INTRODUCTION

More than 100 million people worldwide are suffering from valvular heart disease which is associated with significant morbidity and mortality. In the past 50 years there is a drastic change in the etiology of valvular heart disease with marked reduction in rheumatic heart disease (RHD) and a substantial increase in degenerative heart disease.

Although, the surgery was the mainstay of treatment for valvular heart disease but in the past 15–20 years transcatheter therapies have grown and overtaken surgery. Based on leaflet material there are two types of artificial heart valves:

1. Mechanical heart valves (MHVs): These are more durable but more thrombogenic. These heart valves have developed from the early caged ball and tilting disk design; to the bileaflet valves mounted on a Dacron or Teflon covered sewing ring.
2. Bioprosthetic heart valves (BHVs): These exhibit more natural hemodynamic properties, are less thrombogenic than MHV but are less durable. These can be implanted via a surgical or transcatheter approach. BHV’s are made from a sheet of bovine pericardium that is mounted on a stent or a frame covered by a fabric which serves as a sewing ring. Earlier porcine BHV’s were used. Now stentless BHV’s provide greater effective orifice areas and lower transprosthetic gradient. All the transcatheter aortic and mitral prosthetic valves (PVs) consist of a bovine or porcine pericardial tissue, trileaflet in shape and mounted on a self-expandable or balloon expandable metallic frame.

There is need for short- or long-term anticoagulation to prevent thrombosis because all foreign bodies (including PV’s) implanted within the human cardiovascular system are potentially thrombogenic. If anticoagulation is not done, thrombosis can lead to stroke and other thromboembolic complications.

Prosthetic valve thrombosis (PVT) is a pathological condition characterized by thrombus formation on the prosthesis with subsequent thromboembolism (TE) and PV dysfunction. Prosthetic valve dysfunction occurs more in mechanical than biological prosthesis and can cause reduced leaflet motion, unpaired leaflet coadaptation, leaflet thickening leading to either stenosis or insufficiency as the primary valve defect.

Four main etiologies may account for PV dysfunction:

1. PV thrombosis
2. Fibrotic pannus ingrowth
3. PV degeneration
4. PV endocarditis with vegetation formation

Determination of the main etiology of PV dysfunction is important because the treatment differs for each of these conditions. The type of PV, its anatomical location and patient specific risks of TE and bleeding risks determine the specific antithrombotic therapy to prevent PV thrombosis.

EPIDEMIOLOGY

As per various reported studies rates of PVT are highly variable and most likely underestimate the true incidence. The risk of PVT and TE events is higher with MHV’s than with BHV’s, higher for right-sided PV’s than left-sided PV’s and higher for PV’s implanted in mitral position than aortic position.

    Mechanical Valve Thrombosis

For about 0.3–1.3% patient-years is the average incidence for obstructive mechanical valve thrombosis. TE complications are more common and occur at a rate of 0.7–6% patient-years. As per recent transesophageal echocardiography (TEE) reports nonobstructive PVT is relatively frequent with a reported incidence as high as 10%. This emphasizes the necessity of postoperative optimal anticoagulation. First postoperative period has a higher incidence of PVT with a stable lower incidence in later years.

    Bioprosthetic Valve Thrombosis

When compared to mechanical prosthesis, thrombosis of a BPV is a rare occurrence. In one meta-analysis of various reports which included 31,874 patient-years reported annual rates of PVT and TE was 0.03 and 0.38% respectively. Higher annual incidence in BHV’s was observed in BHV’s implanted in the tricuspid position. Incidence was also higher with stented porcine BHV’s than with stent less BHV’s. Incidence is highest in the first 3 months.

    Transcatheter Prosthetic Valves

There were no cases of PVT in the PARTNER (Placement of Aortic Transcatheter Valves) and CORE valve trials. In the PARTNER EU registry only one case of PVT was reported in the 130 transcatheter aortic valve replacement (TAVR) patients.

PATHOPHYSIOLOGY

According to the principles of Virchow’s triad, the three main factors involved in endovascular thrombosis involve (1) surface, (2) hemodynamic, and (3) hemostasis related factors. Surface endothelia represent the biocompatibility of the prosthesis valve and interaction between the prosthesis and the suture zone. It takes few weeks for tissue cicatrization and endothelization to be complete. Artificial surfaces promote clotting through a complex series of interconnected processes, which include incomplete prosthesis endothelization, leaflet damage, leaflet deterioration, stent fracture, and prosthesis mal positioning.

Hemodynamic factors include low cardiac output, prosthesis mal positioning, anatomical prosthesis position, prosthetic hemodynamic profile, and hyper viscosity. PVT has been reported 20 times more frequently with tricuspid valve than with mitral valve because of slower stream flow in the right sided chambers. Similarly, mitral PVT is 2–3 times more common than aortic PVT.

Hemostatic factors: In high-risk patients especially those undergoing transcatheter therapies primary or secondary hypercoagulability maybe a frequent risk factor. Acquired causes of hypercoagulability include chronic kidney disease, anemia, smoking, and obesity. Local tissue injury during surgical or transcatheter valve replacement may expose tissue factors to the blood and activate extrinsic coagulation pathways.

PATHOLOGY

Prosthetic valve thrombosis is usually a sub-acute or chronic process rather than occurring acutely. Main pathological entity is characterized by organized thrombus with multiple clot layers. Several studies suggest that thrombosis occurs along with other mechanisms of PV dysfunction such as fibrotic pannus ingrowth, structural degeneration and vegetations of PV endocarditis. Fibrotic pannus is defined as an exaggerated biological reaction to the implanted foreign body which leads to reduced leaflet motion and manifests clinically as PV dysfunction. Pannus is generally unaffected by routine anticoagulants. Another factor responsible for PV dysfunction is bioprosthetic degeneration which is influenced by host related and valve related factors.

CLINICAL PRESENTATION

Patients with PV dysfunction with or without thrombosis may present with progressive dyspnea and signs of heart failure or systemic TE. PVT may also be an incidental finding at the time of echocardiographic follow-up. Subsequent TE may or may not occur after PVT. Arterial TE after surgical or transcatheter heart valve replacement should be considered prosthesis related unless proven otherwise. Arterial TE manifests with signs and symptoms related to the territory of vessel occluded.

Right-sided TE arises from pulmonary or tricuspid valve thrombus or vegetation and can cause pulmonary embolism. In patients presenting with fever, infectious endocarditis should be suspected, and diagnostic blood cultures should be performed. Biological test usually shows normal inflammatory markers. Concentration of D-dimer may be raised.

On first suspicion of PVT, a careful clinical examination should be performed with special attention on muffling or disappearance of prosthetic sounds and the appearance of a new regurgitant or stenotic murmur.

IMAGING

    Cinefluoroscopy

All the available mechanical valves are radiopaque, and cinefluoroscopy is an important part of diagnostic evaluation. However, this technique will not be helpful in nonobstructive PVT or differentiating pannus or thrombus.

    Transthoracic Echocardiography

Transthoracic echocardiography (TTE) is an essential part of diagnostic assessment. Particular attention should be directed at transvalvular flow, gradient and inspection of the prosthesis. Color Doppler can provide useful information. Direct signs of PVT include abnormal movement of the prosthesis or visualization of a paraprosthetic thrombus.

Limitation of TTE includes the quality of the acoustic window, nonobstructive PVT and artefacts associated with the prosthesis. Hence, if clinical suspicion remains then we should perform TEE.

    Transesophageal Echocardiography

In most of the cases the high-resolution imaging of TEE will provide important diagnostic information which will also guide treatment. Direct signs of PVT include immobility or reduced leaflet mobility and presence of thrombi on either side of the prosthesis. Pannus is usually annular in location. Pannus formation is more frequent on aortic than a mitral prosthesis. TEE has a much greater sensitivity than TTE for the diagnosis of bioprosthetic thrombosis.

TREATMENT

Various therapeutic modalities available include surgery, fibrinolysis, heparin treatment or optimization of anticoagulant and antiplatelet therapy.

    Nonobstructive Left-sided Prosthetic Valve Thrombosis

Management can be divided according to the thrombus size.

• For large (>5 mm) nonobstructive thrombi surgery may be indicated in cases of failure of heparin treatment particularly in the presence of large mobile and pedunculated thrombi.
• For small (<5 mm) nonobstructive thrombi medical treatment is preferred. This will comprise of heparin therapy for 1 week or adjustment of warfarin therapy with addition of low dose aspirin (100 mg). There is a significant risk of systemic embolism.

    Obstructive Left-sided Prosthetic Valve Thrombosis

Obstruction of a mechanical prosthesis requires aggressive treatment i.e., surgery or fibrinolysis. According to the American College of Cardiology/American Heart Association guidelines surgery is the preferred treatment for the left-sided PVT. Fibrinolysis should be reserved for poor functional class patients with high-surgical risk or contradiction to surgery.

    Right-sided Obstructive Prosthetic Valve Thrombosis

Obstruction of a tricuspid or pulmonary prosthesis is usually considered for fibrinolysis. Surgery is reserved for cases of fibrinolysis failure.

CONCLUSION

Cardiac valve replacement is becoming increasingly common because of valvular disease in aging populations. The mortality associated with obstructive PVT is approximately 10% independent of treatment modality. Thus, prompt identification of valve dysfunction and timely treatment mitigate the risk of catastrophic outcomes. Therapeutic strategy will be influenced by prosthesis location, presence or absence of valvular obstruction and by patient’s clinical status.

SUGGESTED READINGS

1.   Dangas GD, Weitz JI, Giustino G, Makkar R, Mehran R. Prosthetic Heart Valve Thrombosis. J Am Coll Cardiol. 2016;68(24):2670-89.

2.   Roudaut R, Serri K, Lafitte S. Thrombosis of prosthetic heart valves: diagnosis and therapeutic considerations. Heart. 2007;93(1):137-42.

3.   Bonnichsen CR, Pellikka PA. Prosthetic Valve Thrombus Versus Pannus: Progress with Imaging. Circ Cardiovasc Imaging. 2015;8(12):e004283.