Cardiovascular diseases are the most common causes of maternal death during pregnancy(8). Knowledge of the risks associated with such conditions in pregnant women and their management is of pivotal importance. However, the number of published cases is limited and most recommendations are class C even in the most recent guidelines (9). The tolerance of valvular heart disease during pregnancy is little recognized since the prevalence of rheumatoid arthritis is decreasing. However, nowadays there is an increase in the age at which women are becoming pregnant; thus the prevalence of pregnant woman with severe cardiac valve disease remains unchanged. The current study, was carried to evaluate our maternofoetal outcomes in pregnant women with severe valve lesions. The recently published Global Rheumatic Heart Disease Registry (REMEDY) included 3343 patients with rheumatic heart disease in 12 African countries, India and Yemen; the median age was 28 years (10). The majority (63.9%) had moderate to severe valvulopathy complicated by congestive heart failure in 33.4%, pulmonary hypertension in 28.8%, atrial fibrillation in 21.8%, stroke in 7.1%, and infectious endocarditis in 4% and major bleeding in 2.7%. In 1,825 women of reproductive age (aged 12-51), only 3.6% used contraception. In a Tunisian study analysing the epidemiological profile of cardiac women who gave birth in a Tunis maternity center between January 2010 and December 2012, out of 19655 deliveries studied, the prevalence of heart disease was 1 in 351 deliveries (0.285%). The mean age was 30.89±5.3 years (ranges between 21 and 42 years). Out of the 56 cases of cardiac women, 35 patients (62.5%) had valvulopathy , which means a prevalence of 0.17%(11). In our cohort, the mean age was 32.5±5.6 years and the prevalence of heart valve disease was about 0.49% and of severe disease was estimated at 0.074%.
Cardiac adverse events
Cardiac complications are frequent in pregnant women with cardiac valve diseases and varied between 13% and 35,6% according to previous studies (12–16) (Table 8) . Certainly the rate of complications will be higher in women with severe lesions, especially when the condition is discovered only during pregnancy. In the CAPREG II study, the overall maternal cardiac event rate during pregnancy for mWHO I, mWHO II, mWHO III, and mWHO IV was 3.1%, 12.8%, 21.1%, and 35.6%, respectively. In our cohort two patients from three showed cardiac events. Pulmonary oedema seems to be the most prevalent complications; the advancement of therapeutic strategies improved the prognosis. Maternal cardiac death or cardiac arrest becomes rare, in the recent CAPREG II study it occurred in 11 pregnancies (0.6%) (13); besides the experience of a tertiary care center including women with pulmonary hypertension, no cardiac death occurred (17). In our series no maternal death was noted; only one case of cardiac arrest occurred because of dyskaliemia and the recovery was obtained. However, cardiac mortality remains much higher than that in the general obstetric population (18–21).
Several studies tried to determine predictors of cardiac events and to conclude the scores relying on theses predictors.
The multicenteric CARPREG (Cardiac Disease in Pregnancy Study) including patients both with congenital and acquired diseases, was the first to develop such risk index. Predictors of cardiac events were left heart obstruction, cyanosis or dyspnea before pregnancy, cardiac antecedents and systolic LV dysfunction (15,22). In the European Registry of Pregnancy and Heart Disease (ROPAC), including 2966 women, valve heart disease account for 25% of pregnant women with cardiovascular disease. Mitral diseases, both stenosis and regurgitation, were the most common valvular lesions (63%), followed by aortic valve disease (23%) (Table 8). In this registry, signs of heart failure before pregnancy, atrial fibrillation and no previous cardiac intervention were strong predictors of cardiac events. In our cohort, cardiac complications occurred especially in stenotic lesions; regurgitant lesions were well tolerated and didn’t impose the termination of pregnancy. In stenotic lesions, increased cardiac output causes a rise in transvalvular gradient of 50%, mainly between the first and second trimesters, (23). That’s why congestive heart failure more commonly occurred in the third trimester or early postpartum, whereas most arrhythmias occurred in the antenatal period.
Mitral stenosis was the most untolerated valve disease and was found as independent predictor of cardiac complications. In fact during pregnancy there will be an increase of cardiac output brought by increased heart rate and stroke volume, and oppositely a decrease of peripheral resistance by a peripheral vasodilatation. The drop of vascular resistance explains the tolerance of regurgitant lesions (6,24–26).
Pregnancy outcomes in two large centers in the United States reported a risk of pulmonary oedema occurrence in pregnant women with mild, moderate and severe mitral stenosis, respectively between 11% and 24%, 34% and 61%, and 56% and 78%. The rate of occurrence of atrial fibrillation varied between 0 and 7% in case of mild stenosis, 10 and 22% in the case of moderate stenosis and between 22 and 33% in case of severe lesions(16,27).
Percutaneous mitral dilation seems to improve remarkably the hemodynamic condition of these patients, then allow even a vaginal delivery in most cases. According to the recent ESC guidelines, Intervention should be considered before pregnancy in patients with MS and valve area <1.5 cm² and should be considered in pregnant patients with severe symptoms or systolic pulmonary artery pressure >50 mmHg despite medical therapy (9).
In our study, the revelation of cardiac valve disease by pregnancy was also found as strong predictor not only of cardiac complications but also neonatal complications, this result accord with other predictors found in the ROPAC registry or the CAPREG II study which is the lack of intervention before pregnancy as well as the delayed pregnancy assessment. Therefore, it is strong recommended to assess pre-pregnancy risk and to counsel all women with known or suspected congenital or acquired cardiovascular and aortic disease (28). It is also recommended to perform risk assessment in all women with cardiac diseases of childbearing age before and after conception, using the mWHO classification of maternal risk(28). Generally, women who receive late pregnancy assessment had more frequent adverse cardiac outcomes during pregnancy, which may be attributed to delayed access to appropriate risk stratification, follow-up, and management plan.
But we noted that in our practice, despite the fact that the rate of illiteracy among women was low (3%), the use of contraception is infrequent, as is the evidence of new pregnancies in cardiac women who had already cardiac complications during pregnancy before treating their heart disease. The cardiologist plays a pivotal role in the therapeutic education of these women and the prescription of an adequate contraception while discussing with the gynecologist.
Obstetrical adverse events
The obstetrical risk remains poorly described in the literature. The main parameter to be evaluated is the mode of delivery, which depends, in this context, on the maternal tolerance of pushing efforts, a trigger and the possibility of epidural analgesia. According to the recent guidelines a delivery plan should be made between 20–30 weeks of pregnancy detailing induction, management of labour, delivery, and post-partum following up; moreover the Induction of labour should be considered at 40 weeks of gestation in all women with cardiac disease (9).
Obstetric complications were 3 to 4 times more common in our population compared to the ROPAC and CAPREG studies (Table 8). The low parity (nulliparous or primiparous) is a predictor of obstetrical events in many studies, especially it increases the risk of preeclampsia (29) (Table 8).
In our cohort premature labour threat was the most common complication. This is mainly due to both uterine muscle hypoxia as well as to acute heart failure, commonly occurred in our patients
Pre-eclampsia was more common in women with aortic valve disease and left ventricle dysfunction because of low cardiac output and, as expected, in nulliparous women and those with pre-existing hypertension. In our series, all the cases of preeclampsia occurred in women treated with intravenous diuretic because of acute heart failure. This is a difficult situation encountered in the daily practice, diuretic results in a placenta hypoperfusion which is the main mechanism of preeclampsia and normally diuretic should be avoided in such patients. The anticoagulant use is also a strong predictor of obstetrical complications mainly haemorrhage. In our cohort this factor increases 8 times the risk of obstetrical events, the association between haemorrhage and anaemia frequently diagnosed in our patients will worsen the prognosis and result in heart decompensation. That’s why it is recommended to anticipate the timing of delivery to ensure safe and effective peripartum anticoagulation.
Neonatal complications
The neonatal prognosis is closely correlated with maternal prognosis. Anyway, in our series we have noted the occurrence of obstetric complications (OR = 15.48, p = 0.001) and the revelation of valvulopathy by pregnancy (OR = 6.95, p = 0.017)as strong predictors of neonatal complications. In fact, the delayed discovery of valvulopathy may expose the foetus to a longer duration of hemodynamic stress, especially with a risk of placental hypoperfusion, hypotrophy and prematurity. The immunological status of these new-borns will also be precarious with a higher risk of hospitalization in neonatology. In the ROPAC registry, the rate of foetal complications among women with WHO IV heart disease was 31%, a rate comparable to our series that was 40%. Predictors of these complications in ROPAC were multigestity, treatment with anticoagulant, diabetes, and life in developing countries (table 8).
Symptomatic women (NYHA class III-IV), and oral anticoagulants, were the main reasons for induced preterm delivery. In case of spontaneous prematurity both inflammatory processes, and utero-placental ischemia can initiate preterm labour (30). Certainly, maternal hypoxia increases cytokines and oxygen free radicals, which may cause abnormal placentation; these conditions mostly occurred in woman with congenital heart disease (31). In our cohort most cases of premature delivery were induced, that’s why pulmonary systolic pressure were significantly higher in mothers of preterm babies. In a Japanese cohort including 857 women with cardiac disease, ischemic cardiac disease followed by valve heart disease were related to the highest risk of induced prematurity , respectively 48.3% and 44.3%; the rate of caesarean section was respectively 81.7% and 68.8%. In our series, we noted only 20% of prematurity; previous studies showed that both induced and spontaneous preterm birth were less common in developing countries than in developed countries. This was explained by the advanced age with uterine dysfunction for the spontaneous prematurity and a quicker access to obstetric care facilities in developed countries.
Study limitations
The main limitations of our study involve the retrospective design from one hand and the small sample size from the other hand. These two limits could be explained by the low prevalence of severe valve disease among pregnant women; as it contra-indicates the conception. Moreover, we included only term pregnancies since abortions and stopped pregnancies are multifactorial, and so we are unable to conclude that there is a relationship between these obstetric events and the severity of valvulopathies.