PAH can be easily missed at first glance. Even with increasing awareness of the disease, patients can still experience long delays between initial symptom onset and a confirmed PAH diagnosis. Consequently, many patients have advanced disease at diagnosis, and this could have an impact on their prognosis. Avoiding a delayed diagnosis and catching it early is crucial for the patient’s future. 

In rare diseases like PAH, symptoms such as fatigue, dyspnoea, or syncope can be confused for something else entirely. Conditions such as asthma, chronic heart failure, connective-tissue disease, or even lack of fitness or depression, are considered before PAH. PAH comprises a group of uncommon conditions characterised by obliterative vasculopathy of the small pulmonary arteries. The likelihood of PAH is increased significantly for patients with connective tissue disease, congenital heart disease, portal hypertension or HIV. 

*Recent reassessment of haemodynamic definitions by the 6th WSPH Task Force suggest mPAP >20mmHg as above the upper limit of normal (>97.5th percentile). 

Make sure that symptoms don’t go unnoticed 

There is no specific clinical sign of PH. Clinical presentation is related either to right heart failure or to associated diseases. 

• Persistent dyspnoea on exertion is the most frequent symptom; and it is present in almost all patients even in the presence of mild haemodynamic abnormalities
• Chest pain, light-headedness and syncope may occur, particularly during physical efforts and are major signs of disease severity 
• Palpitations are frequent during physical efforts and may reveal true cardiac arrhythmias 
• Other symptoms of PAH include fatigue and weakness
• Haemoptysis may complicate PAH and could be life-threatening, justifying embolisation of dilated bronchial arteries 
• Hoarseness of the voice may occasionally be noted and is due to compression of the left laryngeal nerve by the dilated pulmonary artery (Ortner’s syndrome) 
• Signs of right heart failure may be observed in the most severe patients, including venous jugular distension, hepato-jugular reflux, hepatomegaly and hepatalgia. 

Earlier detection of PAH would allow earlier treatment and better outcomes.  

Rare but deadly – Rare diseases are more common than you might think. In fact, one in 17 people will be affected by one at some point in their lives.1 Pulmonary arterial hypertension (PAH) is a rare disease, which is often diagnosed late2 and the prognosis for patients with (PAH) depends on the severity of disease at diagnosis. Therefore, mortality and morbidity rates remain high. 

Because it is a rare condition, it is understandable that healthcare practitioners may consider other more common diseases with similar symptoms2 before screening for PAH. So, although PAH might seem unlikely, when patients present with any of its symptoms, take time to thoroughly investigate it as a possibility. Early diagnosis could prolong lives and improve quality of life. 

Screening for PAH – PAH should be considered as a possible diagnosis when certain symptoms are noted, and thought must be given as to whether the patient requires referral for further investigation. 

The possible symptoms of PAH are:  

• Weakness 
• Peripheral oedema 
• Chest pain 
• Angina 
• Breathlessness (dyspnoea) 
• Abdominal distension 
• Palpitations during physical exercise 
• Fatigue 
• Cough 
• Syncope 
• Dizziness 
• Cool extremities. 

Persistent dyspnoea on exertion is the most frequent symptom. 

The New York Heart Association (NYHA) provides a classification system for the clinical evaluation of dyspnoea. 

At time of diagnosis, 70% of patients are in NYHA FC III or IV. Additionally, particular attention should be paid to patients with associated conditions and/or risk factors for the development of PAH. 

Risk factors include:  

• Family history 
• Connective tissue disease 
• Congenital heart disease 
• Human immunodeficiency virus (HIV) infection 
• Portal hypertension 
• A history of drug or toxin intake known to induce PAH.

Following identification of high-risk patients, a fast-tracked referral to a PH centre for screening, is recommended by current PH diagnostic guidelines (6th WSPH Task Force). 

When PAH is suspected, clinical history, symptoms, signs, electrocardiogram (ECG), chest radiograph, echocardiogram, PFTs, CT of the chest and a V/Q scan are all required to exclude diagnosis of left heart disease, lung disease or chronic thromboembolic pulmonary hypertension (CTEPH). 

Echocardiography is recommended as a first-line non-invasive diagnostic investigation in case of suspicion of PH. Cardiologists, echocardiographers and sonographers can learn more on how to detect the signs of PH by using the EchoRight™ mobile app, which highlights the importance of right heart examination. To confirm diagnosis of PAH, referral to a PH specialist centre for right heart catheterisation (RHC), is required. 

Diagnostic-based algorithms can be found in the 2015 ESC/ERS clinical guidelines for the diagnosis and treatment of PH,6 as well as the 6th WSPH Task Force 2018. 

Time is crucial for patients with PAH 

Pulmonary arterial hypertension (PAH) is a rare disease, which is often diagnosed late2 and the prognosis for patients with (PAH) depends on the severity of disease at diagnosis. 

Despite progress in treatments, mortality from PAH remains high.2 However risk assessment data show that patients with PAH who achieve and maintain a low-risk status with treatment have improved long-term outcomes. 

Accessing the right treatment at the right time  

Patients across all risk categories have poor survival,3 therefore treatment strategies should target the improvement of long-term outcomes, with the goal of achieving a low-risk status.  

3 KEY PATHWAYS  

PAH-specific therapies have been developed to target one of three major pathways known to be involved in the development of PAH. To achieve the best outcomes, patients need to receive treatments that target these pathways at the right time: 

With timely use, treatments targeting all three pathways can improve the PAH patients’ prognosis and survival. 

The current treatment strategy is based on the severity of the newly diagnosed PAH patient. Clinical, exercise, right ventricular function and haemodynamic parameters are combined to define a low-, intermediate-, or high-risk status according to the expected one-year mortality. 

The current treatment strategy can be divided into three main steps:  

1. The initial approach includes general measures, supportive therapy, referral to expert centres and acute vasoreactivity testing for the indication of chronic CCB therapy

2. The second step includes initial therapy with high-dose CCB in vasoreactive patients or drugs approved for PAH in non-vasoreactive patients according to the prognostic risk of the patient

3. The third part is related to the response to the initial treatment strategy; in the case of an inadequate response, the role of combinations of approved drugs and lung transplantation are proposed

Combination therapy in PAH  

Due to the involvement of all three pathways in disease progression, combining drugs (using two or more classes of drugs together) to simultaneously target multiple pathways involved in the disease pathogenesis, may improve treatment success in PAH.9 Evidence to support combination therapy is growing: 

• In treatment-naive and newly diagnosed (incident) PAH patients, initial combination therapy can improve symptoms, exercise capacity and outcome compared with initial monotherapy
• Non-responders to acute vasoreactivity testing who are at low or intermediate risk should be treated with initial oral combination therapy with an ERA and a PDE5i (2015 ESC/ERS PH guidelines).

The current treatment algorithm provides the most appropriate initial strategy, including monotherapy, or double or triple combination therapy. 

References available on request.