What are the diagnostic steps and management strategies for pulmonary hypertension (PH)?

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Diagnosis and Management of Pulmonary Hypertension

The diagnosis of pulmonary hypertension requires a stepwise approach starting with echocardiography as the first-line non-invasive investigation, followed by right heart catheterization to confirm the diagnosis with a mean pulmonary arterial pressure ≥25 mmHg. 1

Definition and Classification

Pulmonary hypertension (PH) is defined as:

  • Mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest as assessed by right heart catheterization 1
  • More recent guidelines have lowered this threshold to >20 mmHg 2

PH is classified into five clinical groups:

  1. Pulmonary arterial hypertension (PAH)
  2. PH due to left heart disease
  3. PH due to lung diseases and/or hypoxia
  4. Chronic thromboembolic PH (CTEPH)
  5. PH with unclear/multifactorial mechanisms

Diagnostic Algorithm

Step 1: Clinical Suspicion

Look for:

  • Breathlessness without obvious heart/lung disease
  • Increasing dyspnoea unexplained by underlying disease
  • Associated symptoms: fatigue, weakness, angina, syncope, abdominal distension 1
  • Physical signs: left parasternal lift, accentuated pulmonary component of S2, tricuspid regurgitation murmur, right ventricular S3 1
  • Advanced signs: jugular vein distension, hepatomegaly, peripheral edema, ascites, central cyanosis 1

Step 2: Initial Non-invasive Evaluation

  • Echocardiography: First-line investigation to estimate probability of PH 1

    • Assess right ventricular size and function
    • Estimate right ventricular systolic pressure
    • Evaluate for left heart disease
    • Look for congenital heart defects
  • Additional tests:

    • ECG: May show right ventricular hypertrophy, right axis deviation
    • Chest radiograph: Enlarged central pulmonary arteries, right heart enlargement
    • Pulmonary function tests with DLCO: Essential for initial evaluation 1
    • Arterial blood gases: To assess oxygenation and ventilation

Step 3: Determine PH Group

  • Ventilation/perfusion (V/Q) scan: Mandatory to rule out CTEPH 1

    • Normal or subsegmental "patchy" defects suggest PAH
    • Multiple segmental perfusion defects suggest CTEPH
  • High-resolution CT: Evaluate for lung disease and PVOD 1

  • Pulmonary angiography: Consider for suspected CTEPH 1

  • Blood tests: Complete biochemistry, hematology, immunology, HIV, thyroid function 1

  • Abdominal ultrasound: Screen for portal hypertension 1

Step 4: Confirmation with Right Heart Catheterization

  • Mandatory for definitive diagnosis 1, 3
  • Measures:
    • Mean pulmonary artery pressure (mPAP ≥25 mmHg)
    • Pulmonary artery wedge pressure (PAWP ≤15 mmHg in pre-capillary PH)
    • Pulmonary vascular resistance (PVR >3 Wood units in PAH)
    • Cardiac output
  • Acute vasoreactivity testing: Required for idiopathic, heritable, and drug-induced PAH to identify potential responders to calcium channel blockers 3

Risk Assessment and Severity Evaluation

Risk stratification into low, intermediate, or high-risk categories based on:

  • WHO functional class
  • Exercise capacity (6-minute walk distance)
  • BNP/NT-proBNP levels
  • Echocardiographic parameters
  • Hemodynamic parameters 1
Risk Parameter Low Risk (<5%) Intermediate Risk (5-10%) High Risk (>10%)
Clinical signs of RV failure Absent Absent Present
WHO functional class I, II III IV
6-minute walk distance >440m 165-440m <165m
BNP <50 ng/L 50-300 ng/L >300 ng/L
NT-proBNP <300 ng/L 300-1400 ng/L >1400 ng/L
Imaging (echo, CMR) RA area <18 cm², no effusion RA area 18-26 cm², minimal effusion RA area >26 cm², pericardial effusion
Hemodynamics CI ≥2.5 L/min/m², RAP <8 mmHg CI 2.0-2.4 L/min/m², RAP 8-14 mmHg CI <2.0 L/min/m², RAP >14 mmHg

Management Strategy

General Measures

  • Avoid pregnancy (high mortality risk) 1
  • Immunization against influenza and pneumococcal infection 1, 3
  • Psychosocial support 1, 3
  • Supervised exercise training for deconditioned patients 1, 3
  • In-flight oxygen for WHO FC III/IV patients 3

Treatment Based on PH Group

Group 1 (PAH)

  • Acute vasoreactivity testing to identify responders to calcium channel blockers 3
  • Treatment algorithm based on risk assessment:
  1. Low/Intermediate Risk (WHO FC II-III):

    • Initial combination therapy with ambrisentan and tadalafil as first choice 3
    • Alternative: Monotherapy with endothelin receptor antagonist, PDE-5 inhibitor, or soluble guanylate cyclase stimulator 3
  2. High Risk (WHO FC IV):

    • Initial combination therapy including IV prostacyclin analog (preferably IV epoprostenol) 3, 4
    • IV epoprostenol has demonstrated reduced 3-month mortality 3, 4
  3. Inadequate Response:

    • Add second class of PAH therapy
    • Consider triple combination therapy for progressive disease 3
    • Consider lung transplantation after inadequate response to maximal therapy 3

Group 2 (PH due to Left Heart Disease)

  • Focus on treating underlying heart condition
  • PAH-specific therapies not recommended 3

Group 3 (PH due to Lung Diseases)

  • Optimize treatment of underlying lung disease
  • Long-term oxygen therapy for hypoxemic patients
  • PAH-specific drugs not recommended 3

Group 4 (CTEPH)

  • Pulmonary endarterectomy is treatment of choice
  • Balloon pulmonary angioplasty for inoperable cases
  • Medical therapy with riociguat for inoperable CTEPH 3

Follow-up and Monitoring

  • Regular assessment every 3-6 months for stable patients 3
  • Evaluate multiple parameters:
    • Clinical assessment and WHO functional class
    • Exercise capacity (6-minute walk test)
    • BNP/NT-proBNP levels
    • Echocardiography
    • Hemodynamics when indicated

Common Pitfalls to Avoid

  • Delayed diagnosis due to non-specific symptoms 3
  • Misclassification of PH group leading to inappropriate treatment 3
  • Failure to refer to specialized PH centers 3
  • Inadequate follow-up and risk assessment 3
  • Underutilization of combination therapy 3
  • Failure to recognize treatment failure early enough to escalate therapy 3
  • Using PAH-specific therapies in PH groups where they are not indicated or potentially harmful 3
  • Riociguat is contraindicated in combination with PDE-5 inhibitors 3

Referral to Expert Centers

Referral to specialized pulmonary hypertension centers is strongly recommended for:

  • Confirmation of diagnosis
  • Comprehensive evaluation
  • Initiation of advanced therapies
  • Ongoing management and follow-up 1, 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Pulmonary hypertension.

Nature reviews. Disease primers, 2024

Guideline

Pulmonary Arterial Hypertension Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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