Diagnosis and Treatment of Pulmonary Hypertension
Diagnostic Approach
In patients with suspected pulmonary hypertension, begin with Doppler echocardiography as the initial screening test, followed by right heart catheterization to confirm diagnosis, establish specific classification, and guide therapy. 1
Initial Screening and Evaluation
Perform transthoracic echocardiography as the first-line noninvasive test to estimate pulmonary artery pressure and assess right ventricular function, though recognize it may be imprecise in determining actual pressures compared to invasive evaluation 1, 2
Obtain ventilation-perfusion (V/Q) scanning in all patients with confirmed or suspected PH to exclude chronic thromboembolic pulmonary hypertension (CTEPH), as a normal scan effectively rules out CTEPH 1
Test for connective tissue disease and HIV infection in patients with unexplained pulmonary arterial hypertension 1
Perform pulmonary function tests and chest imaging to identify underlying lung disease that may contribute to PH 1, 2
Definitive Diagnosis
Right heart catheterization is mandatory to confirm the presence of PH (mean PAP ≥25 mmHg), establish the specific diagnosis (pre-capillary vs. post-capillary), determine severity, and guide therapeutic decisions 1, 3
Pulmonary hypertension is defined hemodynamically as mean pulmonary arterial pressure ≥25 mmHg at rest, with pre-capillary PH characterized by pulmonary wedge pressure ≤15 mmHg 1
Classify PH into one of five WHO groups based on hemodynamics and underlying etiology: Group 1 (pulmonary arterial hypertension), Group 2 (left heart disease), Group 3 (lung disease), Group 4 (CTEPH), or Group 5 (unclear/multifactorial mechanisms) 1, 4, 5
Critical Pitfall to Avoid
Do not rely on echocardiography alone for diagnosis or treatment decisions—right heart catheterization is essential before initiating PAH-specific therapy 1, 3
Treatment Approach for Pulmonary Arterial Hypertension (Group 1)
All patients with confirmed PAH should be referred immediately to a specialized pulmonary hypertension center with expertise in diagnosis and management before initiating therapy. 1, 6, 7
Vasoreactivity Testing
Perform acute vasoreactivity testing in all patients with idiopathic PAH, heritable PAH, and drug-induced PAH using short-acting agents (IV epoprostenol, adenosine, or inhaled nitric oxide) 1, 3
Define a positive vasoreactive response as a fall in mean pulmonary artery pressure of at least 10 mmHg to ≤40 mmHg with increased or unchanged cardiac output 1
Initiate high-dose calcium channel blockers only in vasoreactive patients (approximately 5-10% of idiopathic PAH) who demonstrate a favorable acute response and have no right heart failure 1, 6
Risk Stratification-Based Treatment
Treatment selection must be guided by comprehensive risk assessment using WHO functional class, 6-minute walk distance, biomarkers (BNP/NT-proBNP), and right ventricular function 6, 3, 7
Low-Risk Patients (estimated 1-year mortality <5%)
- Present in WHO functional class I-II with 6-minute walk distance >440m and preserved right ventricular function 6, 3
- Initiate oral combination therapy targeting multiple pathways as first-line treatment 3, 7
- Treatment goal is to achieve and maintain low-risk status 6, 3
Intermediate-Risk Patients (estimated 1-year mortality 5-10%)
- Present in WHO functional class III with moderately impaired exercise capacity and signs of right ventricular dysfunction 6, 3
- Begin with oral combination therapy and escalate to sequential combination therapy if inadequate response 3, 7
High-Risk Patients (estimated 1-year mortality >10%)
- Present in WHO functional class III-IV with progressive disease and severe right ventricular dysfunction or failure 6, 3
- Initiate intravenous prostacyclin analogues (epoprostenol) immediately, as this improves survival in high-risk patients 3, 7, 8
- Epoprostenol should be started at 2 ng/kg/min and increased in increments of 2 ng/kg/min every 15 minutes until dose-limiting effects occur 8
Critical Treatment Pitfalls
- Never use calcium channel blockers empirically without documented acute vasoreactivity, as this can worsen outcomes 1
- Do not abruptly lower the dose or withdraw prostacyclin therapy, as this can cause rebound pulmonary hypertension and death 8
- Avoid ACE inhibitors, ARBs, and beta-blockers in PAH patients unless specifically required for comorbidities 6, 3
Treatment for Chronic Thromboembolic Pulmonary Hypertension (Group 4)
Surgical pulmonary endarterectomy is the treatment of choice for all patients with CTEPH and should be performed at experienced centers with mortality rates <10%. 1, 7
Surgical Evaluation and Management
Refer all patients with suspected CTEPH to centers with expertise in both medical and surgical management for interdisciplinary evaluation 1
Initiate lifelong anticoagulation with vitamin K antagonists (target INR 2.0-3.0) in all CTEPH patients 1, 7
Perform pulmonary endarterectomy in deep hypothermia circulatory arrest for operable patients, as this can be curative 1, 7
Consider riociguat for inoperable CTEPH or persistent/recurrent PH after surgery 1, 7
Evaluate balloon pulmonary angioplasty in experienced centers for patients who are not surgical candidates 1
Supportive Care and General Measures
Essential Supportive Therapies
Administer diuretics for fluid overload management with careful monitoring of electrolytes and renal function 6, 3, 7
Provide supplemental oxygen to maintain arterial oxygen saturation >90% 3, 7
Recommend supervised exercise training for physically deconditioned PAH patients already on medical therapy 6, 3, 7
Ensure immunization against influenza and pneumococcal infection for all PAH patients 6
Provide psychosocial support as part of comprehensive care 6
Critical Contraindications
Monitoring and Follow-up
Conduct comprehensive reassessments every 3-6 months in stable patients using WHO functional class, 6-minute walk distance, biomarkers, echocardiography, and right heart catheterization when indicated 3, 7
The primary treatment goal is achieving and maintaining low-risk status, defined as WHO functional class I-II, 6-minute walk distance >440m, and preserved right ventricular function 6, 3, 7
Escalate therapy promptly if patients fail to achieve or maintain low-risk status with current treatment 3, 7
Consider lung transplantation for patients with inadequate response to maximal medical therapy, particularly those in WHO functional class III-IV 1, 7
Treatment for Other PH Groups
Group 2 (Left Heart Disease) and Group 3 (Lung Disease)
Optimize treatment of the underlying cardiac or pulmonary condition as the primary therapeutic strategy 1
Do not use PAH-approved drugs in patients with PH due to lung diseases, as clinical trials have not demonstrated benefit and may cause harm 1
Provide long-term oxygen therapy in patients with chronic hypoxemia from lung disease 1
Refer to expert PH centers only if signs of severe PH/severe right ventricular failure are present for individualized assessment 1