الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
The past 50 years have witnessed remarkable progress
in the development of safe, hemodynamically favorable
mechanical heart valves. Much of that progress has come
about by simple trial and error and certainly some has
resulted from unexpected fortuitous events. It is remarkable
that two of the six mechanical heart valves currently
available for implantation (the Starr-Edwards ball valve
and the St. Jude Medical bileaflet valve) are virtually
unchanged from the original models implanted in 1965 and
1977, respectively. Four other mechanical valves approved
for implantation (Omniscience, Omnicarbon, Medtronic-
Hall, and Carbomedics valves) have been in use for more
than 16 years with essentially no mechanical failures.
Pyrolytic carbon, a compatible and virtually indestructible
biomaterial that has been adapted from the nuclear fuel
industry, has enabled much of the progress. Eventually,
with the right valve design and the right valve material, it is
conceivable that we may someday have a mechanical valve
that does not require lifelong anticoagulation therapy.
The overall complications associated with prosthetic
heart valves can be divided into six main categories:
structural valvular deterioration, non-structural dysfunction,
valve thrombosis, embolism, bleeding and endocarditis. On
the one hand, bioprosthetic heart valves are plagued with
leaflet calcification and leaflet tearing. On the other,
mechanical heart valves are associated with haemolysis,
platelet activation and thromboembolic events arising from
clot formation and their subsequent detachment.
These complications are believed to be associated with
non-physiological blood flow patterns in the vicinity of
heart valves.
The performance of artificial heart valves is closely
governed by the fluid mechanics within these valves,
which, in turn, is strongly related to the geometry,
material and mechanism of the valve design. The obvious
engineering challenge is to design an optimal heart valve.
Such a challenge is currently being pursued in three main
directions. In the first direction, researchers have taken a
step back from the concept of artificial devices and have
taken the route of engineering a living tissue valve with as
many characteristics of the native heart valve as possible.
In the second direction, engineers are developing
advanced computational fluid dynamics (CFD) tools to
accurately predict the fluid mechanics in the vicinity of
heart valves down to the resolution of individual blood
cells. Finally, in the third direction, research is being
conducted to pinpoint the exact coagulation mechanisms
triggered by haemodynamics in heart valves using ex vivo
and in vitro experiments, thus opening avenues to improve
on existing designs based on direct coagulation measures.
The patients with prosthetic heart valves require
chronic oral anticoagulation, and so physicians must be
mindful of the thromboembolic and bleeding risks related
to chronic anticoagulant therapy. Currently, only vitamin K
antagonists are approved for this indication.
The estimated risk of a thromboembolic event depends
on the type of prosthesis and its anatomical position (aortic,
mitral, or tricuspid).There are no universal dosage
recommendations for VKAs, but rather each patient should
have their therapy tailored via serial INR monitoring.
The incidence of major bleeding in patients with
mechanical valves treated with warfarin, or its derivatives,
is approximately 1.4 per 100 patient-years.
The incidence of major embolism (defined as causing
death, residual neurologic deficit, or peripheral ischemia
requiring surgery) in the absence of antithrombotic therapy
for patients with mechanical valves has been suggested to
be approximately 4 per 100 patient-years. This risk
decreases to 2.2 per 100 patient-years with only antiplatelet
therapy, and is further reduced to 1 per 100 patient-years
with warfarin, including valves in both the mitral and aortic
Guidelines recommend that patients with mechanical
valves in the aortic position should have an INR of 2.0–3.0
and an INR of 2.5–3.5 with valves in the mitral position.
AS, Thromboembolic and bleeding events are not
equivalent in terms of mortality risk. The one-year survival
after ischemic stroke is about 80%, whereas the one-year
survival after intracerebral hemorrhage is only about
20%,so many studies and clinical trials were introduced
and still ongoing targeting low intensity anticoagulation,
and good control of INR management.
These trials took many directions in 1990s
retrospective studies provided supportive evidence for the
use of low-intensity anticoagulation in patients with
mechanical cardiac prostheses, then the AREVA study
published in 1996 stated that: In selected patients with
mechanical prostheses, moderate anticoagulation (targeting
INR 2:3) prevents thromboembolic events as effectively as
conventional anticoagulation (targeting INR 3:4.5) and
reduces the incidence of hemorrhagic events. In
2000Another trial targeted an INR of 2:2.5 but with small
dose of antiplatlets showed efficacy in preventing
thromboembolism as conventional higher standard mono
therapy (INR bet. 2.5:3.5) with lesser hemorrhagic
complications.
Depending on the hypothesis that a specific design of
prosthetic heart valve can be safely used in the mitral or
aortic position with lower anticoagulation intensities, the
results of part of the PROACT trial published in 2013
stated that INR may be maintained safely between 1.5-2.0
in AVR patients after implantation of ON-X bileaflet
mechanical prosthesis. In combination with low-dose
aspirin, this therapy resulted in significantly lower risk of
bleeding than customary INR 2.0-3.0, without significant
increase in TE.
Another clinical trial in 2010 targeted an INR of
1.5:2.5 in AVR without adding aspirin showed effective
anticoagulation and lesser hemorrhagic complications.
One of the recent studies of patients receiving warfarin
therapy for moderate-intensity anticoagulation showed high
incidence of major bleeding when INR was >2.4 and an
INR of 1.8–2.4 appeared to be associated with the lowest
incidence rate of major bleeding or thromboembolic events.
The effectiveness and safety of a low-intensity of
anticoagulation in patients targeting low INR levels should
be further examined in randomized clinical trials.
Quality of oral anticoagulation and long-term outcome
after mechanical heart valve (MHV) replacement with self
management (Self-M) of OA is superior to conventional
anticoagulation treatment), as proven by different studies
improving long-term outcome, treatment quality and
quality of life after MHV replacement. Therefore, it should
be offered to all patients willing to perform Self-M.