How to differentiate between pre-capillary and post-capillary pulmonary hypertension?

Differentiating Pre-Capillary from Post-Capillary Pulmonary Hypertension

The definitive method to differentiate between pre-capillary and post-capillary pulmonary hypertension is right heart catheterization with measurement of pulmonary arterial wedge pressure (PAWP) ≤15 mmHg for pre-capillary PH and >15 mmHg for post-capillary PH. 1

Hemodynamic Definitions

Pre-Capillary Pulmonary Hypertension

• Mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest
• PAWP ≤15 mmHg
• Pulmonary vascular resistance (PVR) ≥3 Wood units
• Includes clinical groups:
  • Group 1: Pulmonary arterial hypertension (PAH)
  • Group 3: PH due to lung diseases/hypoxia
  • Group 4: Chronic thromboembolic PH (CTEPH)
  • Group 5: PH with unclear/multifactorial mechanisms

Post-Capillary Pulmonary Hypertension

• mPAP ≥25 mmHg at rest
• PAWP >15 mmHg
• Can be further classified as:
  • Isolated post-capillary PH (Ipc-PH): Diastolic pressure gradient (DPG) <7 mmHg and/or PVR ≤3 WU
  • Combined pre-capillary and post-capillary PH (Cpc-PH): DPG ≥7 mmHg and/or PVR >3 WU
• Corresponds to clinical Group 2: PH due to left heart disease

Diagnostic Algorithm

1. Right Heart Catheterization (RHC): Gold standard for diagnosis and differentiation 1

   • Directly measures mPAP, PAWP, and allows calculation of PVR
   • Essential for accurate classification

2. Calculating Key Hemodynamic Parameters:

   • PVR = (mPAP - PAWP) / Cardiac Output
   • Diastolic Pressure Gradient (DPG) = Diastolic PAP - mean PAWP
   • Transpulmonary Gradient (TPG) = mPAP - PAWP

3. Fluid Challenge Test:

   • In cases with borderline PAWP (12-15 mmHg) or suspected occult left heart disease
   • Administration of 500 mL saline over 10 minutes
   • Helps unmask left heart disease that may be compensated at rest 2

Non-Invasive Indicators

While RHC remains the gold standard, certain non-invasive findings can suggest the type of PH:

1. Echocardiography:

   • Atrial volume ratio (right atrial volume/left atrial volume):

     • 1.0 suggests pre-capillary PH

     • <0.5 suggests post-capillary PH 3
   • Left ventricular dysfunction or significant valvular disease suggests post-capillary PH
   • Right ventricular hypertrophy with normal left heart suggests pre-capillary PH

2. ECG and Biomarkers:

   • Absence of right ventricular strain pattern on ECG and NT-proBNP <80 pg/mL makes pre-capillary PH unlikely 4

3. Cardiac MRI:

   • Can assess right ventricular function, pulmonary artery flow patterns
   • MPA pulsatility >40% has high sensitivity and specificity for mild PH 1

Clinical Implications

The distinction between pre-capillary and post-capillary PH is crucial for treatment decisions:

• Pre-capillary PH: May benefit from PAH-specific therapies (phosphodiesterase-5 inhibitors, endothelin receptor antagonists, prostanoids) 2

• Post-capillary PH: PAH-specific therapies are not recommended; treatment should focus on underlying left heart disease 1, 2

• Combined pre- and post-capillary PH: Has the worst prognosis among PH groups and requires careful management of both components 5

Pitfalls to Avoid

1. Relying solely on echocardiography: Cannot reliably distinguish between pre- and post-capillary PH

2. Overlooking diastolic dysfunction: Patients with normal ejection fraction may still have post-capillary PH due to diastolic dysfunction

3. Misinterpreting borderline PAWP values: Values between 12-15 mmHg require careful assessment, possibly with fluid challenge

4. Failing to recognize combined forms: Some patients have features of both pre- and post-capillary PH, representing a pathophysiological continuum 6

5. Not accounting for volume status: Diuretic therapy may "pseudo-normalize" PAWP in patients with left heart disease 1

Remember that accurate differentiation between pre-capillary and post-capillary PH is essential for appropriate treatment selection and has significant implications for patient outcomes in terms of morbidity, mortality, and quality of life.