A Guide to Managing Pulmonary Hypertension

Understanding pulmonary hypertension: definitions, causes, and diagnostic approach

Pulmonary hypertension (PH) is a pathophysiologic condition characterized by elevated pressure in the pulmonary arterial circulation, which may lead to right ventricular dysfunction and progressive symptoms such as exertional dyspnea, fatigue, syncope, and peripheral edema. Clinicians broadly classify PH into groups based on etiology: pulmonary arterial hypertension (PAH, Group 1), PH due to left heart disease (Group 2), PH due to chronic lung disease and/or hypoxia (Group 3), chronic thromboembolic pulmonary hypertension (CTEPH, Group 4), and PH with unclear or multifactorial mechanisms (Group 5). Proper classification matters because it directly influences diagnostic tests, therapeutic options, and prognosis. A thorough initial evaluation begins with a detailed history and physical examination focused on symptom onset, progression, risk factors such as connective tissue disease, HIV, portal hypertension, drug exposures, family history, and potential thromboembolic events. Baseline testing typically includes an electrocardiogram to assess right heart strain patterns and an echocardiogram to estimate pulmonary artery systolic pressure and evaluate right ventricular size, function, and valvular disease. While noninvasive testing provides important clues, right heart catheterization remains the gold standard to confirm elevated mean pulmonary artery pressure, measure pulmonary vascular resistance, and assess hemodynamic response to vasodilators when indicated. Additional objective testing helps determine the underlying cause: high-resolution chest imaging or CT pulmonary angiography to assess interstitial lung disease or chronic thromboembolic disease; ventilation-perfusion scanning to evaluate for mismatched perfusion defects suspicious for chronic thromboembolism; pulmonary function testing and arterial blood gases for obstructive or restrictive lung disease and hypoxemia; sleep studies when sleep-disordered breathing is suspected; and targeted laboratory studies for connective tissue disease markers, HIV, liver disease, and thyroid function. Functional assessment with the six-minute walk test, cardiopulmonary exercise testing when available, and biomarkers such as brain natriuretic peptide (BNP or NT-proBNP) help quantify disease impact and guide follow-up. Accurate staging and risk stratification require combining clinical status, functional testing, hemodynamics, and biomarkers to identify patients at low, intermediate, or high risk of clinical deterioration. Early recognition of high-risk features — including rapidly progressive symptoms, syncope, marked right ventricular dysfunction on imaging, or severely abnormal hemodynamics — should prompt expedited specialist referral and consideration of aggressive or combination therapy. Equally important is distinguishing PAH from PH due to left heart disease or lung disease, because therapies approved for PAH can be ineffective or harmful when applied in other PH groups. For example, vasodilator therapy intended for pulmonary vascular remodeling may worsen ventilation-perfusion matching in advanced lung disease. Thus, multidisciplinary evaluation with cardiology, pulmonology, rheumatology, and when indicated, hematology or transplant services, is a cornerstone of accurate diagnosis and individualized management planning.

Evidence-based management strategies, monitoring, and pathways to advanced care

Management of pulmonary hypertension is multifaceted and must be tailored to the underlying cause, hemodynamic severity, comorbid conditions, and patient goals. General supportive measures play a foundational role across all PH groups and include targeted treatment of contributory conditions such as left heart failure, chronic lung disease, obstructive sleep apnea, and chronic thromboembolic disease. In hypoxemic patients, supplemental oxygen improves symptoms and may slow progression in some settings; vaccination against influenza and pneumococcus reduces infectious complications; and judicious diuretic therapy addresses volume overload while avoiding renal dysfunction. Anticoagulation is indicated in selected patients, particularly those with confirmed chronic thromboembolic disease or specific prothrombotic risks, after individualized risk assessment. Pharmacologic therapy for pulmonary arterial hypertension (Group 1) centers on agents that target three main molecular pathways implicated in pulmonary vascular remodeling and vasoconstriction: the nitric oxide–cyclic GMP pathway (e.g., phosphodiesterase type 5 inhibitors and soluble guanylate cyclase stimulators), the endothelin pathway (endothelin receptor antagonists), and the prostacyclin pathway (prostacyclin analogues and prostacyclin receptor agonists). Therapeutic decisions are guided by baseline risk assessment and response to therapy: low- or intermediate-risk patients may start with oral combination therapy, while high-risk or rapidly progressive patients frequently require early initiation of parenteral prostacyclin-based regimens and close multidisciplinary monitoring. For patients with chronic thromboembolic pulmonary hypertension (CTEPH) who have surgically accessible disease, pulmonary thromboendarterectomy remains the treatment of choice and can be curative; for inoperable cases or residual disease after surgery, balloon pulmonary angioplasty or targeted medical therapy may improve hemodynamics and symptoms. Throughout treatment, close monitoring of functional capacity, biomarkers, imaging of right ventricular function, and hemodynamics when clinically warranted is essential to detect progression or therapeutic failure. Dose adjustments, sequential combination therapy, or escalation to advanced modalities should be considered systematically using guideline-based risk reassessments at regular intervals. Management also addresses medication safety and interactions: many PH drugs have important hepatic metabolism considerations, require laboratory monitoring for liver function and blood counts, and have potential interactions with other medications the patient may be taking. Patient education about adherence, symptom recognition (notably worsening dyspnea, chest pain, syncope, rapid weight gain from fluid retention), and when to seek urgent care is critical. Given the complex nature of advanced therapies and potential for rapid decompensation, care in or consultation with dedicated pulmonary hypertension centers improves outcomes by providing access to specialized diagnostics, multidisciplinary expertise, advanced therapies, clinical trials, and transplant assessment. Rehabilitation services, including supervised exercise programs adapted for PH, can improve functional capacity and quality of life; psychosocial support and palliative care resources should be integrated early for symptom management and to align care with patient priorities. Finally, participation in clinical trials may offer access to novel agents and contributes to evolving standards of care; clinicians and patients should discuss trial eligibility and the balance of risks and benefits in the context of available approved treatments. Regular reassessment, individualized therapeutic pathways, and coordination among primary care, specialty teams, and allied health professionals form the backbone of high-quality, patient-centered management for pulmonary hypertension.