Management of risks of prosthetic valves during pregnancy

INTRODUCTION — Pregnancy presents a unique set of problems for women with prosthetic heart valves. Prosthetic heart valves may be mechanical or bioprosthetic (the latter including heterografts and homografts).

Mechanical heart valves are associated with an increased incidence of thromboembolic events during pregnancy. Therapeutic anticoagulation throughout pregnancy is essential to reduce the risk of thromboembolic complications [1], but given the absence of adequate prospective controlled trials and the differing maternal and fetal risks associated with various anticoagulants, the optimum anticoagulant regimen is uncertain [2-4].

Bioprosthetic valves typically do not require anticoagulation (unless there are other thromboembolic risk factors). However, bioprostheses have a significantly higher incidence of valve failure than mechanical valves. This is an important concern for young women, who must consider the potential need for future additional valve surgery if they have a bioprosthetic valve. (See 'Preconception evaluation and counseling' below.)

Management of prosthetic valves during pregnancy is discussed here. The following issues are discussed separately:

●Antithrombotic therapy for a prosthetic valve (including anticoagulation therapy for a mechanical valve) during pregnancy. (See "Management of antithrombotic therapy for a prosthetic heart valve during pregnancy".)

●Pregnancy and native valve disease (including valve intervention or surgery prior to pregnancy). (See "Pregnancy and valve disease" and "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

PRECONCEPTION EVALUATION AND COUNSELING

Overview — Women of childbearing age who have prosthetic heart valves should receive preconception (or initial if the patient presents during pregnancy) assessment including clinical evaluation, 12-lead electrocardiogram, transthoracic echocardiogram (TTE), and counseling by a pregnancy heart team including a cardiologist with expertise in managing patients with valvular heart disease during pregnancy [1]. The baseline TTE enables assessment of valve function and hemodynamics, identification of valve dysfunction that may require treatment prior to pregnancy, and comparison if valve thrombosis is suspected during pregnancy. In some cases, the consequences of longstanding valve disease or comorbid conditions (eg, left ventricular dysfunction or pulmonary hypertension) result in prohibitive risks, and pregnancy should be avoided. However, many women with prosthetic heart valves can safely complete a pregnancy with careful management. (See "Pregnancy and valve disease", section on 'Preconception or initial evaluation'.)

For women with native valve disease with an indication for valve intervention prior to conception, counseling should include a detailed discussion of the risks and benefits of various options such as surgical valve repair, valve replacement with a mechanical prosthesis or bioprosthesis, or percutaneous intervention. For patients requiring a valve replacement, discussion should include the trade-off between risk of thrombus and thromboembolism with mechanical valves (with associated need for therapeutic anticoagulation and related risks, particularly during pregnancy) compared with the longer-term risk of limited durability of valve repair of bioprosthetic valves [1]. (See "Pregnancy and valve disease", section on 'Interventions prior to pregnancy'.)

Counseling regarding anticoagulant therapy — For women with prosthetic valves requiring anticoagulant therapy (those with mechanical valves and selected patients with bioprosthetic valves with a specific indication for anticoagulation), preconception counseling should include an informed discussion about the risks of valve thrombosis, the requirement for continuation of therapeutic anticoagulation throughout pregnancy, and the maternal and fetal risks associated with available anticoagulation options. The patient should also be informed that some risk of life-threatening complications of valve thrombosis such as stroke (caused by thromboembolism) or valve obstruction remains regardless of the anticoagulant regimen utilized. Discussion of these risks should be included in counseling patients about future plans, including whether to forgo pregnancy. (See 'Risks associated with prosthetic valves' below and "Contraception: Counseling and selection".)

Women with regular menstrual periods receiving anticoagulation and attempting to conceive should be advised to continue vitamin K antagonists (eg, warfarin) until they are pregnant because the risk of warfarin embryopathy (defects in cartilage and bone) is low in the first five weeks of gestation. They should closely monitor their menses and, if delayed, promptly undergo a pregnancy test. Women with irregular menstrual periods receiving anticoagulation and attempting to conceive should undergo periodic (eg, monthly) pregnancy testing. If the plan is to use therapeutic low molecular weight heparin for at least the first trimester, a plan should be made as to how this will be arranged once pregnancy is confirmed. Warfarin teratogenicity is discussed in detail separately. (See "Use of anticoagulants during pregnancy and postpartum", section on 'Already taking warfarin' and "Management of antithrombotic therapy for a prosthetic heart valve during pregnancy".)

PREGNANCY RISK ASSESSMENT AND FOLLOW-UP — The frequency of follow-up during pregnancy in women with cardiovascular disease is adjusted according to risk. We agree with the following recommendations based upon the modified World Health Organization (WHO) classification as described in the 2018 European Society of Cardiology (ESC) guidelines for management of cardiovascular disease during pregnancy [5] (see "Pregnancy and valve disease", section on 'Modified WHO classification'):

●Patients with mechanical valves are included in modified WHO class III, which indicates significantly increased risk of maternal mortality or severe morbidity. These patients require expert counseling and follow-up in a center with cardiology and obstetric expertise in pregnancy and heart disease. Anticoagulation monitoring is often best done in conjunction with a thrombosis clinic, and the ESC 2018 and American College of Cardiology/American Heart Association 2020 guidelines recommend at least weekly anti-Xa measurements [1,5]. Intensive monitoring including monthly or bimonthly cardiology and obstetric review is recommended during pregnancy.

●Patients with bioprosthetic valves are included in modified WHO class II, which indicates small increased risk of maternal mortality or moderate increase in morbidity. Cardiology follow-up at least every trimester is recommended, though more frequent visits may be required on an individual basis.

Of note, patients with prosthetic heart valves with high-risk conditions such as severe pulmonary arterial hypertension of any cause or severe systemic ventricular dysfunction (left ventricular ejection fraction <30 percent, New York Heart Association functional class III or IV) are included in modified WHO class IV (instead of the above classes), which indicates extremely high risk of maternal mortality or severe morbidity with pregnancy contraindicated. If pregnancy occurs, termination should be discussed as it may be life-saving for the mother. If pregnancy continues, the frequency of follow-up is as for class III.

In addition to the above scheduled follow-up, a follow-up echocardiogram is indicated to evaluate the hemodynamics of the prosthetic valve and ventricular function in a pregnant patient with a prosthetic valve who develops symptoms (eg, dyspnea) or change in physical examination [1]. Elevated transvalvular gradients are expected during pregnancy due to increased cardiac stroke volume. A transthoracic echocardiogram (TTE) is generally the initial test to evaluate aortic and mitral prosthetic valves, though a transesophageal echocardiogram (TEE) is required if prosthetic valve thrombus is suspected (eg, with obstruction or an embolic event) [1]. In addition, a TEE examination is suggested for patients with suspected prosthetic valve regurgitation if TTE examination is not adequate to assess the severity of disease. (See "Mechanical prosthetic valve thrombosis or obstruction: Clinical manifestations and diagnosis" and "Echocardiographic evaluation of prosthetic heart valves" and "Pregnancy and valve disease" and "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes".)

RISKS ASSOCIATED WITH PROSTHETIC VALVES

Overview — Outcomes of pregnancies in women with prosthetic valves vary considerably and are dependent on many factors including valve type and function, anticoagulant use, ventricular systolic function, pulmonary artery pressures, and other maternal cardiac and obstetric comorbidities. Evaluation by an expert in pregnancy and heart disease is important for preconception counseling and to optimize management during pregnancy. The following risks of prosthetic valves may cause complications during pregnancy; among these risks, the risks of anticoagulant therapy and prosthetic valve thrombosis (PVT; causing valve obstruction or thromboembolism) are major and potentially life-threatening issues for pregnant women with prosthetic (particularly mechanical) valves.

●Maternal and fetal risks of anticoagulant therapy to prevent valve thrombosis. Therapeutic anticoagulation with frequent monitoring is essential in all pregnant women with mechanical prosthetic heart valves to prevent valve thrombosis, which poses a risk of valve obstruction and thromboembolism [1,2,5]. Therapeutic anticoagulation is also associated with significant increased risk of maternal bleeding (approximately 25 percent), particularly peripartum [6]. Anticoagulation is generally not required for bioprosthetic valves, although there are some exceptions (eg, with concurrent atrial fibrillation or prior bioprosthetic valve thrombosis). Management of antithrombotic therapy to prevent valve thrombosis during pregnancy is discussed separately. (See "Management of antithrombotic therapy for a prosthetic heart valve during pregnancy".)

●PVT may lead to thromboembolism and/or valve obstruction. In patients with mechanical valves, the risk of valve thrombosis is especially high when therapeutic anticoagulation is not maintained. Bioprosthetic valve thrombosis does occur, although the risk of valve thrombosis is lower than with a mechanical valve. Management of PVT during pregnancy is discussed below. (See "Mechanical prosthetic valve thrombosis or obstruction: Clinical manifestations and diagnosis" and "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Management" and 'Prosthetic valve thrombosis' below.)

●Prosthetic valve dysfunction including:

•Valve obstruction (caused by valve thrombosis, pannus formation, prosthesis-patient mismatch, bioprosthetic valve fibrosis, and/or calcification). (See "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Management" and 'Prosthetic valve thrombosis' below.)

•Transvalvular regurgitation and paravalvular regurgitation. Structural valve failure resulting in transvalvular regurgitation is much more common with bioprosthetic valves than with mechanical valves. Late paravalvular regurgitation is most commonly caused by prosthetic valve endocarditis. (See "Clinical manifestations and diagnosis of surgical aortic and mitral prosthetic valve regurgitation" and "Management and prognosis of surgical aortic and mitral prosthetic valve regurgitation".)

●Prosthetic valve endocarditis. (See "Prosthetic valve endocarditis: Epidemiology, clinical manifestations, and diagnosis" and 'Infective endocarditis' below.)

●Hemolysis is common but usually mild and subclinical with prosthetic valves implanted since the 1990s; hemolysis severe enough to cause anemia is usually associated with paravalvular regurgitation or bioprosthetic valve degeneration. (See "Overview of the management of patients with prosthetic heart valves", section on 'Hemolytic anemia'.)

Patients with prosthetic valve dysfunction and/or ventricular dysfunction are at risk for heart failure (HF) and arrhythmias. (See 'Prosthetic valve dysfunction' below.)

The magnitude of risk for pregnancies in women with prosthetic valves was illustrated by the following studies:

●A systematic review of 11 studies of 499 pregnancies in over 300 women with prosthetic valves (256 mechanical and 59 bioprosthetic) from 1995 to 2014 showed a maternal mortality rate of 1.2 percent with a rate of 1.8 percent in women with mechanical valves and 0.7 percent in those with bioprosthetic valves, a pregnancy loss rate of 21 percent, and perinatal mortality of 5 percent of births [7]. (See "Perinatal mortality", section on 'Perinatal death'.)

●Data from the prospective, observational, worldwide Registry of Pregnancy and Cardiac disease (ROPAC), including 212 patients with a mechanical valve, 134 patients with a bioprosthetic heart valve, and 2620 other patients without a prosthetic valve, identified a maternal mortality rate of 1.4 percent (two or three deaths were directly valve-related) for those with mechanical valves, 1.5 percent (neither of the two deaths was clearly valve-related) for those with bioprosthetic valves, and 0.2 percent in those without prosthetic valves [6]. Overall, only 58 percent of women with mechanical valves compared with 79 percent with bioprosthetic valves had a pregnancy free of serious adverse maternal and fetal events [6].

●Data from a prospective UK cohort of 58 pregnant women with a mechanical valve identified a maternal mortality rate of 9 percent, and 41 percent of women suffered serious morbidity; 29 percent had significant postpartum bleeding, 16 percent sustained valve thrombosis or dysfunction, and 9 percent suffered a cerebrovascular accident. Of note, in 71 percent of women, low molecular weight heparin was used throughout pregnancy, a higher rate than in the above studies [8].

Prosthetic valve thrombosis

Risk — Prosthetic valve thrombosis is a potentially life-threatening complication as it can cause valve obstruction and thromboembolism. The hypercoagulable state of pregnancy increases the risk of valve thrombus formation among women with prosthetic valves [1,8]. The risk of valve thrombosis and thromboembolic events depends upon the type and location of the prosthetic valve, as well as a number of other clinical features. Mechanical prosthetic heart valves have a higher thromboembolic risk than bioprosthetic valves or homografts [9], so patients with mechanical valves require long-term therapy with an anticoagulant plus aspirin, while most patients with bioprosthetic valves require only long-term, low-dose aspirin therapy. (See "Management of antithrombotic therapy for a prosthetic heart valve during pregnancy".)

Factors that increase the risk of prosthetic valve thrombosis and thromboembolism include (see "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Clinical manifestations and diagnosis"):

●History of a prior thromboembolic event

●Atrial fibrillation

●Prosthesis in the mitral position [8]

●Multiple prosthetic valves [8]

●Small valve size

Therapeutic anticoagulation throughout pregnancy is essential to reduce the risk of complications of valve thrombosis (such as thromboembolism and valve obstruction) of mechanical valves [1], but given the absence of adequate prospective controlled trials, the optimum anticoagulant regimen is uncertain [2-4]. Maternal and fetal complications associated with the different anticoagulant regimens in women with mechanical and prosthetic valves and management guidelines are reviewed separately. (See "Management of antithrombotic therapy for a prosthetic heart valve during pregnancy".)

Bioprosthetic valves, independent of position, do not usually require long-term anticoagulation unless other thromboembolic risk factors are present (such as atrial fibrillation or history of prior bioprosthetic valve thrombosis). Aspirin therapy is recommended for the patient with a bioprosthetic valve [1], and this therapy is continued during pregnancy. (See "Antithrombotic therapy for mechanical heart valves" and "Management of antithrombotic therapy for a prosthetic heart valve during pregnancy".)

Management of valve thrombosis — Valve thrombosis occurring during pregnancy is managed similarly to that for valve thrombosis in nonpregnant patients, but decisions regarding choice and timing of therapy require weighing maternal and fetal risks of treatment options in discussion with the patient. (See "Management of mechanical prosthetic valve thrombosis and obstruction" and "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Management".)

Urgent management — Urgent management is required for patients with left-sided mechanical or bioprosthetic valve thrombosis with high-risk features: moderately to severely symptomatic (New York Heart Association [NYHA] functional class III or IV) obstruction or high-risk left-sided valve thrombus (ie, a mobile thrombus >0.3 cm in diameter or any thrombus with area ≥1.0 cm²). Management includes urgent Heart Valve Team assessment to guide the choice between fibrinolysis and surgery. For nonpregnant patients in this setting, surgery is generally preferred to fibrinolysis, as fibrinolysis is less efficacious with severe symptoms and the risk of complications is higher in patients with large thrombus size. (See "Management of mechanical prosthetic valve thrombosis and obstruction", section on 'Recommendations for urgent therapy' and "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Management", section on 'For moderate to severe symptoms of obstruction'.)

By contrast, for selected pregnant hemodynamically stable patients with obstructive left-sided mechanical valve thrombosis, we agree with the American College of Cardiology/American Heart Association valve guideline that it is reasonable to treat with slow-infusion, low-dose fibrinolytic therapy [1] rather than valve surgery, based on limited evidence [10]. As described below, a systematic review of observational data suggests that streptokinase or recombinant tissue-type plasminogen activator [tPA] can be efficacious in patients with obstructive mechanical valve thrombosis including those with NYHA class III or IV symptoms and/or large thrombus [11]. Limited data suggest that fetal risk as well as maternal risk may be lower with low-dose, slow-infusion fibrinolytic therapy than with surgery, although direct comparative data are lacking. tPA is a highly fibrin-specific drug. There is only minimal transplacental passage of tPA, which is not sufficient to cause fibrinolytic effect in the fetus, but there is a risk of placental hemorrhage. The systematic review suggests that complication rates of thrombolytic therapy are not increased in pregnancy and that fibrinolytics should not be withheld for potentially life-threatening prosthetic valve thrombosis [11]. (See 'Evidence' below and 'Fibrinolytic regimen' below.)

Nonurgent management — The nonurgent management of left-sided mechanical or bioprosthetic valve thrombosis and right-sided valve thrombosis during pregnancy is generally similar to that in nonpregnant patients. An exception is in patients with left-sided bioprosthetic valve thrombosis refractory to prolonged anticoagulation; during pregnancy, fibrinolytic therapy may be attempted prior to evaluation for valve surgery. (See "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Management", section on 'For valve thrombosis' and "Management of mechanical prosthetic valve thrombosis and obstruction", section on 'Nonurgent management'.)

Fibrinolytic regimen — For pregnant patients with mechanical or bioprosthetic valve thrombosis who have an indication for fibrinolytic therapy, we use an echocardiogram-guided low-dose, slow-infusion (25 mg of tPA infused over six hours with no bolus) protocol (repeated, if needed, once every 24 hours up to six times to a maximum total dose of 150 mg), based upon limited evidence from observational studies [10]. Unfractionated heparin 70 IU/kg bolus with an infusion of 16 IU/hour (up to 1000 IU/hour) with a target activated partial thromboplastin time (aPTT) of 1.5 to 2.0 times the mean reference range is administered after the termination of each tPA infusion. If repeat thrombolytic infusion is needed, heparin is held until the aPTT is <50 seconds, then tPA infusion is started. (See 'Evidence' below and "Management of mechanical prosthetic valve thrombosis and obstruction".)

The need for repeat fibrinolytic infusion is determined by the findings of echocardiography (transthoracic and transesophageal) after each fibrinolytic infusion [10]. Fibrinolytic infusions are repeated until the following criteria for success are achieved or the maximum total dose has been administered.

●For patients with obstructive PVT, fibrinolytic success is defined as attainment of at least two of the following three criteria: Doppler documentation of resolution of increased transvalvular gradient, a reduction by ≥50 percent in thrombus area or length, and improvement in symptoms.

●For patients with nonobstructive PVT, fibrinolytic success is defined as attainment of a ≥50 percent reduction in thrombus area or length.

Anticoagulation after thrombus resolves — When a mechanical or bioprosthetic prosthetic valve thrombus resolves with anticoagulant therapy (eg, intravenous heparin therapy) or fibrinolytic therapy, this therapy is generally transitioned to a vitamin K antagonist (VKA), which is continued during the remainder of pregnancy and transitioned to heparin only prior to delivery. The superior protection against valve thrombosis associated with VKA is particularly important in this setting. The risks and benefits of VKA and other anticoagulants during each stage of pregnancy should be discussed with the patient. The transition from VKA to heparin prior to delivery is discussed separately. (See "Management of antithrombotic therapy for a prosthetic heart valve during pregnancy", section on 'Peripartum management'.)

Evidence — Experience with the management of valve thrombosis in pregnant women is limited. Controlled data do not exist, and published reports are mostly from case series.

In a systematic review, 66 cases were described, with fibrinolytics used in 38 cases and urokinase or streptokinase in 20 cases. There were seven cases (11 percent) of major bleeding, two maternal deaths, and four thromboembolic complications, with one fetal death and five miscarriages [11].

In the largest reported series of fibrinolysis as the initial therapy for mechanical valve thrombosis during pregnancy, 24 women with 25 pregnancies complicated by 28 episodes of PVT (obstructive, nonobstructive with recent systemic thromboembolism and thrombus diameter >5 mm, or asymptomatic mobile thrombus ≥10 mm) were treated with tPA using a low-dose, slow-infusion protocol (25 mg delivered intravenously over six hours without a bolus) [10]. Patients with large thrombi were included (with obstruction, mean thrombus area was 1.7 cm² with range 0.8 to 6.0 cm²; without obstruction, mean thrombus area was 0.9 cm² with range 0.4 to 1.8 cm²). A TEE was performed within one hour after each fibrinolytic therapy session, and repeated doses of tPA were administered if prosthetic valve thrombus persisted (mean tPA dose 49 mg).

●All patients had successful fibrinolysis, with no maternal mortality and five miscarriages occurring one to five weeks after fibrinolytic therapy (20 percent; not higher than the expected rate in this population). There were no episodes of thromboembolism after fibrinolytic therapy.

Of note, fibrinolysis was successful in all 14 patients with NYHA class III or IV symptoms. This high rate of efficacy of fibrinolysis in pregnant patients with moderate to severe symptoms differs from the low efficacy of fibrinolysis seen in nonpregnant patients with this level of symptoms (see "Management of mechanical prosthetic valve thrombosis and obstruction", section on 'For left-sided PVT'). A possible reason for this difference is that obstruction was due to pure thrombus (rather than thrombus plus pannus) and was detected at an earlier stage in the pregnant patients.

●There were five miscarriages (20 percent; two in the first trimester, three in the second trimester). This miscarriage rate was similar to that seen in pregnant women not on oral anticoagulants. There were 20 live births including one delivery at 30 weeks gestation as a result of placental hemorrhage after three fibrinolytic therapy sessions; the baby was found to have complete hearing loss.

●Three patients declined fibrinolytic therapy and proceeded with surgery; one of these patients died undelivered during surgery.

The above results were compared with outcomes from case reports from 1979 to 2012 of 31 patients with 32 pregnancies complicated by 38 episodes of PVT treated with a variety of fibrinolytic agents and regimens [10]. With these older (higher dose, faster infusion) fibrinolytic regimens, average fibrinolytic success was 76 percent, maternal mortality was 10 percent, and fetal/neonatal mortality was 28 percent.

There is scant published experience with fibrinolytic therapy for patients with bioprosthetic valve thrombosis [12].

Evidence on use of an ultraslow fibrinolytic regimen in nonpregnant patients is discussed separately. (See "Management of mechanical prosthetic valve thrombosis and obstruction", section on 'Evidence'.)

Limited data suggest that cardiac surgery during pregnancy is associated with maternal risk similar to that for nonpregnant women but with high fetal mortality rates (approximately 20 to 30 percent), particularly when surgery is performed at less than 28 weeks gestation, as discussed separately. (See "Pregnancy and valve disease" and "Pregnancy and valve disease", section on 'Cardiac surgery during pregnancy'.)

Prosthetic valve dysfunction — The increased physiologic demands of pregnancy (increased blood volume and cardiac output) may result in the development or exacerbation of HF in patients with ventricular dysfunction and/or dysfunction of prosthetic or native valves. (See "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes".)

Prosthetic valve dysfunction may include valve obstruction, valve regurgitation (transvalvular or paravalvular), or both. Symptomatic patients may require repeat valve surgery. Bioprosthetic valves have a significantly higher incidence of valve failure than mechanical valves. This may be of particular concern for young women, who must consider the potential for future valve surgery if they have a bioprosthesis.

Given the fetal risks posed by cardiac surgery during pregnancy, repeat valve surgery during pregnancy should be avoided, if possible. As for patients with severe native valve disease, patients with severe prosthetic valve dysfunction should be evaluated and counseled on the timing of repeat valve surgery and pregnancy (see "Pregnancy and valve disease", section on 'Cardiac surgery during pregnancy'). In patients with severe bioprosthetic valve dysfunction, a valve-in-valve intervention is a potential alternative to valve surgery, although experience during pregnancy is limited [13]. (See "Management of mechanical prosthetic valve thrombosis and obstruction" and "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Management" and "Management and prognosis of surgical aortic and mitral prosthetic valve regurgitation".)

The management of valve disease and HF during pregnancy is discussed in detail separately. (See "Pregnancy and valve disease" and "Management of heart failure during pregnancy".)

Infective endocarditis — Antibiotic prophylaxis in patients with prosthetic valves for vaginal or cesarean delivery is discussed separately. (See "Pregnancy and valve disease", section on 'Endocarditis prophylaxis'.)

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

●Preconception assessment – Women of childbearing age who have prosthetic heart valves should receive preconception assessment including clinical evaluation, 12-lead electrocardiogram, transthoracic echocardiogram, and counseling by a pregnancy heart team including a cardiologist with expertise in managing patients with valvular heart disease during pregnancy. (See 'Preconception evaluation and counseling' above.)

●Follow-up – The frequency of follow-up during pregnancy in women with cardiovascular disease is adjusted according to risk (eg, the modified World Health Organization [WHO] classification as described in the 2018 European Society of Cardiology guidelines for management of cardiovascular disease during pregnancy). (See 'Pregnancy risk assessment and follow-up' above and "Pregnancy and valve disease", section on 'Modified WHO classification'.)

●Risks associated with prosthetic valves – Prosthetic valves are associated with complication risks during pregnancy. For pregnant women with mechanical valves, the risks of prosthetic valve thrombosis (PVT; leading to valve obstruction or thromboembolism) and the maternal and fetal risks of anticoagulant therapy to prevent valve thrombosis are major issues. (See 'Risks associated with prosthetic valves' above.)

●Prosthetic valve thrombosis – PVT is a potentially life-threatening complication as it can cause valve obstruction and thromboembolism. The hypercoagulable state of pregnancy increases the risk of valve thrombus formation among women with mechanical valves. (See 'Prosthetic valve thrombosis' above.)

•General approach – PVT occurring during pregnancy is generally managed similarly to that for valve thrombosis in nonpregnant patients, but selection and timing of therapy includes weighing maternal and fetal risks of treatment options in discussion with the patient. (See "Management of mechanical prosthetic valve thrombosis and obstruction" and "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Management" and 'Management of valve thrombosis' above.)

•Urgent management – Urgent management is required for patients with left-sided mechanical or bioprosthetic valve thrombosis with high-risk features: moderately to severely symptomatic (New York Heart Association functional class III or IV) obstruction or high-risk left-sided valve thrombus (ie, a mobile thrombus >0.3 cm in diameter or any thrombus with area ≥1.0 cm²). Management includes urgent Heart Valve Team assessment to guide the choice between fibrinolysis and surgery. For pregnant patients requiring urgent management of valve thrombosis, we suggest a low-dose, slow-infusion fibrinolytic regimen rather than valve surgery (Grade 2C). (See 'Urgent management' above and 'Management of valve thrombosis' above and 'Fibrinolytic regimen' above and 'Evidence' above.)

•Nonurgent management – The nonurgent management of left-sided mechanical or bioprosthetic valve thrombosis and right-sided valve thrombosis during pregnancy is generally similar to that in nonpregnant patients. An exception is in patients with left-sided bioprosthetic valve thrombosis refractory to prolonged anticoagulation; during pregnancy, fibrinolytic therapy may be attempted prior to evaluation for valve surgery. (See "Management of mechanical prosthetic valve thrombosis and obstruction", section on 'Nonurgent management' and "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Management", section on 'For valve thrombosis' and 'Nonurgent management' above.)

●Prosthetic valve dysfunction – The increased physiologic demands of pregnancy (increased blood volume and cardiac output) may result in the development or exacerbation of heart failure in patients with ventricular dysfunction and/or dysfunction of prosthetic or native valves. Given the fetal risks posed by cardiac surgery during pregnancy, repeat valve surgery during pregnancy should be avoided, if possible. (See 'Prosthetic valve dysfunction' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Robyn A North, MBChB, PhD, FRACP, Beverley Hunt, MD, FRCP, FRCPath, William Gaasch, MD, Catherine Otto, MD, and Charles Lockwood, MD, MHCM, who contributed to earlier versions of this topic review.