Pulmonary Arterial Hypertension in Pregnancy
Highlights
- The World Health Organization (WHO) classifies PAH as class IV maternal cardiac risk (mWHO IV) and avoidance of pregnancy is strongly recommended.2,7 Right heart failure is the most common cause of death in these patients because they are unable to compensate for the physiological changes of pregnancy (View Highlight)
- PAH secondary to Eisenmenger’s syndrome is associated with the highest mortality in pregnancy, followed by IPAH (View Highlight)
- The 6th World Symposium on Pulmonary Hypertension (WSPH) defines PH as an mPAP ≥20 mmHg (View Highlight)
- Precapillary PH secondary to pulmonary vascular disease is further defined by a pulmonary vascular resistance (PVR) of >3 wood units (WU) and a pulmonary artery wedge pressure <15 mmHg (View Highlight)
- There are three main processes that result in increased PVR. These are sustained pulmonary vasoconstriction; cellular proliferation in the intimal, medial and adventitial layers of the pulmonary vessels; and localised thrombi formation further obstructing pulmonary capillary flow (View Highlight)
- Normally, increased progesterone levels promote pulmonary vasodilation and recruitment of non-perfused pulmonary arterioles. In PAH, the normally thin walled and distensible pulmonary vasculature is thickened and chronically vasoconstricted. The non-compliant pulmonary arteries are unable to accommodate for the increased cardiac output and plasma volume, leading to further increases in PVR and RV strain. The right ventricle becomes highly vulnerable to ischaemia and failure (View Highlight)
- Before labour, the most hazardous period in PAH is between 20 and 30 weeks when cardiac output peaks (View Highlight)
- During labour the sympathetic stimulation from pain, fluid shifts and changes in intrathoracic pressure from the Valsalva manoeuvre during the second stage increase PVR further. These induce rapid changes in the preload-dependent right ventricle, which can lead to catastrophic cardiovascular collapse (View Highlight)
- Immediately postpartum, the autotransfusion of ∼500 ml of blood from the uterine contraction and shifts of extracellular fluid into the intravascular compartment can lead to sudden RV overload (View Highlight)
- The highest risk for mortality in PAH is immediately postpartum, with physiological changes taking 3–6 months to normalise (View Highlight)
- Idiopathic pulmonary arterial hypertension in particular has an increased risk of thrombosis and evidence suggests better survival outcomes when these patients are anticoagulated (View Highlight)
- patients with Eisenmenger’s syndrome are at increased risk of haemorrhage as a result of intrinsic deficiencies of vitamin K-dependent clotting factors and the risk of thrombocytopenia (View Highlight)
- Termination of pregnancy is recommended and considered safest in the first trimester. It should also be considered up to viability in the second trimester, but it becomes more perilous as gestation increases (View Highlight)
- Medical termination is considered safest and recommended with mifepristone (View Highlight)
- WHO functional class (WHO-FC) is the best prognostic indicator of survival in PAH and any deterioration in functional status should prompt immediate investigation (View Highlight)
- Brain natriuretic peptide (BNP/NT-proBNP) is the most commonly used biochemical marker in PAH. Brain natriuretic peptide concentrations routinely double in pregnancy but remain within normal limits and BNP is therefore a useful indicator of worsening cardiac function (View Highlight)
- Endothelin-1 causes vasoconstriction of smooth muscle when bound to endothelin-A receptors (View Highlight)
- Bosentan, ambrisentan and macitentan are widely used endothelin receptor antagonists. However, they are contraindicated because of teratogenicity and are labelled category X in pregnancy (View Highlight)
- The nitric oxide and prostacyclin (PGI2) pathways are diminished in PAH, which leads to a decrease in production of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), respectively, amplifying vasoconstriction and abnormal cell proliferation. (View Highlight)
- Phosphodiesterase 5 (PDE5) inhibitors target the nitric oxide pathway. Sildenafil, an oral selective PDE5 inhibitor, is recommended as the first-line agent in pregnant patients with WHO-FC I/II and normal RV function. (View Highlight)
- Prostacyclin analogues target the PGI2 pathway. These can be given parenterally (epoprostenol), inhaled (iloprost) or subcutaneously (treprostinil) (View Highlight)
- If required, diuretic therapy is used judiciously to avoid adverse effects on the fetus. Furosemide should be first line because spironolactone has teratogenic effects (View Highlight)