PAH is a rare and severe disease characterised by progressive narrowing of the pulmonary arteries. If left untreated, it eventually results in right heart failure and death.2,3 Knowing the signs and symptoms of PAH can help prolong your patient's life. Explore below to find out more.
Pulmonary hypertension (PH) refers to elevated blood pressure in the pulmonary arteries and can be caused by various pulmonary and cardiac pathologies that increase pulmonary arterial pressure (PAP). PAH describes a subgroup of patients with PH characterised by the presence of pre-capillary PH, defined as mean PAP >20 mmHg, mean pulmonary arterial wedge pressure ≤15 mmHg and pulmonary vascular resistance (PVR) >2 Woods units, in the absence of other causes of PH. 4
Types: Idiopathic PAH, Heritable PAH, Drug induced PAH, Associated PAH
Types: IpcPH, CpcPH
Prevalence: Very common
Types: non-severe PH, severe PH
Types: CTEPH, Other pulmonary obstructions
Types: hematological disorders, systemic disorders
Optimized treatment of underlying disease:
Potentially: PAH drugs (trials)
IPAH is the most common form of PAH, accounting for approximately 50–60% of cases in Europe and the USA.4 It occurs sporadically without a family history or other identifiable risk factors.5
HPAH accounts for approximately 6% of PAH cases and includes patients with a family history of PAH and those carrying a mutation in a gene known to be associated with PAH.6
PAH can be associated with exposure to certain drugs or toxins, particularly appetite suppressants, such as aminorex, fenfluramine derivatives and benfluorex. These drugs have been confirmed to be risk factors for PAH and many have been withdrawn from the market.7 Since then, additional new drugs have been identified or suspected as potential risk factors for PAH, including bosutinib, sofosbuvir and leflunomide.8
PAH affects the small vessels of the pulmonary circulation. Changes to the pulmonary vasculature lead to the typical symptoms of PAH. Symptoms, such as dyspnoea, are often non-specific and can be associated with a number of underlying conditions.10
These symptoms may be accompanied with a cough, sometimes with haemoptysis. Some patients may even develop hoarseness, caused by compression of a nerve in the chest by an enlarged pulmonary artery.4As PAH advances, patients can develop a bluish discolouration due to cyanosis. The continued strain on the heart can lead to swelling of the face, ankles, abdomen and feet due to oedema.4 Too often patients only present when they are no longer able to continue with daily activities. By this time, the disease may have progressed to a point where the patient is bedridden from shortness of breath or other symptoms.
Adapted from Humbert et al. 2022
Click to enlarge the image below to see all the clinical signs that point to PAH.
Adapted from Humbert et al. 2022
The increase in pulmonary arterial pressure (afterload) makes the right heart work harder, resulting in right ventricular hypertrophy, and leading to the typical symptoms of PAH.11 Initially, the heart is able to compensate for the increased pressure;12 however, as the disease progresses, the right ventricle (RV) becomes dilated, eventually resulting in a number of potential consequences:
PAH is a rare, progressive disease.21 Without treatment, PAH carries a poor prognosis.22 The course of PAH is variable and the rate at which disease progression occurs depends on the type of PAH as well as several other factors, such as the underlying aetiology of the patient's disease, age, associated conditions and comorbidities.4,23 While there is currently no cure for the disease, modern PAH therapies can markedly improve a patient's symptoms and slow the rate of clinical deterioration.11
PAH, pulmonary arterial hypertension
A number of registries over the years have reported baseline characteristics and outcome data on >10,000 patients with PAH, providing important insights into the evolving epidemiology of PAH and facilitating the development of prognostic indicators for the disease.24
PAH has been thought to predominantly affect younger individuals, mostly females;24,30 this is currently true for Heritable PAH, which affects twice as many females as males. However, recent data from the USA and Europe suggest that PAH is now frequently diagnosed in older patients (i.e. those aged ≥ 65 years, who often present with cardiovascular comorbidities, resulting in a more equal distribution between sexes).24
Though the exact causes behind the development of PAH remain unknown, research has led to a better understanding of the underlying pathophysiology. PAH is a complex, multifactorial condition involving numerous biochemical pathways and different cell types.2
Narrowing of the pulmonary arteries occurs in PAH as a result of vascular remodelling, which involves changes to all three layers of the vessel wall via multiple pathological mechanisms.2Vascular remodelling leads to chronic elevation of PVR and PAP. This, in turn, leads to increased afterload on the right ventricle, eventually progressing to right heart failure.2,17
Adapted from Gaine et al. 20102
The prominent pathological features of PAH include:2,18,19
Adapted from Gaine et al. 200018
The increase in PAP (afterload) strains the right side of the heart. Initially, the right ventricle can compensate for the increased afterload by undergoing remodelling, including increased contractility, hypertrophy and dilatation. As PAH progresses, however, the heart can no longer compensate and becomes uncoupled from its load.17,20
Adapted from Vonk Noordegraaf et al. 201329
Several hormonal processes are involved in the pathogenesis of PAH. Each of these are targeted by different, currently approved therapies.4
Adapted from Humbert et al. 2022
Find out about the different strategies that can help you diagnose PAH in a timely manner.
Patients with suspected PAH should be referred to a PH Center for further investigation and treatment.
Would you like to know more about the screening and management of pulmonary arterial hypertension? Book an appointment with a Janssen product specialist by clicking the button below.
IpcPH: Isolated post-capillary Pulmonary Hypertension; CpcPH: Combined post-capillary Pulmonary Hypertension; PEA: pulmonary endarterectomy; BPA: balloon pulmonary angioplasty; HHT: hereditary hemorrhagic teleangiectasia; Ea: arterial elastance; Ees: end-systolic elastance