Pulmonary arterial hypertension (PAH) is a progressive and life-threatening disorder characterized by elevated pressure in the pulmonary arteries, leading to right heart failure and, eventually, death if left untreated. This document provides a thorough summary of the causes, diagnostic approaches, risk assessment, prognosis, and treatment strategies for PAH.
What Causes Pulmonary Arterial Hypertension?
The pathogenesis of PAH is complex and multifactorial. It is classified as Group 1 in the World Health Organization's (WHO) classification of pulmonary hypertension. The main etiologies include:
- Idiopathic PAH (IPAH): Occurs in the absence of any identifiable cause and is the most common form of PAH.
- Heritable PAH: Genetic mutations, particularly in the BMPR2 gene, as well as ALK1, ENG, and SMAD9, play a role.
- Drug- and Toxin-Induced PAH: Triggered by certain drugs (e.g., fenfluramine derivatives, methamphetamines, and some chemotherapy agents).
- Associated Conditions: Includes connective tissue diseases (systemic sclerosis, lupus), congenital heart diseases, HIV infection, portal hypertension, and schistosomiasis.
- Persistent Pulmonary Hypertension of the Newborn (PPHN): Rare, affecting infants shortly after birth.
The underlying mechanism involves vasoconstriction, vascular remodeling, inflammation, and in situ thrombosis within the pulmonary arteries, increasing pulmonary vascular resistance and pressure.