcication accounted for structural valve deteriorations
in 89.5% of 411 porcine bioprosthetic valve explants for redo
Mean time of function (mos) N.Explants Ca++ SVD (%)
124.8±51.8 411 368 (89.5%)
(SVD: structural valve deterioration)
From Bottio T. and Thiene G., unpublished
O
issue stabilization by
collagen cross-linking
Host-immunological
response masking
issue sterilization
Graft cell devitalization
Free aldehyde residuals
with toxic effects on host
Fig. 9.1 Glutaraldehyde xation pros vs. cons
porcine Epic link of St. Jude Medical, Tween80-ethanol in
Carpentier Edwards bioprosthetic valves (Fig.9.4).
Freedom from structural valve deterioration (SVD) of
Hancock Standard vs. Hancock II valves showed a signicant gain in the durability (Fig.9.5).
M. Valente (*) · M. d. Barbera · G. Thiene
Department of Cardiac, Thoracic, Vascular Sciences and Public
Health, University of Padua Medical School, and Cardiovascular
Pathology Unit, University Hospital of Padua, Padua, Italy
e-mail: marialuisa.valente@unipd.it; mila.dellabarbera@unipd.it;
gaetano.thiene@unipd.it
U. Bortolotti
Section of Cardiac Surgery, Cardio-thoracic and Vascular
Department, University Hospital of Pisa, Pisa, Italy
e-mail: uberto.bortolotti@med.unipi.it
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
G. Thiene et al. (eds.), Pathology of Cardiac Valve Disease, https://doi.org/10.1007/978-3-031-35498-4_9
153
154
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Chemical cross-linking
Cell death of BP tissue
Calcium
Phosphorus of membrane
phospholipids from cell debris
Apatite crystal formation
Valve failure
Fig. 9.2 Cascade of events leading to structural deterioration of bioprosthetic valves
M. Valente et al.
a b
Fig. 9.3 Calcium deposits upon cell debris at transmission electron microscopy (a). Spectroscopy of mineralization: the ratio between calcium
and phosphorus content is in keeping with apatite (b). From Thiene G, Valente M, J Heart Valve Dis, 2011
Follow-up, years
Freedom from SVD
9 Anticalcication Strategies toIncrease Bioprosthetic Valve Durability
155
Fig. 9.4 Anticalcication
strategies in different
bioprosthetic valve models
Fig. 9.5 Actuarial freedom
from structural valve
deterioration (SVD) of the
Hancock II vs. Hancock I
porcine bioprosthetic valves
in patients aged 65years or
older. SVD appears much
later in Hancock II than in
Hancock I.From Valfrè etal.,
J Thorac Cardiovasc Surg,
2006
Sodium dodecyl sulphate
Carpentier-Edwards bioprosthetic valves
1.00
0.90
0.80
0.70
0.60
0.50
0.40
0.30
0.20
0.10
0.00
At risk:
Hck II
Hck St
924
33
Hancock II
Hancock St
768
19
Medtronic:
Hancock II
Tween 80 + Ethanol
594
17
419
16
267
15
Ethanol
155
9
77
7
SJM:
Epic Linx
p=0.001
33515
3
0246
810121415
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