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Diagnostic Approach to Pulmonary Hypertension

Definition and Hemodynamic Criteria

• Pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg (to exclude left heart disease)
• Pulmonary vascular resistance (PVR) ≥ 3 Wood units

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WHO Clinical Classification (5 Groups)

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Step-by-Step Diagnostic Approach

Step 1 - Clinical Suspicion (History & Symptoms)

• Progressive exertional dyspnea (most common presenting symptom)
• Fatigue, weakness
• Angina, syncope or pre-syncope on exertion (suggests low cardiac output)
• Peripheral edema, abdominal distension (right heart failure)

• Connective tissue disease (scleroderma, SLE, MCTD, RA)
• Prior pulmonary embolism or DVT
• HIV infection, cirrhosis/portal hypertension
• Congenital heart disease
• Drug/toxin exposure (anorexigens, methamphetamine, dasatinib)
• Family history of PAH (BMPR2 mutation)

Step 2 - Physical Examination

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Step 3 - Initial Investigations

A. Electrocardiogram (ECG)

• Right axis deviation
• RV hypertrophy (tall R in V1, deep S in V5-V6)
• Right atrial enlargement (P pulmonale: peaked P in II > 2.5 mm)
• Right bundle branch block
• RV strain pattern: S1Q3T3 pattern
• Note: ECG has low sensitivity in early/mild PH

B. Chest X-Ray (CXR)

• Prominent central pulmonary arteries (hilar fullness)
• Peripheral vascular pruning (oligemia at periphery) - characteristic of PAH
• Cardiomegaly, RV enlargement (loss of retrosternal space on lateral view)
• Dilated right descending pulmonary artery (> 16 mm)
• Clues to etiology:
  • Interstitial infiltrates - ILD
  • Hyperinflated lungs - COPD
  • Regional oligemia - CTEPH
  • Plethoric lung fields throughout - congenital left-to-right shunt

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Step 4 - Echocardiography (KEY Non-Invasive Test)

1. Estimated PASP by Doppler of tricuspid regurgitant jet (sensitivity 80-100%; correlation with invasive measurement r = 0.6-0.9)
   • PASP = 4 × (TR velocity)² + RAP
2. RV changes: RV hypertrophy and dilation, reduced RV systolic function, reduced TAPSE (< 1.8 cm = worse survival)
3. Septal flattening (D-shaped LV in systole) - pressure overload pattern
4. Pericardial effusion - marker of severity
5. LV compression from RV dilation
6. Evidence of left heart disease: LV dysfunction, left-sided valvular disease, left atrial enlargement (diastolic dysfunction)

• Low probability: TRV ≤ 2.8 m/s, no other signs
• Intermediate probability: TRV ≤ 2.8 m/s with other signs, OR TRV 2.9-3.4 m/s without signs
• High probability: TRV > 3.4 m/s, OR TRV 2.9-3.4 m/s with other signs

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Step 5 - Laboratory Investigations

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Step 6 - Pulmonary Function Tests (PFTs)

• Spirometry + lung volumes: Exclude obstructive (COPD) or restrictive (ILD) disease
• DLCO:
  • Mildly reduced in PAH
  • Severely reduced (< 40% predicted) = suggests ILD or PAH with venous/capillary involvement (PVOD)
• ABG: Hypoxemia common; hypercapnia suggests hypoventilation

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Step 7 - Ventilation-Perfusion (V/Q) Scan

• Critical test to exclude CTEPH (Group IV)
• Sensitivity for CTEPH is higher than CT-PA alone
• One or more segmental mismatched perfusion defects warrants CT pulmonary angiography or conventional pulmonary angiography
• May be abnormal in PAH with venous/capillary involvement and fibrosing mediastinitis
• A normal V/Q scan essentially excludes CTEPH

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Step 8 - CT Imaging

• HRCT chest: Assess for ILD, emphysema, mediastinal fibrosis, PVOD (ground-glass opacities, septal lines, lymph node enlargement)
• CT pulmonary angiography: Confirms CTEPH if V/Q scan is suspicious; determines surgical feasibility (endarterectomy); should NOT be used as the primary screen for CTEPH
• Additional CT findings in PAH: Dilated main PA (> 29 mm), main PA:Aorta ratio > 1

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Step 9 - Sleep Study

• Nocturnal oximetry / polysomnography if:
  • Symptoms of sleep-disordered breathing (snoring, witnessed apneas, daytime somnolence)
  • Daytime hypercapnia on ABG
  • Nocturnal desaturations on oximetry

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Step 10 - Right Heart Catheterization (RHC) - Gold Standard

• Confirming diagnosis of PH
• Determining hemodynamic severity
• Differentiating group (PAH vs. left heart disease vs. others)
• Guiding therapy
• Performing acute vasodilator testing

• PVR = (mPAP - PAWP) / Cardiac Output
• Serial O2 saturations at each level detect "step-up" (left-to-right shunting)
• PAWP measured at end-expiration to avoid respiratory artifact
• Left heart catheterization may be added to measure LVEDP directly (if PAWP is discrepant or left heart disease is suspected)

• Performed at time of RHC in selected PAH patients
• Agents: inhaled nitric oxide, IV adenosine, or IV epoprostenol
• Positive response (Sitbon criteria): mPAP fall ≥ 10 mmHg to an absolute value ≤ 40 mmHg, with unchanged or increased cardiac output
• ~7% of patients with idiopathic PAH respond positively - these may be treated with calcium channel blockers

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Diagnostic Algorithm (Summary Flowchart)

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Functional Assessment - WHO/NYHA Functional Classification

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Risk Stratification

• WHO FC I or II
• 6MWT distance > 440 m
• Normal or near-normal BNP/NT-proBNP
• No RV failure, no pericardial effusion, normal cardiac index

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Key Points to Remember for Exam

1. Echo is the initial screening test; RHC is the gold standard for confirming diagnosis.
2. V/Q scan is the investigation of choice to screen for CTEPH - CT-PA alone may miss it.
3. New mPAP threshold is > 20 mmHg (updated from the old > 25 mmHg - per 2022 ESC/ERS guidelines).
4. PAH diagnosis requires mPAP > 20 mmHg + PVR ≥ 3 WU + PAWP ≤ 15 mmHg.
5. Acute vasodilator testing identifies the ~7% who may respond to calcium channel blockers.
6. BNP/NT-proBNP reflects RV strain and is key for severity and monitoring.
7. DLCO < 40% suggests ILD or PVOD rather than pure PAH.
8. The S1Q3T3 and RV strain pattern on ECG indicate significant PH.

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• Fishman's Pulmonary Diseases and Disorders, 2-Volume Set (Table 72-6, 72-7)
• The Washington Manual of Medical Therapeutics (Chapter 10, Fig. 10-1)
• Goldman-Cecil Medicine, International Edition (Chapter 69)
• Braunwald's Heart Disease