Since evidence from controlled randomized trials is lacking in this field, most of the current management recommendations and strategies for pregnancy in AC are based on observational and non-randomized studies or data derived from registries or expert consensus. Therefore, only scarce data are available to guide cardiologists and obstetricians.
Obstetric outcomes: induction, labor, and delivery
Data on obstetric, fetal, and pediatric outcomes of pregnancies in women with AC are summarized in Table
1. There were 648 live births from 692 pregnancies in 367 women with AC who were included into the analysis of nine studies with published data on pregnancies in AC. Single case reports were not included.
The majority of pregnant women with AC underwent vaginal delivery. Cesarean section was performed in 78 of 431 (18%) women with AC summarized in this review (Table
1), with <10% being for maternal medical reasons and >90% for obstetric indications. Hodes et al. [
31] reported cesarean sections in 11 of 39 women with AC (28%), all but one (HF) for obstetric indications. Another large study recently published by Wu et al. [
69] reported similar results with cesarean section in 44 of 224 Chinese women (20%). Castrini et al. [
13] and Gandjbakhch et al. [
27] both reported lower rates of cesarean sections in their cohorts (7 and 13%, respectively). However, all rates of cesarean sections are within normal ranges for a given socio-economic region. No thromboembolic or bleeding complications were reported for elective cesarean sections in patients with AC.
Maternal and offspring outcomes
Data on maternal outcomes of pregnancies in women with AC are summarized in Table
2. There were 648 live births from 692 pregnancies in 367 women with AC and a mean age of 29 years at first pregnancy that were included in the analysis of nine studies with published data on pregnancies in AC. Single case reports were not included. In 171 of 231 patients (74%) in whom genetic testing was reported, a pathogenic mutation was detected. In the control group (from four studies), 193 nulliparous women with AC were compared with the pregnant cohort of 324 women. The results demonstrated similar event rates for mortality, SCD, aborted SCD, VA, and HF in both groups. However, these results are prone to selection bias since women in the control group with younger age at symptom onset and more severe AC manifestation may have been advised against pregnancy.
In all, 33 of 241 women (14%) reported a worsening of symptoms during 425 pregnancies (8%). The event was defined either as a new onset of sustained VT, VF, syncope, or frequent PVC, or as an increase in PVC numbers by more than 100%.
Hodes et al. [
31] reported data from the combined AC registries of the Johns Hopkins Hospital (Baltimore, USA) and the Dutch Interuniversity Institute (Netherlands). The authors reported on 26 women with diagnosed AC and 39 pregnancies >13 weeks of gestation. At last follow-up (mean, 6.5 years), all women with AC after pregnancy were alive and without the need for cardiac transplantation. Acceleration of disease progression with HF was observed in two women (5%), both with pre-existing right or biventricular dysfunction and both with successful outpatient management without the need for hospitalization. There were five pregnancies complicated by single episodes of sustained VT (13%) without an increased likelihood of experiencing a first sustained VA during pregnancy [
31]. In women with AC, new onset or acceleration of VA occurred in less than 10% of pregnancies. Pregnancy-related VA were primarily related to the phenotypical severity rather than pregnancy itself.
Platonov and Castrini et al. [
13,
48] recently published similar results in their latest series from the Scandinavian Nordic Registry, including 261 pregnancies in 120 women with AC. They reported two maternal SCD, five aborted SCD, five heart transplantations, and a total of 41 events during long-term follow-up. However, in only two of 120 women or two of 261 pregnancies (1.7 and 0.8%, respectively) did sustained VT occur during pregnancy, in another five patients within 2 years after completed pregnancy [
48]. One patient experienced deep vein thrombosis, complicating the postpartum course [
13]. The cumulative event rates during the long-term follow-up were higher, reflecting the prolonged interval between pregnancy and established diagnosis of AC.
Both groups [
13,
31,
48] found no difference in clinical event rates (including mortality, SCD, aborted SCD, heart transplantation, HF, and VA) compared with control groups of women with AC who had not given birth. In agreement with others [
27], both reported no evidence for acceleration of VA and HF, either during pregnancy or early or late after childbirth. They concluded that pregnancy was not the driving force for disease progression in AC.
Similar results were recently published by Wu et al. [
69], who analyzed 224 pregnancies in 120 patients including 30 spontaneous and two medical abortions. In all, 12 cardiac adverse events were recorded during pregnancy, including new-onset frequent PVC in three, increased previous PVC numbers by more than 100% in five, and syncope in two patients. Sustained VT and HF requiring hospitalization occurred in one patient each. In comparison with a control group of 37 nulliparous women with AC, there was no difference in the core outcome parameters.
In contrast to other publications, however, Wu et al. [
69] reported an all-cause mortality rate of 23% (
n = 36 of 120) during the long-term median follow-up of 8 (1–32) years. However, only two of 36 deaths were sudden, and none with a diagnosis of AC. The majority of deaths occurred very late after previous pregnancies. Risk factors for all-cause mortality included earlier age at first symptom onset and decreased left ventricular ejection fraction (LVEF), whereas pregnancy did not influence the long-term survival. The study cohort differed significantly from other publications by a much longer follow-up and a substantially higher risk profile, including a history of cardiac arrest (40%), sustained VT/VF (74%), HF (33%), heart transplantation (17%), catheter ablation (50%), and ICD implantation (17%) [
69]. Similar to the studies by Castrini and Platonov [
13,
48], the majority of pregnancies (in 76% of women) occurred long before the diagnosis of AC was made.