Pathophysiology

Several cellular mechanisms are implicated in the pathogenesis of PH [9]:

• Mutations in the bone morphogenetic protein receptor-2 (a member of the transforming growth factor-beta family)
• Allelic variations in the serotonin transporter (5-HTT)
• Reduced bioavailability of endogenous nitric oxide
• Alteration in the metabolism of cyclic nucleotides
• Imbalance in the metabolism of prostanoids (prostacyclin and thromboxane A2)
• Release of peptide mediators by the vascular endothelium (e.g. endothelin-1)

Prolonged PH can lead to right heart failure due to sustained increases in pulmonary artery pressure and right ventricle (RV) afterload.

Right ventricular function worsens in parallel to elevations of the pulmonary artery pressure. Chronic pressure overload stimulates the RV to hypertrophy over time. This hypertrophy, coupled with reduced contractility, causes a reduction in coronary blood flow to the RV myocardium, which can produce right ventricular ischaemia and dilation.

Right ventricular enlargement progresses to tricuspid annular dilation and regurgitation, and subsequent displacement of the inter-ventricular septum toward the left ventricle. Alterations in the left ventricle are then observed secondary to right ventricular overload. Left sided heart failure ensues, as evidenced by depressed left ventricular functional curves, and increased LV end diastolic and pulmonary capillary wedge pressures.

The cascade that follows is a slippery slope that leads to increased RV end diastolic pressure, lower extremity oedema, increased jugular venous pressures, congestive hepatomegaly, decreased oxygenation, decreased tissue perfusion, and ultimately, cardiovascular collapse.

Learning Bite

Patients with prolonged PH may present to the ED with acute right heart failure due to sustained increases in pulmonary artery pressure and right ventricle (RV) afterload.