Guideline Essentials: ESC/ERS 2022 Recommendations on Pulmonary Hypertension for Primary Care

Guidelines presents Guideline Essentials, a new type of summary that: 

• features expert clinician commentary on the guidance
• adds context through comparisons with other guidelines
• makes lengthy guidelines easier to navigate for healthcare professionals.

Overview

This Guidelines summary covers a selection of the recommendations from the 2022 European Society of Cardiology (ESC) and European Respiratory Society (ERS) guideline for the diagnosis and treatment of pulmonary hypertension (PH).

This summary is for primary care doctors and focuses on initial diagnosis and referral. However, it also includes some relevant changes to the guideline since the 2015 version and some additional general points.

In an expert commentary, Professor Raj Thakkar assesses the significance of the guidance for UK primary care.

Please refer to the full guideline for further recommendations, further details, background information, and information on rationale and strength of recommendations.

Please refer to the Guidelines secondary care summary for a summary of recommendations relevant to secondary care.

Reflecting on your Learnings

Reflection is important for continuous learning and development, and a critical part of the revalidation process for UK healthcare professionals. Click here to access the Guidelines Reflection Record.

Key Changes in the 2022 Guidance

The 2022 version of the ESC/ERS guideline has an emphasis on diagnosing and treating pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Changes to the guideline include:

• the haemodynamic definition of PH has been amended to a mean pulmonary arterial pressure (mPAP) of more than 20 mmHg—this metric would normally be found on an echocardiogram report
• PAH is defined as pulmonary vascular resistance (PVR) of more than 2 Wood units, and pulmonary arterial wedge pressure (PAWP) of 15 mmHg or less (see Expert Comment 1)
• the main diagnostic algorithm for PH has been simplified to a three-step approach consisting of:
  • suspicion by first-line physicians (see Expert Comment 2)
  • detection by echocardiography (see Expert Comment 2)
  • confirmation with right heart catheterisation (RHC) in PH centres
• a recommendation for expedited referral for high-risk or complex patients and emergency admission for unstable or decompensated patients
• screening strategies for patients with predisposing factors such as scleroderma and in patients at risk of heritable pulmonary arterial hypertension (HPAH) to shorten the time from symptom onset to diagnosis of PH
• supervised exercise training is now recommended in patients with PAH or CTEPH under medical therapy.

Diagnosis

• The main objective of the diagnostic approach in the ESC/ERS guideline is to raise early suspicion of PH and ensure that patients with a high probability of PAH, CTEPH, or other types of severe PH are rapidly referred to specialist PH centres
• The secondary aim is to facilitate the effective classification, risk assessment, and treatment of patients by identifying comorbidities and underlying diseases (particularly left heart disease [group 2 PH] and lung disease [group 3 PH])
• A three-step approach to diagnosis is recommended to achieve these aims:
  • step 1: suspicion of a cardiac or respiratory disorder
    • initial evaluation in primary care
  • step 2: detection and PH probability assessment
    • noninvasive lung and cardiac testing in secondary care including echocardiography, chest X-ray, and computed tomography, depending on suspected cause (such as pulmonary embolic disease)
  • step 3: confirmation
    • comprehensive work-up in a specialist PH centre including invasive assessment if needed.

Primary Care Evaluation

• For patients with unexplained exertional dyspnoea, or other symptoms and signs raising suspicion of PH or its underlying causes, the initial evaluation in primary care should include:
  • comprehensive medical history
  • family history
  • thorough physical examination (to include, but not be limited to, examination of fingernails (for clubbing) and peripheries, heart rate and rhythm, blood pressure [BP], pulse oximetry, and cardiac and respiratory auscultation)
  • resting electrocardiogram (ECG)
  • in addition to routine tests, blood testing to determine the patient’s brain natriuretic peptide/N-terminal pro-brain natriuretic peptide (BNP/NT-proBNP)
• See Expert Comment 3.

Symptoms

• Symptoms are primarily associated with ventricle (RV) dysfunction; these may include (in order of likelihood from early to late as the disease progresses):
  • dyspnoea on progressively minor exertion—this is the cardinal symptom of PH
  • rapid exhaustion
  • fatigue
  • bendopnoea (dyspnoea on bending forward)
  • haemoptysis
  • palpitations
  • syncope during exertion (or shortly after)
  • exercise-induced abdominal distension and nausea
  • fluid retention leading to weight gain
• Thoracic compression may rarely cause symptoms in a few patients with PAH with pronounced pulmonary artery dilation; this can happen at any disease stage, even in patients with otherwise mild functional impairment:
  • hoarseness due to left laryngeal recurrent nerve compression (Ortner’s syndrome)
  • exertional chest pain due to dynamic left coronary artery compression
  • dyspnoea, wheezing, cough, lower respiratory tract infection, and atelectasis due to bronchial compression.

Signs

• Clinical signs of PH may include:
  • cyanosis (central, peripheral [such as to the lips or digits], or mixed)
  • systolic murmur of tricuspid regurgitation
  • diastolic murmur of pulmonary regurgitation
  • accentuated pulmonary component of second heart sound
  • RV third heart sound
• Clinical signs of RV backward failure may include:
  • distended and pulsating jugular veins
  • abdominal distension
  • peripheral oedema
  • hepatomegaly
  • ascites
• Clinical signs of RV forward failure may include:
  • peripheral cyanosis
  • dizziness
  • pallor
  • prolonged capillary refill
  • cool extremities
• The following signs may indicate underlying causes of PH:
  • auscultatory findings, such as pulmonary crackles, wheezing, or murmurs (indicative of lung or heart disease)
  • digital clubbing (indicative of cyanotic congenital heart disease, fibrotic lung disease, bronchiectasis, liver disease, or pulmonary veno-occlusive disease)
  • differential clubbing or cyanosis (indicative of patent ductus arteriosus with shunting or Eisenmenger’s syndrome)
  • deep vein thrombosis sequelae or venous insufficiency (indicative of CTEPH)
  • sclerodactyly, Raynaud’s syndrome, digital ulceration, or gastro-oesophageal reflux disease (indicative of systemic sclerosis)
  • telangiectasia (indicative of hereditary haemorrhagic telangiectasia or systemic sclerosis).

Characteristic Clinical Features of Different Forms of PH

• Group 1 (PAH)
  • young, female patients tend to be affected more than other groups
  • can affect a variety of people of any age and gender, and diagnosis in males should not be delayed
  • phenotype and associated conditions will affect clinical presentation
  • oxygen is uncommonly required for hypoxaemia, except for in conditions associated with low lung diffusion capacity for carbon monoxide or right-to-left shunting
• Group 2 (PH associated with left heart disease)
  • patients are mostly elderly
  • patients are mostly females in cases of heart failure with preserved ejection fraction
  • history and clinical features are suggestive of left heart disease
  • oxygen requirement for hypoxaemia is uncommon
• Group 3 (PH associated with lung disease)
  • patients are mostly elderly, and are predominantly male
  • the patient’s history and clinical features are suggestive of lung disease
  • patients commonly have a history of smoking
  • oxygen requirement for hypoxaemia is common
  • profound hypoxaemia is often present in severe PH
• Group 4 (PH associated with pulmonary artery obstructions)
  • patients are of variable ages, but prevalence is equal in elderly men and women
  • patients have a history of venous thrombo-embolism (VTE); CTEPH may occur in patients with no history of VTE
  • patients have risk factors for CTEPH
  • oxygen requirement for hypoxaemia is generally uncommon; however, it can be common in severe cases with predominantly distal pulmonary artery occlusions.

Electrocardiogram

• A normal ECG does not exclude the presence of PH
• ECG abnormalities can:
  • raise suspicion of PH
  • offer prognostic information
  • detect arrhythmias
  • identify signs of left or right heart disease
• Right axis deviation has a high predictive value for PH in adults with suspected PH, such as those with unexplained dyspnoea on exertion
• If ECG is normal and biomarkers (BNP/NT-proBNP) are normal, the likelihood of PH is low
• Typical ECG abnormalities in patients with PH include:
  • RV hypertrophy (R/S >1, with R >0.5 mV in V1; R in V1+S in lead V5 >1 mV)
  • right bundle branch block—complete or incomplete (qR or rSR patterns in V1)
  • P pulmonale (P >0.25 mV in lead II)
  • right or sagittal axis deviation (QRS axis >90° or indeterminable)
  • in advanced PH: RV strain pattern (ST depression/T-wave inversion in the right pre-cordial V1–4 and inferior II, III, aVF leads)
  • patients with PAH can present with a prolonged QT interval corrected for heart rate (nonspecific), which can reflect RV dysfunction and delayed myocardial repolarisation and is an independent predictor of mortality.

Chest X-ray

• The guideline recommends that chest X-rays be conducted in secondary care when investigating suspected PH (see Expert Comment 3, in the above section Primary Care Evaluation)
• The guideline notes that it would be unusual for a chest X-ray to be normal in a patient with PH, but that a normal chest X-ray does not rule out PH.

Referral

• To facilitate the three-step diagnostic process, awareness and collaboration between first-line, specialised medicine, and PH centres is vital to enable early diagnosis and improve outcomes
• Patients with unexplained exertional dyspnoea and/or suspected PH should be referred for lung and heart assessment by specialists (see Expert Comment 4)
• Fast-track referral to a PH centre (see Expert Comment 4) should be made expediently in case of:
  • warning signs such as rapid progression of symptoms, severely reduced exercise capacity, pre-syncope or syncope on mild exertion, signs of right heart failure
  • suspicion of PAH
  • suspicion of CTEPH, for example, history of pulmonary embolism, permanent intravascular devices, inflammatory bowel disease, essential thrombocythaemia, splenectomy, high-dose thyroid hormone replacement, and malignancy
• Patients with the following warning signs must be immediately referred as in-patients for initial work-up at a nearby hospital or PH centre:
  • clinical signs of RV failure
  • rapidly evolving or severe symptoms (WHO functional class III/IV)
  • signs of low cardiac output state
  • poorly tolerated arrhythmias
  • syncope
  • compromised or deteriorated haemodynamic status (hypotension, tachycardia).

Patients with Pulmonary Arterial Hypertension

See the full guideline or the Guidelines secondary care summary for full information on the treatment of different types of PH. The following recommendations may be of use to primary care practitioners because patients with PAH require comprehensive multidisciplinary care.

General Measures for Patients with Pulmonary Arterial Hypertension

• The following measures are recommended for patients with PAH:
  • supervised exercise training for patients on medical treatment
  • psychosocial support
  • immunisation against SARS-CoV-2, influenza, and Streptococcus pneumoniae
  • diuretic treatment for patients with signs of RV failure and fluid retention
  • treatment of iron deficiency, if required
  • long-term oxygen therapy for patients whose arterial blood oxygen pressure is <8 kPa (60 mmHg) on at least two occasions
  • in-flight oxygen administration for patients using oxygen or whose arterial blood oxygen pressure is <8 kPa (60 mmHg) at sea level
  • multidisciplinary consultation at a specialist PH centre on occasions when anaesthesia is needed
• The following are not generally recommended for patients with PAH:
  • anticoagulation, except on an individual basis
  • angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors, sodium–glucose co-transporter-2 inhibitors, beta-blockers, and ivabradine, unless required for comorbidities such as high blood pressure, coronary artery disease, left heart failure, or arrhythmias.

Pulmonary Arterial Hypertension in Women of Childbearing Potential

• Counsel patients at diagnosis about the potential risks of pregnancy
• Include advice against becoming pregnant
• Refer patients for psychological support if needed
• Provide patients with tailored contraceptive advice, reinforcing the risks of contraceptive failure
• For women who consider pregnancy or who become pregnant, offer prompt counselling at an experienced PH centre, covering:
  • genetic counselling
  • shared decision making
  • psychological support for patients and families
• Pregnancy terminations should be carried out in specialist PH centres with psychological support for patients and families
• For women who want to have children, consider counselling on adoption or surrogacy with preconception genetic counselling
• Avoid endothelin receptor antagonists and riociguat in pregnancy due to their potential teratogenicity.

Expert Commentary on the Guidance

Professor Raj Thakkar 

Primary Care Cardiology Lead, Oxford AHSN/HIN; Honorary Visiting Professor, Cardiff University, School of Medicine; President Elect, Primary Care Cardiovascular Society; National Primary Care Workstream Co-Lead, Cardiac Transformation Programme, NHS England

PH describes a heterogenous group of conditions that is often poorly understood, underdiagnosed, undercoded, and undertreated. Patients with PH often present to primary care, either overtly or surreptitiously and, as such, it is essential that community clinicians consider PH as a diagnosis when faced with a breathless patient, or when considering complications of long-term conditions such as heart failure, heart valve disease, or chronic lung disease. Failure to diagnose and refer these patients in a timely fashion can have serious life-limiting consequences for the patient, as well as a dramatic impact on their family and indeed the health and social care system at large. Otherwise, these patients are at risk of presenting to the emergency department in extremis. 

There are several subtypes of PH, and—to make matters more complicated for nonspecialists—there are several potential underlying causes, including diseases of the pulmonary arteries themselves (PAH) and lung and cardiac causes. Equally as complicated are the treatment and monitoring regimes for these patients. 

It is certainly not the expectation of this guideline summary that primary care nonspecialists become experts in PH, nor is that required. By the same token, primary care professionals are not expected to make the diagnosis of PH. It is, however, essential that we as community specialists have a working understanding of PH, consider it in our differential diagnosis, refer appropriately, and support patients holistically. Primary care is also essential in the context of care coordination, crisis management, individualised care when patients develop frailty, and palliative care. 

There are some new additions to the 2022 guidance published by the ESC and the ERS that are highly relevant to the primary care audience. One of the key areas to consider is the early diagnosis of PH and timely referral of patients with suspected disease. The guideline describes how these patients may present and the relevant investigations that may be initiated by primary care. There is no substitute for robust history taking and face-to-face clinical examination, but the underlying message here is to consider the diagnosis in the first place. 

It would be my recommendation to carefully consider the guideline and its implications for both your personal practice and your area of work. Presenting the guideline to colleagues and putting in place measures to reduce the risk of missing PH across your patient population should also be considered. Finally, auditing those with a history of breathlessness in whom PH may have been overlooked, or diagnosed but not coded, is certainly worthwhile. 

Useful Resources

For Clinicians

• Connolly M, Kovacs G—Pulmonary hypertension: a guide for GPs(2012)
• National Pulmonary Hypertension Centres of the UK and Ireland—Consensus statement on the management of pulmonary hypertension in clinical practice in the UK and Ireland(2008)
• Galiè N, Hoeper M, Humbert M et al—Guidelines for the diagnosis and treatment of pulmonary hypertension(2009)
• NICE—Chronic obstructive pulmonary disease in over 16s: diagnosis and management (2019)
• Royal Papworth Hospital NHS Foundation Trust—Guidelines for referring patients with pulmonary hypertension (2021)
• NHS England—Commissioning policy: targeted therapies for use in pulmonary hypertension in adults(2015)
• Information on pulmonary hypertension for medical professionals on the Patient website.

For Patients

• Information on pulmonary hypertension from the NHS
• Pulmonary Hypertension Association UK
• Information on pulmonary hypertension from Asthma and Lung UK.