Mechanical heart valves and
Anticoagulation
Dr. Alkesh ZALA
Basic Physician trainee,
Dept. of Cardiology,
John Hunter hospital.
Today’s discussion:
 Case review
 The currently Available and most commonly
Used mechanical prostheses.
 What determines the Choice of valves?
 Risk of Valve Thrombosis WITHOUT
Anticoagulation
 What are the INR Targets for these valves?
 Are the New Generation Valves Really LESS
THORMBOGENIC?
CASE
 75 year old lady with subdural bleed
 On warfarin for st. Jude’s bileaflet AVR alond with
Bentall procedure in 2003
 2007 – Embolic vertebrobassilar embolic stroke –
Valve blammed THOUGH INR 3.2
 Aspirin added and INR target now 3.5 - 4
 INR within target range on presentation
 Surgical drainage on presentation day 4
 Heparin infusion on day 5 & Warfarin recommenced
on regular dose on day 7 – TOO EARLY?
 Day 9 – increasingly confused with headache.
 Repeat CT – Acute subdural with midline shift
Urgent surgical drainage
 Repeat CT on day13 – subdural stable.
No focal Neurological deficit
Heparin started
Cardiology involved with regards to anticoagulation
advise
Summary: Elderly lady with st. Jude’s bileaflet valve
along with Bentall’s procedure. Prior probable embolic
stroke related to the Mechanical valve
Risk of valve thrombosis
Vs
Serious risk of intracranial bleeding
 Weighing the risk of valve thormbosis and serious
significant risk of recurrence of the intracranial bleed:
- Go OFF anticoagulation for 1-2 weeks.
- Warfarin restarted next week
Uneventful recovery without any further complications.
“Gamble - Turns Out To Be a Winner “
Or
“A rational evidence based decision”
“An ideal Prosthetic valve”
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Unidirectional flow
Durable : 40million cycles/year
Blood compatible: no thrombus, embolus
Central flow: Laminar not turbulent
Closing not damaging blood cells
Last but not the least important – It should be quiet
Evolution of Prosthetic Heart Valves
The development of the original balland-cage valve design can be
attributed to the bottle stopper in
1858
In the early 1950’s, it led to the idea
of a prosthetic heart valve
consisting of a cage with a mobile
spherical poppet
First implanted in a human in a closed
procedure in September of 1952.
In 1953, marked successful use of
the heart and lung machine, paving
the way for the 1st open heart
operations
Early valves
 In the 1960s, the Starr–Edwards ball-and-cage
mechanical prosthesis became the standard
replacement valve for nearly a decade.
 The tilting disc valve became more widely used in the
1970s to overcome some of the inherent problems of the
ball-and-cage model.
 Both of these designs, however, were plagued by
hemodynamic
limitations
and
thromboembolic
complications.
 In the 1980s, the St. Jude Medical bileaflet prosthesis
supplanted the earlier devices as the most commonly
implanted prosthetic heart valve. Since then, additional
bileaflet devices with numerous design modifications
have been developed and continue to be used today.
Different types of prosthetic valves. A, Bileaflet mechanical valve (St. Jude Medical). B, Monoleaflet mechanical valve (MedtronicHall). C, Caged ball valve (Starr-Edwards,). D, Stented porcine bioprosthesis (Medtronic Mosaic). E, Stented pericardial bioprosthesis
(Carpentier-Edwards Magna). F, Stentless porcine bioprosthesis (Medtronic Freestyle). G, Transcatheter bioprosthesis expanded over
a balloon (Edwards SAPIEN). H, Self-expandable percutaneous bioprosthesis (CoreValve,)edtronic).
Bileaflet valves
 Two semicircular leaflets that rotate about struts
attached to the valve housing
 Good hemodynamic performance - improved flow
characteristics, lower transvalvular pressure
gradients, less blood flow turbulence, improved
hemodynamics at a given annular diameter, a larger
orifice area and low bulk and flat profile
 the least thrombogenic of the artificial valves
 most commonly implanted mechanical valves
FDA-approved prosthetic heart valves
Haemodynamics of blood flow
 However, inspite of improved design and
haemodynamics – still haunted by numerous
complications and the most dreaded one of
valve thrombosis
Why not always use a Bioprosthetic
valve !!
 Developed primarily to overcome the risk of
thromboembolism that is inherent in all
mechanical prosthetic valves
 Major problem – DURABILITY. Cuspal tears,
degeneration, fibrin deposition, perforation,
fibrosis, and calcification.
 Rate of tissue failure – by 10 years 30% and
upto 60% by 15 years.
Choice of Valves
 Major task is to weigh the advantage of
durability and the disadvantages of the risks
of thromboembolism and anticoagulant
treatment inherent with mechanical valves
 The next step is to choose a prosthesis model
that provides superior hemodynamic
performance to prevent prosthesis-patient
mismatch (PPM) and thereby minimize
postoperative trans-prosthetic gradients.
Criteria for selection of an aortic valve in patients undergoing aortic valve
replacement (AVR)
ACC/AHA guideline
Class I - There is evidence and/or general agreement for the choice of a mechanical or bioprosthetic valve in patients undergoing AVR in the following settings
• A mechanical valve in patients who already have a mechanical valve in the mitral or tricuspid position.
• A bioprosthetic valve in patients who will not take or are incapable of taking warfarin or have a major
contraindication to warfarin therapy.
Class IIa - The weight of evidence or opinion is in favor of the choice of a mechanical or
bioprosthetic valve in patients undergoing AVR in the following settings
• A bioprosthesis in patients ≥65 years of age who do not have risk factors for thromboembolism.
• Patient preference can be considered in patients less than 65 years of age:
1. A mechanical valve is reasonable in patients who do not have a contraindication to warfarin therapy.
2. A bioprosthetic valve may be chosen after a detailed discussion of the risks of warfarin therapy compared to
the likelihood of repeat valve replacement in the future.
• A homograft when aortic valve re-replacement is performed for active prosthetic valve endocarditis.
Class IIb - The weight of evidence or opinion is less well established for the choice of a
mechanical or bioprosthetic valve in patients undergoing AVR in the following setting
A bioprosthesis in women of child-bearing age to avoid the problems associated anticoagulation during pregnancy.
Data from Bonow, RO, Carabello, BA, Chatterjee, K, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease. A report of the Force on
Practice Guidelines (Writing committee to revise the 1998 guidelines for thAmerican College of Cardiology/American Heart Association Task e management of patients with
valvular heart disease). J Am Coll Cardiol 2006; 48:e1.
Criteria for selection of an Mitral valve in patients undergoing Mitral valve
replacement (MVR)
ACC/AHA guideline
Class I - There is evidence and/or general agreement for the choice of a mechanical
or bioprosthetic valve in patients undergoing MVR in the following settings
• A bioprosthetic valve in patients who will not take or are incapable of taking
warfarin or have a major contraindication to warfarin therapy.
Class IIa - The weight of evidence or opinion is in favor of the choice of a
mechanical or bioprosthetic valve in patients undergoing MVR in the following
settings
• A bioprosthesis in patients ≥65 years of age who do not have risk factors for
thromboembolism.
 Among patients < 65 years of age
1. Mechanical valve in patients with long standing Atrial fibrillation
2. A bioprosthetic valve may be chosen in patients in sinus rhythm who elect
this for lifestyle considerations after a detailed discussion of the risks of
warfarin therapy compared to the likelihood of repeat MVR in the future
Data from Bonow, RO, Carabello, BA, Chatterjee, K, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease. A report of the Force on
Practice Guidelines (Writing committee to revise the 1998 guidelines for thAmerican College of Cardiology/American Heart Association Task e management of patients with
valvular heart disease). J Am Coll Cardiol 2006; 48:e1.
Patient tailored prosthesis
JHH Choice
 Mechanical valves represent about 5 – 10% of total
valve replacement ? Reason
 Preferred mechanical valve – Bileaflet valve
 Mechanical valves – Mitral > Aortic
(However, Repair preferred over Replacement)
 Apart from co-morbidities and Patient preference
 AVR- Age 60
 MVR – Age 70
Courtesy: Dr. Taranpreet Singh
Cardiothoracic surgeon,
John Hunter Hospital
Thrombosis with Mechanical valve
 Mechanical prostheses remains burdened with the risk of
thrombosis – potentially fatal
 Valve thrombosis is any thrombus in the absence of
infection attached to or near an operated valve that
occludes part of the blood flow path or that interferes with
the function of the valve.
 Risk factors:
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inadequate or discontinued anticoagulant therapy
previous endocarditis
the prosthetic valve model used
LV dysfunction, LA dilatation
Hypercoagulable states
Prosthesis Thrombogenicity
 Low: St Jude Medical, On-X, Carbomedics, Medtronic
Hall;
 Medium: bileaflet valves with insufficient data, BjorkShiley;
 High: Lillehei-Kaster, Omniscience, Starr-Edwards.
Philippe Pibarot, P. et al, Selection of the Optimal Prosthesis and Long-Term Management. Circulation. 2009; 119: 1034-1048
Rate of thrombosis
 In absence of anticoagulation: 8.6 per 100 patientyears.
 With anticoagulation: risk is reduced to 1% to 3% per
year.
 Valve thrombosis is increased with valves in the
mitral position. Highest in the Tricuspid position.
 ?? Rate with remote valves
Ref: Hurst's the Heart, 12th Edition
ACC/AHA guideline summary: Treatment of
prosthetic heart valve thrombosis
Class IIa - The weight of evidence or opinion is in favor of the usefulness of the following
modalities in patients with prosthetic heart valve thrombosis
• Emergency surgery for thrombosis in a left-sided prosthetic heart valve in patients with New York Heart
Association (NYHA) class III-IV symptoms.
• Emergency surgery for thrombosis in a left-sided prosthetic heart valve with a large clot burden.
• Fibrinolytic therapy for thrombosis in a right-sided prosthetic heart valve in patients with New York Heart
Association (NYHA) class III-IV symptoms and/or a large clot burden.
Class IIb - The weight of evidence or opinion is less well established for the usefulness of the
following modalities in patients with prosthetic heart valve thrombosis
• Fibrinolytic therapy as a first-line approach for thrombosis in a left-sided prosthetic heart valve in patients with
NYHA class I-II symptoms and a small clot burden.
• If surgery is either high risk or not available:
1. Fibrinolytic therapy as a first-line approach for thrombosis in a left-sided prosthetic heart valve in patients
with NYHA class III-IV symptoms and a small clot burden.
2. Fibrinolytic therapy in patients with an obstructed, thrombosed left-sided prosthetic heart valve, class II-IV
symptoms and, a large clot burden.
• Unfractionated heparin as an alternative to fibrinolytic therapy in patients with NYHA class I-II symptoms and a
small clot burden.
Bonow, RO, Carabello, BA, Chatterjee, K, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease. A report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines (Writing committee to revise the 1998 guidelines for the management of patients with valvular heart disease). J Am Coll Cardiol 2006;
48:e1.
Anticoagulation guidelines
 ACC/AHA guideline summary: Antithrombotic therapy in patients with
mechanical heart valves
Class I - There is evidence and/or general agreement that antithrombotic therapy is indicated in
patients with mechanical heart valves in the following settings:
• Warfarin to achieve a goal INR of 2.0 to 3.0 after:
1. Aortic valve replacement (AVR) with bileaflet mechanical or Medtronic Hall valves if no risk factors* are
present.
• Warfarin to achieve a goal INR of 2.5 to 3.5 after:
1. AVR with bileaflet mechanical or Medtronic Hall valves if risk factors* are present.
2. AVR with Starr-Edwards or disc valves other than Medtronic Hall if no risk factors* are present.
3. Mitral valve replacement (MVR) with any mechanical valve.
• Role of aspirin:
1. After AVR or MVR in patients who cannot take warfarin, at a dose of 75 to 325 mg/day.
2. At a dose of 75 to 100 mg/day in addition to warfarin in all patients with mechanical valves and in patients with
biological valves who have risk factors*.
Class IIa - The weight of evidence or opinion is in favor of the usefulness of antithrombotic therapy in
patients with mechanical heart valves in the following setting:
• In the first three months after AVR, warfarin to achieve a goal INR of 2.5 to 3.5.
Class IIb - The weight of evidence or opinion is less well established for the usefulness of
antithrombotic therapy in patients with mechanical heart valves in the following setting:
• In high-risk patients in whom aspirin cannot be used, clopidogrel (75 mg/day) or warfarin to attain a goal INR of 3.5 to
4.5.
Bonow RO, Carabello BA, Chatterjee K, et al. 2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease. A report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines (Writing committee to revise the 1998 guidelines for the management of patients with valvular heart disease). Circulation 2008; 118:e523.
European College of Cardiology guideline
General principles
Thromboembolic risk is related to two factors:
Thrombogenicity of the mechanical valve
1.
Low - Medtronic Hall, St Jude Medical (without Silzone), CarboMedics AVR
2.
Medium - Bileaflet valves with insufficient data, Bjork-Shiley
3.
High - Lillehei Kaster, Omniscience, Starr Edwards
Presence or absence of risk factors: atrial fibrillation, left atrial dimension >50 mm, mitral valve gradient, left ventricular ejection fraction <35 percent,
spontaneous echo contrast, mitral, tricuspid, or pulmonary valve replacement, or a hypercoagulable state.
Recommendations for anticoagulation
Until the INR is stable, intravenous unfractionated heparin (to achieve an activated partial thromboplastin time of 1.5 to 2.0) is probably safer than
subcutaneous unfractionated heparin or low molecular weight heparin which, is used, should be accompanied by anti-factor XA monitoring,
particularly in patients with renal failure or obesity.
• For low thrombogenicity valves, warfarin (or other vitamin K antagonist) to achieve a goal INR of 2.5 if no risk factors and 3.0 if risk factors.
• For medium thrombogenicity valves, warfarin (or other vitamin K antagonist) to achieve a goal INR of 3.0 if no risk factors and 3.5 if risk factors.
• For high thrombogenicity valves, warfarin (or other vitamin K antagonist) to achieve a goal INR of 3.5 if no risk factors and 4.0 if risk factors.
Addition of antiplatelet therapy
• Relative indications
1.
Concurrent arterial disease
2.
Coronary artery stenting
3.
Recurrent embolism, but only after treatment of risk factors and optimization of anticoagulation fail to abolish the problem
4.
4. With caged ball valves, with dipyridamole being preferred to aspirin
• Relative contraindications
1.
History of gastrointestinal bleeding, particularly associated with ulcer disease or angiodysplasia.
2.
Hyperresponders to aspirin, with excessively prolonged bleeding time.
3.
Poorly controlled hypertension, because of the risk of intracerebral hemorrhage.
4.
Elderly patients, particularly women over age 75.
5.
Patients who take multiple medications, require frequent courses of antibiotics, or have erratic INR control.
Butchart, EG, Gohlke-Barwolf, C, Antunes, MJ, et al. Recommendations for the management of patients after heart valve surgery. Eur Heart J 2005; 26:2463.
 The AREVA trial compared moderate
anticoagulation (INR 2.0–3.0) to the usual
regimen of INR 3.0–4.5. A similar risk in
thromboembolic events was found in both
arms, whereas the bleeding risk was higher in
the high intensity group
Acar J, Iung B, Boissel JP et al. AREVA. Multicenter randomized trial comparison of low-dose versus standard-dose anticoagulation in patients with mechanical prosthetic
heart valves . Circulation 1996; 94: 2107 12.
International Normalized Ratio (INR)–specific incidence of all adverse events in patients with mechanical valves (all episodes of
thromboembolism, all major bleeding episodes, and unclassified stroke) according to INR (A). The dotted lines represent the 95%
confidence interval and according to INR, age, and position of valve (B). Incidence of thromboembolic events according to INR and
patient age (upper graph) or prosthesis position (lower graph).
S.C. Cannegieter, F.R. Rosendaal, A.R. Wintzen, F.J.M. van der Meer, J.P. Vandenbroucke, and E. Briet
N Engl J Med 1995; 333:11-17July 6, 1995
 LOWERING-IT trial established that the proposed LOW-INR
target is safe and feasible in low-risk patients after bileaflet
aortic mechanical valve replacement.
 prospective open-label, single-center, randomized controlled trial: age 20
to 60 years, a single-valve replacement with a bileaflet valve in the aortic
position
 Low risk 396 patients: 197 in low INR (1.5-2.5) AND 199 in standard INR
group (2.0 – 3.0).
 Results - similar thrombotic events and a significant reduction of bleeding
occurrence in the low INR group
Torella, M. Torella, D. LOWERing the INtensity of oral anticoaGulant Therapy in patients with bileaflet mechanical aortic valve replacement: Results from the “LOWERING-IT”
Trial. American heart Journal – Volume 160, Issue 1 (July 2010)
Are new generation valves really less
thrombogenic?
 All Mechanical valves models are vulnerable
to thrombus formation due to high shear
stress, stagnation, and flow separation.
 The quest to find a less thormbogenic valve
was one of the prime driving force in the
development of the newer heart valves
 Less thrombogenic materials and an improved
valve and hinge design has reduced the
propensity for thrombus formation and the
need for aggressive anticoagulation.
 A meta-analysis of 46 trial - a higher risk of embolic
complications in patients with a caged-ball valve. The
incidence of total thromboembolism was 30% lower
for patients with a tilting disk valve, and 50% lower for
patients with a bileaflet valve.
Cannegieter SC, Rosendaal FR, Torn M. Oral anticoagulant treatment in patients with mechanical heart valves: how to reduce the risk of thromboembolic and bleeding complications.
Journal of Internal Medicine,Volume 245, Issue 4, pages 369–374, April 1999
 In the cohort study of 1608 patients with mechanical
heart valves: a clearly higher risk of
thromboembolism in patients with caged-ball valves.
An incidence of 0.5 per 100 patient-years was found
for the bileaflet valves, of 0.7 per 100 patient-years for
the tilting disk valves, and of 2.5 per 100 patient-years
for the caged-ball valves
Cannegieter SC, Rosendaal FR, Wintzen AR, Van Der Meer Fjm, Vandenbroucke JP, Briët E. Optimal oral anticoagulant therapy in patients with mechanical heart valves. N
Engl J Med 1995; 333: 11 17.
Guideline
 Which valves are less thormobogenic and safe to be managed
with lower INR targets??
The quest continues…
“Eight Commandments”:
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Embolism Prevention
Durability
Ease and Security of Attachment
Preservation of Surrounding Tissue Function
Reduction of Turbulance
Reduction of Blood Trauma
Reduction of Noise
Use of Materials Compatible with Blood
References
 Acar J, Iung B, Boissel JP et al. AREVA. Multicenter randomized trial comparison of low-dose
versus standard-dose anticoagulation in patients with mechanical prosthetic heart valves .
Circulation 1996; 94: 2107 12.
 Bonow, RO, Carabello, BA, Chatterjee, K, et al. ACC/AHA 2006 guidelines for the
management of patients with valvular heart disease. A report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines (Writing
committee to revise the 1998 guidelines for the management of patients with valvular
heart disease). J Am Coll Cardiol 2006; 48:e1.
 Braunwald's Heart Disease - A Textbook of Cardiovascular Medicine, 9th ed.
 Cannegieter SC, Rosendaal FR, Wintzen AR, Van Der Meer Fjm, Vandenbroucke JP, Briët E.
Optimal oral anticoagulant therapy in patients with mechanical heart valves. N Engl J Med
1995; 333: 11 17.
 Hurst's the Heart, 12th Edition
 Torella, M. Torella, D. LOWERing the INtensity of oral anticoaGulant Therapy in patients
with bileaflet mechanical aortic valve replacement: Results from the “LOWERING-IT” Trial.
American heart Journal – Volume 160, Issue 1 (July 2010)
 Uptodate
Questions?