Nonspecific symptoms can lead to delay in diagnosis1-3
The diagnostic process begins after clinical suspicion based on symptoms and physical exam, and typically includes several different types of tests to help narrow down potential diagnoses—although an RHC is the only test that can definitely diagnose PAH. However, symptoms of right-sided heart dysfunction due to PAH are nonspecific, which can lead to delayed evaluation and diagnosis.1-4 Delayed diagnosis is common; thus patients often are diagnosed at FC III or IV.5
Symptom onset
Symptoms are related to right ventricular dysfunction6
Typical presentation includes exertional symptoms7
- Dyspnea
- Fatigue
Due to nonspecific symptoms, the time between symptom onset and diagnosis is often >2 years4
Diagnosis
As disease progresses, symptoms start to occur at rest as the RV fails to compensate against the increased PVR7
- Syncope
- Lower extremity edema
- Abdominal distention
- Angina
Common misdiagnoses or comorbid conditions that delay diagnosis8,9:
- PH-LHD
- COPD
- Asthma
- Obesity
PAH diagnostic criteria
Clinical characteristics of PAH are nonspecific1,2 and are mainly related to progressive RV dysfunction6
PAH diagnosis
A series of tests may be performed to confirm diagnosis and identify an optimal therapeutic approach. Diagnosis begins with a medical assessment that provides information about risk factors that may predispose a patient toward a particular classification of PAH as well as facilitate decisions about further diagnostic testing.10
Elements of PAH diagnosis10:
- Signs and symptoms
- Physical examination
- Laboratory tests
- Chest x-ray
- Echocardiography
- RHC
- Dizziness and/or lightheadedness9
- Presyncope/Syncope9
- Cough9
- Rapid, hard, or irregular heartbeat (palpitations)9
- Chest pain (angina)9
- Dyspnea on exertion9
- Dyspnea at rest9
- Swollen abdomen (ascites)9
- Swollen legs (edema)9
- Swollen ankles (edema)9
Feeling tired or worn out (fatigue)9
Diagnostic investigations
Cardiac
- EKG
- Echo
- Cardiac MRI
Respiratory
- Pulmonary function test
- Arterial blood gases
- Overnight oximetry
Blood
- PAH serology (eg, antinuclear antibodies)
- Genetics
Imaging
- Chest radiograph
- V/Q scan
- High-resolution CT
- CTPA
- MRI
- Abdominal ultrasound
- CT pulmonary angiography
- FDG-PET
Exercise
- CPET
- 6-minute walk test (see downloadable how-to guide)
Get your guide to learn more about administering the 6‑minute walk test
Download How-To GuidePhysical exam findings7
Extracardiac exam findings
- Jugular vein distension
- Hepatomegaly
- Peripheral edema
- Ascites
- Lung examination is usually normal
Cardiac findings that reflect RV functional and structural changes
- Left parasternal shift
- Loud pulmonary component of the second heart sound
- Pansystolic murmur of tricuspid regurgitation
- Diastolic murmur of pulmonary insufficiency
- RV third heart sound
Echocardiography evaluation
The Echo can be used to assess variables of pulmonary hypertension. However, RHC is required to confirm diagnosis.4,11
Probability of PH based on Echo findings12
Probability of PH based on Echo findings12
Low:
- Peak tricuspid regurgitant velocity is ≤2.8 m/s or not measurable with no presence of other echocardiographic signs suggestive of pulmonary hypertension
Intermediate:
- Peak tricuspid regurgitant velocity is ≤2.8 m/s or not measurable with presence of other echocardiographic signs suggestive of pulmonary hypertension
- Peak tricuspid regurgitant velocity is 2.9 to 3.4 m/s or with no presence of other echocardiographic signs suggestive of pulmonary hypertension
High:
- Peak tricuspid regurgitant velocity is 2.9 to 3.4 m/s with presence of other echocardiographic signs suggestive of pulmonary hypertension
- Peak tricuspid regurgitant velocity is >3.4 m/s
Echo findings suggestive of RV dysfunction in PH
The Echos above show the progressive dilation of the RV and RA in PAH. In end-stage PAH, the RV may cause the interventricular septum to bow outward and compress the LV. Other signs of RV dysfunction that can be found on Echo include13,14:
- Presence of pericardial effusion
- Ratio between RV and LV basal diameter >1
- Loss of IVC inspiratory collapse
- Tricuspid regurgitation
- Increased RV systolic dysfunction
- TAPSE
RHC is required for a definitive diagnosis of WHO Group 1 PAH4
The 2022 ESC/ERS Guidelines recommend that patients with unexplained exertional dyspnea, syncope, and/or signs of RV dysfunction should be assessed for suspected PH/PAH using transthoracic echocardiography with a confirmed diagnosis ultimately dependent on hemodynamic results obtained from RHC.4
- PAWP ≤15 mm Hg
- PVR* >2 WU
- mPAP >20 mm Hg
- Normal12: 14 ± 3 mm Hg
Hemodynamic values obtained during RHC4:
- Confirm diagnosis of PAH
- Evaluate severity of PAH
- Assess congenital heart defects
- Exclude left-side heart disease
- Assess response to vasodilator challenge
- Assess key hemodynamic parameters
- Guide treatment decisions
Diagnostic algorithm
The diagnostic process begins after clinical suspicion of PH based on symptoms and physical examination.4
Although many tests can hone suspicion of PAH, an RHC must be performed to definitively diagnose PAH. Current treatment guidelines recommend that PAH patients be evaluated at a PAH center for confirmation.4
Download the diagnostic algorithm flowchart
A guide that goes through sequential steps of testing and decision making to help reach a possible diagnosis of PAH.
Baseline risk assessment is critical
Treatment guidelines recommend calculating patient risk status at baseline to inform prognosis and initial treatment decisions. The 2022 ESC/ERS Guidelines further recommend risk assessment be performed as often as every 3 months; routine risk assessment can help you adjust your management plan according to risk-based treatment algorithms.4,12,15
An objective, multiparameter risk assessment is required because no single data point (eg, NT-proBNP) provides sufficient prognostic information on its own.12 Therefore, risk assessments should incorporate information derived from several sources, including clinical assessment, exercise testing, laboratory testing, Echo, and RHC.4