What is the diagnostic workup and treatment for pulmonary hypertension?

From the Guidelines

The diagnostic workup for pulmonary hypertension begins with a thorough clinical evaluation followed by echocardiography, which is the initial screening tool to estimate pulmonary artery pressure, as recommended by the most recent guidelines 1. If pulmonary hypertension is suspected, right heart catheterization is essential for definitive diagnosis, confirming a mean pulmonary artery pressure ≥25 mmHg at rest. Additional testing includes:

• Pulmonary function tests
• Ventilation-perfusion scanning
• Chest CT
• Sleep studies
• Blood tests to identify underlying causes

Treatment depends on the specific type of pulmonary hypertension. For pulmonary arterial hypertension (Group 1), medications include:

• Endothelin receptor antagonists (ambrisentan 5-10 mg daily, bosentan 62.5-125 mg twice daily)
• Phosphodiesterase-5 inhibitors (sildenafil 20 mg three times daily, tadalafil 40 mg daily)
• Prostacyclin analogs (epoprostenol 2-40 ng/kg/min IV, treprostinil 1.25-40 ng/kg/min subcutaneous or IV)
• Soluble guanylate cyclase stimulators (riociguat 0.5-2.5 mg three times daily)

For Group 2-5 pulmonary hypertension, treatment focuses on the underlying cause. Supportive measures include:

• Oxygen therapy for hypoxemia
• Diuretics for fluid overload
• Anticoagulation in selected cases Advanced therapies include atrial septostomy and lung transplantation for refractory cases, as suggested by recent studies 1. These treatments work by targeting pathways involved in vasoconstriction, cell proliferation, and vascular remodeling to reduce pulmonary vascular resistance and improve right ventricular function. The importance of a comprehensive diagnostic approach and tailored treatment strategy is emphasized in the latest guidelines 1, highlighting the need for a multidisciplinary approach to managing pulmonary hypertension.

From the FDA Drug Label

Sildenafil tablets are indicated for the treatment of pulmonary arterial hypertension (WHO Group I) in adults to improve exercise ability and delay clinical worsening. The diagnostic workup and treatment for pulmonary hypertension is not fully described in the provided drug labels.

• Treatment: Sildenafil is indicated for the treatment of pulmonary arterial hypertension (PAH) to improve exercise ability and delay clinical worsening 2.
• Diagnostic workup: Not described in the provided drug labels. The FDA drug label does not answer the question.

From the Research

Diagnostic Workup for Pulmonary Hypertension

• The diagnostic workup for pulmonary hypertension (PH) involves a series of investigations to confirm the diagnosis, determine the clinical PH group, and evaluate the functional and hemodynamic impairment 3.
• The workup should identify the risk factors for PH, such as left heart disease, lung diseases associated with alveolar hypoxia, and chronic thromboembolism, versus the conditions associated with PAH group 1, such as scleroderma, human immunodeficiency virus, anorexigen use, and liver disease 3.
• Right heart catheterization plays an essential role in the diagnosis, categorization, and risk stratification of patients with pulmonary hypertension 4, 5.
• The definition of PH is a mean pulmonary artery pressure ≥ 25 mm Hg at rest, measured during right heart catheterization, and the term pulmonary arterial hypertension (PAH) describes a subpopulation of patients with PH characterized hemodynamically by the presence of pre-capillary PH 5.

Treatment for Pulmonary Hypertension

• Pulmonary vasodilator testing is performed during the initial workup, and a positive acute pulmonary vasodilator test predicts better survival and response to calcium channel blocker (CCB) therapy 6.
• The use of intravenous epoprostenol or nitric oxide (NO) is supported by the ACCP guidelines and the 4th World Symposium on Pulmonary Hypertension as the preferred agents for pulmonary vasodilator testing 6.
• Prostacyclin (epoprostenol) is a valuable agent in severe pulmonary arterial hypertension for non-responders to acute vasodilator testing, and treatment with epoprostenol has been shown to improve functional capacity and hemodynamics in patients with PAH 7.
• The choice of medical agent is based on right heart catheterization with acute vasodilator testing, and the treatment is complex and demands considerable patient involvement 7.

Diagnostic Evaluation and Classification

• A comprehensive diagnostic evaluation of cardiovascular physiology in patients with pulmonary vascular disease, such as the PVDOMICS program, involves an extensive invasive hemodynamic evaluation, including repeated measurements at rest and during several provocative physiological challenges 4.
• The PVDOMICS program aims to reclassify pulmonary hypertension groups based on clustered phenotypic and phenomic characteristics, and the comprehensive right heart catheterization protocol holds promise to clarify the diagnosis and clustering of pulmonary hypertension patients into cohorts beyond the traditional 5 World Symposium on Pulmonary Hypertension groups 4.
• Early diagnosis of PAH remains difficult, and screening programs in asymptomatic patients are feasible only in high-risk populations, particularly in patients with systemic sclerosis, for whom a combination of clinical assessment and pulmonary function testing has a higher predictive value than echocardiography alone 5.