Escolar Documentos
Profissional Documentos
Cultura Documentos
www.elsevier.com/locate/ejcts
Abstract
Objective: Mitral homograft (MH) can represent an interesting alternative for valve replacement in the young. However, concerns have
been expressed about the durability of valve allografts in children. We report our experience with MH replacement in young patients.
Methods: From 1993 to 1997, 13 young patients aged 3 25 years (mean 15 ^ 6 years) underwent total mitral valve (MV) replacement with
a cryopreserved homograft (CH). All but one had previously undergone one or more cardiac operations. The indications were rheumatic
disease (6), acute and subacute endocarditis (2), congenital heart disease (4), and systemic lupus endocarditis (1). Results: No in hospital
deaths are reported. Discharge echocardiogram showed a well-functioning MH in all but one patient. One patient was lost to follow-up.
Follow-up ranged from 0.7 to 6.6 years (4.1 ^ 2.2). On follow-up two patients were doing well. Two patients died without reoperation and
both had MV stenosis. Seven patients (54%) required reoperation: mean delay 4.17 years (0.7 7). In all cases, thickening, shrinking and
calcification of the allograft were present. None of these seven had contributive histopathologic changes. One patient presenting recurent MV
insufficiency will require a reoperation. Conclusion: MV homograft is a safe and reproducible technique, but does not provide durable results
and should not be used in young patients.
q 2003 Elsevier Science B.V. All rights reserved.
Keywords: Mitral valve homograft; Mitral valve reconstruction
Table 4
Echocardiographic results: early and late evaluation correlated with the clinical outcomea
Mean gradient (mmHg) MVI Delay (years) Mean gradient (mmHg) MVI Outcome
1 6 1 4.76 20 0 Dead
2 0 0 6.6 0 4 To be reoperated
3 7 1 2.4 15 2 Reoperated
4 4 1.5 6.3 5 2 Doing well
5 0 0 5.4 0 4 Reoperated
6 0 1 0.7 14 4 Reoperated
7 2 2 6.3 2 4 Reoperated
8 0 0 1.3 9 0 Reoperated
9 5 2 7 8 2 Doing well
10 4 2 2.3 20 1 Dead
11 4 1 4.4 23 2 Reoperated
12 0 0 Lost to follow-up
13 9 1 2.4 20 1 Reoperated
Mean 13 4.1 13
SD 3.2 2.2 7
Min 0 0.7 0
Max 2 7 23
a
MVI, mitral valve insufficiency.
S. Chauvaud et al. / European Journal of Cardio-thoracic Surgery 23 (2003) 560566 563
4. Discussion
Fig. 1. Actuarial rate of complications (KaplanMeier). (a) Freedom from In our series we performed a side to side suture of the
reoperation. (b) Freedom from complication combining reoperation and papillary muscle [4] and no rupture of papillary muscle
mitral dysfunction (without reoperation).
occurred. This complication which can occur irrespective of
the age [12] was prevented. Special attention was given to
the position of the posterior papillary muscle [13] in order to
avoid valve distortion. One of our patients did not receive a
3.5. Pathology of explanted valves prosthetic ring (patient 6) and had nevertheless good early
result. Unfortunately, reoperation was necessary 0.7 years
Five explanted valves underwent microscopic examin- later for leaflet retraction, but without annulus dilatation.
ation. The papillary muscles appeared to be fibrotic in all Intraoperative control echocardiography demonstrated
cases and in one, necrosis was present. Absence of leaflet one early stenosis and three patients with a mild MV
tissue endothelium was encountered in all explanted valve. insufficiency. There was no correlation between excellent
Massive fibrosis of the stroma was at the origin of a total early results and/or mild residual MV insufficiency regard-
disorganization of the leaflet structure. The fibrosa and the ing the evolution toward valve deterioration. In this series, a
spongiosa were totally replaced by fibrosis in most cases technical factor predisposing to valve failure can be
with hemorrhage in the stroma (Fig. 2a). Intense neovascu- excluded except in the patient presenting residual MV
larization was present in one specimen, (Fig. 2b) on the stenosis after implantation.
leaflet and on the chordae (patient 8). Calcification was
present with ulcerated plaques (Fig. 2c) (patients 11 and 13) 4.2. Homograft storage
associated with thrombosis (Fig. 2d). The inflammatory
cells when present were non-specific: lymphocytes B and A large debate regarding the durability of cryopreserved
macrophages (Fig. 3 and Table 5). versus homovital homograft exists. Most results were
Table 5
Pathology of the explanted valves
Patient Endothelium Fibrosis Calcification Neovascularization Inflammatory cells Thrombosis Papillary muscle
6 0 0 Lymphocytes 0 Fibrotic
7 0 Micro 0 0 Fibrotic
8 Fibrosis 0 Necrotic
11 0 Fibrotic
13 0 0 0 Fibrotic
564 S. Chauvaud et al. / European Journal of Cardio-thoracic Surgery 23 (2003) 560566
Fig. 2. Histologic changes of the stroma. Hematoxylin and eosin stain. (a) Hemorrhage associated with fibrosis (original magnification 100). (b)
Subendothelial leaflet calcification (original magnification 100). (c) Inflammatory cells, most of them are macrophages (original magnification 50). (d)
Neovascularization with extensive fibrosis (original magnification 50).
elaborated from the aortic homograft experience. In [14]. On mid-term examination, explantation of cryopre-
cryopreservation without antibiotics, viability of endothelial served aortic homografts do not demonstrate cell growth or
cells is decreased but still present 3 weeks after harvesting metabolic function [15], even when collagen appeared to be
preserved. In explanted aortic homografts from living
donors, the structure of the collagen is perserved early
after explantation [15]. Low dose antibiotics (homovital
aortic homograft) appear to decrease immunologic stimu-
lation (in vitro) [16].
The storage technique used in our series when the MH
was obtained from a multiorgan donor is a combination of
the two described techniques. Due to the conditions during
multiorgan harvesting it appeared appropriate to use low
dose antibiotics for 24 h in order to assure a sterile
homograft. No correlation between the two groups (anti-
biotics and cryopreservation versus cryopreservation alone)
regarding the incidence of homograft valve degeneration
was observed.
4.3. Immunology
Fig. 3. Histologic changes of the endothelium. Thrombosis adherant to the
leaflet tissue and absence of endothelium cells, the stroma is highly fibrotic. Very little is known with respect to the antigenicity of the
Hematoxylin and eosin stain (original magnification 50). MV. Aortic homografts in primates appear to have a
S. Chauvaud et al. / European Journal of Cardio-thoracic Surgery 23 (2003) 560566 565
decreased antigenicity [17]. One of the main differences aortic allografts in young recipients. J Thorac Cardiovasc 1993;105:
between the aortic valve and the MV is the presence of 93442.
[8] Rajani B, Mee RB, Ratliff NB. Evidence for rejection of homograft
muscle tissue in the subvalvular apparatus of the MV. cardiac valves in infants. J Thorac Cardiovasc Surg 1998;115:111 7.
Muscular tissue results in greater immunologic stimulation [9] Kumar AS, Choudhary SK, Mathur A, Saxena A, Roy R, Chopra P.
and production of antibodies from the recipient [8]. Homograft mitral valve replacement: five years results. J Thorac
Conditioning of papillary muscles with glutaraldehyde [9] Cardiovasc Surg 2000;120:450 8.
[10] Doty DB, Acar C. Mitral valve replacement with homograft. Ann
was presumed to decrease immunologic stimulation and the
Thorac Surg 1998;66:212731.
risk of necrosis. However, the rate of papillary muscle [11] Chauvaud S, Kalangos A, Berrebi A, Gaer J, Acar C, Carpentier A.
dysfunction was not reduced by glutaraldehyde as reported Systemic lupus erythematosus valvulitis: mitral valve replacement
by Kumar et al. [9] and this technique is no longer used. with a homograft. Ann Thorac Surg 1995;60:1803 5.
One of our patients (patient 11) received cyclosporin [12] Yankah AC, Sievers HH, Lange PE, Bernhard A. Clinical report on
stentless mitral allografts. J Heart Valve Dis 1995;4:404.
following homograft insertion. However, immunodepres- [13] Cochran RP, Kunzelman KS. Effect of papillary muscle position on
sion did not prevent early failure (0.7 years) and this patient mitral valve function: relationship to homografts. Ann Thorac Surg
was reoperated. Attempts at immunodepression with 1998;66:S15561.
azothioprine have been used in children undergoing [14] Lang SJ, Girodano MS, Cardon-Cardo C, Summers BD, Staiano-
cryopreserved aortic allograft [18]. Allo-immune human Coico L, Hajjar DP. Biochemical and cellular characterization of
cardiac valve tissue after cryopreservation or antibiotic preservation.
leukocyte antigens (HLA) antibody response in such cases J Thorac Cardiovasc Surg 1994;108:63 7.
was not reduced and the influence on graft dysfunction was [15] Mitchell RN, Jonas RA, Schoen FJ. Pathology of explanted
not significant. A high incidence of infection was underlined cryopreserved allograft heart valves: comparison with aortic valves
by Hawkins et al. as an important drawback to this protocol from orthotopic heart transplants. J Thorac Cardiovasc Surg 1998;
115:118 27.
[19].
[16] Johnson DL, Sloan C, OHalloran A, Yacoub MH. Effect of antibiotic
Experimental studies such as cyclosporine in the rat [20] pretreatment on immunogenicity of human heart valves and
or g interferon [21] in vitro have been demonstrated to component cells. Ann Thorac Surg 1998;66:S2214.
decrease T-cell response to valve allograft. However, [17] Kawauchi M, Nakajima J, Takeda M, Oka T, Takamoto S. Aortic
immunodepression cannot be extensively used in children. valves are antigenic but less so than myocardium. J Thorac
Cardiovasc Surg 1998;116:532.
Blood group mismatch appears to have no effect on the [18] Shaddy RE, Lambert LM, Fuller TC, Profaizer T, Thompson DD,
outcome of the homograft as previously published by Baker SI, Osborne KA, Hawkins JA. Prospective randomized trial of
Schutz et al. [22] and confirmed in our series. Production of azathioprine in cryopreserved valved allografts in children. Ann
antibodies to HLA has not been proven to be a risk of Thorac Surg 2001;71:437.
homograft degeneration [23]. [19] Hawkins JA, Breinholt JP, Lambert LM, Fuller TC, Profaizer T,
McGough EC, Shaddy RE. Class I and Class II anti-HLA antibodies
In conclusion, due to the early occurrence of degener- after implantation of cryopreserved allograft mateiral in pediatric
ation, MV homograft replacement should not be used in patients. J Thorac Cardiovasc Surg 2000;1198:32430.
young patients. [20] Legare JF, Ross DB, Issekutz TB, Ruigrok W, Creaser K, Hirsch GM,
Lee T. Prevention of allograft heart valve failure in a rat model.
J Thorac Cardiovasc Surg 2001;122:310 7.
[21] Batten P, McCormack AM, Rose ML, Yacoub MH. J Thorac
References Cardiovasc Surg 2001;122:129 35.
[22] Schutz A, Fischlein T, Breuer M, Haushofer M, Uhlig A, Detter C,
Kemkes BM, Hammer C, Reuchart B. Cytoimmunological monitor-
[1] Baskett RJ, Ross DB, Nanton MA, Murphy DA. Factors in the early ing after homograft valve replacement. Eur J Cardiothorac Surg 1994;
failure of cryopreserved homograft pulmonary valves in children: 8(11):609 12.
preserved immunogenicity? J Thorac Cardiovasc Surg 1996;112: [23] Smith JD, Hornick PI, Rasmi N, Rose ML, Yacoub MH. Effect of
11709. HLA mismatching and antibody status on homovital aortic valve
[2] Jones TK, Lupinetti FM. Comparison of Ross procedures and aortic homograft performance. Ann Thorac Surg 1998;66:S212 5.
valve allografts in children. Ann Thorac Surg 1998;66:S170 3.
[3] Luciani GB, Casali G, Santini F, Mazucco A. Aortic root replacement
in adolescents and young adults: composite graft versus homograft or
autograft. Ann Thorac Surg 1998;66:S189 93. Appendix A. Conference discussion
[4] Acar C, Tolan M, Berrebi A, Gaer J, Gouezo R, Marchix T, Gerota J,
Chauvaud S, Fabiani JN, Deloche A, Carpentier A. Homograft Dr V. DiSesa (Philadelphia, Pennsylvania, USA): Do you have a
replacement of the mitral valve graft selection, technique of similar experience with aortic homografts in young patients? And do you
implantation, and results in forty-three patients. J Thorac Cardiovasc believe that an immune reaction is a significant component of your
Surg 1996;111:36780. observations?
[5] Gross C, Klima U, Mair R, Brucke P. Aortic homografts versus Dr Chauvaud: We have not an extensive experience of aortic valve
replacement in children and young patients.
mechanical valves in aortic valve replacement in young patients: a
Reviewing all the literature on this subject, there is a lot of confusion
retrospective study. Ann Thorac Surg 1998;66:S194 7.
about the causes of degeneration. Most probably its from immunologic
[6] Plunkett MD, Schneider DJ, Shah JJ, Bash SE, Bond LM, Geiss DM. origin, but its not totally clear which kind of process is involved.
Homograft replacement of mitral valve in children. Ann Thorac Surg Dr C. Yankah (Berlin, Germany): I congratulate you for this very
1998;66:849 52. interesting study and results with the critical comments. I do also agree with
[7] Clarke DR, Campbell DN, Hayward AR, Bishop DA. Degeneration of your conclusion, entirely, that this type of valve replacement is not suitable
566 S. Chauvaud et al. / European Journal of Cardio-thoracic Surgery 23 (2003) 560566
for children or young patients. My question is more technical. How did you homograft. Definitely, as Sylvain just mentioned, its the durability that
size the valves for the replacement? doesnt seem to meet the expectation, and we do not feel that we can
Dr Chauvaud: We followed strictly the Acars guidelines regarding to recommend today using a mitral homograft in a young patient. This could
the size of the annulus of the recipient compared to the size of a homograft have been a good alternative to bioprosthetic valve since there is no idea of
and also the length of the anterior leaflet. We adapted the length of the substitute in this age group. But meanwhile, waiting for the complete results
chordae to the distance between the tip of a papillary muscle to the of our series, which has now a 10-year follow-up, we feel that it is not a
annulus,during the implantation of the homograft. good alternative in this age group.
Dr A. Moritz (Frankfurt, Germany): May I ask you, the difference Dr C. Mestres (Barcelona, Spain): You just mentioned that there is
between the durability of the aortic homograft is not as catastrophic as this degeneration in both the chordae tendineae. But at which level, tip of the
mitral homograft, fortunately. But the durability of the pulmonary side papillary muscle, halfway the chordae in the subleaflet area, or whatever?
seems to be somewhat better than the aortic, so it may very well be that the And you say that 20 h before cryopreservation, that means how was warm
mechanical stress plays a role. Do you have any experience, or do you ischemic time and cold ischemic time on the average?
know, there are only a few cases I think reported about the tricuspid
Dr Chauvaud: Regarding the final aspect of a chordae tendineae, there
homograft, is there an improved durability compared to the mitral?
is an absence of endothelium and the collagen is totally disorganized, the
Dr Chauvaud: In our experience, and in what is published on the
inflammatory response on the chordae is very weak. Inflammation is much
tricuspid replacement with mitral homograft on the tricuspid valve, patients
more important on the leaflet tissue itself. The ischemic time was 25 h
are adults. And we know that a gradient of 5 10 mm could be well
tolerated on the right side. At the present time, I have no data, about early between harvesting and cryopreservation. Is that the answer you expected?
degeneration of mitral homograft on the right side compared to what I Dr Mestres: I was asking how long was the warm ischemic time and the
presented on the left side. cold ischemic time?
Dr Acar: I just wish to make a comment in addition to Dr Chauvauds Dr Chauvaud: The warm ischemic time is very short. As soon as the
presentation. Regarding the durability of the mitral homograft, presently we heart is arrested, it is placed in cold saline, which is not cryopreservation.
are reviewing the whole series of patients. We have a series of over 90 And later it is prepared for cryopreservation.
cases, including two-thirds of complete homograft and one-third of partial