This document discusses prosthetic valve thrombosis (PVT), including its definition, pathogenesis, incidence, diagnosis, and treatment. PVT occurs when a blood clot forms on an artificial heart valve, interfering with its function. It is more common with mechanical valves and in the mitral position. Diagnosis involves blood tests, imaging like echocardiography and fluoroscopy. For non-obstructive small clots on the left side, initial treatment is usually heparin. Larger or obstructive clots may require surgery or fibrinolysis.

1. Prosthetic Valve Thrombosis
Dr. Khine Thazin Myint

2. • Introduction
• Definition
• Pathophysiology
• Incidence
• Epidemiology
• Diagnosis
• (i) Blood test
• (ii) Imaging
• Treatment
1. Medical Rx
2. Surgical Rx

3. Prosthetic Valve Thrombosis (PVT)
• Prosthetic valve thrombosis (PVT) is a rare but serious complication of
valve replacement, most often encountered with mechanical prostheses.
• The significant morbidity and mortality associated with this condition
warrants rapid diagnostic evaluation.
• However, diagnosis can be challenging, mainly because of variable clinical
presentations and the degree of valvular obstruction.

4. Definition
• Prosthetic valve thrombosis (PVT) is defined by any thrombus,
• in the absence of infection,
• attached to or near an operated valve,
• occluding part of the blood flow or interfering with valvular function.

5. Pathogenesis
1. Molecular interactions
2. Influence of transprosthetic blood flow
3. Local hypercoagulability

6. 1. Molecular interactions
• The first mechanism involves the molecular interaction
• between corpuscular blood components, plasma and artificial
surfaces.
• The initial adsorption of plasma proteins (fibrinogen) on the artificial
surface is generally followed by platelet adhesion.

7. 2. Influence of transprosthetic blood flow
• The second mechanism can occur in three ways.
• First, unphysiological flow that involves rapidly changing flow
directions (‘turbulent flow’) may result in a blood-borne increase in
shear stress and consequently in a structurally and metabolically
damaged endocardium, causing it to lose its resistance to thrombosis

8. • Second, blood stasis in recirculation areas downstream from the
prosthesis.
• Clot formation starts on the outflow side of the Prosthesis.
• Because the velocity of the transprosthetic flow near the valve housing is
low.
• Finally, chronic, subclinical haemolysis
• occur as a consequence of the accelerated destruction of thrombocytes
and erythrocytes with shortened intravascular lifespans.

9. 3. Local hypercoagulability
• All factors that promote clotting or platelet aggregation, permanently or temporarily,
increase the risk for local thrombosis.
• these factors are inadequate or unstable anticoagulation,
• loss of atrial contraction (atrial fibrillation),
• sporadic use of a variety of drugs,
• malignancies or systemic diseases,
• defects on the prosthetic surface,
• incomplete endothelialization of the sewing ring, and other hypercoagulable states.

10. Incidence
• Average 0·2% per patient-year after aortic and
• 1·8% per patient-year after mitral valve replacement,
• The risk for PVT appears to be twice as high in mitral as in aortic valve
replacement, and
• is more than three times higher for a tricuspid valve prosthesis

11. Epidemiology
• Mechanical valve thrombosis
• The incidence of obstructive PVT varies between 0.3–1.3% patient per years.
• Thromboembolic complications are more frequent and occur at a rate of 0.7–
6% patient years.
• Non‐obstructive PVT is a relatively frequent finding in the postoperative
period, with a reported incidence as high as 10% in recent (TEE) studies.

12. • Bioprosthetic valve thrombosis
• Rare occurrence when compared to mechanical prostheses.
• Bioprosthetic PVT is usually diagnosed in the early postoperative period,
when endothelialisation of the suture zone is not yet complete.

13. Diagnosis
• Clinical presentation
• Highly variable, depending on the presence or absence of obstruction.
• Severe obstructive PVT is typically associated with overt heart failure,
• whereas non‐obstructive PVT is often an incidental finding or can present as an
embolic episode.
• Partial obstruction (for example, obstruction of one leaflet) can manifest itself with
abnormal dyspnoea, or systemic embolism and rarely fever.
• In the presence of fever, diagnostic blood cultures should be performed to rule out
infectious endocarditis.

14. • The typical clinical finding in PVT
• cardiac auscultation may detect absence of prosthetic click or
• presence of new systolic or diastolic murmur.

15. Blood tests
• Routine periodic blood testing after mechanical valve replacement should include
• INR (prothrombin time) to monitor adequacy of anticoagulation
• (Inadequate anticoagulation may be associated with increased risk of prosthetic
valve thrombosis)
• Lactate dehydrogenase (to detect possible hemolysis)
• Plasma D‐dimer level has high specificity but low sensitivity for detecting
prosthetic heart valve thrombosis

16. Imaging studies
• Fluoroscopy
• As all mechanical valves available are radio‐opaque, fluoroscopy is an
important part of the diagnostic evaluation of suspected PVT.
• However, this technique will not be helpful in identifying
non‐obstructive PVT or differentiating pannus from thrombus.
• Hence, additional diagnostic procedures are often necessary.

17. Benefits of fluoroscopy
• Noninvasive
• May be used to evaluate opening and closing angle of prosthetic valve
leaflets
• Can detect motion of leaflets and base ring
• Can detect leaflet restriction
• Can assess integrity of mechanical prosthetic heart valve components

18. • Patient should be positioned so that leaflets are perpendicular to the
x‐ray tube.
• Not suitable for evaluation of bioprosthetic heart valves because of the
radiolucent properties of biological leaflets.
• Better than TTE and TEE for visualization of leaflet motion in aortic
position
• Comparable to TTE and TEE for visualization of leaflet motion in mitral
position

20. • Transthoracic echocardiography ( TTE )
• By providing direct visualization of the prosthesis and a measure of
transvalvular gradients, TTE is an essential part of diagnostic assessment
• Using color Doppler, abnormal transprosthetic flow or central regurgitation,
indicating abnormal valve closure, can be observed.
• Pulmonary artery pressures and cardiac output should also be measured.
• Direct signs of PVT include abnormal movement of the prosthesis (immobile
hemi‐disc, incomplete or delayed opening) or visualization of a paraprosthetic
thrombus.

21. • For mitral prostheses, a mean gradient >8 mm Hg and an effective area
⩽1.3 cm2 is indicative of PVT .
• For aortic prostheses, criteria for PVT are a mean gradient >45 mm Hg and an
obstructive index <0.25.
• In the case of small size aortic prostheses (for example, mechanical valve
sizes 19 or 21), diagnosis can be difficult when considering that these
prostheses often have “normally” elevated gradients, due to local turbulent
flow across the main orifice and potential patient–prosthesis mismatch.

22. • Limitations of TTE include
• quality of the acoustic window,
• artefacts associated with the prosthesis, and non‐obstructive PVT (where
TTE will usually be normal).
• In conditions of low cardiac output, transvalvular gradients can be within the
normal range despite significant prosthetic valve obstruction, so‐called
“silent Doppler PVT”.
• Hence if clinical suspicion remains, the investigation should be completed
with a TEE study.

24. • Transesophageal echocardiography ( TEE )
• Direct signs of PVT include immobility or reduced leaflet mobility, and the
presence of thrombus on either side of the prosthesis, with or without
obstruction.
• Thrombi have to be differentiated from a fibrous pannus, which is usually
annular in location.
• Indirect TOE signs of PVT are the disappearance of the normal physiological
prosthesis regurgitant flow, the presence of central prosthesis regurgitation,
and pronounced spontaneous echo contrasts in the left atrium

26. • Benefits of TEE include
• Proximity of probe to anatomical structures improves visualization of
anatomic abnormalities and dysfunction,
• better visualization of leaflet thickening, leaflet prolapse, and flail cusps
• Evaluation of PHV leaflet motion and assessment of regurgitation,
• identification of prosthetic and bioprosthetic valve obstruction.
• Better visualization of valve thrombosis, especially in the mitral position
• May be combined with Doppler ultrasound

27. • Limitations of TEE include
• Semi‐invasive
• Prosthetic valves may produce acoustic shadowing
• May not differentiate active from healed vegetations in patients with
infective endocarditis, thickened valves or nodules from vegetations
and
• thrombosis from pannus or vegetation
• difficulty visualizing leaflet motion in aortic position

29. Thrombus or pannus?
• Some distinguishing features between thrombus and pannus in terms of when they
occur after mechanical valve replacement surgery and the echocardiographic
appearance.
• Inadequate anticoagulation with warfarin should raise suspicion of thrombus.
• Pannus formation usually occurs many years after mechanical valve replacement,
compared with thrombus, which may occur at any time.
• Pannus is more commonly associated with mechanical valves in the aortic position
but can occur in association with any mechanical valves. When observed on mitral
prosthetic valves, they most often occur on the atrial side of the prosthesis.
• Typically presenting as a very dense immobile echo

33. TREATMENT
• Once diagnosis of PVT is confirmed, several therapeutic modalities can be
considered:
• Surgery, fibrinolysis, heparin treatment, or optimisation of anticoagulant and
antiplatelet therapy.
• Treatment can be separated according to presence of obstruction and
prosthesis location.
• The type of prosthesis (mechanical or biological) does not have particular
therapeutic implications, as the choice between surgery and medical
treatment will have to take into account the same considerations.

34. • Left-sided mechanical valves
• Valve obstruction from a small thrombus (less than 1 cm in diameter or 0.8
cm2 in area),
• recent onset (fewer than 14 days) and
• associated with mild symptoms (NYHA, class I-II)
• can be treated initially with a trial of 24 to 48 hours of intravenous
unfractionated heparin
• with a goal activated partial thromboplastin time (APTT) of 1.5 to 2 times the
control value.

35. • The patient should be monitored clinically,
• TTE should be performed every two to four hours, and
• TEE should be performed daily to assess the valve status.
• Improvement in valve function and gradient should be followed by
warfarin and continued intravenous heparin
• until the INR is in the range of 3 to 4 for aortic prostheses and 3.5 to
4.5 for mitral prostheses.

36. • If there is no improvement in valve function and gradient after 24
hours,
• thrombolytic therapy with recombinant tissue plasminogen activator
(rTPA)
• (10-mg intravenous bolus followed by 90-mg intravenous infusion over
two hours or,
• alternatively, 20-mg intravenous bolus followed by 30-mg infusion over
three hours) should be considered.

37. • Should be followed by warfarin and intravenous unfractionated heparin
until the INR is (3 to 4 for aortic valve prostheses) and (3.5 to 4.5 for mitral
prostheses).
• Patients in whom thrombolytic therapy is partially successful (the valve
gradient is improved but not normalized) present a challenge.
• Options include both subcutaneous unfractionated heparin twice daily to
achieve an APTT of 1.5 to 2 times control and warfarin therapy with a target
INR of 2.5 to 3.5 for three months.

38. • Emergency surgery is recommended for patients with
1. severe symptoms (NYHA class III-IV) and left-sided valve thrombosis,
regardless of thrombus size and
2. the thrombus size is large (more than 1 cm in diameter or greater
than 0.8 cm2 in area), regardless of symptoms.

40. • Right-sided mechanical valves
• A trial of IV heparin followed by thrombolytic therapy is the mainstay of
treatment.
• followed by warfarin and intravenous unfractionated heparin until INR is in
the range of 3.5 to 4.5.
• Partially successful thrombolytic therapy may be followed by subcutaneous
unfractionated heparin twice daily to achieve an APTT of 1.5 to 2 times
control.
• Surgery should be considered if heparin and thrombolytic therapy fail.

41. Medications
Thrombolytic therapy
Indications for thrombolytic therapy (AHA/ACC) 2014 recommendations
For left‐sided thromboses
• recent‐onset (< 14 days) ,(NYHA) functional class I‐II symptoms, and small thrombus (<
0.8 cm2) (AHA/ACC Class IIa, Level B)
• first‐line therapy for NYHA functional class III‐IV symptoms, and small clot burden if
surgery is high risk or not available (AHA/ACC Class IIb, Level B)
• NYHA functional class II‐IV symptoms, and large clot burden if emergency surgery is
high risk or not available (AHA/ACC Class IIb, Level C)

42. • Right‐sided thromboses
• Consider for thrombosed right‐sided prosthetic heart valve (AHA/ACC
Class IIa, Level B)
• Consider for thrombosed right‐sided prosthetic heart valves with
NYHA functional class III‐IV symptoms or large clot burden (AHA/ACC
Class IIa, Level C)

43. Choice of thrombolytic agent
• Options include streptokinase, urokinase, and recombinant tissue
plasminogen activator (rt‐PA)
• Considerations when choosing thrombolytic agent
• Cost
• Time to attain maximal pharmacologic effect (rt‐PA is faster)
• Half‐life of thrombolytic agent (rt‐PA has faster effect reversion), important if urgent
surgery might be required due to failure of thrombolysis
• Experience with use of particular agent

44. Dosage and delivery of thrombolytic agents
• rt‐PA
• initial dose 10 mg bolus
• maintenance dose 90 mg infusion over 2 hours
• streptokinase
• loading dose 500,000 units over 20 minutes
• maintenance dose 1,500,000 units over 10 hours
• urokinase less effective than rt‐PA or streptokinase

45. • In patients with hemodynamic instability, short protocol
recommended for patients
• rtPA 10 mg bolus IV plus 90 mg rtPA in 90 minutes with
unfractionated heparin
• Streptokinase 1,500,000 units in 60 minutes without UFH
• Longer infusion duration may be used in stable patients

46. Contraindications to thrombolytic therapy
• A history of intracranial bleeding
• Recent cranial trauma
• Gastrointestinal or genitourinary bleeding within 21 days
• Hemorrhagic retinopathy;
• The presence of large, mobile thrombi
• Severe hypertension
• Hypotension or cardiogenic shock
• Major surgery within the previous two weeks

47. Anticoagulant therapy
• Start anticoagulant therapy after successful thrombolytic therapy
• Start unfractionated heparin IV until vitamin K antagonist (VKA) achieves
INR of 3‐4 for aortic prosthetic valve and 3.5‐4.5 for mitral prosthetic valve
• Continuous infusion unfractionated heparin indicated at end of
thrombolytic therapy
• Usual starting dose of heparin 1,000 units/hour

48. • Monitor activated partial thromboplastin time (aPTT) every 6‐8 hours and
adjust heparin infusion rate accordingly for first 48 hours
• after discontinuing thrombolysis resume oral anticoagulation therapy and
combine with heparin until optimum INR achieved
• Heparin infusion with frequent measurement of aPTT begins when aPTT
more than 2 times control levels and can be converted to warfarin (INR
2.5‐3.5) plus aspirin (81‐100 mg/day)

49. Surgery and procedures
• For prosthetic valve thrombosis
• Emergency operation is recommended for patients
• with thrombosed left‐sided prosthetic valve and (NYHA) functional class III‐IV
symptoms (AHA/ACC Class I, Level B)
• Emergency operation is reasonable for patients
• with thrombosed left‐sided prosthetic valve and mobile or large thrombus (area ≥
0.8 cm2) (AHA/ACC Class IIa, Level C)

50. • Surgery may be considered first for patients with
• Left atrial thrombus
• Active bleeding
• Within first 4 days after valve replacement
• Surgical options include
• Replacement of prosthesis
• if prosthesis functioning normally, thrombectomy may be preferred
• Surgery can be performed 24 hours after discontinuation of thrombolysis or 2 hours after
thrombolytic activity reversed with protease inhibitors.

51. THANK YOU