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............................................................................................................................................................................. challenging. Mechanical valves offer excellent haemodynamic performance and long-term durability, but the need for anticoagulation increases maternal and foetal mortality and morbidity, and the risk of major cardiac events during pregnancy is much higher than with bioprosthetic valves.196,211,212 However, bioprosthetic valves in young women are associated with a high-risk of structural valve deterioration resulting in the risk of going through pregnancy with a dysfunctional valve, and eventually in the inevitable need for re-operation. Transcatheter valve implantation (currently especially in pulmonary valves) and the Ross procedure in aortic valve disease (pulmonary autograft in the aortic position and pulmonary homograft) are alternative options to be considered.5 Data on pregnancy after a Ross procedure are scarce but indicate low-risk in the absence of aortic dilatation.213 A desire for pregnancy is a class IIa indication for a biological valve.204 In young women who wish to become pregnant in the future, the pregnancy heart team should be involved in the choice of a specific prosthesis. The final choice should be made after extensive sharing of information and discussion with the patient.

6.4.2 Pregnancy risk with bioprostheses The risk of maternal cardiovascular complications in women with a bioprosthesis is low in those with no or minimal bioprosthesis dysfunction and uncompromised ventricular function. When significant bioprosthesis dysfunction is present, the risk of complications can be significant. Pre-pregnancy assessment and counselling, as well as follow-up, medical treatment, and indications for intervention, are comparable with those for pregnancies with native valve dysfunction.

6.5 Mechanical prostheses and

anticoagulation In women with mechanical valves, pregnancy is associated with a very high-risk of complications (WHO risk classification III). In the ROPAC registry, the chances of an event-free pregnancy with a live birth were 58% for women with a mechanical valve, compared with 79% for women with a bioprosthesis and 78% for women with heart disease but no valve prosthesis.196 A recent study from the UK reported a favourable outcome for mother and baby in only 28% of cases.214 The main risks are related to the need for anticoagulation therapy (valve thrombosis and haemorrhagic complications). Additional risks are related to ventricular and valvular dysfunction.

6.5.1 Maternal risk The risk of valve thrombosis is markedly increased during pregnancy. The risk is lower with adequate dosing of anticoagulant therapy, and depends on the type and position of the mechanical valve, and on additional patient-related risk factors.204 In the ROPAC registry, valve thrombosis occurred in 4.7% of 202 pregnancies and mortality was 20%.196 In the UK study, maternal mortality related to thrombotic complications or valve dysfunction occurred in 9% and severe morbidity in 41% (16% thrombo-embolic complications).214 The risk of valve thrombosis is relatively low with VKAs throughout pregnancy (0–4%).196,215–219 Scarce evidence concerning UFH in the first trimester or throughout pregnancy indicates a high-risk of valve thrombosis (9–33%); additional risks are thrombocytopenia and osteoporosis.215,218,219 LMWH is also associated with the risk of valve thrombosis.196,214,215,219–222 Because the dose requirement markedly increases due to increased renal clearance, monitoring of anti-Xa levels with dose adjustment decreases the risk. LMWH throughout pregnancy with anti-Xa monitoring and dose adjustment according to peak levels carries a valve thrombosis risk of 4.4–8.7%.219,223 Suboptimal target anti-Xa levels or poor compliance often contribute to valve thrombosis, but several valve thromboses occured with peak anti-Xa levels within the target range of 1.0–1.2 IU/mL.221,222 Valve thrombosis occurs in 5.8–7.4% when LMWH is used in the first trimester only, which is similar to using LMWH throughout pregnancy.196,215,219,223 However, the high-risk of valve thrombosis in the UK study was mainly related to the use of LMWH throughout pregnancy. The occurrence of valve thrombosis with adequate peak anti-Xa levels has raised concerns about the safety of this approach. Fast renal clearance can result in subtherapeutic trough (pre-dose) anti-Xa levels despite adequate peak levels, but data on pregnancies with LMWH dosing according to trough and peak anti-Xa levels are limited to case reports.5,224–226 In conclusion, there are unresolved questions concerning LMWH in pregnant women with mechanical valves, including optimal anti-Xa levels, the importance of peak vs. trough levels, the best time intervals for anti- Xa monitoring, and the duration of use.

Current evidence (lacking adequate randomized studies) indicates that the use of VKAs throughout pregnancy, under strict INR control, is the safest regimen to prevent valve thrombosis.196,215–219 LMWH is possibly superior to UFH for preventing valve thrombosis.196,219,223

6.5.2 Obstetric and offspring risk All anticoagulation regimens carry an increased risk of miscarriage and haemorrhagic complications, including post-partum haemorrhage and retroplacental bleeding leading to premature birth and foetal death.196,216,218,220,221 ROPAC shows that VKAs during the first trimester are associated with an increased risk of miscarriage compared with LMWH or UFH (28.6% vs. 9.2%), and the live birth rate is lower, in line with other literature.196 Two systematic reviews concluded that the risk of foetal loss is dose-related (foetal loss rate with low-dose VKA is 13.4–19.2%, total foetal loss rate with VKA is 32.5%). Foetal loss rate with a combined heparin/VKA regimen is 22.7%,and with LMWH throughout pregnancy is 12.2%.217,219 Comparison between studies is hampered by reporting differences, and conclusions concerning the safety of low-dose VKA are controversial.5,196,217,219,223,227 VKA use in the first trimester results in embryopathy (limb defects, nasal hypoplasia) in 0.6–10% of cases.216,218,219,228 UFH and LMWH do not cross the placenta, therefore substitution of VKA with UFH or LMWH in weeks 6–12 almost eliminates the risk of embryopathy. The embryopathy risk is also dose-dependent (0.45–0.9% with low-dose warfarin).217,219 Additionally, there is 0.7–2% risk of foetopathy (e.g. ocular and central nervous system abnormalities, intracranial haemorrhage) with VKAs in the second and third trimester.216,219,223,228–230 Foetopathy has been described with UFH but not with LMWH throughout pregnancy.219,223 Vaginal delivery while the mother is on VKAs is contraindicated because of the risk of foetal intracranial bleeding.228 Haemorrhagic complications in the mother occur with all regimens, but the incidence is lower with VKA throughout pregnancy than with LMWH/UFH throughout pregnancy.219 Addition of low-dose aspirin to VKA or heparin has no proven advantage in preventing valve Downloaded from academic.oup.com/eurheartj/article/39/34/3165/5078465 by guest on 07 October 2026