Management of Valvular Disease in Pregnancy: Global Perspective
Management of Valvular Disease in Pregnancy: Global Perspective
Patients with symptomatic significant valvular lesion, in particular those with additional pulmonary hypertension or left-ventricular dysfunction should be seen at a minimum of 4–8 week intervals until 36 weeks and then weekly until delivery. Where there is evidence of cardiac decompensation or significant obstetric complications, such as pre-eclampsia, patients should be admitted early and managed aggressively with a low threshold for delivery, particularly in the case of pre-eclampsia where the combination of hypertension, increased vessel permeability, and enhanced thrombotic risk makes the management of women with PHV significantly more complicated.
The hypercoagulability of pregnancy causes an increase in mechanical valve thrombosis. Anticoagulation in pregnancy with coumarin derivates reduces the risk of mechanical valve thrombosis with tight control but is linked to an increased risk of miscarriage, foetal embryopathy, and late foetal loss and it has been suggested that the effects are dose-dependent. On the other hand, low-molecular weight heparins (LMWHs) have been used during pregnancy and proved to be effective in many conditions, but in patients with an PHV, several cases of valve thrombosis have been reported suggesting that the use of LMWH may be associated with a higher risk of valve thrombosis. The risk of valve thrombosis may improve in the future when adequate measurements of peak and through levels are established and implemented in routine care. At the moment, there is not one optimal regimen and an individualized strategy is warranted. Risk factors for having a thromboembolic event include having an PHV in mitral or tricuspid position, suffering from atrial fibrillation or having a history of a thromboembolic event. It is important to understand the risks and benefits of the different strategies and to discuss these risks with the patients. Recent recommendations on options for anticoagulation in pregnancy are summarized in Table 3, which has been adapted from the recent ESC Guidelines on Cardiovascular Disease during Pregnancy.
Table 4 presents a practical approach for pregnant women with mechanical prosthetic valves, adapted from Pieper et al. In our practice, we consider prescribing low-dose Aspirin, in addition to coumarin derivates or heparin, in high-risk pregnant women who, e.g. have had repeated valve replacements, with impaired function due to pannus ingrowth, double valve replacement or with previous thrombus.
All the recommendations are limited by the paucity of data on pregnancy outcomes in women with the contemporary newer and less thrombogenic valves, such as the St Jude valves, compared with the older types of valves. This means that we are probably overestimating the thrombotic event risk. All anticoagulation regimens are understudied and large prospective comparative studies are needed. Indeed, with the newer valves, it might be possible that Vit K antagonists (coumarin derivates) can be used in lower doses reaching an INR level of only 1.5–2.5, but this remains to be proved. The use of newer anticoagulants is currently contraindicated for PHV. If pregnancy occurs while taking one of these agents it is wise to switch to LMWH (or warfarin).
De Santo et al. demonstrated that a 3 months pre-implantation trial period of anticoagulation allowed the identification of those 94% of young women where INRs of between 1.5 and 2.5 could be achieved with a low dose of <5 mg of warfarin which was shown not to cause embryopathies. In this study, more than half of the patients fell pregnant and did not show any need for increasing the warfarin dose beyond 5 mg. All of them delivered healthy babies through Ceasarean section in Week 36 after warfarin was stopped for 2 days. For patients in LMICs, in which the infrastructure for such a high-surveilance approach is not available, there is equally hope for mechanical valves even in mitral position.
Sillesen et al. reported on the pregnancy outcome in 79 women who had 155 pregnancies after valve replacement with PHV in Denmark. There were four thromboembolic complications in women with mitral prosthesis on unfractionated heparin. Two women died during pregnancy, one from failure, and one from postpartum bleeding. Compared with healthy women there was significantly more postpartum bleeding (P<0.0021), premature birth (P < 0.00000001), and congenital malformations (<0.044) in the women with PHV.
Soma-Pillay et al. studied the effect of warfarin dosage on maternal and foetal outcomes in pregnant women with PHVs. Of the 52 pregnancies managed, 41 had MV, two aortic valves, and nine double valve prosthesis. There were no maternal deaths or cases of valve thrombosis, but 9.7% had maternal 'near misses'. Forty-one foetuses were exposed to warfarin in the first trimester and there were five (12%) cases of warfarin embryopathy. The authors did not find a significant difference in the live birth rate, average birth weights, or miscarriage rates between the three warfarin dosage groups. The stillbirth rate increased with increasing doses of warfarin.
The decision on appropriate therapeutic regimen for women with single-valve replacement in mitral or aortic position or double valve replacements needs to be based on the individual case scenario taking level of system resources, access of patients to health care, and distance to appropriate testing of INR and anti-Xa into consideration.
Management During Pregnancy
Antenatal Care
Patients with symptomatic significant valvular lesion, in particular those with additional pulmonary hypertension or left-ventricular dysfunction should be seen at a minimum of 4–8 week intervals until 36 weeks and then weekly until delivery. Where there is evidence of cardiac decompensation or significant obstetric complications, such as pre-eclampsia, patients should be admitted early and managed aggressively with a low threshold for delivery, particularly in the case of pre-eclampsia where the combination of hypertension, increased vessel permeability, and enhanced thrombotic risk makes the management of women with PHV significantly more complicated.
Anticoagulation
The hypercoagulability of pregnancy causes an increase in mechanical valve thrombosis. Anticoagulation in pregnancy with coumarin derivates reduces the risk of mechanical valve thrombosis with tight control but is linked to an increased risk of miscarriage, foetal embryopathy, and late foetal loss and it has been suggested that the effects are dose-dependent. On the other hand, low-molecular weight heparins (LMWHs) have been used during pregnancy and proved to be effective in many conditions, but in patients with an PHV, several cases of valve thrombosis have been reported suggesting that the use of LMWH may be associated with a higher risk of valve thrombosis. The risk of valve thrombosis may improve in the future when adequate measurements of peak and through levels are established and implemented in routine care. At the moment, there is not one optimal regimen and an individualized strategy is warranted. Risk factors for having a thromboembolic event include having an PHV in mitral or tricuspid position, suffering from atrial fibrillation or having a history of a thromboembolic event. It is important to understand the risks and benefits of the different strategies and to discuss these risks with the patients. Recent recommendations on options for anticoagulation in pregnancy are summarized in Table 3, which has been adapted from the recent ESC Guidelines on Cardiovascular Disease during Pregnancy.
Table 4 presents a practical approach for pregnant women with mechanical prosthetic valves, adapted from Pieper et al. In our practice, we consider prescribing low-dose Aspirin, in addition to coumarin derivates or heparin, in high-risk pregnant women who, e.g. have had repeated valve replacements, with impaired function due to pannus ingrowth, double valve replacement or with previous thrombus.
All the recommendations are limited by the paucity of data on pregnancy outcomes in women with the contemporary newer and less thrombogenic valves, such as the St Jude valves, compared with the older types of valves. This means that we are probably overestimating the thrombotic event risk. All anticoagulation regimens are understudied and large prospective comparative studies are needed. Indeed, with the newer valves, it might be possible that Vit K antagonists (coumarin derivates) can be used in lower doses reaching an INR level of only 1.5–2.5, but this remains to be proved. The use of newer anticoagulants is currently contraindicated for PHV. If pregnancy occurs while taking one of these agents it is wise to switch to LMWH (or warfarin).
De Santo et al. demonstrated that a 3 months pre-implantation trial period of anticoagulation allowed the identification of those 94% of young women where INRs of between 1.5 and 2.5 could be achieved with a low dose of <5 mg of warfarin which was shown not to cause embryopathies. In this study, more than half of the patients fell pregnant and did not show any need for increasing the warfarin dose beyond 5 mg. All of them delivered healthy babies through Ceasarean section in Week 36 after warfarin was stopped for 2 days. For patients in LMICs, in which the infrastructure for such a high-surveilance approach is not available, there is equally hope for mechanical valves even in mitral position.
Sillesen et al. reported on the pregnancy outcome in 79 women who had 155 pregnancies after valve replacement with PHV in Denmark. There were four thromboembolic complications in women with mitral prosthesis on unfractionated heparin. Two women died during pregnancy, one from failure, and one from postpartum bleeding. Compared with healthy women there was significantly more postpartum bleeding (P<0.0021), premature birth (P < 0.00000001), and congenital malformations (<0.044) in the women with PHV.
Soma-Pillay et al. studied the effect of warfarin dosage on maternal and foetal outcomes in pregnant women with PHVs. Of the 52 pregnancies managed, 41 had MV, two aortic valves, and nine double valve prosthesis. There were no maternal deaths or cases of valve thrombosis, but 9.7% had maternal 'near misses'. Forty-one foetuses were exposed to warfarin in the first trimester and there were five (12%) cases of warfarin embryopathy. The authors did not find a significant difference in the live birth rate, average birth weights, or miscarriage rates between the three warfarin dosage groups. The stillbirth rate increased with increasing doses of warfarin.
The decision on appropriate therapeutic regimen for women with single-valve replacement in mitral or aortic position or double valve replacements needs to be based on the individual case scenario taking level of system resources, access of patients to health care, and distance to appropriate testing of INR and anti-Xa into consideration.