Pulmonary hypertension

Pulmonary hypertension is defined as a resting mean pulmonary arterial pressure of 25 mmHg or greater at right heart catheterisation, which is a hemodynamichaemodynamic feature that is shared by all types of pulmonary hypertension in the Dana Point classification system. A resting mean pulmonary arterial pressure of 20mmHg or less is considered normal, while mean pulmonary arterial pressures ranging between 21-24 mmHg are considered abnormal requiring further investigation about the clinical course of disease.

Terminology

The use of the term pulmonary arterial hypertension(PAH) is restricted to those with a haemodynamic profile in which high pulmonary pressure results from elevated precapillary pulmonary resistance and normal pulmonary venous pressure and is measured as a pulmonary wedge pressure of 15 mmHg or less. This correpondscorresponds to the haemodynamic profiles of groups 3, 4, and 5 in the Dana Point classification system, which was updated during the 4^th World Symposium on Pulmonary Hypertension.

Epidemiology

Epidemiology varies with the underlying cause, and risk factors (conditions that are associated with pulmonary hypertension, without however a definite causal relationship). Overall, there is a female predilection.

Risk factors include ³

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

Clinical presentation

Classical clinical presentation of pulmonary arterial hypertension is the combination of dyspnoea (especailly(especially 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

PAH is defined as a mean pulmonary arterial pressure >25 mmHg at rest ¹¹ or >30 mmHg with exercise and pulmonary capillary wedge pressure ≤15 mmHg 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 pulmonary hypertension 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 and/or repeated pulmonary emboli
  • arteritis

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

Alternative classifications include:

• primary and secondary pulmonary arterial hypertension (outdated)
• precapillary versus post-capillary ⁶
• 2003 third world symposium on pulmonary arterial hypertension classification
• 2008 fourth world symposium on pulmonary arterial hypertension classification ¹¹: Dana point classification of pulmonary hypertension

Radiographic features

Plain radiograph

By the time the diagnosis of pulmonary arterial hypertension is made, 90% of patients have an abnormal chest radiograph ³ although sensitivity and specificity is low ¹². 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

HRCTHigh resolution CT (HRCT) chest, 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 chest and CTPACT pulmonary angiography (CTPA) can also identify changes in the pulmonary vasculature and the heart. Features include:

Extra-cardiacExtracardiac vascular signs

• enlarged pulmonary trunk (measured at pulmonary artery bifurcation on an axial slice vertical to its long axis)
  • >29 mm diameter is often used as a general predictive cut-off ^6,10-11 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 pulmonary hypertension in patients with interstitial lung disease (specificity ~40%)
    • a diameter of <29 mm does not necessarily exclude pulmonary hypertension
  • sex-specific reference values obtained from the Framingham Heart study suggest cut-off values 27 mm for women and 29 mm for men (on ECG-gated non contrast-contrast CT ) ¹⁴ 
• main pulmonary artery (pulmonary trunk) to ascending aorta ratio
  • higher ratio correlates with higher PA pressure
  • the ratio obtained on the axial image at the bifurcation of the right pulmonary artery ¹⁴
  • adult: normal ratio is less than 1.0
  • children: normal up to a ratio of around 1.09 ¹⁵
• enlarged pulmonary arteries
• mural calcification in central pulmonary arteries ⁶
  • most frequently seen in patients with Eisenmenger phenomenon
• evidence of previous pulmonary emboli
• a segmental artery-to-bronchial diameter ratio of 1:1 ¹¹-1.25 ¹³ or more in three or four lobes in the presence of a dilated (≥29 mm) main pulmonary artery and absence of significant structural lung disease has a specificity of 100% for the presence of pulmonary hypertension ^{11, 13,13}

Cardiac signs

ECG-gated CTPA ideally required:

• right ventricular hypertrophy: defined as wall thickness of >4 mm
• straightening or bowing (towards the left ventricle) of the interventricular septum
• right ventricular dilatation (a right ventricle–to–left ventricle diameter ratio of more than 1:1 at the midventricular level on axial images)
• decreased right ventricular ejection fraction
• ancillary features
  • dilatation of the inferior vena cava and hepatic veins
  • pericardial effusion

Parenchymal signs

• centrilobular ground-glass nodules
  • especially common in patients with idiopathic pulmonary arterial hypertension
  • pathologically: represent cholesterol granulomas, which are caused by ingestion of red blood cells by pulmonary macrophages, a result of repeated episodes of pulmonary haemorrhage
• neovascularity: tiny serpiginous intrapulmonary vessels that often emerge from centrilobular arterioles but do not conform to usual pulmonary arterial anatomy: can be seen as a manifestation of severe pulmonary hypertension

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

Traditionally pulmonary angiography has been the gold standard to identify small peripheral occlusions and to better quantify the 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, iloprost
• endothelin antagonists e.g. bosentan, sitaxsentan, ambrisentan
• phosphodiesterase inhibitors e.g. dipyridamole 

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 three years in untreated patients ⁵. Patients typically succumb to right heart failure or sudden death.

Differential diagnosis

• pulmonary arterial dilatation can occur in the absence of pulmonary hypertension in some people with pulmonary fibrosis ¹⁶.
• for an enlarged pulmonary artery also consider - idiopathic dilatation of the pulmonary trunk

As a broad differential on plain film consider

• differential of an enlarged pulmonary trunk on chest radiography