53.4 Valvular heart disease

Valvular heart disease is a frequent underlying heart disease in pregnant women. Mitral stenosis is often rheumatic in origin, while aortic stenosis is more often congenital. Stenotic lesions carry a high risk of complications. Mitral stenosis with a valve area less than 1.5 cm² should be considered for pre-pregnancy intervention, especially when balloon valvulotomy is an option, since the risk of maternal and fetal complications is high. For women with aortic stenosis, pre-pregnancy intervention should be considered when the woman is symptomatic, or when left ventricular function or exercise testing is abnormal. Regurgitant lesions carry a lower risk than stenotic lesions. Women with a mechanical prosthesis have a high risk of complications during pregnancy and should be managed in a centre of expertise. Vitamin K antagonists are associated with embryopathy, but only in the first trimester and mainly when higher dosages are needed. Vitamin K antagonists are superior to prevent valve thrombosis. Vitamin K antagonists are advised in the first trimester when the daily dose requirement is low, and are preferred in the second and third trimester. During the first trimester, alternative options are unfractionated or low-molecular-weight heparins with intensive monitoring of anticoagulation effect. Heparins are also used from the 36th week of pregnancy until delivery. Most women with valvular disease can deliver vaginally.

Mitral stenosis (MS) is poorly tolerated during pregnancy since increased cardiac output and tachycardia cause a sharp increase in mitral gradient and upstream pressures. In young women, MS is almost always of rheumatic origin. MS remains a leading cause of pregnancy-related mortality in low-income countries.¹ Awareness on MS remains justified in high-income countries where migrations account for persisting prevalence of MS.²

Auscultatory recognition of MS is often challenging because of dyspnoea and the diagnosis is frequently made by echocardiography. Mitral valve area as assessed by planimetry is the reference measurement of the severity of MS.³ Doppler pressure half-time depends on other factors but is applicable during pregnancy. Mitral gradient and systolic pulmonary artery pressure reflect the tolerance of MS ( Figure 53.4.1(online)). Echocardiographic evaluation of mitral anatomy and mitral regurgitation is important to assess the feasibility of percutaneous mitral commissurotomy (PMC). Transoesophageal echocardiography is indicated to rule out left atrial thrombosis before PMC.

There is a high risk of heart failure during pregnancy when the valve area is 1.5 cm² or less, even when women were asymptomatic before pregnancy.⁴ When severe dyspnoea occurs, there is a high risk of peripartum pulmonary oedema threatening the life of both mother and fetus.⁵ Atrial fibrillation worsens haemodynamic tolerance and requires curative anticoagulant therapy, as for left atrial thrombus or prior embolism.

The risk of fetal complications depends on the severity and duration of heart failure. Prematurity occurs in 20–30% of cases, intrauterine growth retardation in 5–20%, and stillbirth in 1–3%.^4,6

Pregnancy should be discouraged when valve area is 1.5 cm² or less and intervention, preferably PMC, is indicated before pregnancy⁷ Exercise echocardiography can be useful in borderline cases.

During pregnancy, clinical and echocardiographic follow-up should be performed monthly or bimonthly according to haemodynamic tolerance. Beta₁-selective blockers are recommended when symptoms or pulmonary hypertension appear. Loop diuretics can be added if symptoms persist, avoiding high doses due to fetal risk.⁷

Persisting symptoms or pulmonary hypertension should lead to consideration of PMC during pregnancy.⁷ It should be performed, preferably after 20 weeks, by experienced operators to keep the risk of complications as low as possible, using a lead apron to protect the abdomen. The risk inherent to any interventional procedure justifies not performing PMC during pregnancy when MS is well tolerated. Open-heart surgery should be avoided given the fetal risk.⁸ Vaginal delivery should be planned by a multidisciplinary team and can be performed safely in women in New York Heart Association class I or II.

Aortic stenosis in young women is rare and is most frequently congenital (bicuspid aortic valve). Asymptomatic mild and moderate aortic stenosis are well tolerated during pregnancy.^5,9 Severe aortic stenosis is associated with significantly increased maternal risk of complications (modified World Health Organization class III) but as long as left ventricular function and exercise testing are normal and the woman is asymptomatic, she need not be counselled against pregnancy.⁷ The main complications are heart failure (10%) and arrhythmias.^10,11

Some literature suggests that offspring may be at risk of preterm birth and growth retardation⁹ but on average the occurrence of these complications is not increased.¹⁰ The risk of congenital heart disease in the offspring is increased, and genetic counselling is advised before pregnancy in women with a bicuspid aortic valve.⁷

The European Society of Cardiology (ESC) Guidelines recommend surgery before pregnancy in women with symptomatic severe aortic stenosis and in women with left ventricular dysfunction (<50%). Exercise testing should be performed to unmask symptoms. When blood pressure response to exercise is abnormal (fall in blood pressure below baseline), intervention before pregnancy should also be considered.

Women with a bicuspid aortic valve are at risk of aortic dilation and aortic surgery should be considered when the aortic diameter is greater than 50 mm (27.5 mm/m²), irrespective of the function of the bicuspid valve.⁷

The frequency of follow-up depends on the severity of aortic stenosis. In severe stenosis, monthly clinical review and echocardiography is advisable. In women with mild or moderate stenosis, follow-up once per trimester may be sufficient. It is expected that the Doppler gradient will increase in pregnant women due to the increase of cardiac output. Valve area measurement is preferred for follow-up of severity of stenosis.

When women become symptomatic, restriction of activities is advised. Heart failure can be treated with diuretics. Early delivery may be considered in women who remain symptomatic despite medical treatment. The preferred mode of delivery is vaginal in women with mild or moderate stenosis, with carefully applied epidural anaesthesia avoiding peripheral vasodilation which may be poorly tolerated. This mode of delivery may also be appropriate for asymptomatic severe aortic stenosis. Caesarean section with general anaesthesia is advised for severe symptomatic stenosis.

Aortic valve surgery during pregnancy can be necessary in rare cases where severe symptoms persist despite medical treatment.⁷

Though moderate and severe left- and right-sided valve regurgitation are associated with an increased risk of maternal complications during pregnancy, maternal risk is lower than with stenotic valve lesions. Mitral valve regurgitation and tricuspid regurgitation have both been identified as predictors of pregnancy complications.¹² The main complications are treatable arrhythmias. However, when women with severe valve regurgitation and ventricular dilation and dysfunction become pregnant, there is a high risk of heart failure.⁶ Even then, in the majority of patients medical treatment will suffice. Heart failure is treated with diuretics. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are contraindicated because of severe fetal harm.¹³

Follow-up during pregnancy consists of clinical evaluation and echocardiography, which is performed once per trimester in mild and moderate disease and more often in severe regurgitation. Vaginal delivery is almost always appropriate, with epidural anaesthesia when regurgitation is severe.⁷

For women of fertile age who need valve surgery, the choice of valve prosthesis is difficult. Mechanical valve prostheses carry a high risk of valve thrombosis in pregnant women. Bioprosthetic valves have a significantly lower complication rate,¹⁴ but the fast deterioration of these valves at a young age exposes young women to the risk of repeat surgery. Valve repair or, in mitral and pulmonary valve stenosis, balloon valvuloplasty always has priority when feasible.⁷ For women with aortic stenosis, the Ross operation is another alternative that should be considered. From the few data that are available, pregnancy seems to carry a low risk in women after the Ross operation.¹⁵

The risk of pregnancy in women with a valvular bioprosthesis is mainly dependent on bioprosthesis function. Risk assessment and management is comparable to women with native valves with similar valve function.⁷

Women with mechanical valve prostheses (MVPs) have a high risk of pregnancy complications. According to the worldwide Registration Of Pregnancy And Cardiac disease (ROPAC), 42% of women with a MVP had serious adverse events during their pregnancies.¹⁴ This is significantly higher than the risk in women with a bioprosthesis.

Women with a MVP need anticoagulation therapy. Unfortunately, vitamin K antagonists (VKAs) (warfarin, acenocoumarol, and phenprocoumon) are associated with embryopathy (abnormalities of face, skeleton, and central nerve system). In an initial review, the risk was 6%; later literature reported lower risks.¹⁶ Embryopathy occurs only with exposure in the first trimester (pregnancy weeks 6–12).¹⁷ Evidence is increasing that this risk is dose dependent. According to a large review, the risk of embryopathy was 0.9% with a warfarin dose of less than 5 mg daily.¹⁸ Another risk associated with VKAs is miscarriage and fetal death. This risk is also likely to be dose dependent, though data in the literature are controversial.^18,19 When a fetus is exposed to a VKA there is an increased risk of fetal intracranial bleeding, which is especially high during vaginal delivery.¹⁷

Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) do not cross the placenta and are therefore not associated with embryopathy. All anticoagulants carry an increased risk of subplacental bleeding which may affect the fetus.

During pregnancy, the risk of valve thrombosis appears higher than outside pregnancy. The magnitude of this risk depends on the type of anticoagulation therapy and on the position of the valve, with right-sided valves carrying a higher risk than left-sided valves while mitral valves have a higher risk than aortic valves. Valve thrombosis is a serious complication that threatens the life of both mother and fetus. In ROPAC, valve thrombosis occurred in 4.7% and was associated with 20% mortality.¹⁴ Effective anticoagulation therapy is challenging in pregnant women due to the hypercoagulative state of pregnancy and changed pharmacokinetics of anticoagulants. Valve thrombosis has been reported in 0–4% of women using VKAs throughout pregnancy.^{13,16,18,20,21,22,23} For UFH, there are limited data reporting a valve thrombosis rate of up to 33%.¹⁶ For LMWH, the rate of valve thrombosis is dependent on adequate anti-Xa level monitoring. The dose requirement increases in pregnant women since LMWHs are cleared renally and glomerular filtration rate increases during pregnancy.¹³ However, even in women who had anti-Xa level monitoring with dose adjustment, valve thrombosis occurred in 9%.⁷ Too low target anti-Xa levels and non-compliance were involved in most women.^{13,24,25,26,27} However, valve thrombosis has also been described in women with adequate peak anti-Xa levels according to current guidelines.²⁴ This may be related to the fast clearance of LMWH resulting in low trough levels despite ‘adequate’ peak anti-Xa levels.²⁸ Therefore it has been advocated to dose according to both peak and trough anti-Xa levels, but the safety and efficacy of this approach still awaits scientific proof.^7,29,30 Both American and European guidelines recommend the use of LMWH or UFH in the first trimester only for women needing a high VKA dose, and after the 36th week of pregnancy.^7,31

Women with a MVP have a higher risk of (postpartum) haemorrhage than women with bioprosthesis. They have more often early deliveries with lower birth weight in their babies and they are more likely to have a caesarean delivery.¹⁴

Women with a MVP should be counselled and managed in centres with expertise in the management of pregnant women with a MPV. It is important to have a thorough discussion pre-pregnancy about the risks of valve thrombosis, embryopathy, bleeding, and pregnancy loss associated with the different anticoagulation regimens. When she uses a low dosage of a VKA (i.e. <5 mg of warfarin, <3 mg of phenprocoumon, or <2mg of acenocoumarol), the woman should be encouraged to continue this medication throughout pregnancy. She should understand that valve thrombosis threatens both her and her unborn baby. For women using a higher dose of VKA, change to UFH with control of activated partial thromboplastin time or to LMWH with anti-Xa level monitoring should be considered during the first trimester (pregnancy weeks 6–12). In the second and third trimester, VKAs are preferred, irrespective of the dose, given the relatively low risk for the fetus and the superiority of VKA therapy to prevent valve thrombosis. The ESC Guidelines recommend that change of anticoagulant therapy is implemented in hospital and that weekly monitoring of the anticoagulation effect is performed. The target international normalized ratio is equal to outside pregnancy. For women using UFH, the target activated partial thromboplastin time is more than twice the control; when LMWH is chosen, the target anti-XA level 4–6 h post dose is 0.8–1.2 U/mL.⁷ From the 36th week onwards, the VKA is discontinued and UFH or LMWH (with activated partial thromboplastin time or anti-Xa level monitoring) should be started, because women with a MPV tend to deliver early and delivery while using a VKA should be avoided, since it renders vaginal delivery impossible because of the risk of fetal intracranial bleeding. LMWH should be replaced by intravenous UFH at least 36 hours before delivery. UFH is discontinued 4–6 h before delivery and started again 4–6 h after delivery, when there is no significant bleeding.⁷ In the guidelines, vaginal delivery is recommended for most women, but when the risk of valve thrombosis is considered, significant caesarean section may be preferable to ensure a short time without anticoagulation therapy.⁷

Dyspnoea or an embolic event should raise the suspicion of valve thrombosis and immediate clinical work-up with echocardiography (transthoracic, usually followed by transoesophageal) is indicated. Fluoroscopy can be performed if necessary with limited fetal risk. The treatment of valve thrombosis is in principle not different from outside pregnancy. When anticoagulation was suboptimal, intravenous UFH should be started in patients who are not critically ill. Surgery should be performed when anticoagulation therapy fails and in critically ill patients with valve obstruction. Fibrinolysis is the first-choice therapy in right-sided thrombosis and when surgery is not available in critically ill patients. It may also be considered in non-critically ill patients when optimizing of anticoagulation had no effect, to avoid surgery, since surgery carries the threat of fetal loss and fetal neurological damage. When considering fibrinolysis, the risks of embolization (10%) and of subplacental bleeding should be taken into account.⁷