Ischaemic heart disease during pregnancy or post-partum: systematic review and case series

We identified two cases matching our inclusion and exclusion criteria.

Our first case is a 25-year-old woman of Hispanic descent, with one previous miscarriage (gravida (G)2, para (P)0). The patient was severely obese with a body mass index of 39 kg/m². She had a history of a transient ischaemic attack, suspected antiphospholipid syndrome and mitral valvuloplasty for mitral regurgitation due to non-bacterial endocarditis. She was referred to the cardiologist for pre-pregnancy counselling. When she was pregnant, her vitamin K antagonist was replaced by acetylsalicylic acid and a full dose of low-molecular-weight heparin during pregnancy until the fifth day post-partum. At 27 weeks of gestation, she presented with complaints of upper abdominal pain. She was diagnosed with pre-eclampsia complicated by haemolysis, elevated liver enzymes and low platelet (HELLP) syndrome (alanine aminotransferase: 143 U/l, thrombocytes: 128 × 10⁹/l). Foetal ultrasonography showed normal growth and the foetal condition judged by cardiotocography was well. The patient was treated with labetalol and magnesium sulphate (MgSO₄). At 29 + 3 weeks of gestation, her condition worsened, and a caesarean section was performed. She delivered a baby girl of 1067 g (50th percentile) with an Apgar score of 6 at 5 min. The neonate had to be admitted to the neonatal intensive care unit because of prematurity. Three days post-partum, the mother presented with syncope. Chest pain was not reported. Electrocardiographic (ECG) monitoring showed ST-segment depression and Q waves, suggesting inferolateral AMI, which was confirmed by elevated troponin T (5.96 μg/l; normal: < 0.014 μg/l). Her coronary angiogram showed no abnormalities. The AMI was presumably caused by a thrombus, embolism or coronary spasm. Both mother and neonate survived. Her medication was upgraded to a beta-blocker, angiotensine I converting enzyme inhibitor, statin, acetylsalicylic acid and vitamin K antagonist. Echocardiography at 6 months showed a mildly reduced left ventricular function. The diagnosis of antiphospholipid syndrome was confirmed.

Our second case is a 42-year-old woman, G1P0. She had a history of insulin-dependent diabetes mellitus, pulmonary embolism and a positive family history for IHD. She was referred to a university hospital by an obstetric clinic at 15 weeks of gestation because of an episode of ventricular tachycardia. Her ECG suggested anterior AMI, which was confirmed by raised troponin (37.77 μg/l) and creatine kinase (2239 U/l) levels. Her coronary angiogram revealed atherosclerotic occlusion of the left main coronary artery. She was treated with stenting of the left coronary artery and medically with acetylsalicylic acid, beta-blocker, clopidogrel and subcutaneous heparin. At 37 weeks of gestation, intrauterine growth retardation and placental insufficiency were suspected. The decision was made to perform an elective caesarean section. She delivered a live born neonate at 37 + 5 weeks. Neonatal Apgar score at 5 min was 10, and birth weight was 2405 g, which is at the fifth percentile for gestational age. Histological examination of the placenta showed a small placenta (weight: < 10th percentile), with diffuse ischaemia, consistent with placental insufficiency. A statin was added to the maternal medical regimen during the post-partum period. Maternal ventricular function remained normal during 6 months of follow-up. A stress test and nuclear scan revealed no signs of recurrent ischaemia. The neonate did well.

We found 128 articles describing IHD presenting during pregnancy and in the post-partum period, with a total of 146 pregnancies, including 6 twin pregnancies and 1 triplet pregnancy. Inclusion is schematically presented in Fig. 1. We excluded several studies for statistical analysis because of incomplete individual data concerning both cardiac and obstetric outcomes. The results of these studies are summarised and compared with our results in a table and are discussed in our discussion section [4‐6, 17‐19]. All articles included were published between 1978 and 2012 and are presented in supplemental Table S1, which is available online.

Risk factors for IHD were present in both women in our case series and in the majority of the women in our review. This is in line with previous literature [4‐6, 17‐19]. Also, this indicates a large impact of lifestyle factors on IHD during pregnancy, as also described in the UK maternal death report [11]. In line with a recently published study in Japanese women, we observed less risk factors in women with coronary artery dissection or thrombus/emboli than in women with atherosclerosis as a cause of AMI, suggesting a different pathophysiology [17].

Women in our review had a relatively high age compared with the average age at time of pregnancy in the USA [21]. This is comparable with previous literature [5, 6, 19]. Coronary dissection is rare outside pregnancy, but it was the main cause of IHD in the women in our review. However, in our more recent cases, thromboembolic coronary events were seen equally frequently. Thromboembolic events may be largely attributed to pregnancy and its hypercoagulable state. Relatively high rates of coronary dissection during pregnancy have previously been described [17]. In line with previous studies, most cases of AMI presented in the third trimester and post-partum period [4, 5, 17]. Especially coronary dissection peaked in these periods, which may be explained by progressive connective tissue weakening and therefore susceptibility for dissection in late pregnancy. Pregnancy-related hypertensive disorders did not seem to contribute to the high incidence of coronary dissection, nor did inherited connective tissue diseases.

In contrast to the atypical presentation of our two cases, in our review, chest pain was the main presenting symptom of IHD. Most of the cases of AMI in our review could be detected on the ECG. In the UK maternal death report, substandard quality of care was observed in 46 % of the women who died due to IHD. This often included delay of cardiac evaluation because IHD was not considered to be a possible diagnosis. Delayed recognition of IHD during pregnancy was also described in a recent Dutch study [18]. In pregnant women with chest pain, especially when they have risk factors, IHD should be considered and an ECG and laboratory investigation should be performed.

A relatively large percentage of women in our systematic review presented with serious complications directly due to AMI, including heart failure, a complication frequently seen in pregnant women with cardiac disease [19, 22]. In line with previous literature, mortality rate during pregnancy in women with IHD was higher than in pregnant women with cardiac disease overall [5, 6, 17, 19]. The slightly lower mortality rate in contemporary cases may be explained by improvement of coronary care.

Pregnancy-related hypertensive disorders found to be associated with IHD during pregnancy were seen more frequently compared with pregnant women with non-ischaemic heart disease [19, 23‐25]. We observed a very high caesarean section rate of 57 %, which was even higher in contemporary cases. This is higher than the caesarean section rate in healthy pregnant women (21 %) [26], higher than in a previous review [6] and higher than in women with congenital or valvular heart disease (38 and 42 %). However, caesarean section rate was comparable with women with cardiomyopathy (58 %) or known IHD (60 %) [19]. The high caesarean section rate was related to the high rate of premature deliveries. This high premature delivery rate and high premature caesarean section rate may be due to several factors, such as the high rate of hypertensive disorders or maternal cardiac reasons for early pregnancy termination. Also, they may possibly be related to physicians’ reluctance for vaginal delivery in women with a recent myocardial infarction. Post-partum haemorrhage was described in 3 % of the women. This is comparable with women with known cardiac disease [23, 27‐29] and only slightly more than in the general population [30, 31].

Perinatal mortality was increased at 4 % and mainly attributable to maternal death and prematurity. Prematurity rate was 3.4–13.2 times higher compared with the prematurity rates in healthy pregnant women [32‐35]. Furthermore, it was even high compared with women with non-ischaemic heart disease [19, 23, 36].A high rate of induced early deliveries may be part of the explanation. However, prematurity rate was comparable in IHD manifesting during pregnancy with IHD manifesting during labour or in the post-partum period, suggesting an additional mechanism for the high prematurity rates. Interestingly, in contrast to reports in women with non-ischaemic heart disease, the incidence of small for gestational age was not elevated [25, 36, 37].