What are the key considerations and management strategies for a patient with suspected pulmonary hypertension?

Pulmonary Hypertension: Must-Know Clinical Essentials

Definition and Diagnosis

Pulmonary hypertension is defined as mean pulmonary arterial pressure ≥25 mmHg at rest on right heart catheterization, with normal mean PAP being 14 ± 3 mmHg. 1

• Right heart catheterization is mandatory to confirm diagnosis, establish specific classification, determine severity, and guide therapy—echocardiography alone cannot make a definitive diagnosis 1, 2
• Pulmonary arterial hypertension (PAH) specifically requires pre-capillary PH with pulmonary artery wedge pressure ≤15 mmHg AND pulmonary vascular resistance >3 Wood units 1
• Transthoracic echocardiography is the key initial screening tool to estimate pulmonary pressure and assess right ventricular function 1, 3
• Ventilation-perfusion scanning is essential to exclude chronic thromboembolic pulmonary hypertension (CTEPH)—a normal scan effectively rules out CTEPH 1, 3

WHO Clinical Classification (5 Groups)

Understanding the classification is critical because each group requires completely different management strategies 1, 3:

• Group 1: Pulmonary Arterial Hypertension (idiopathic, heritable, drug-induced, or associated with connective tissue disease, HIV, portal hypertension, congenital heart disease)
• Group 2: PH due to left heart disease (systolic/diastolic dysfunction, valvular disease)
• Group 3: PH due to lung disease and/or hypoxia (COPD, interstitial lung disease)
• Group 4: Chronic thromboembolic pulmonary hypertension (CTEPH)
• Group 5: PH with unclear/multifactorial mechanisms

Essential Diagnostic Workup

When PH is suspected, the following must be performed systematically 1, 3:

• Echocardiography with Doppler to estimate right ventricular systolic pressure, assess right atrial/ventricular enlargement, pericardial effusion, and evaluate for left heart disease or intracardiac shunting 1
• Pulmonary function tests with DLCO to evaluate for underlying lung disease 1
• Ventilation-perfusion scan (not CT angiography) as the primary test to exclude CTEPH 1
• Testing for connective tissue disease and HIV in all unexplained PAH cases 1
• 6-minute walk test to assess functional capacity and disease severity 1
• Right heart catheterization for definitive hemodynamic confirmation and vasoreactivity testing 1, 2

Critical Management Principles

Referral to Expert Centers

All patients with PAH or CTEPH must be referred to specialized pulmonary hypertension centers with multidisciplinary expertise—centers should follow at least 50 PAH/CTEPH patients and receive at least 2 new referrals monthly 1, 2

Vasoreactivity Testing

Acute vasoreactivity testing with short-acting agents (IV epoprostenol, adenosine, or inhaled nitric oxide) is mandatory for all patients with idiopathic PAH to identify the small subset (~5-10%) who may respond to calcium channel blockers 1, 4

• A positive response is defined as a fall in mean PAP of ≥10 mmHg to ≤40 mmHg with increased or unchanged cardiac output 1
• Only vasoreactive patients should receive high-dose calcium channel blockers—empiric use without documented vasoreactivity is contraindicated 1, 5

Treatment Strategy Based on Risk Stratification

The treatment approach is algorithmically structured based on prognostic risk assessment 1, 4:

Low-risk patients (1-year mortality <5%): WHO Functional Class I-II, 6-minute walk distance >440m, normal or near-normal right ventricular function 1, 4

Intermediate-risk patients (1-year mortality 5-10%): WHO Functional Class III, moderately impaired exercise capacity, signs of right ventricular dysfunction 4

High-risk patients (1-year mortality >10%): WHO Functional Class III-IV, progressive disease, severe right ventricular dysfunction or failure 4

Pharmacological Treatment for PAH

For high-risk PAH patients, intravenous epoprostenol is first-line therapy as it is the only medication proven to reduce mortality 2, 6

• Epoprostenol is initiated at 2 ng/kg/min and increased in 2 ng/kg/min increments every 15 minutes until dose-limiting effects occur 6
• Administered via continuous IV infusion through a central venous catheter using an ambulatory pump 6
• Never abruptly discontinue or reduce dose—can cause fatal rebound pulmonary hypertension 6

For vasoreactive patients, high-dose calcium channel blockers are first-line therapy 2, 5

For WHO Functional Class II patients, oral phosphodiesterase-5 inhibitors or endothelin receptor antagonists are initial therapy 2, 5

For WHO Functional Class III patients, consider oral therapies or prostacyclin analogues depending on risk assessment 5

Treatment Goals

The primary goal is achieving and maintaining low-risk status, specifically 1, 2, 4:

• WHO Functional Class I-II 1
• 6-minute walk distance >440 meters (though lower values may be acceptable in elderly or patients with comorbidities) 1, 2
• Normal or near-normal right ventricular function 2, 4
• Follow-up assessments every 3-6 months in stable patients 2, 5

Essential Supportive Care

Diuretics are recommended for fluid overload with careful monitoring of electrolytes and renal function 2, 5

Oxygen supplementation should maintain arterial oxygen saturation >90% at all times 1, 2, 5

Anticoagulation with warfarin is recommended for idiopathic PAH patients 1, 2

Immunization against influenza and pneumococcal infection is mandatory 1, 4

Critical Warnings and Contraindications

Pregnancy must be avoided—it carries 30-50% mortality risk in PAH patients 1, 4

Excessive physical activity that leads to distressing symptoms is contraindicated, though supervised exercise training should be considered for deconditioned patients on medical therapy 1

For air travel, in-flight oxygen should be considered for WHO Functional Class III-IV patients or those with arterial oxygen pressure <60 mmHg 1

In elective surgery, epidural anesthesia is preferred over general anesthesia whenever possible 1

Psychosocial support is essential given the significant psychological, social, and emotional impact of this life-threatening disease 1

Special Considerations for CTEPH

Surgical pulmonary endarterectomy is the treatment of choice for eligible CTEPH patients 3

Balloon pulmonary angioplasty should only be performed in experienced, high-volume CTEPH centers 1

Riociguat is the only licensed targeted therapy for inoperable or persistent/recurrent CTEPH 3

Group 2 and 3 PH Management

For PH due to left heart disease or lung disease, treat the underlying condition—the axiom is "treat the lung, not the pressure" 1, 3

PAH-approved drugs are not recommended for Group 2 or 3 PH and may cause harm 1