Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Management

INTRODUCTION — Replacement of a diseased heart valve with a prosthetic valve exchanges the native disease for prosthesis-related complications [1,2]. Complications include prosthetic valve obstruction (including prosthetic valve thrombosis [PVT] and pannus formation), patient-prosthesis mismatch, embolic events, bleeding, prosthetic valve regurgitation (valvular and paravalvular), infective endocarditis, and prosthetic valve-related hemolysis. Thrombus forming on a bioprosthetic valve can be nonobstructive or obstructive and may or may not cause clinical thromboembolic events [3-6]. (See "Overview of the management of patients with prosthetic heart valves".)

This topic discusses the diagnosis and management of surgical or transcatheter bioprosthetic valve thrombosis (BPVT), thromboembolism, and obstruction for individuals who are not pregnant.

Related issues are discussed separately:

●Clinical manifestations and initial evaluation of BPVT and obstruction. (See "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Clinical manifestations and diagnosis".)

●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 and thrombosis during pregnancy differs from the approach presented here. (See "Management of risks of prosthetic valves during pregnancy", section on 'Risks associated with prosthetic valves'.)

GENERAL APPROACH — Management of BPVT, thromboembolism, and obstruction involves addressing the acute risk and selection of therapy for long-term management. The evaluation of BPVT and obstruction is linked to management since some therapies (such as valve surgery or a trial of anticoagulant therapy) may both identify the cause of prosthetic valve obstruction and treat it.

Factors influencing the choice of therapy include the acuity and severity of symptoms of obstruction and the cause of obstruction [1,2,7-9]. We favor not including thrombus size in selecting initial strategy for BPVT as thrombus size cannot be reliably quantified due to prosthesis imaging artifact, and data are lacking on the significance of thrombus size for bioprosthetic valves. Causes of obstruction other than thrombus or pannus (such as endocarditis) should be excluded. (See "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Clinical manifestations and diagnosis", section on 'Differential diagnosis'.)

The vast majority of patients with BPVT are treated with anticoagulation alone. Of note, some patients with subclinical BPVT experience spontaneous resolution without use of anticoagulant therapy; this has been demonstrated with both transcatheter and surgically implanted aortic valve prostheses [10]. (See 'For valve thrombosis' below and 'For valve thrombosis' below and 'Antithrombotic therapy' below.)

Referral to a multidisciplinary Heart Valve Team is recommended for patient with bioprosthetic valve obstruction and/or BPVT who may require fibrinolysis, valve surgery, or transcatheter valve intervention. (See 'Referral to Heart Valve Team' below.)

The approach described here is based largely on expert opinion. Randomized controlled data for the therapy of BPVT are not available, and each therapeutic option has important limitations, including risk of periprocedural morbidity and mortality with valve surgery or transcatheter intervention, risk of bleeding and systemic embolization with fibrinolytic therapy, and risk of failure to improve with intravenous heparin therapy. Similar recommendations are included in the 2020 American College of Cardiology/American Heart Association [1] and 2021 European Society of Cardiology valve disease guidelines [2].

FOR NO OR MILD SYMPTOMS OF OBSTRUCTION — For patients with BPVT, thromboembolism, or bioprosthetic valve obstruction with no or mild symptoms (New York Heart Association [NYHA] class I or II) of obstruction, management is aimed at treating any symptoms of heart failure (HF) and treating the obstruction (eg, thrombus or pannus) or source of thromboembolism.

Temporizing medical care — Symptomatic HF caused by obstruction is treated with cautious use of diuretics and antihypertensive agents, given the risk of hemodynamic instability with attempted therapy. (See 'Temporizing medical care' below.)

Treatment of cause of obstruction — Management of bioprosthetic valve obstruction is based upon the presumptive cause (thrombosis, pannus/calcification, or pannus/calcification plus thrombus).

For valve thrombosis — For patients with presumptive BPVT with no or mild symptoms (NYHA class I or II) of obstruction, treatment is aimed at thrombus resolution. We suggest the following approach based on observational data and our clinical experience (see 'Antithrombotic therapy' below):

●Trial of therapeutic anticoagulation – We suggest an initial 30-day trial of therapeutic oral anticoagulant plus aspirin 75 to 100 mg orally daily.

•With no concurrent indication for anticoagulation – For patients with BPVT with no concurrent indication for anticoagulation (such as atrial fibrillation [AF]), vitamin K antagonist (VKA) is the preferred anticoagulant (target international normalized ratio [INR] generally 2.5). We do not routinely use therapeutic heparin bridging anticoagulation for minimally symptomatic patients, but this can be considered on an individual basis.

Patients post-transcatheter aortic valve implantation should not be routinely treated with the combination of a direct oral anticoagulant (DOAC; also referred to as non-vitamin K oral anticoagulants [NOAC]) plus antiplatelet agent in the absence of a concurrent indication for anticoagulation, given the excess risk of death or thromboembolic events identified with rivaroxaban (10 mg daily) plus low-dose aspirin in the GALILEO trial [11] (see "Transcatheter aortic valve implantation: Antithrombotic therapy", section on 'Without concurrent indication for therapeutic anticoagulation'). Although evidence is lacking on the effect of rivaroxaban in patients with BPVT, we favor avoiding this agent in this setting until more data are available.

•With a concurrent indication for anticoagulation – For patients with a concurrent indication for anticoagulation, the choice of anticoagulant is based upon the indication for anticoagulation and other clinical factors, but VKA (target INR 2.5) is generally preferred. Although a DOAC is generally preferred for patients with AF with risk factors favoring anticoagulation (see "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Choice of anticoagulant'), in patients with BPVT and AF, VKA is preferred, given reports of BPVT and thromboembolic events occurring in patients with bioprosthetic valves during DOAC treatment [11-13].

●Assess response – After at least 30 days of therapeutic anticoagulation, evaluate symptoms and signs of obstruction and perform imaging by transthoracic echocardiography (TTE) and, when needed, either transesophageal echocardiography (TEE; preferably three-dimensional) or four-dimensional multidetector computed tomography to reassess valve gradient and valve appearance.

•Adequate response – For patients with BPVT who respond to VKA therapy (defined as ≥50 percent reduction in mean gradient), VKA therapy is continued for at least six months after thrombus resolution and long-term antithrombotic therapy is instituted, as discussed below. (See 'Long-term management after an event' below.)

•Inadequate response – If there is inadequate reduction in valve gradient (defined as less than 50 percent reduction in mean gradient), the adequacy of anticoagulation should be evaluated and:

-If stable – If the patient is stable and the transvalvular gradient is not increasing, anticoagulation may be continued for successive 30-day intervals followed by reassessment of valve gradient and appearance. If there is no response despite adequate oral anticoagulant therapy, we suggest evaluation for another cause, such as endocarditis (if not already excluded) or hypercoagulable state, and referral to a Heart Valve Team for valve surgery/intervention. (See 'Referral to Heart Valve Team' below.)

-If worsening – If the patient’s symptoms of obstruction are worsening or the transvalvular gradient is increasing with lack of resolution of thrombus after one or more 30-day trials of VKA and aspirin, we suggest evaluation for another cause, such as endocarditis (if not already excluded) or hypercoagulable state, and referral to a Heart Valve Team for consideration of valve surgery and possible alternative options (a valve-in-valve (ViV) procedure or fibrinolytic therapy). However, in our experience, fibrinolytic therapy is unlikely to improve clinical status in patients with a bioprosthetic valve who have failed a 30-day trial of VKA. Scant data are available on the optimum duration of anticoagulation prior to a trial of fibrinolytic therapy. (See 'Referral to Heart Valve Team' below.)

For pannus or calcification — If a patient with mildly symptomatic obstruction has a presumptive diagnosis of pannus or calcification, the patient is referred to a Heart Valve Team for an individualized assessment of the risk/benefit of valve surgery or transcatheter intervention. The approach to choosing between open surgery and transcatheter intervention is the same as that described below for patients with moderately to severely symptomatic obstruction. (See 'Referral to Heart Valve Team' below and 'For pannus or calcification' below and 'Transcatheter intervention' below and 'Surgery' below.)

For pannus/calcification plus thrombus — Patients with clinical and imaging features consistent with BPVT plus pannus or calcification with moderately to severely symptomatic obstruction are referred to a Heart Valve Team for consideration of the options of fibrinolysis or surgery. Surgery is generally preferred in this setting because fibrinolysis has no effect on pannus and is thus unlikely to result in complete resolution of the obstruction. Fibrinolysis is an option only for hemodynamically stable patients who have clear evidence of predominant thrombus. The presence of thrombus is a relative contraindication to a ViV procedure. (See 'Referral to Heart Valve Team' below.)

For other bioprosthetic valve findings — Some patients evaluated for BPVT and/or obstruction have findings that are nondiagnostic. The following approach is suggested for such patients:

●Bioprosthetic cusp thickening/mass strongly suggestive of thrombus with normal cusp motion and no bioprosthetic valve obstruction – In this setting, we suggest treatment as for patients with a presumptive diagnosis of BPVT (see 'For valve thrombosis' above). Of note, some patients with BPVT have spontaneous resolution without anticoagulant therapy [10,14]. Whether subclinical bioprosthetic thrombosis is associated with increased risk of stroke and other embolic events remains uncertain. Given the slight signal of excess risk noted in the Partner 3 trial [10] and our previous observation that BPVT may lead to early degeneration, at this time we favor anticoagulation over observation.

●Limited bioprosthetic cusp motion with no bioprosthetic valve thickening/mass and no bioprosthetic valve obstruction – Bioprosthetic valve cusp immobility alone is not diagnostic of BPVT [15]. Patients with bioprosthetic valves should continue to take routine antithrombotic therapy (eg, aspirin 75 to 100 mg orally daily after the first three to six months for patients with surgical bioprosthetic valves) and undergo close (eg, within three months) clinical and echocardiographic follow-up to assess for development of symptoms or change in bioprosthetic valve appearance or gradient.

●No or nonspecific bioprosthetic valve abnormalities with no bioprosthetic valve obstruction – For patients with no or nonspecific bioprosthetic valve abnormalities (eg, mild nonspecific bioprosthetic cusp thickening with normal cusp motion), routine antithrombotic therapy and follow-up is recommended. (See "Overview of the management of patients with prosthetic heart valves", section on 'Schedule of follow-up' and "Antithrombotic therapy for surgical bioprosthetic valves and surgical valve repair".)

FOR MODERATE TO SEVERE SYMPTOMS OF OBSTRUCTION — Patients with moderately to severely symptomatic (New York Heart Association [NYHA] functional class III or IV) bioprosthetic valve obstruction require urgent management including temporizing medical care, expedited evaluation, and urgent Heart Valve Team assessment to guide further care. Limited evidence is available on management in this setting. (See 'Components of short-term management' below.)

Temporizing medical care — Temporizing supportive medical care for moderately to severely symptomatic bioprosthetic valve obstruction includes respiratory support as needed and cautious treatment of hypertension, hypotension, HF, and volume overload. Medical therapies such as diuretics and antihypertensive agents pose the risk of destabilizing the patient with symptomatic bioprosthetic valve obstruction. These are temporizing measures for patients awaiting definitive treatment of the cause of obstruction and palliative measures for patients who are not candidates for definitive therapy (eg, patients with obstructive pannus who are not candidates for valve surgery or transcatheter valve intervention). Limited data are available on the efficacy of medical management of HF in this setting, but the expected prognosis with only medical treatment of HF is poor given the known natural history of medically treated severe symptomatic valve stenosis.

Therapeutic anticoagulation is promptly initiated if BPVT is the suspected cause of obstruction and fibrinolysis is not the chosen therapy. For patients with BPVT who are taking a vitamin K antagonist (VKA) and require urgent therapy, VKA is held, and intravenous (IV) unfractionated heparin (UFH) and low-dose aspirin (75 to 100 mg orally daily) are added. The antithrombotic protocol for patients undergoing fibrinolysis is described below. (See 'Fibrinolytic protocol' below.)

Urgent Heart Valve Team assessment — Patients with bioprosthetic valve obstruction causing moderate to severe symptoms require urgent evaluation by a Heart Valve Team (including cardiologists with expertise in evaluation of valvular heart disease, specialists in advanced cardiovascular imaging, interventional cardiologists and surgeons with expertise in treatment of valvular heart disease, cardiovascular nurses, cardiovascular anesthesiologists, and intensivists involved in periprocedural care) [1,2] to guide expedited diagnostic evaluation and the choice among therapeutic options, as described below. (See 'Treatment of cause of obstruction' below and 'Referral to Heart Valve Team' below.)

Treatment of cause of obstruction — The presumptive cause of moderately to severely symptomatic bioprosthetic valve obstruction (thrombosis versus pannus/calcification) guides therapeutic choices.

For valve thrombosis — Most patients with BPVT can be successfully treated with anticoagulant therapy; only a minority require emergency surgery or fibrinolysis. The therapeutic sequence is based upon the severity of symptoms:

●With shock – Patients with obstructive BPVT causing cardiogenic shock require immediate intervention.

•For left-sided BPVT – For patients with left-sided (aortic or mitral) BPVT, we suggest surgery (redo bioprosthetic valve replacement) rather than fibrinolysis. This recommendation is based upon indirect evidence from observational studies in patients with mechanical PVT showing low efficacy and high rates of complications in patients with moderate to severe symptoms treated with fibrinolytic therapy. (See 'Referral to Heart Valve Team' below and 'Fibrinolysis' below and 'Surgery' below and "Management of mechanical prosthetic valve thrombosis and obstruction", section on 'Fibrinolytic therapy'.)

•For right-sided BPVT – For patients with right-sided (pulmonic or tricuspid) BPVT we suggest fibrinolysis rather than surgery. This recommendation is based upon very limited observational evidence in patients with right-sided obstructive BPVT and indirect evidence from observational studies in patients with mechanical PVT. (See 'Referral to Heart Valve Team' below and 'Fibrinolysis' below and "Management of mechanical prosthetic valve thrombosis and obstruction", section on 'For right-sided PVT'.)

●Without shock – Moderately to severely symptomatic patients without cardiogenic shock are generally started on IV UFH ( (table 1); target activated partial thromboplastin time [aPTT] of 1.5 to 2.5 times the control value; anti-factor Xa activity 0.3 to 0.7 IU/mL) in addition to aspirin 75 to 100 mg orally daily with close monitoring.

•If no improvement – If there is no clinical and echocardiographic improvement on IV UFH in 48 to 72 hours, surgery or thrombolytic therapy should be considered. (See 'Referral to Heart Valve Team' below and 'Surgery' below and 'Fibrinolytic protocol' below.)

•With improvement – If there is a response to UFH in 48 to 72 hours, oral anticoagulation is begun (generally VKA). When VKA is started, IV UFH or subcutaneous low molecular weight heparin is continued (as heparin bridging) until the international normalized ratio (INR) is at target for two days.

For pannus or calcification — Patients with moderate to severe symptoms (NYHA functional class III or IV) due to bioprosthetic valve obstruction caused by pannus or calcification require urgent intervention; the treatment options are surgery or transcatheter intervention:

•For high surgical risk – For patients with a high estimated risk of complications with open surgical therapy (ie, Society of Thoracic Surgeons [STS] operative risk score >8 percent or a >15 percent risk of mortality at 30 days) as judged by a Heart Valve Team, we suggest a transcatheter valve-in-valve (ViV) procedure at a center with expertise in this procedure. For patients with preexisting patient-prosthesis mismatch (see "Choice of prosthetic heart valve for surgical aortic or mitral valve replacement", section on 'Prosthetic valve-patient mismatch') with worsening obstruction, the ViV procedure may involve cracking of the existing bioprosthetic valve. This procedure may provide incomplete resolution of obstruction but may be performed as a temporary procedure in critically ill patients with reassessment for operative candidacy following stabilization. (See 'Referral to Heart Valve Team' below and 'Transcatheter intervention' below.)

•For low surgical risk – Patients with a low or intermediate estimated risk of complications with open surgical therapy (ie, STS operative risk score ≤8 percent or a ≤15 percent risk of mortality at 30 days) are referred to a Heart Valve Team to evaluate the choice between surgical valve replacement and a ViV procedure. For patients with preexisting aortic valve patient-prosthesis mismatch (see "Choice of prosthetic heart valve for surgical aortic or mitral valve replacement", section on 'Prosthetic valve-patient mismatch') with worsening obstruction, root enlargement surgery may be required to enable insertion of a larger valve prosthesis. The choice of therapy is guided by the patient’s values and preferences as well as local resources and expertise. The available limited observational data suggest similar operative mortality, lower operative morbidity, similar long-term mortality, and higher risk of paravalvular regurgitation with ViV compared with surgical valve replacement. (See 'Referral to Heart Valve Team' below and 'Transcatheter intervention' below.)

For pannus/calcification plus thrombus — For patients with clinical and imaging features consistent with BPVT plus pannus with moderately to severely symptomatic obstruction, the treatment options are fibrinolysis or surgery. Surgery is generally preferred in this setting because fibrinolysis has no effect on pannus and would be unlikely to result in complete resolution of the obstruction. Fibrinolysis is an option only for hemodynamically stable patients who have clear evidence of predominant thrombus. (See 'Referral to Heart Valve Team' below.)

COMPONENTS OF SHORT-TERM MANAGEMENT

Antithrombotic therapy — Limited evidence is available to guide management of patients with BPVT. Observational studies suggest that most obstructive or nonobstructive BPVT can be successfully treated with an anticoagulant (eg, vitamin K antagonist [VKA], such as warfarin) as an alternative to surgery, transcatheter valve intervention, or fibrinolysis [16-19] (movie 1). In a report including 15 patients with BPVT treated with VKA, improvement was observed in all initially symptomatic patients (with only one patient developing symptoms during therapy) and time to detection of improvement in gradient ranging from 25 to 362 days [16]. Three of the four patients with tricuspid BPVT improved more than 100 days after initiation of antithrombotic therapy.

In a longer follow-up of 77 patients who responded to VKA, we found that mitral prostheses respond faster to VKA than aortic and tricuspid prostheses. Importantly, over half of the patients required anticoagulation for longer than three months to achieve full recovery [20].

Referral to Heart Valve Team — Patients with BPVT and/or bioprosthetic valve obstruction with an indication for fibrinolysis, valve surgery, or transcatheter intervention are referred to a multidisciplinary Heart Valve Team (including cardiologists with expertise in evaluation of valvular heart disease, specialists in advanced cardiovascular imaging, interventional cardiologists and surgeons with expertise in treatment of valvular heart disease, cardiovascular nurses, cardiovascular anesthesiologists, and intensivists involved in periprocedural care) [1,2]. This team performs an individualized assessment of the risk/benefit of treatment options, including consideration of the following factors modified from the 2020 American College of Cardiology/American Heart Association valve guidelines [1]. The Heart Valve Team facilitates balanced discussion with the patient of all appropriate options shared decision-making process reflecting the patient’s values and preferences.

These factors impacting choice of therapy are based largely on data in patients with left-sided mechanical valve thrombosis (see "Management of mechanical prosthetic valve thrombosis and obstruction", section on 'For left-sided PVT').

●Factors favoring fibrinolysis (over surgical or transcatheter approaches) are high surgical risk, high estimated risk with a transcatheter valve-in-valve (ViV) procedure, no contraindication to fibrinolysis, first-time episode of valve thrombosis, absence of left atrial thrombus, lack of other indications for cardiac surgery (eg, coronary artery bypass grafting [CABG] or other valve surgery), right-sided valve prosthesis, and lack of available surgical expertise.

●Factors favoring surgery include imaging features consistent with pannus, low surgical risk, presence of left atrial thrombus, concomitant indication for cardiac surgery (eg, CABG or other valve surgery), contraindication to fibrinolysis, and available surgical expertise.

●Factors favoring transcatheter intervention (ViV procedure) include imaging features consistent with pannus, high surgical risk, absence of valve thrombosis and absence of left atrial thrombus, no other need for cardiac surgery, no evidence of endocarditis, and available interventional expertise.

For patients with an indication for surgery or transcatheter intervention who are not candidates for intervention (eg, because the patient’s life expectancy is ≤1 year or the patient’s quality of life is not expected to improve with intervention), palliative care may be appropriate.

Fibrinolysis

Fibrinolytic protocol — For patients with BPVT with an indication for fibrinolysis (also known as thrombolysis), we suggest use of the following ultraslow infusion low-dose protocol based upon observational studies largely in patients with mechanical PVT described separately (see "Management of mechanical prosthetic valve thrombosis and obstruction", section on 'Fibrinolytic therapy'). Follow-up imaging is performed to evaluate the efficacy of fibrinolytic therapy, with TTE generally used to identify effect on the bioprosthetic valve gradient in cases of obstruction and TEE generally used to identify thrombus size and prosthesis appearance.

●Assess for contraindications to fibrinolytic therapy (which are the same as those in the setting of myocardial infarction). (See "Acute ST-elevation myocardial infarction: The use of fibrinolytic therapy", section on 'Contraindications'.)

•If thrombolysis is contraindicated, refer for valve surgery (redo valve replacement) or transcatheter valve intervention.

●If no contraindications to fibrinolysis, hold anticoagulants and wait until international normalized ratio (INR) is <2.5 (or activated partial thromboplastin time [aPTT] <50 seconds or anti-factor Xa activity <0.3 IU/mL if patient was receiving unfractionated heparin [UFH]). Aspirin 75 to 100 mg orally daily is continued or initiated.

●Administer intravenous (IV) 25 mg alteplase infused over 25 hours with no bolus. IV UFH is held during infusion of the fibrinolytic agent. We suggest continuing aspirin during infusion of fibrinolytic therapy. The alteplase infusion is followed by a six-hour infusion of UFH (70 unit/kg bolus and 16 unit/kg/hour [up to 1000 units/hour] with a target aPTT of 1.5 to 2.5 times the control value; anti-factor Xa activity 0.3 to 0.7 IU/mL).

●For patients with bioprosthetic valve obstruction with adequate baseline TTE assessment of transvalvular gradients, perform follow-up TTE to assess the prosthetic valve gradient.

•If gradient is reduced, perform TEE:

-If TEE shows partial resolution of thrombus (<75 percent reduction in size), repeat 25 mg alteplase infusion over 25 hours followed by a six-hour infusion of UFH, and then repeat TEE.

-If TEE shows complete resolution of thrombus (≥75 percent reduction in size), stop alteplase and start oral anticoagulant. VKA is initiated with therapeutic heparin (IV UFH or subcutaneous low molecular weight heparin [LMWH]) bridging until the INR is at target for two consecutive days. (See 'Long-term management after an event' below.)

•If gradient is not improved, repeat 25 mg alteplase infusion over 25 hours followed by six-hour infusion of UFH, and then repeat TTE.

●For patients with nonobstructive thrombosis (or with presumed obstruction with inadequate assessment of transvalvular gradient on TTE), repeat TEE.

•If thrombus is completely resolved (≥75 percent reduction in size), stop alteplase and start oral anticoagulant. VKA is initiated with therapeutic heparin (UFH or LMWH) bridging until the INR is at target for two consecutive days. (See 'Long-term management after an event' below.)

•If thrombus is unchanged or only partially resolved (<75 percent reduction in size), repeat 25 mg alteplase infusion over 25 hours followed by UFH six-hour infusion, then repeat TEE.

●For patients with persistent thrombus on repeat TEE, the alteplase 25 mg infusion over 25 hours followed by UFH six-hour infusion can be repeated as needed (with TEE evaluation after each cycle of alteplase followed by UFH) up to a maximum cumulative dose of 200 mg of alteplase. Most patients are expected to require three or fewer fibrinolytic sessions [8,9]. If presumed thrombus persists despite treatment with the maximum cumulative dose of alteplase, the diagnosis of thrombus should be reassessed. (See "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Clinical manifestations and diagnosis", section on 'Differential diagnosis'.)

Evidence on fibrinolysis — Limited evidence is available to guide fibrinolytic agent use in patients with BPVT. Largely indirect observational data are available on the efficacy and safety of fibrinolytic treatment regimens for BPVT, as most of the available data are for patients with mechanical PVT, as discussed in detail separately. Publications on fibrinolysis in patients with BPVT are largely limited to case reports [16,21-23]. Studies using an echocardiogram-guided ultraslow infusion, low-dose fibrinolytic protocol in patients with mechanical PVT have demonstrated high rates of efficacy (85 to 90 percent or higher) with relatively low rates of complications (eg, 6.7 percent, including a 0.8 percent mortality rate, with a 25-hour infusion) [8]. Complications following fibrinolytic therapy include major bleeding, systemic embolism, recurrent PVT, and death [24-26]. Risk factors for complications in patients with mechanical PVT receiving slow (or ultraslow) infusion fibrinolytic therapy include New York Heart Association (NYHA) class III or IV and large thrombus size (eg, area on TEE ≥1 cm² [8,9]). (See "Management of mechanical prosthetic valve thrombosis and obstruction", section on 'Evidence'.)

Transcatheter intervention — Transcatheter valve implantation in an obstructed bioprosthetic valve is the procedure of choice for patients with symptomatic severe bioprosthetic obstruction that does not respond to anticoagulation therapy with high surgical risk (ie, Society of Thoracic Surgeons [STS] operative risk score >8 percent or a >15 percent risk of mortality at 30 days). For patients with symptomatic bioprosthetic valve obstruction who are judged by a Heart Valve Team to be at intermediate or low risk for complications with open surgical therapy (ie, STS operative risk score ≤8 percent or a ≤15 percent risk of mortality at 30 days), the options are surgical valve replacement or a transcatheter ViV procedure at a center with expertise in this procedure.

Aortic valve-in-valve procedure — Meta-analyses of observational studies of patients with bioprosthetic aortic valve dysfunction have found a lower 30-day mortality rate and similar one-year mortality rate associated with aortic ViV procedure compared with redo surgical aortic valve replacement in patients with aortic prosthetic valve dysfunction [27,28]. A meta-analysis of 12 observational studies with 16,207 patients with bioprosthetic valve dysfunction (8048 who underwent a ViV procedure and 8159 who underwent redo surgery) compared 30-day outcomes [27]. In matched populations, ViV was associated with lower rates of mortality (odds ratio [OR] 0.419, 95% CI 0.278-0.632) and major bleeding (OR 0.48, 95% CI 0.28-0.80) and shorter hospital stay (OR -3.30, 95% CI -4.52 to -2.08). However, ViV transcatheter aortic valve implantation (TAVI) was associated with higher rates of severe patient-prosthesis mismatch (OR 4.63, 95% CI 3.05-7.03) and myocardial infarction (OR 1.50, 95% CI 1.01-2.23). Another meta-analysis found a similar one-year mortality rate (risk ratio [RR] 1.06, 95% CI 0.69-1.61) and one- to five-year mortality rate (RR 1.15, 95% CI 0.99-1.32; p = 0.06) with ViV compared with redo surgery [28].

The limited available data on ViV for degenerated transcatheter aortic valves suggest outcomes similar to those for ViV treatment of surgical bioprosthetic valves. An observational study compared 25 patients who underwent a ViV procedure for a dysfunctional transcatheter aortic valve with 74 patients who underwent ViV for a dysfunctional surgical bioprosthetic valve [29]. Most patients in both treatment groups had prosthetic valve obstruction. The rate of residual mean gradient >19 at day 1 was 20.8 percent for treated transcatheter valves and 33.8 percent for treated surgical valves. One-year mortality was 9.4 percent for treated transcatheter valves and 13.4 percent for treated surgical valves.

Mitral valve-in-valve procedure — Limited data suggest that transcatheter mitral ViV can also be performed safely in selected patients with results comparable to those with surgical therapy. A report of the STS/American College of Cardiology Transcatheter Valve Therapy Registry included 349 patients who underwent mitral ViV or valve-in-ring procedures [30]. The median patient age was 76 years, and median STS-predicted risk of mortality for mitral valve replacement was 11 percent. The observed hospital mortality was 7.2 percent, and the 30-day mortality rate was 8.5 percent. Postoperative complications included AF in 4 percent, cardiac arrest in 3.4 percent, stroke in 1.1 percent, acute kidney injury requiring dialysis in 2.9 percent, life-threatening bleeding in 4.6 percent, and major vascular access complication in 0.6 percent.

A review of later (>3 months) outcomes following mitral ViV or valve-in-ring procedures included seven studies with a total of 93 patients [31]. The mortality rate after a mean follow-up of 14 months was 20.5 percent. Four cases of valve thrombosis were reported more than 30 days after a ViV procedure in patients not receiving an oral anticoagulant. One patient underwent a second ViV implantation due to transcatheter valve migration two months after an initially successful procedure.

Tricuspid valve procedures — Case reports of patients with tricuspid bioprosthetic valve stenosis have described percutaneous balloon valvotomy [32,33] or ViV replacement [34-36] as alternatives to surgical valve replacement, but long-term outcomes are unknown.

Surgery — A limitation of surgical management of bioprosthetic valve obstruction is the high risk of redo bioprosthetic valve replacement, with operative mortality rates around 5 to 10 percent and survival varying from 40 to 50 percent at 10 years [37-39]. The operative mortality following redo bioprosthetic valve replacement is generally higher than that for primary valve replacement (eg, 4.6 versus 2.2 percent) [37]. However, some studies have found that a nonurgent redo procedure in patients with NYHA functional class I/II symptoms and absence of active endocarditis has the same surgical risk as a first valve surgery [40].

Limited data are available on the comparison of surgical and other treatment options for symptomatic severe bioprosthetic valve obstruction. However, indirect data are available from observational studies of patients with symptomatic severe native valve disease showing high mortality risk for patients treated medically, lack of efficacy of medical therapy, and association between surgical treatment and improved symptoms and survival rates.

As an example, in patients with symptomatic severe aortic stenosis, natural history studies have shown that average survival after the onset of these symptoms is only two to three years. There is a high risk of sudden death in symptomatic patients who are followed conservatively. Studies have found that corrective surgery (or TAVI) in this setting is followed by symptomatic improvement and a substantial increase in survival. (See "Indications for valve replacement for high gradient aortic stenosis in adults", section on 'Symptomatic patients'.)

LONG-TERM MANAGEMENT AFTER AN EVENT — Patients with BPVT treated with antithrombotic therapy and/or fibrinolytic therapy are at risk for progressive or recurrent PVT, with one in four patients experiencing a subsequent episode of BPVT at follow-up [19,21,41]. Furthermore, despite successful initial anticoagulant therapy, patients appear to be at risk of early bioprosthetic degeneration [41]. Thus, patients with BPVT or thromboembolism require careful follow-up including an optimized antithrombotic (anticoagulant plus antiplatelet) regimen as described below, although evidence to guide management is limited.

When BPVT or thromboembolism occurs, a key step is to determine which antithrombotic agents (eg, vitamin K antagonist [VKA], aspirin) the patient was taking at the time the complication developed and the adequacy of any anticoagulation (including recent duration of time in the therapeutic range). The risk of bleeding complications with increased intensity of antithrombotic therapy should also be assessed. If the patient was not adhering to the recommended antithrombotic therapy (eg, daily low-dose aspirin therapy) when BPVT developed, institution of adequate therapy is the first therapeutic step [1,2]. (See "Antithrombotic therapy for surgical bioprosthetic valves and surgical valve repair", section on 'Surgical bioprosthetic valve' and "Transcatheter aortic valve implantation: Antithrombotic therapy".)

The following general approach is based upon the antithrombotic therapy the patient was receiving when BPVT or thromboembolism developed. However, the antithrombotic regimen selected for each patient is based upon an individualized assessment of the estimated benefits and risks (including bleeding) of antithrombotic therapy.

●For patients not taking any antithrombotic therapy – Aspirin 75 to 100 mg orally daily is instituted concomitantly with a course of VKA (target international normalized ratio [INR] of 2.5) for at least six months after thrombus resolution; aspirin is continued indefinitely after completion of the course of VKA.

●For patients taking antithrombotic therapy

•For patients taking an oral anticoagulant (eg, VKA with therapeutic INR) but not receiving aspirin – Aspirin 75 to 100 mg orally daily is added and continued indefinitely.

•For patients taking aspirin (with confirmed adherence) but no anticoagulant – Aspirin 75 to 100 mg orally daily is continued indefinitely with addition of oral anticoagulant (eg, VKA with target INR of 2.5). For patients with a bioprosthetic valve with thromboembolism or valve thrombosis, VKA is generally the preferred anticoagulation, as BPVT has been observed in some patients treated with direct oral anticoagulant.

We continue oral anticoagulant for at least six months after thrombus resolution. For patients who are at low risk for bleeding, we continue oral anticoagulant therapy indefinitely to reduce the risk of BPVT recurrence.

•For patients treated with aspirin plus VKA with subtherapeutic INR – VKA management is optimized with an INR target of at least 2.5. Strategies for VKA management may include patient education, more frequent monitoring, and management by a dedicated anticoagulation clinic. Aspirin 75 to 100 mg orally daily is continued indefinitely.

•For patients treated with aspirin plus VKA with INR at target INR of 2.5 – Aspirin 75 to 100 mg orally daily is continued indefinitely. The target INR for VKA is increased to 3.

•For patients treated with aspirin plus VKA with INR at target INR of 3.0 – Aspirin 75 to 100 mg orally daily is continued indefinitely. The target INR for VKA is increased to 3.5.

The above approach is similar to that presented in the 2020 American College of Cardiology/American Heart Association and 2021 European Society of Cardiology valvular heart disease guidelines [1,2].

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" and "Society guideline links: Anticoagulation in pregnancy".)

SUMMARY AND RECOMMENDATIONS

●General considerations – Management of bioprosthetic valve thrombosis (BPVT), thromboembolism, and bioprosthetic valve obstruction involves acute and long-term management. (See 'General approach' above.)

●Management for mild or no obstructive symptoms – For patients with BPVT, thromboembolism, or bioprosthetic valve obstruction with no or mild symptoms (New York Heart Association [NYHA] class I or II) of obstruction, management is aimed at treating any symptoms of heart failure (HF) and treating the obstruction (eg, thrombus or pannus) or source of thromboembolism. (See 'For no or mild symptoms of obstruction' above.)

•For valve thrombosis – For patients with BPVT, we suggest a 30-day trial of therapeutic oral anticoagulant plus aspirin 75 to 100 mg orally daily (Grade 2C). The oral anticoagulant used in this setting is generally a vitamin K antagonist (VKA; eg, warfarin). (See 'For valve thrombosis' above and 'Antithrombotic therapy' above.)

-Adequate response – For patients who respond to oral anticoagulant (defined as ≥50 percent reduction in mean gradient), anticoagulation is continued for at least six months after thrombus resolution while long-term antithrombotic therapy is instituted. (See 'Long-term management after an event' above.)

-Inadequate response – For patients with inadequate reduction in valve gradient, the adequacy of oral anticoagulation should be evaluated.

If the patient is stable and the transvalvular gradient is not increasing, oral anticoagulation may be continued for successive 30-day intervals followed by reassessment of valve gradient and appearance.

If the patient’s symptoms of obstruction are worsening or the transvalvular gradient is increasing with lack of thrombus resolution after one or more 30-day trials of VKA, evaluation for a hypercoagulable state and referral to a Heart Valve Team for valve surgery is appropriate. Other possible options include a valve-in-valve (ViV) procedure or fibrinolytic therapy, although the efficacy of the latter option is uncertain. (See 'General approach' above.)

•For pannus or calcification – Patients in this setting are referred to a Heart Valve Team for an individualized assessment of the risk/benefit of redo surgical valve replacement or transcatheter ViV intervention. (See 'For pannus or calcification' above and 'General approach' above and 'Transcatheter intervention' above and 'Surgery' above.)

●Management for moderate to severe symptoms of obstruction – Patients with moderately to severely symptomatic (NYHA class III or IV) bioprosthetic valve obstruction require urgent management, including temporizing medical care and Heart Valve Team assessment. (See 'For moderate to severe symptoms of obstruction' above and 'Components of short-term management' above.)

•For valve thrombosis (see 'For valve thrombosis' above)

-With shock – For patients with left-sided (aortic or mitral) BPVT, we suggest surgery (redo valve replacement) rather than fibrinolysis (Grade 2C). For patients with right-sided (pulmonic or tricuspid) BPVT, we suggest fibrinolysis rather than surgery (Grade 2B). (See 'General approach' above and 'Fibrinolysis' above and 'Surgery' above.)

-Without shock – For patients in this setting, we suggest prompt initiation of intravenous unfractionated heparin (UFH) with close monitoring (Grade 2C). If there is no response within 48 to 72 hours, surgery or fibrinolysis should be considered. Oral anticoagulant therapy (generally VKA) is started after a favorable initial response. When VKA is initiated, bridging heparin therapy is used. (See 'Antithrombotic therapy' above.)

•For pannus or calcification (see 'For pannus or calcification' above)

-For high surgical risk – For patients with high risk of complications with surgical therapy (ie, Society of Thoracic Surgeons [STS] operative risk score >8 percent or a >15 percent risk of mortality at 30 days), we suggest a transcatheter ViV procedure at a center with expertise in this procedure (Grade 2C). (See 'Transcatheter intervention' above.)

-For low surgical risk – Patients with a low or intermediate risk of complications with surgical therapy (ie, STS operative risk score ≤8 percent or a ≤15 percent risk of mortality at 30 days) are referred to a Heart Valve Team for an individualized assessment of the risk/benefit of redo surgical valve replacement or transcatheter ViV intervention. (See 'Surgery' above and 'Transcatheter intervention' above.)

●Long-term antithrombotic therapy – For patients not adhering to the recommended antithrombotic therapy (eg, daily low-dose aspirin therapy) when BPVT developed, institution of adequate therapy is the first therapeutic step. For patients with low bleeding risk who developed BPVT or thromboembolism while taking aspirin only or VKA only, we suggest treatment with both aspirin 75 to 100 mg daily and VKA (Grade 2C). The target international normalized ratio (INR) for VKA is generally 2.5, with higher targets for patients with thrombotic complications while taking both aspirin and VKA with a documented therapeutic INR. (See 'Long-term management after an event' above.)