Pregnancy still contraindicated in pulmonary arterial hypertension related to congenital heart disease: True or false?

In patients with pulmonary arterial hypertension (PAH), including those with pulmonary arterial hypertension related to congenital heart disease (PAH-CHD), pregnancy is traditionally contraindicated.1 Contraception for birth control is recommended, and in the case of pregnancy occurring, termination should be discussed at an early stage, taking into account that even this might be a high-risk procedure. However, some women with PAH-CHD may contemplate becoming pregnant despite the stated risk, and there are also pregnant women being diagnosed with PAH-CHD during pregnancy. The gestational haemodynamic changes taking place even in a woman without cardiovascular disease are remarkable.2 In patients with PAH-CHD, the increase in plasma volume, the incompetence to achieve the expected fall in pulmonary vascular resistance, the decrease in systematic vascular resistance that causes further hypoxia in Eisenmenger patients due to the escalation of the right-to-left shunting, the volume shifts during delivery and the prothrombotic milieu can all contribute to right ventricular dysfunction and as a result to poor clinical outcome (Figure 1).3 The tendency for arrhythmias may be increased from the additional volume load on the already pressure-overloaded right heart.4 Τhe effect of sex hormones during pregnancy in the pulmonary vascular bed is complex and not yet clearly defined.5 Pathophysiology of right heart failure in pregnant patients with pulmonary arterial hypertension related to congenital heart disease. RV: right ventricle In the past, mortality rates in pregnant patients with PAH were reported to be very high, reaching 30–56%.6 Nowadays, mortality during pregnancy is still prohibitively elevated, but considerably lower compared with the past.7 Detailed management plan, multidisciplinary approach (cardiologist, obstetrician, anaesthesiologist and neonatologist) and use of PAH targeted therapy have all played a key role in this direction. The main causes of death, most often postpartum, are right heart failure, pulmonary hypertensive crisis and pulmonary thrombosis.1 In this issue of the European Journal of Preventive Cardiology, Li et al. present the outcomes of pregnancy in 93 patients (94 pregnancies) with PAH-CHD who were admitted for delivery in a tertiary centre during a period of 5.5 years.8 The study was single-centre retrospective in design. However, it included the largest cohort of pregnancies in this population until now and is the first that used the current clinical classification of PAH related to CHD according to European Society of Cardiology/European Respiratory Society guidelines for the diagnosis and treatment of pulmonary hypertension.9 Interestingly, in more than a third of the cohort the establishment of PAH-CHD diagnosis occurred during pregnancy, which was also a finding in previous studies.10,11 Notably, some of the patients were referred late in their pregnancies as emergencies in the tertiary centre.8 Maternal outcomes during pregnancy in patients with pulmonary arterial hypertension related to congenital heart disease. Calculation based on the completed pregnancies (abortions and miscarriages were excluded) SD: standard deviation; ES: Eisenmenger syndrome; PAH-CHD: pulmonary arterial hypertension related to congenital heart disease Maternal outcomes during pregnancy in patients with pulmonary arterial hypertension related to congenital heart disease. Calculation based on the completed pregnancies (abortions and miscarriages were excluded) SD: standard deviation; ES: Eisenmenger syndrome; PAH-CHD: pulmonary arterial hypertension related to congenital heart disease In total, 6.4% of pregnant women died, 35.1% developed heart failure and 10.6% experienced a pulmonary hypertension crisis. Patients with left-to-right shunt had more favourable outcome compared with Eisenmenger patients and those with repaired defects. However, since diagnosis of PAH was achieved by right heart catheterisation in only half of the patients, there might be some patients in the left-to-right shunt group who, based on an echocardiographic diagnosis of elevated pulmonary pressures, might have relatively low pulmonary vascular resistance due to elevated cardiac output, and therefore absence of pulmonary vascular disease. Fοetal/neonatal complications were also more common among Eisenmenger patients. Independent predictive factors of the composite endpoint of maternal death, heart failure and pulmonary hypertension crisis were low arterial blood oxygen saturation, elevated brain natriuretic peptide levels and presence of pericardial effusion on echocardiography.8 In general, their real-life data support that the mortality is not as high as in the past and PAH targeted treatment might have contributed to this decreased rate. However, mortality and morbidity still remain high. Low resting oxygen saturation was also associated with maternal and fοetal complications in a multicentre study from France.12 Resting oxygen saturation should be regularly checked along with right ventricular function by echocardiography in the follow-up of pregnant patients with PAH-CHD. Furthermore, natriuretic peptide levels and presence of pericardial effusion on echocardiography should also be taken into account in the risk stratification since both parameters indicate right ventricular impairment and are generally used for risk assessment in the PAH population.9 The vast majority of the studied population underwent a planned Caesarean section with regional anaesthesia (almost half had a scheduled pre-term delivery before 37 weeks to avoid maternal decompensation in the very late stages of pregnancy). General anaesthesia was a predictor of maternal mortality in a systematic review of pregnancy outcomes in PAH-CHD, with patients receiving general anaesthesia being four times more likely to die compared with patients receiving regional anaesthesia.13 This was also the case in the study by Li et al., since general anaesthesia was associated with high risk of death, especially when unplanned. General anaesthesia decreases cardiac contractility and increases pulmonary vascular resistance during intubation as well as due to the positive pressure ventilation. Therefore, regional anaesthesia with gradual uptitration should be preferred. Bolus administration is not recommended in order to avoid hypotension. The results of Li and colleagues’ study are also in line with the results of the worldwide Registry of Pregnancy and Cardiac Disease (ROPAC), confirming the high complication rate in a mixed population of pregnant patients with pulmonary hypertension.10 One out of the 28 (3.6%) PAH-CHD patients registered in ROPAC died and more than one-third of them developed heart failure (Table 1). Neonatal complications were also common in these patients. Patients with mildly elevated pulmonary artery pressure had a lower rate of mortality compared with patients with severe PAH. Notably, the majority of complications occurred mostly in early (<1 week) but also in late postpartum (up to six months) period, rather than during pregnancy. In conclusion, timely referral to tertiary expert care, a multidisciplinary approach and PAH targeted therapies have majorly contributed to the decrease of mortality in pregnant PAH-CHD patients. However, the rates of mortality and morbidity still remain high and, therefore, pregnancy in these patients should be discouraged. Prospective multicentre studies or registry data are required to determine the exact pregnancy related risk in PAH-CHD. The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The author(s) received no financial support for the research, authorship, and/or publication of this article.