What is the management and treatment of pulmonary hypertension?

Management and Treatment of Pulmonary Hypertension

All patients with suspected pulmonary hypertension must be referred to an expert referral center before initiating therapy, as this is a complex, multidisciplinary condition requiring specialized diagnostic evaluation and treatment algorithms that vary significantly based on PH classification. 1

Diagnostic Confirmation and Classification

• Right heart catheterization is mandatory to confirm the diagnosis, with PH defined as mean pulmonary arterial pressure ≥25 mmHg at rest 1
• Pre-capillary PAH is specifically defined by pulmonary artery wedge pressure ≤15 mmHg and pulmonary vascular resistance >3 Wood units 1
• Vasoreactivity testing during catheterization is essential for all patients with idiopathic, heritable, or drug-induced PAH to identify the 5-10% who may respond to calcium channel blockers 1, 2, 3
• Risk stratification using WHO functional class, 6-minute walk distance, biomarkers, and right ventricular function determines treatment intensity 1, 2

Treatment by PH Group Classification

Group 1: Pulmonary Arterial Hypertension (PAH)

For vasoreactive patients (positive acute vasodilator response):

• High-dose calcium channel blockers are first-line therapy 1, 2, 4
• This applies to only 5-10% of idiopathic PAH patients who demonstrate acute vasodilator response 1

For non-vasoreactive patients, treatment is risk-stratified:

Low-risk patients (WHO FC I-II, 6-minute walk >440m, estimated 1-year mortality <5%):

• Initial oral monotherapy or combination therapy with endothelin receptor antagonists, phosphodiesterase-5 inhibitors, or prostacyclin analogs 1, 2, 3

Intermediate-risk patients (WHO FC III, moderately impaired exercise capacity, estimated 1-year mortality 5-10%):

• Initial oral combination therapy targeting multiple pathways is recommended 1, 3, 4

High-risk patients (WHO FC III-IV, severe right ventricular dysfunction, estimated 1-year mortality >10%):

• Intravenous prostacyclin analogs, specifically epoprostenol, are recommended as they improve survival 3, 5
• Epoprostenol is initiated at 2 ng/kg/min and increased in 2 ng/kg/min increments every 15 minutes until dose-limiting effects occur 5
• Administered via continuous intravenous infusion through a central venous catheter using an ambulatory pump 5

Sequential combination therapy:

• Add additional agents targeting different pathways if inadequate response to initial therapy 1, 3, 4

Group 2: PH Due to Left Heart Disease

• Do not use PAH-specific therapies as they are not recommended and may cause harm 3, 4
• Optimize treatment of the underlying cardiac condition (heart failure, valvular disease) 2, 4

Group 3: PH Due to Lung Disease

• Long-term oxygen therapy to maintain saturation >90% is the primary intervention for COPD-related PH 3, 4
• Do not use PAH-specific vasodilators as they may worsen ventilation-perfusion mismatch and gas exchange 3, 4
• Treat the underlying lung disease optimally 1

Group 4: Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

• Surgical pulmonary endarterectomy in deep hypothermia circulatory arrest is the treatment of choice for operable patients 1, 3, 4
• Operability assessment must be performed by a multidisciplinary expert team at a specialized center 1, 4
• Balloon pulmonary angioplasty is an option for selected patients at experienced centers 1
• Riociguat is approved for inoperable CTEPH or persistent/recurrent PH after surgery 3
• Lifelong anticoagulation is mandatory for all CTEPH patients 3

Group 5: PH with Unclear/Multifactorial Mechanisms

• Treat the underlying disease; treatment of PH is secondary 1
• The principle is "treat the lung, not the pressure" 1
• No randomized controlled trials support PAH-specific drugs in this group 1

General Supportive Measures

Essential for all PAH patients:

• Diuretics for fluid overload with careful monitoring of electrolytes and renal function 2, 3, 4
• Oxygen supplementation to maintain saturation >90% 3, 4
• Immunization against influenza and pneumococcal infection 2
• Supervised exercise training for physically deconditioned patients already on medical therapy 2, 3
• Psychosocial support as part of comprehensive care 2

Critical contraindications:

• Pregnancy must be avoided due to 30-50% mortality risk 2, 3, 4
• ACE inhibitors, angiotensin receptor blockers, and beta-blockers are not recommended unless required for comorbidities 2

Treatment Goals and Monitoring

• The primary goal is achieving and maintaining low-risk status (WHO FC I-II, 6-minute walk distance >440m, preserved right ventricular function) 2, 3, 4
• Follow-up assessments every 3-6 months in stable patients using clinical parameters, exercise capacity, biomarkers, and imaging 3, 4
• Reassess risk stratification at each visit to guide treatment escalation 1, 2

Advanced Therapies

• Lung transplantation should be considered for patients with inadequate response to maximal medical therapy 3, 4
• Atrial septostomy may be considered in highly selected cases at expert centers 6

Critical Pitfalls to Avoid

Never abruptly discontinue PAH-specific medications:

• Patients on chronic prostacyclin therapy can develop rapid right ventricular failure and death if therapy is interrupted 5, 7, 8
• If a patient presents to the emergency department, immediately restart their home PAH medications 8

Avoid fluid overload in right ventricular dysfunction:

• Use vasopressors and inotropes rather than aggressive fluid boluses in hypotensive patients 7, 8
• Excessive preload worsens right ventricular ischemia and function 7

Intubation carries high risk:

• Avoid if possible as positive pressure ventilation reduces venous return and worsens right ventricular function 7
• Hypoxemia and hypercapnia also worsen right-sided heart function, creating a difficult clinical scenario 7, 8

Referral center requirements:

• Adult centers should follow at least 50 PAH/CTEPH patients and receive at least 2 new referrals monthly 1
• Must have multidisciplinary team including PH physicians, specialized nurses, radiologists, and access to intensive care, catheterization laboratory, and surgical services 1