What are the management options for pulmonary hypertension?

Management of Pulmonary Hypertension

Critical First Step: Accurate Classification

The absolute priority in managing pulmonary hypertension is identifying which WHO clinical group is responsible for the presentation, as each group demands a fundamentally different treatment approach and carries distinct prognoses. 1

The 2015 ESC/ERS guidelines define pulmonary hypertension as mean pulmonary arterial pressure ≥25 mmHg at rest on right heart catheterization, with normal mean PAP being 14 ± 3 mmHg. 1 The five WHO groups are:

• Group 1: Pulmonary arterial hypertension (PAH) - characterized by pre-capillary PH with PAWP ≤15 mmHg and PVR >3 Wood units 1
• Group 2: PH due to left heart disease (most common) 2, 3
• Group 3: PH due to lung disease/hypoxia 2
• Group 4: Chronic thromboembolic pulmonary hypertension (CTEPH) 2
• Group 5: PH with unclear/multifactorial mechanisms 1

Essential Diagnostic Workup

Right heart catheterization is mandatory to confirm diagnosis, establish classification, determine severity, and guide therapy. 4 Additional critical testing includes:

• Vasoreactivity testing with short-acting agents (mandatory for idiopathic PAH to identify calcium channel blocker responders) 4
• Ventilation-perfusion scanning to exclude CTEPH 4
• Hemodynamic assessment including cardiac index, pulmonary vascular resistance, and right atrial pressure 5

All patients must be managed at specialized pulmonary hypertension centers with multidisciplinary expertise. 4

Treatment Algorithm for Group 1 PAH

High-Risk Patients (WHO Functional Class IV, Hypotension, Right Heart Failure)

Intravenous epoprostenol is the first-line therapy for high-risk PAH patients, as it is the only medication proven to reduce mortality. 4, 6

• Start at 2 ng/kg/min and increase in 2 ng/kg/min increments every 15 minutes until dose-limiting effects occur 5
• Administer via continuous infusion through a central venous catheter using an ambulatory pump 5
• In the pivotal trial, 8 of 40 patients (20%) receiving conventional therapy died at 12 weeks versus 0 of 41 receiving epoprostenol (p=0.003) 5
• Average maintenance dose is approximately 9.2 ng/kg/min 5

For hypotensive PAH patients (systolic BP <90 mmHg), inotropic support is the cornerstone rather than aggressive fluid resuscitation, as the failing right ventricle cannot tolerate volume overload. 6

Vasoreactive Patients (Positive Acute Vasodilator Response)

High-dose calcium channel blockers are first-line therapy for the small subset of patients demonstrating favorable acute vasodilator response. 4 Regular follow-up is essential to confirm sustained response. 4

WHO Functional Class II Patients

Oral phosphodiesterase-5 inhibitors (sildenafil) or endothelin receptor antagonists are recommended as initial therapy. 4 These represent the foundation of treatment for lower-risk patients.

WHO Functional Class III Patients

Either oral therapies or prostacyclin analogues should be selected based on comprehensive risk assessment. 4 The 2015 ESC/ERS guidelines emphasize that combination therapy may be appropriate for patients not responding adequately to monotherapy. 4

Treatment for Group 4 CTEPH

Surgical pulmonary endarterectomy is the treatment of choice for chronic thromboembolic pulmonary hypertension. 2 For inoperable patients, riociguat (a soluble guanylate cyclase stimulator) has proven efficacy, and balloon pulmonary angioplasty is emerging as an option. 1, 2

Treatment for Groups 2 and 3 PH

Pulmonary vasodilator treatment has not been proven safe or effective for PH due to left heart disease or lung disease. 2 Management should focus on treating the underlying cardiac or pulmonary condition. 2, 3

Supportive Care Measures

• Diuretics for fluid overload with careful monitoring of electrolytes and renal function 4, 6
• Oxygen supplementation to maintain arterial oxygen saturation >90% 4, 6
• Anticoagulation in most PAH patients (particularly idiopathic PAH) 1
• Avoid abrupt dose reductions or withdrawal of PAH-specific therapies, as this can precipitate acute decompensation 5

Monitoring and Treatment Goals

Follow-up assessments every 3-6 months in stable patients are recommended. 4 The treatment goal is achieving and maintaining low-risk status, defined by:

• 6-minute walk distance >440 meters 4
• WHO Functional Class I-II 4
• Normal or near-normal right ventricular function 4

Adjustments to therapy should be made based on clinical response and hemodynamic parameters. 4

Advanced Therapies and Transplantation

Patients with severe disease failing maximal medical therapy should be referred for lung transplantation evaluation. 4 Veno-arterial ECMO may bridge awake end-stage patients to transplantation. 6

Critical Pitfalls to Avoid

• Never use PAH-specific vasodilators in Group 2 or 3 PH without expert consultation, as they may worsen outcomes 2
• Never give aggressive fluid boluses to hypotensive PAH patients with right ventricular failure 6, 7
• Never discontinue chronic PAH medications abruptly, as patients can rapidly deteriorate and die 6, 7
• Avoid intubation when possible in decompensated PAH, as positive pressure ventilation worsens right ventricular function 7