Cor Vasa 2007, 49(1):25-33 | DOI: 10.33678/cor.2007.010

Pulmonary hypertension in chronic lung disease

Jiří Widimský

Klinika kardiologie, Institut klinické a experimentální medicíny, Subkatedra kardiologie IPVZ, Praha, Česká republika

Unlike pulmonary arterial hypertension, pulmonary hypertension in chronic lung diseases is defined by a mean pulmonary artery pressure ≥ 20 mmHg (being ≥ 25 mm Hg in pulmonary arterial hypertension) and a capillary wedge pressure below 12 mmHg. The estimated prevalence and incidence of pulmonary hypertension due to lung diseases is 2-6/1,000 patients and 1-3/10,000 patients, respectively; the latter being a 100-fold of the incidence of idiopathic pulmonary arterial hypertension.
Pulmonary hypertension in the presence of chronic obstructive pulmonary disease (COPD) is caused by alveolar hypoventilation leading to alveolar hypoxia and pulmonary vasoconstriction. The result is endothelial dysfunction and remodeling of smaller pulmonary arteries.
Respiratory acidosis exacerbates hypoxic pulmonary hypertension, respiratory alkalosis decreases hypoxic pulmonary hypertension. Pulmonary hypertension associated with COPD becomes more severe in the presence of polycytemia and hypervolemia. The primary cause of pulmonary artery remodeling seems to be hypoxia-induced endothelial damage. Endothelial dysfunction results in increased production of the vasoconstrictors endothelin and thromboxane A2 and decreased production of the vasodilators NO and prostacyclin.
Remodelling of the smaller pulmonary arteries in the presence of lung diseases is characterized by hypertrophy of the medial musculature in tiny pulmonary arteries, smooth muscle formation in pulmonary arterioles, and endothelial cell and fibroblast proliferation. The anatomical changes in pulmonary arteries and arterioles occurring in lung diseases are reversible.
There is individual variability in the susceptibility of pulmonary vessels to hypoxia in man. This may partly explain the various degrees of pulmonary hypertension in hypoxic pulmonary hypertension.
Pulmonary hypertension in COPD is usually mild to moderate. Mean pulmonary artery pressure is in the range of 20-42 mmHg, and progression of pulmonary hypertension is slow, at an average rate of 0.5-0.6 mmHg per year. A more rapid rate of progression is seen in patients with severe hypoxemia or those with severe pulmonary hypertension.
While, initially, mean pulmonary artery pressure at rest is normal, at a workload of 40 W during steady state exercise will rise to over 30 mmHg; this is referred to as exercise-induced pulmonary hypertension.
Presence of exercise-induced pulmonary hypertension suggests a higher likelihood of development of resting pulmonary hypertension at a later time. Repeated increases in pulmonary artery pressure seem to contribute to the development of heart failure. Likewise, pulmonary hypertension during sleep (particularly REM sleep) tends to exacerbate in parallel with deteriorating hypoxemia.
Exacerbation of pulmonary hypertension occurs also during acute airway infection along with deterioration of respiratory insufficiency when mean pulmonary artery pressure rises by as much as 20 mmHg and these episodes may contribute to the development of right-heart failure.
Severe pulmonary hypertension occurs in about 10% COPD patients except for cases whereby these are examined during acute exacerbation or are obese with primary alveolar hypoventilation or have a syndrome of sleep apnea. Severe pulmonary hypertension may be caused by concomitant diseases such as left-heart disease (mitral or aortic valve disease), left-heart failure, CHD, hypertension, cardiomyopathy or pulmonary embolism. Causes of severe pulmonary hypertension in COPD include individual differences in the reactivity of pulmonary vessels to hypoxia, differences in the degree of remodelling, and genetic differences. Vascular remodelling in these patients resembles pulmonary vascular remodelling in pulmonary arterial hypertension.
Although pulmonary hypertension in lung diseases is usually mild, less frequently moderate, and rarely severe, mean pulmonary artery pressure is the best prognostic factor in multivariate analysis.
A major development in the non-invasive diagnosis of pulmonary hypertension was the introduction of Doppler echocardiography; however, this method may be associated with considerable problems in COPD patients. Every effort should be made to identify right ventricular dilatation. A useful tool for assessing the presence of right ventricular hypertrophy is determination of right ventricular free wall thickness. In most cases, absence of abnormal right ventricular size and function rules out pulmonary hypertension.
Initially, right ventricular ejection fraction at rest is normal, rising with increasing workload. On progression, right ventricular ejection fraction is normal at rest but does not increase during exercise or even decreases, quite paradoxically, at a later stage.
In resting pulmonary hypertension, right ventricular ejection fraction is decreased already at rest. The techniques used to assess right ventricular function at rest and during exercise include radionuclide ventriculography and echocardiography. Right ventricular function and size can also be assessed using spiral CT-angiography or, ideally, nuclear magnetic resonance imaging.
In conclusion, the review points to pitfalls in the diagnosis of right-heart failure and defines the potential role of vasodilator therapy, particularly in patients with severe pulmonary hypertension.

Keywords: Pulmonary hypertension in COPD; Cor pulmonale; Development and prognosis of pulmonary hypertension in COPD

Published: January 1, 2007  Show citation