What are the signs, symptoms, and diagnostic approaches for pulmonary hypertension?

Signs, Symptoms, and Diagnosis of Pulmonary Hypertension

Clinical Presentation

The most common presenting symptom of pulmonary hypertension is unexplained dyspnea on exertion, which appears disproportionate to any underlying disease and should prompt immediate diagnostic evaluation. 1

Cardinal Symptoms

• Dyspnea on exertion is the predominant symptom, occurring in 60% of patients at presentation and representing the earliest manifestation 2, 3
• Syncope, particularly with exertion, indicates severely compromised cardiac output and advanced disease 2, 1
• Fatigue and weakness result from decreased cardiac output and are common presenting complaints 2, 4
• Chest pain occurs due to right ventricular ischemia or compression of the left main coronary artery by dilated pulmonary arteries 2, 4
• Palpitations may indicate underlying arrhythmias 2

Physical Examination Findings

Early Disease Signs:

• Left parasternal lift indicates right ventricular hypertrophy and pressure overload in 90% of cases 3
• Accentuated pulmonary component of second heart sound (loud P2) at the left second intercostal space is present in 90% of idiopathic PAH patients 3
• Right ventricular S4 gallop (apical S4) is audible in 38% of PAH patients, reflecting high right ventricular filling pressure and decreased ventricular compliance 3
• Elevated jugular venous pressure with prominent "a" waves indicates high right ventricular filling pressure 3

Advanced Disease Signs:

• Elevated jugular venous pressure with prominent V waves indicates severe right ventricular failure 4
• Hepatomegaly and pulsatile liver from hepatic congestion 4
• Peripheral edema and ascites from right heart failure 4
• Cool extremities due to low cardiac output and peripheral vasoconstriction 4
• Right ventricular S3 gallop in advanced failure 4
• Hypotension and diminished pulse pressure in severe cases 4

Important Clinical Pearls

• The absence of orthopnea and paroxysmal nocturnal dyspnea argues against left-sided heart disease as the cause of symptoms 3
• Digital clubbing should raise suspicion for pulmonary veno-occlusive disease, congenital heart disease, interstitial lung disease, or liver disease rather than idiopathic PAH 4

Diagnostic Algorithm

Step 1: Initial Screening Tests

When PH is suspected based on symptoms and physical examination, obtain:

• Transthoracic Doppler echocardiography is the first-line non-invasive diagnostic test with sensitivity of 79-100% and specificity of 68-98% for detecting moderate PH 1
• Electrocardiogram demonstrates right axis deviation (79% sensitive) and right ventricular hypertrophy (87% sensitive in established PAH) 3
• Chest radiograph may show enlarged pulmonary arteries and right heart chambers 1
• Pulmonary function tests with DLCO to assess for underlying lung disease 1
• Arterial blood gas analysis to evaluate gas exchange 1

Step 2: Echocardiographic Assessment

Echocardiography must evaluate:

• Estimated pulmonary artery systolic pressure using tricuspid regurgitation velocity 1, 3
• Right ventricular size and function 3
• Structural left heart abnormalities including valvular disease, left atrial enlargement, and left ventricular dysfunction 1
• Tricuspid regurgitation severity 3

Step 3: Mandatory Screening for CTEPH

• Ventilation/perfusion (V/Q) or perfusion lung scan is mandatory to exclude chronic thromboembolic PH, as this is a potentially curable form 1
• Contrast CT angiography of the pulmonary artery is recommended if CTEPH is suspected to delineate complete obstruction, bands, webs, and intimal irregularities 1

Step 4: High-Resolution CT Chest

• High-resolution CT provides critical information for identifying interstitial lung disease or emphysema (Group 3 PH) and detecting pulmonary veno-occlusive disease 1

Step 5: Definitive Diagnosis with Right Heart Catheterization

Right heart catheterization is mandatory to confirm the diagnosis of PH and define hemodynamic characteristics. 1, 3

Hemodynamic Diagnostic Criteria:

• Mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest defines pulmonary hypertension 2
• Pulmonary arterial hypertension (PAH) requires mPAP ≥25 mmHg, pulmonary arterial wedge pressure ≤15 mmHg, and pulmonary vascular resistance >3 Wood units 2
• Cardiac index should be measured to assess cardiac output 2

Clinical Classification

Once PH is confirmed hemodynamically, classify into one of five clinical groups 1:

1. Pulmonary arterial hypertension (PAH) - includes idiopathic, heritable, drug-induced, and associated forms (connective tissue disease, HIV, portal hypertension, congenital heart disease, schistosomiasis) 2
2. PH due to left heart disease - systolic dysfunction, diastolic dysfunction, valvular disease 2
3. PH due to lung diseases and/or hypoxia - COPD, interstitial lung disease, sleep-disordered breathing 2
4. Chronic thromboembolic PH (CTEPH) and other pulmonary artery obstructions 2
5. PH with unclear/multifactorial mechanisms - hematological disorders, systemic disorders, metabolic disorders 2

Indications for Immediate Referral to PH Center

Immediate referral to a specialized PH center is indicated for: 1

• Syncope, especially with exertion
• Rapidly progressing symptoms
• Clinical or echocardiographic signs of severe PH and/or severe right ventricular dysfunction

Critical Diagnostic Pitfalls

• Open or thoracoscopic lung biopsy is contraindicated in patients with PAH due to high risk and lack of diagnostic benefit 1
• Exercise-induced PH lacks sufficient data to support its definition as a diagnostic entity 2
• Normal mean PAP at rest is 14 ± 3 mmHg, with upper limit of normal of 20 mmHg; the significance of mean PAP between 21-24 mmHg remains unclear 2