Pulmonary hypertension. Pathophysiology and current concepts of medication therapy

Abstract

Chronic pulmonary hypertension (PHT) is characterized by permanently increased pulmonary artery pressure. Diagnostic criteria are a mean pulmonary arterial pressure above 25 mmHg at rest and above 30 mmHg during exercise. Pulmonary arterial hypertension is characterized by progressive obliteration of the pulmonary vascular bed, which results in progressive right heart failure and death. Pathologic processes behind the complex vascular changes associated with PHT include vasoconstrictor/vasodilator imbalance, thrombosis, misguided angiogenesis and inflammation. The function of the pulmonary endothelium is altered with decreased production of vasodilators such as prostacyclin and nitric oxide and an increased production of endothelins, finally resulting in pulmonary vascular remodelling. A new diagnostic classification of pulmonary hypertension (PHT) was proposed at the World Health Organization (WHO) Pulmonary Hypertension Meetings held in Evian in 1998 and in Venice in 2003. This classification reflects recent advances in the understanding of pulmonary hypertensive diseases. Depending on the underlying disease and the localization of the vascular lesion, five different subgroups of PHT are formed. An exact diagnostic classification is necessary for application of the current treatment options for the different forms of PHT. Target of therapy is besides avoiding local thrombosis by anticoagulation and treatment of vasoconstriction, the prevention of vascular remodelling. For patients with advanced pulmonary arterial hypertension (PAH; NYHA stages III and IV) treatment with prostanoids (inhalative, oral, subcutaneous or intravenous), with endothelin-receptor antagonists or with a phosphodiesterase inhibitor can be indicated. Whether initial or adjunct combined therapy provides additional clinical benefits to patients with severe pulmonary arterial hypertension needs further investigation, but first results are promising.