Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Clinical manifestations and diagnosis

INTRODUCTION — Replacement of a diseased heart valve with a prosthetic heart valve exchanges the native disease for prosthesis-related complications [1-3]. Complications include prosthetic valve obstruction (including prosthetic valve thrombosis [PVT] and pannus formation), embolic events, bleeding, prosthetic valve regurgitation (valvular and paravalvular), infective endocarditis, and prosthetic valve-related hemolysis. (See "Overview of the management of patients with prosthetic heart valves".)

This topic discusses the clinical manifestations and diagnosis of surgical or transcatheter bioprosthetic valve thrombosis (BPVT), thromboembolism, and obstruction.

Related issues are discussed separately:

●Risk of thrombotic complications (thromboembolism and valve thrombosis) of surgical and transcatheter bioprosthetic valves. (See "Antithrombotic therapy for surgical bioprosthetic valves and surgical valve repair", section on 'Risk of thrombotic complications with a surgical bioprosthetic valve' and "Transcatheter aortic valve implantation: Complications", section on 'Valve thrombosis' and "Transcatheter aortic valve implantation: Antithrombotic therapy".)

●Antithrombotic therapy to reduce the risk of thrombotic bioprosthetic valve complications. (See "Antithrombotic therapy for surgical bioprosthetic valves and surgical valve repair" and "Transcatheter aortic valve implantation: Antithrombotic therapy".)

●Management of bioprosthetic obstruction, thromboembolism, and thrombosis.

•For individuals who are not pregnant. (See "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Management".)

•For individuals who are pregnant. (See "Management of risks of prosthetic valves during pregnancy", section on 'Risks associated with prosthetic valves'.)

PATHOPHYSIOLOGY — PVT and valve obstruction are partially overlapping conditions.

Thrombotic complications — Thrombus forming on a bioprosthetic valve can cause thromboembolism and/or BPVT. BPVT can be nonobstructive or obstructive and may or may not be associated with clinical thromboembolic events [4-7],. The incidence of these complications is discussed separately. (See "Antithrombotic therapy for surgical bioprosthetic valves and surgical valve repair", section on 'Risk of thrombotic complications with a surgical bioprosthetic valve'.)

Valve dysfunction — Bioprosthetic valve dysfunction includes valve obstruction, regurgitation, and mixed stenosis and regurgitation. These conditions can occur days to years after valve replacement. Causes of bioprosthetic valve dysfunction include structural degeneration/pannus formation (which may be accompanied by calcification), thrombosis [8], and rarely, infective endocarditis [9]. These causes can occur concurrently (eg, concurrent thrombus and pannus or concurrent thrombus and endocarditis) [9]. Pannus formation is caused by fibrous tissue ingrowth around the prosthetic valve. The incidence of bioprosthetic valve dysfunction is discussed separately. (See "Choice of prosthetic heart valve for surgical aortic or mitral valve replacement", section on 'Valve durability' and "Transcatheter aortic valve implantation: Complications", section on 'Longer-term complications'.)

●Obstruction – Normally functioning bioprosthetic valves are intrinsically obstructive compared with normal native valves. Prosthetic valve obstruction is defined as an impairment to flow above and beyond that usually seen under baseline hemodynamic conditions for the specific bioprosthetic valve type and size. This usually manifests as an increase in the transvalvular pressure gradient and a decrease in effective prosthetic orifice area compared to baseline ("fingerprint" data obtained immediately postimplantation).

Pannus is a more common cause of bioprosthetic valve obstruction than thrombosis, but the two causes often present similarly. Some studies suggest that BPVT has been an underrecognized cause of valve obstruction, as discussed separately. (See "Antithrombotic therapy for surgical bioprosthetic valves and surgical valve repair", section on 'Bioprosthetic valve thrombosis'.)

●Regurgitation – Bioprosthetic valve regurgitation is most commonly caused by structural degeneration, as discussed separately. (See "Clinical manifestations and diagnosis of surgical aortic and mitral prosthetic valve regurgitation".)

The valve dysfunction caused by BPVT is predominantly obstruction (stenosis), sometimes mixed obstruction and regurgitation, and, least frequently, isolated regurgitation (respectively 54, 33, and 11 percent in one series [10]). (See "Clinical manifestations and diagnosis of surgical aortic and mitral prosthetic valve regurgitation".)

CLINICAL MANIFESTATIONS

Symptoms and signs — Clinical manifestations in patients with bioprosthetic valve obstruction range from an incidentally detected change in valve appearance or valve gradient observed on an echocardiogram performed for other reasons, thromboembolism, symptoms and signs of heart failure (HF) caused by valve dysfunction (eg, dyspnea, fatigue, rales, cardiogenic shock), presyncope or syncope, and, rarely, sudden death [11].

Symptoms and signs of a thromboembolic event may occur with or without concurrent valve obstruction. Left-sided PVT (mitral or aortic) may cause systemic embolic events such as stroke or, rarely, myocardial infarction [12,13]. Right-sided (tricuspid or pulmonic) PVT may cause pulmonary emboli; tricuspid PVT can also cause systemic emboli via paradoxical embolization.

Initial tests

●Laboratory tests – Initial laboratory tests include a complete blood count, an international normalized ratio (INR) in patients who have been treated with warfarin, and an electrocardiogram (ECG) in patients presenting with HF or signs of an acute coronary syndrome.

If the hemoglobin level is low, evaluation of anemia should include a hemolysis work-up (assessment of the peripheral smear, reticulocyte count, and serum lactate dehydrogenase (LDH), bilirubin, free hemoglobin, and haptoglobin levels), as discussed separately. Bioprosthetic valve obstruction or regurgitation is sometimes associated with hemolysis. (See "Overview of the management of patients with prosthetic heart valves", section on 'Hemolytic anemia' and "Diagnosis of hemolytic anemia in adults", section on 'Laboratory confirmation of hemolysis'.)

Additional testing for patients with suspected HF, including assessment of natriuretic peptide levels (B-type natriuretic peptide [BNP] or N-terminal pro-BNP [NT-proBNP]) [14], is discussed separately. (See "Heart failure: Clinical manifestations and diagnosis in adults".)

●Electrocardiogram – An ECG is indicated in patients presenting with symptoms suggestive of HF (eg, dyspnea, edema), an acute coronary syndrome (eg, chest pain), or stroke. The ECG is generally nondiagnostic in patients with BPVT or thromboembolism. However, the ECG may help identify other causes of symptoms such as an acute coronary syndrome or arrhythmia (eg, atrial fibrillation). As noted above, coronary thromboembolism from a prosthetic valve is a rare cause of myocardial infarction. (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department", section on 'Electrocardiogram assessment' and "Heart failure: Clinical manifestations and diagnosis in adults", section on 'Initial testing' and "Initial assessment and management of acute stroke" and "Initial assessment and management of acute stroke", section on 'Initial assessment'.)

●Echocardiogram – The key role of echocardiography in the diagnosis and evaluation of BPVT or obstruction is discussed below. (See 'Initial echocardiography' below.)

INITIAL EVALUATION — Our approach to evaluating patients with suspected BPVT and/or bioprosthetic valve obstruction includes an initial clinical evaluation (including transthoracic echocardiogram [TTE]), further evaluation (including three-dimensional [3D] transesophageal echocardiography [TEE] and/or four-dimensional [4D] computed tomography [CT]), and application of diagnostic criteria.

When to suspect BPVT or obstruction — BPVT and/or obstruction should be suspected in a patient with a prosthetic valve with a new or changed murmur or symptoms and signs of HF (eg, dyspnea, fatigue, pulmonary crackles, syncope, cardiogenic shock). In some patients, the first sign of PVT or obstruction is an incidentally detected change in valve appearance (restricted leaflet motion with leaflet thickening or mass) and/or increased valve gradient observed on echocardiography (see 'Symptoms and signs' above). Of note, European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association (ACC/AHA) guidelines on valvular heart disease differ in their recommendations on echocardiographic surveillance. The ESC guideline recommends yearly echocardiography for all bioprostheses [3], whereas the ACC/AHA guideline recommends yearly echocardiographic evaluation for TAVR, but only at five years or symptom change for surgical bioprostheses [2].

Prosthetic valve thromboembolism should be suspected in a patient with a prosthetic valve presenting with a stroke or other thromboembolic event. However, since thromboembolism in a patient with a prosthetic valve may or may not originate from the prosthesis, other causes should also be evaluated, as described below.

Initial echocardiography — As an initial step in evaluating patients with suspected PVT, obstruction, or thromboembolism, we suggest imaging by TTE:

●Comprehensive TTE evaluation should start with a meticulous inspection of the bioprosthetic valve appearance. This step is frequently overlooked, but strongly endorsed by the American Society of Echocardiography [15] and European Association of Cardiovascular Imaging [16]. Abnormal cusp thickness and mobility (movie 1 and movie 2) and presence of regurgitation (prosthetic or periprosthetic) provide important clues of prosthetic dysfunction, although TTE views may be limited. (See "Echocardiographic evaluation of prosthetic heart valves".)

The TTE study is compared with the baseline ("fingerprint") TTE that is routinely obtained in all patients after implantation of a surgical or transcatheter valve. If fingerprint TTE data are not available, comparison should be performed with published data on normal range, included in imaging guidelines [15] and/or available from the manufacturer website. (See "Overview of the management of patients with prosthetic heart valves" and "Transcatheter aortic valve implantation: Periprocedural and postprocedural management".)

●The second step is measurement of the prosthetic mean transvalvular pressure gradient and calculation of effective orifice area (see 'Diagnosis of obstruction' below). Significant changes compared to baseline are highly suggestive of prosthetic dysfunction. However, immobilization of a single cusp does not necessarily result in a change in transvalvular gradients [17].

●The final step in TTE evaluation is an assessment of left and right ventricular function, which will provide hemodynamic context to compare findings with the "fingerprint" echocardiogram.

●TTE is the preferred initial test for assessment of prosthetic valve function. However, commonly used algorithms have limited ability to correctly identify the cause of high gradients, with an overall accuracy of 57 to 62 percent in a series of 266 patients with a known mechanism of aortic bioprosthetic dysfunction [18]. A novel algorithm combining visual cues with Doppler indexes had an overall accuracy of 83 percent. Similarly, in a study of TTE examinations of 324 mitral bioprostheses (of which 88 were dysfunctional) and 647 mitral mechanical prostheses (138 dysfunctional), a proposed algorithm based on a combination of TTE indexes was incorrect 28 percent of the time when diagnosing obstruction, 33 percent when diagnosing regurgitation, and missed pathologic regurgitation in 8 percent of patients deemed normal [19].

●Given the limitations of TTE evaluation and associated algorithms, we have a low threshold to recommend advanced imaging with 3D TEE or 4D cardiac CT angiography whenever prosthetic dysfunction is suspected. (See "Echocardiographic evaluation of prosthetic heart valves".)

Diagnosis of obstruction — Prosthetic valve obstruction is identified by a mean transvalvular pressure gradient that is >50 percent compared with baseline (or by a mean gradient ≥20 mmHg or an increase in mean gradient ≥10 mmHg for an aortic prosthesis [20]). Other causes of an elevated gradient, such as high flow, patient-prosthesis mismatch, or pressure recovery, should be excluded. (See 'Differential diagnosis' below.)

If a prior postoperative baseline TTE is not available for comparison, a prosthetic valve gradient above established normal values (above the 95% CI) for valves of that type and size (eg, normal values compiled in the 2009 American Society of Echocardiography guidelines [15] and the 2016 European Association of Cardiovascular Imaging recommendations [16]) is suggestive of prosthetic valve obstruction, although patient-prosthesis mismatch may also be a cause. (See "Choice of prosthetic heart valve for surgical aortic or mitral valve replacement", section on 'Prosthetic valve-patient mismatch'.)

Other causes of an elevated gradient, such as a high-output state, should be excluded. (See 'Initial evaluation' above and 'Differential diagnosis' below.)

ADDITIONAL EVALUATION

Role of advanced imaging — We suggest evaluation with advanced imaging when bioprosthetic valve thrombosis, thromboembolism, and/or obstruction is suspected after initial evaluation and imaging by TTE.

This evaluation is expedited in patients with bioprosthetic valve obstruction causing moderate or severe symptoms (New York Heart Association [NYHA] functional class III or IV). (See "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Management", section on 'For moderate to severe symptoms of obstruction'.)

The choice between 3D TEE or 4D CT is made based upon test availability, prior imaging results, patient characteristics, bioprosthetic valve location, and clinician/center experience. In select patients, both imaging modalities are performed for further assessment of the bioprosthetic valve.

Both 3D TEE and 4D CT enable assessment of bioprosthetic valve leaflet appearance and motion including detection of bioprosthetic leaflet thickening and restricted leaflet motion. While TEE is generally the test of choice for identifying causes of emboli other than BPVT, cardiac CT is also helpful for identifying alternative diagnoses as it can identify vegetations with accuracy approaching that of TEE [21], and cardiac CT with a delayed imaging acquisition protocol can identify atrial thrombi with accuracy nearing that of TEE [22,23].

●When to start with 3D TEE - 3D TEE is indicated in the following settings, as it may detect prosthetic thrombi and other abnormalities that are not well visualized by TTE or 2D TEE [24] (see "Echocardiographic evaluation of prosthetic heart valves"):

•If TTE assessment of bioprosthetic valve function is suboptimal, 3D TEE is preferred as it may be helpful in assessing bioprosthetic valve obstruction (elevated transvalvular gradient) and regurgitation. (See 'Diagnosis of obstruction' above.)

•For bioprosthetic mitral and tricuspid valves, 3D TEE is preferred.

•For patients with contraindications to CT (including contraindication to CT contrast), TEE is preferred.

•For patients with a thromboembolic event (eg, stroke) and/or suspected infective endocarditis, TEE is generally preferred.

●When to start with 4D CT:

•4D CT is preferred for the patient with contraindication to TEE.

•4D CT is preferred for a patient known to have suboptimal TEE prosthetic valve images.

•4D CT may be preferred for transcatheter aortic bioprosthetic valves, particularly if prior TEE images are suboptimal. (See "Imaging for transcatheter aortic valve implantation", section on 'Long-term follow-up'.)

If the bioprosthetic valve is not adequately visualized by TEE or 4D CT, we suggest performing the alternate test, if feasible.

Diagnosis of BPVT or pannus — The presence of increased cusp thickness with restricted leaflet mobility is suggestive of BPVT or pannus. BPVT is presumptively diagnosed when both of the following features are present on TEE and/or 4D CT with characteristics consistent with BPVT:

●Increased cusp thickness – BPVT appears as diffuse or focal soft echodense cusp thickness >2mm on TEE or hypoattenuated leaflet thickening (HALT) [25] on 4D CT with the following features:

•Respects cusp edges – With BPVT, the valve thickening usually respects the cusp edges. In contrast, pannus usually appears to overlay the valve (figure 1 and figure 2 and figure 3).

•Downstream – BPVT is generally located on the downstream side of the bioprosthetic valve (figure 2 and figure 3 and movie 3 and movie 4) [26], although mitral BPVT has also been visualized on the upstream side of the valve [27].

•No or mild calcification – BPVT is usually associated with no more than mild cusp calcification. Greater calcification is usually associated with a degenerated bioprosthetic valve rather than thrombus (figure 1 and figure 2 and figure 3). However, the presence of valve calcification does not rule out a thrombotic component, particularly if other imaging features clearly suggest thrombus.

●Restricted leaflet mobility – Restrictive bioprosthetic leaflet mobility is a key feature of BPVT identified by TTE, TEE, or 4D CT (movie 3 and movie 5 and movie 6 and movie 4), but cusp immobility alone is not diagnostic of BPVT, as cusp immobility is also seen with bioprosthetic valve degeneration and pannus formation (movie 7 and movie 8 and movie 9 and movie 10) [28]. Furthermore, abnormal cusp mobility can be detected by intraoperative TEE of apparently normal bioprostheses, possibly due to focal hemodynamic milieu [29].

BPVT should be distinguished from other causes of prosthetic cusp thickening, such as endocarditis. The diagnosis of BPVT may be confirmed by resolution of prosthetic valve thickening/mass with anticoagulation or pathologic inspection after prosthesis removal. (See "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Management", section on 'Antithrombotic therapy'.)

Limited data are available on distinguishing bioprosthetic valve thrombus and pannus on echocardiography. Echocardiographic diagnostic criteria (greater than 50 percent increase in mean prosthetic valve gradient from baseline within five years, increased cusp thickness, and impaired cusp mobility) were developed based upon a retrospective study of 32 patients with BPVT [30] and confirmed in a prospective study of 52 patients with suspected BPVT followed for a mean of 85 weeks [31]. Presence of all three criteria predicted a positive response (≥50 percent reduction in mean valve gradient) to vitamin K antagonist therapy with a sensitivity of 88 percent, specificity of 93 percent, positive predictive value of 91 percent, and negative predictive value of 85 percent [31].

Diagnosis of thromboembolism — When a patient with a bioprosthetic valve experiences a presumed thromboembolic event (eg stroke), a diagnosis of thromboembolism from the bioprosthetic valve is made after excluding other causes of stroke and embolic events. In patients with bioprosthetic valve thromboembolism, thrombus may or may not be visualized on the bioprosthetic valve. (See "Overview of the evaluation of stroke" and 'For valve thromboembolism or thrombosis' below.)

Evaluate thrombophilia — Patients with bioprosthetic valves who develop BPVT or thromboembolism should undergo evaluation for an inherited thrombophilia. The most concerning inherited thrombophilias are those associated with a personal or strong family history of thrombosis, including antithrombin (AT) deficiency and homozygosity or compound heterozygosity for the factor V Leiden and/or prothrombin G20210A. (See "Screening for inherited thrombophilia in asymptomatic adults" and "Evaluating adult patients with established venous thromboembolism for acquired and inherited risk factors".)

DIFFERENTIAL DIAGNOSIS

For valve obstruction — Valve obstruction should be distinguished from other causes of left ventricular outflow tract (LVOT) obstruction or increased prosthetic transvalvular pressure gradients, such as patient-prosthesis mismatch, prosthetic valve regurgitation, endocarditis, and increased stroke volume (eg, due to high-output state).

●Patient-prosthesis mismatch – Comparison with a baseline postoperative TTE and patient characteristics is helpful in distinguishing a new valve obstruction from patient-prosthesis mismatch (with which the transvalvular gradient would be similarly elevated in postoperative studies assuming body habitus has not changed). (See "Choice of prosthetic heart valve for surgical aortic or mitral valve replacement", section on 'Prosthetic valve-patient mismatch'.)

●Regurgitation – Bioprosthetic valve regurgitation (transvalvular or paravalvular) should be excluded by TTE and/or TEE. TEE is particularly helpful for diagnosis of prosthetic/periprosthetic mitral or tricuspid regurgitation. Bioprosthetic valve regurgitation is most commonly caused by structural degeneration. BPVT is a less common cause. Transvalvular prosthetic valve regurgitation should be distinguished from paravalvular regurgitation. (See "Clinical manifestations and diagnosis of surgical aortic and mitral prosthetic valve regurgitation" and "Echocardiographic evaluation of prosthetic heart valves", section on 'Prosthetic valve regurgitation'.)

●Increased stroke volume – A clinical history suggestive of a high-output state (such as sepsis or severe anemia [32]) as well as echocardiographic evidence of hyperdynamic left ventricular systolic function and elevated LVOT velocities are suggestive of increased stroke volume as a cause of transiently increased transvalvular gradients. (See "Causes and pathophysiology of high-output heart failure".)

●Left ventricular outflow tract obstruction – For patients with suspected prosthetic aortic valve obstruction, imaging (primarily by TTE) is also helpful in identifying alternate causes of LVOT obstruction, including interventricular septal hypertrophy and protruding mitral prosthesis. (See "Echocardiographic evaluation of prosthetic heart valves", section on 'Prosthetic aortic stenosis'.)

In patients with prosthetic valve obstruction and symptoms and signs of HF, alternate or concomitant causes of these findings (such as left ventricular systolic and/or diastolic dysfunction, respiratory disorders, or deconditioning) should be evaluated. (See "Approach to the patient with dyspnea" and "Heart failure: Clinical manifestations and diagnosis in adults".)

For valve thromboembolism or thrombosis — The differential diagnosis of thromboembolism or stroke from a prosthetic valve includes other cardiogenic and noncardiogenic sources [33]. Patients with a prosthetic valve who have a stroke or other thromboembolic event should undergo a comprehensive cardiovascular and neurologic evaluation including an ECG, monitoring for occult atrial fibrillation, brain imaging, and vascular imaging. The diagnosis and evaluation of embolic stroke and other embolic events are discussed separately. (See "Overview of the evaluation of stroke" and "Initial assessment and management of acute stroke" and "Clinical diagnosis of stroke subtypes" and "Clinical features and diagnosis of acute lower extremity ischemia" and "Acute mesenteric arterial occlusion".)

BPVT should be distinguished from other causes of prosthetic cusp thickening and impaired valve leaflet mobility, including prosthetic valve endocarditis (PVE). While PVE generally presents with signs and symptoms of invasive infection, it occasionally has an occult presentation and is detected by test findings (eg, presence of vegetation and positive blood cultures). If a diagnosis of PVE is uncertain, follow-up testing (ie, repeat TEE, CT, positron emission tomography, and other testing for PVE) is recommended to determine whether or not PVE is present. Clinical manifestations, diagnosis, and management of PVE are discussed separately. (See "Prosthetic valve endocarditis: Epidemiology, clinical manifestations, and diagnosis" and "Antimicrobial therapy of prosthetic valve endocarditis" and "Surgery for prosthetic valve endocarditis".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiac valve disease".)

SUMMARY AND RECOMMENDATIONS

●Bioprosthetic valve thrombosis and valve obstruction – These are partially overlapping conditions. (See 'Pathophysiology' above.)

•Thrombotic complications of bioprosthetic valves – Thrombus forming on a bioprosthetic valve can cause thromboembolism and/or bioprosthetic valve thrombosis (BPVT). BPVT may be subclinical or cause symptomatic valve dysfunction. The valve dysfunction caused by BPVT is predominantly obstruction (stenosis), sometimes mixed obstruction and regurgitation, and, least frequently, isolated regurgitation. (See 'Pathophysiology' above.)

•Bioprosthetic valve obstruction – Causes of bioprosthetic valve obstruction include structural degeneration/pannus formation, thrombosis, and, rarely, infective endocarditis. These causes can occur separately or concurrently.

●Clinical manifestations – Thrombus on a bioprosthetic valve can result in symptoms and signs of thromboembolism and/or valve thrombosis with valve dysfunction (obstruction and/or regurgitation). (See 'Clinical manifestations' above.)

•Incidental finding – Evidence of valve thrombosis or obstruction may be identified by cardiac imaging (eg, echocardiography) in a patient with no symptoms.

•Thromboembolic manifestations – Symptoms and signs of thromboembolism vary with the location of the prosthetic valve. Left-sided (mitral or aortic) BPVT can cause systemic embolic events such as stroke or, rarely, myocardial infarction. Right-sided (tricuspid or pulmonic) BPVT may cause pulmonary emboli; tricuspid BPVT can also rarely result in systemic embolic events via paradoxical embolization. (See 'Symptoms and signs' above.)

•Manifestations of valve dysfunction – Clinical manifestations of bioprosthetic valve dysfunction range from an incidentally detected change in prosthetic valve appearance or gradient on an echocardiogram performed for other reasons, a new murmur consistent with valve obstruction and/or regurgitation, symptoms and signs of heart failure caused by valve dysfunction (eg, dyspnea, fatigue, pulmonary crackles, cardiogenic shock), and, rarely, sudden death. (See 'Symptoms and signs' above.)

●Evaluation and diagnosis

•Initial evaluation – The initial clinical evaluation includes transthoracic echocardiography (TTE) to assess bioprosthetic valve appearance, valve function (including mean transvalvular gradient and effective orifice area), and other potential sources of embolism. (See 'Initial evaluation' above.)

•Further evaluation – If BPVT, thromboembolism, or obstruction is suspected after the initial evaluation, additional evaluation involves advanced imaging (three-dimensional transesophageal echocardiography [3D TEE] and/or four-dimensional computed tomography [4D CT]), and exclusion of other causes of symptoms and signs (such as infective endocarditis). (See 'Additional evaluation' above.)

•Diagnosis

-Obstruction – Prosthetic valve obstruction is identified by a mean transvalvular pressure gradient that is >50 percent compared with baseline (or by a mean gradient ≥20 mmHg or an increase in mean gradient ≥10 mmHg for an aortic prosthesis [20]). Valve obstruction should be distinguished from other causes of left ventricular outflow tract obstruction or increased prosthetic transvalvular pressure gradients. (See 'Diagnosis of obstruction' above and 'For valve obstruction' above.)

-Bioprosthetic valve thrombosis or pannus – The presence of increased cusp thickness with restricted leaflet mobility is suggestive of BPVT or pannus. BPVT is presumptively diagnosed when both increased cusp thickness (generally with no or mild calcification) and decreased cusp mobility are present on 3D TEE, and/or 4D CT with characteristics consistent with BPVT. Prosthetic valve endocarditis should be excluded. (See 'Diagnosis of BPVT or pannus' above.)

-Thromboembolism – When a patient with a bioprosthetic valve experiences a presumed thromboembolic event (eg, stroke), a diagnosis of thromboembolism from the bioprosthetic valve is made after excluding other causes of stroke and embolic events. (See 'Diagnosis of thromboembolism' above and 'For valve thromboembolism or thrombosis' above and "Overview of the evaluation of stroke".)