Pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) has many causes and is a source of significant mortality in affected individuals. 

Epidemiology

Epidemiology varies with the underlying cause, and risk factors (conditions that are associated with PAH, without however a definite causal relationship). There is an overall female predilection.

Risk factors include ³:

• drugs and toxins
  
  • aminorex
  • fenfluramine
  • dexfenfluramine
  • toxic rapeseed oil
  • amphetamines
  • l-tryptophan
• HIV Infection
• portal hypertension & liver disease
• connective tissue disease

Clinical presentation

Classical clinical presentation of pulmonary arterial hypertension is the combination of dyspnoea (especailly with exercise) with symptoms and signs of elevated right heart pressures, including peripheral oedema and abdominal distention ^2-3.

An ECG may demonstrate right ventricular strain and hypertrophy.

Pathology

Pulmonary arterial hypertension is defined as a mean pulmonary arterial pressure exceeding 25mmHg at rest or > 30mmHg with exercise and pulmonary capillary wedge pressure ≤ 15 mm Hg measured by cardiac catheterisation ^3-4. It can result from either increased pulmonary venous resistance (most common) or increased pulmonary venous flow, such as with a left-to-right shunt ².

Even in cases of increased flow, the main factor in generating severe PAH is an arteriopathy, which has four main components ³:

1. muscular hypertrophy
2. intimal thickening
3. adventitial thickening
4. plexiform lesions : focal proliferation of endothelial channels

The earliest change is muscular hypertrophy in muscular arteries which, over time, results in changes in the more proximal arteries. Eventually fibrosis of the wall occurs, at which point the process is irreversible ².

Classification

In addition to cases of idiopathic pulmonary arterial hypertension, there are numerous known causes , and these can be divided in many ways. A simple unofficial classification is to divide causes of secondary PAH anatomically:

• chest wall and upper airways e.g.
  
  • kyphoscoliosis
• pulmonary veins and left heart e.g.
  
  • chronic left heart failure
  • mitral valve stenosis
  • hypoplastic left heart syndrome (HLHS)
• pulmonary capillaries and pulmonary parenchyma e.g.
  
  • emphysema
  • asthma
  • cystic fibrosis (CF)
• pulmonary arteries e.g.
  
  • chronic / repeated pulmonary emboli
  • arteritis

See : causes of pulmonary arterial hypertension for a more complete list

Alternative classifications include :

• primary and secondary pulmonary arterial hypertension (out dated)
• pre capillary versus post capillary ⁶
• 2003 third world symposium on pulmonary arterial hypertension classification

Radiographic features

Plain film

By the time the diagnosis of pulmonary arterial hypertension is made, 90% of patients have an abnormal chest radiograph ³. Features include:

• elevated cardiac apex due to right ventricular hypertrophy
• enlarged right atrium
• prominent pulmonary outflow tract
• enlarged pulmonary arteries
• pruning of peripheral pulmonary vessels

CT

HRCT of course is indispensable in assessing the lung parenchyma and to identify possible causative processes (e.g interstitial lung disease, COPD etc..).

In pulmonary capillary haemangiomatosis small ill-defined centrilobular nodules and interlobular septal thickening may be apparent ³.

Additionally, routine CT and CTPA can also identify changes in the pulmonary vasculature and the heart. Features include:

• right ventricular enlargement
• straightening or bowing (towards the left ventricle) of the interventricular septum
• enlarged pulmonary trunk
  • > 29 mm diameter is often used as a general predictive cut-off ^6,10 however a recent study suggests: ⁷
    • 31.6 mm may be a more statistically robust cut-off in patients without interstitial lung disease (specificity 93%)
    • pulmonary trunk enlargement is a poor predictor of PAH in patients with interstitial lung disease (specificity ~ 40%)  
  • larger than the adjacent ascending aorta
• enlarged pulmonary arteries
• mural calcification in central pulmonary arteries ⁶
  • most frequently seen in patients with Eisenmenger phenomenon
• evidence of previous pulmonary emboli

MRI

MRI and MR angiography have an increasing role in the management of pulmonary arterial hypertension, as dynamic imaging of both the heart and pulmonary circulation can be achieved.

Angiography / DSA

Traditionally pulmonary angiography has been the gold standard to identify small peripheral occlusions and to better quantify degree of stenosis. Increasingly this has been replaced by better quality CTPA and cardiac CT.

Care needs also to be taken when performing a pulmonary angiogram in patients with severe pulmonary hypertension.

Treatment and prognosis

Medical therapy includes ⁴:

• calcium channel antagonists
• nitric oxide
• prostanoids e.g. epoprostenol, treprostinil, iloporst
• endothelin antagonists e.g. bosentan, sitaxsentan, ambrisentan
• phosphodiesterase inhibitors

In selected cases combined heart and lung transplantation can be performed ⁵. In patients with very high right heart pressures, an atrial septostomy has also been performed but is associated with high immediate mortality and reduces oxygenation due to the right-left shunt formed.

In cases where pulmonary arterial hypertension is due to proximal pulmonary emboli, pulmonary thromboendarterectomy is a surgical option.

Despite extensive research and recent advances in medical management prognosis remains poor, with a mean survival of only 3 years in untreated patients ⁵. Patients typically succumb to right heart failure or sudden death.

Differential diagnosis

For plain film appearances consider

• differential of enlarged pulmonary trunk on chest radiography