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36.
An Improved Crosslinking Method To Inhibit Glycosaminoglycan
Degradation In Bioprosthetic Heart Valves
* Naren R. Vyavahare; Sagar R. Shah; Devanathan . Raghavan
Clemson University, Clemson, SC, United States
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OBJECTIVES: Out of approximately 300,000 heart valve replacement surgeries,
40% involve the use of glutaraldehyde crosslinked bioprosthetic heart valves
derived either from porcine aortic valves or bovine pericardium.
Glutaraldehyde is known to be an excellent fixative for the collagenous
component of these valves. However, it does not stabilize valvular
glycosaminoglycans (GAGs) and valvular GAGs are lost during fixation,
storage, in vitro cyclic fatigue, and after subdermal implantation. This GAG
loss may be partly responsible for the degeneration of the bioprosthetic
valves. The objective of this study is to stabilize porcine aortic valvular
GAGs using GAG-targeted fixation chemistries.
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METHODS: Previously, sodium metaperiodate oxidation of GAGs prior to
glutaraldehyde crosslinking was found to stabilize GAGs better than
glutaraldehyde alone, but it was only partially effective against enzymatic
degradation of GAGs. In the present study, we employed 1-ethyl-3-(3-dimethyl
aminopropyl) carbodiimide and n-hydroxysuccinimide chemistry to link neomycin
trisulfate, a GAG-enzyme inhibitor, to the cuspal tissue prior to
glutaraldehyde fixation.
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RESULTS: Cusps with linked neomycin trisulfate were found to be resistant
to in vitro and in vivo enzymatic degradation of GAGs, and in vitro local
buckling. They also retained more GAGs after in vitro cyclical fatigue than
glutaraldehyde fixed valves. Addition of neomycin trisulfate did not alter
tissue physico-mechanical properties. Cusps with GAG-targeted fixation
chemistry showed significantly reduced calcification when subdermally
implanted in rats than those crosslinked with glutaraldehyde alone; however,
calcification was not inhibited by GAG stabilization.
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CONCLUSIONS: Retention of valvular GAGs in addition to anti-calcification
treatments may ultimately improve the durability of the bioprosthetic heart
valves.
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37. Successful Long-term Prevention Of
Bioprosthetic Calcification With Triglycidylamine-
2-(2-mercaptoethyl)aminoethylidene-1,1-bisphosphonate
Jeanne M. Connolly1; H S. Rapoport1; Ivan
S. Alferiev1; Robert C. Gorman2; Joseph
H. Gorman2; * Robert J. Levy1
1The Childrens Hospital of Philadelphia, Philadelphia, PA,
United States; 2University of Pennsylvania School of Medicine,
Philadelphia, PA, United States
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OBJECTIVES: The use of glutaraldehyde fixed bioprosthetic heart valves is
frequently complicated by calcification; stentless designs in particular are
adversely affected by aortic wall calcification. We have previously described
enhanced resistance to calcification when the polyepoxide crosslinker
triglycidylamine (TGA) is used to prepare cuspal components of bioprosthetic
heart valves compared to glutaraldehyde (Glut). We hypothesize that TGA may
also be useful in facilitating the covalent inclusion of
2-(2-mercaptoethyl)aminoethylidene-1,1-bisphosphonate (MABP) into
biomaterials, thus enhancing calcification resistance of the aortic wall
components of bioprostheses.
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METHODS: TGA and MABP were synthesized and used to crosslink porcine
aortic cusps, bovine pericardium, porcine aortic wall and type I (bovine)
collagen. Control heterograft materials were crosslinked with Glut.
Calcification resistance and mechanisms were evaluated using rat subdermal
implants, sheep aortic valve interstitial cell(AVIC) cultures, and
non-cellular enzyme activity assays.
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RESULTS: Rat subdermal porcine aortic wall heterograft implants fixed with
TGA/MABP at pH 7.4 demonstrated a complete inhibition of calcification at 90
days (Ca=1.7±0.1μg/mg), compared to severely calcified Glut-pretreated
implants (Ca=251±37μg/mg), and to TGA (without MABP)-fixed aortic wall
(Ca=177±12μg/mg). AVIC grown on pretreated substrates paralleled these
results, and studies suggest that an important step in the calcification
cascade is alkaline phosphatase (ALP) activity, which is inhibited by
pretreatment with TGA plus MABP.
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CONCLUSIONS: TGA/MABP-pretreatment of heterografts results in calcification
resistance that may be due to mechanisms including ALP inhibition. Treatment
of bioprosthetic heart valves with TGA/MABP may increase durability and allow
their use in much younger patients, sparing them the morbidity of
anticoagulation associated with mechanical valves.
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38. Patient Outcome After Aortic Valve
Replacement With Mechanical Or Bioprostheses: Weighing Lifetime
Anticoagulant-related Event Risk Against Reoperation Risk
Martijn W. van Geldorp1; * W.R. E. Jamieson2;
* Jian . Ye2; * Guy J. Fradet2; *
A. P. Kappetein1; * Johanna J. Takkenberg1;
* Ad J. Bogers1
1Erasmus University Medical Center, Rotterdam, , Netherlands;
2University of British Columbia, Vancouver, , Canada
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OBJECTIVES: Although results of AVR with different valve prostheses are well
documented in terms of survival, patient life-time risks of (valve related)
events are less well explored. We used a large dataset of 3934 patients who
received isolated AVR with either a bioprosthesis (73%) or a mechanical
prosthesis (27%) between 1982-2003 to simulate outcome of patients after AVR
with either valve type.
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METHODS: Data on postoperative and long-term survival were collected and
analyzed. Using microsimulation we compared total age and gender-specific
life-expectancy (LE), event-free life-expectancy (EFLE), reoperation-free
life-expectancy (RFLE), and life-time risks of reoperation and valve related
events between both valve types.
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RESULTS: Total follow-up was 26,467 patient-years. Mean follow-up was 6.1
years in the biological and 8.5 years in the mechanical arm. Mean age was 70
and 58 years for bioprosthesis and mechanical respectively, and percentage of
CABG 47% and 28%. For a 58 year old male (mean age in mechanical group) LE,
EFLE and RFLE for biological versus mechanical prostheses were respectively
12.6 vs 12.2; 10.4 vs 9.7; 11.1 vs 11.7. Life-time risk of reoperation was
27% vs 5.7%.
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CONCLUSIONS: Even for patients under 60, LE and certainly EFLE is better with
a bioprosthesis, only RFLE is lower. Comparing life-time event risks between
different types of valve prostheses provides new insight into patient outcome
after AVR, and can help in patient selection and counselling. When combined
with careful measurement of individual patient preferences this will provide
the ultimate key to optimized informed decision making.
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39. Surgery Superior To Thrombolytic Therapy In Treatment Of
Obstructed Mechanical Cardiac Valves
Hesham . Hegazy2; Maie . Al Shahid1;
Walid . Hassan1; Mohammed . Al Amri1; Bahaa
Michel . Fadel1; Nathem . Akhras1; *
Zohair Yousef . Al Halees1
1King Faisal Specialist Hospital and Research Center, Riyadh, ,
Saudi Arabia; 2Saud Al Babtain Cardiac Center, Dammam, ,
Saudi Arabia
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OBJECTIVES: Despite advances in the design of prosthetic heart valves,
mechanical obstruction remains a major complication of valve replacement.
Recent reports suggested thrombolytic therapy (TT) as an alternative to
surgery. We sought to review our experience with TT versus surgery.
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METHODS: Between 1985-2004, 70 pts were diagnosed with mitral or aortic
mechanical valve obstruction. Diagnosis was based on clinical and
echocardiographic findings ± transesophageal echo ± cinefluroscopy. All pts
were initially started on heparin. Thrombolytic thearpy was introduced 1992.
A decision for surgery or TT depended on hemodynamics, treating physician
preference and "thrombus burden". The success of TT was monitored
both clinically and by echo.
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RESULTS: Mean age was 33 years (2-60). There were 61% females of whom 7
were pregnant at time of diagnosis. Half of the pts were with pulmonary edema
and 63% in NYHA-FC III-IV. The effective orifice area was markedly reduced
with elevated transvalvular gradient by echo in 56 pts (80%). Hemodynamic
improvement was achieved by heparin alone in 7(10%). Thrombolysis was used in
18 pts and was only successful in 7 pts (39%) of whom 2 suffered major CVA's
but with good outcome. Three pts died and therapy failed in 8 pts who
subsequently had surgery, 4 of those had obstruction by pannus formation
only. Total of 53 pts underwent surgery (8 after failed TT + 45 without TT)
with 2 deaths (3.7%) and no strokes.
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CONCLUSIONS: Surgical treatment of mechanical valve obstruction results in
higher success rate, lower mortality, and less complications as compared to
thrombolytic therapy.
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40. Early Anticoagulation Regimen After Mechanical Valve
Implantation And related Complications
Deepak . Puri; Varinder . Sarwal; Ambuj . Choudhary;
Manoranjan . Sahoo; T.S. . Mahant
Fortis Hospital Mohali, Mohali, Punjab, India
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OBJECTIVES: Anticoagulation is started early after mechanical valve
replacement as risk of thromboembolic complications is high in first six
months after surgery. There is no consensus on optimal protocol to prevent
early thrombogenic complications without increasing risk of post-operative
hemorrhagic events. We present our comparative analysis of various
anticoagulation protocols from our institute.
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METHODS: Between July 2001 to October 2006, 503 patients had mechanical
valve implantation, were divided into three comparable groups depending on
anticoagulation regime, Group-A (221 patients) received only oral
anticoagulation from first post-operative day, Group-B (159) were initiated
LMW Heparin in addition and Group-C (123 patients) unfractionated Heparin
within twelve hours after surgery in addition to oral anticoagulation and
continued till target INR achieved.
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RESULTS: Mean post-operative drainage after 48 hours was 514.08±202
(Group-A), 783.36±369.67 (Group-B) and 718.39±305.46 (Group-C). 2 patients in
Group-A, 12 in Group-B and 9 in Group-C required reinsertion of
intercostal/pericardial drain for collections. Seven patients had temponade
(Group B-7, Group C-5) and 9 required re-exploration for excessive drainage
more than 48 hours after surgery (Group B-5, Group C-4). Incidence of valve
thrombosis within first six months was three (one in each group). Two had
suboptimal INR third had INR >5 with congestive hepatic failure. All three
were successfully thrombolised and recovered after initial ventilatory and
inotropic support. Incidence of thromboembolic stroke was low in all groups.
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CONCLUSIONS: Early oral anticoagulation alone provides optimum anticoagulation
and is associated with minimum complications. Early supplementation with
Heparin increases risk of hemorrhagic complications without decreasing
thromboembolic risk.
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