What are the laboratory findings in Pulmonary Arterial Hypertension (PAH)?

From the Guidelines

Laboratory findings in pulmonary arterial hypertension (PAH) include elevated brain natriuretic peptide (BNP) or N-terminal pro-BNP levels, which reflect right ventricular strain and correlate with disease severity, as recommended by the 2015 ESC/ERS guidelines 1.

Key Laboratory Findings

• Elevated BNP or N-terminal pro-BNP levels
• Complete blood count may show polycythemia due to chronic hypoxemia
• Liver function tests can reveal abnormalities from hepatic congestion
• Arterial blood gases typically demonstrate hypoxemia with respiratory alkalosis
• Autoimmune markers like ANA, anti-centromere, and anti-Scl-70 antibodies may be positive in PAH associated with connective tissue diseases
• HIV testing is recommended as HIV infection can cause PAH
• Thyroid function tests are important as both hypo- and hyperthyroidism can worsen PAH
• D-dimer and other coagulation studies help exclude chronic thromboembolic disease
• Elevated uric acid levels correlate with disease severity and prognosis

Recommended Laboratory Assessment

The 2015 ESC/ERS guidelines recommend a basic laboratory workup, including blood counts, international normalized ratio (INR), serum sodium, potassium, creatinine, uric acid, aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and bilirubin 1. Additionally, troponin, uric acid, iron status, and thyroid function should be checked at least once a year or whenever the patient presents with clinical worsening 1.

Timing of Laboratory Assessment

The guidelines suggest the following timing for laboratory assessment:

• At baseline
• Every 3-6 months
• Every 6-12 months
• 3-6 months after changes in therapy
• In case of clinical worsening 1

From the FDA Drug Label

The reconstituted solution of epoprostenol for injection has a pH ranging from 11 to 13 and is increasingly unstable at a lower pH. 12 CLINICAL PHARMACOLOGY 12. 1 Mechanism of Action Epoprostenol has 2 major pharmacological actions: (1) direct vasodilation of pulmonary and systemic arterial vascular beds, and (2) inhibition of platelet aggregation. 12. 2 Pharmacodynamics In animals, the vasodilatory effects reduce right- and left-ventricular afterload and increase cardiac output and stroke volume. 14 CLINICAL STUDIES 14. 1 Clinical Trials in Pulmonary Arterial Hypertension (PAH) Acute Hemodynamic Effects Acute intravenous infusions of epoprostenol for up to 15 minutes in patients with idiopathic or heritable PAH or PAH associated with scleroderma spectrum of diseases (PAH/SSD) produce dose-related increases in cardiac index (CI) and stroke volume (SV) and dose-related decreases in pulmonary vascular resistance (PVR), total pulmonary resistance (TPR), and mean systemic arterial pressure (SAPm). The effects of epoprostenol on mean pulmonary arterial pressure (PAPm) were variable and minor Chronic Infusion in Idiopathic or Heritable PAH Hemodynamic Effects Chronic continuous infusions of epoprostenol in patients with idiopathic or heritable PAH were studied in 2 prospective, open, randomized trials of 8 and 12 weeks’ duration comparing epoprostenol plus conventional therapy to conventional therapy alone. Dosage of epoprostenol was determined as described in DOSAGE AND ADMINISTRATION (2) and averaged 9. 2 ng/kg/min at study’s end. Conventional therapy varied among patients and included some or all of the following: anticoagulants in essentially all patients; oral vasodilators, diuretics, and digoxin in one half to two thirds of patients; and supplemental oxygen in about half the patients Except for 2 New York Heart Association (NYHA) functional Class II patients, all patients were either functional Class III or Class IV. As results were similar in the 2 studies, the pooled results are described. Chronic hemodynamic effects were generally similar to acute effects Increases in CI, SV, and arterial oxygen saturation and decreases in PAPm, mean right atrial pressure (RAPm), TPR, and systemic vascular resistance (SVR) were observed in patients who received epoprostenol chronically compared to those who did not. Table 11 illustrates the treatment-related hemodynamic changes in these patients after 8 or 12 weeks of treatment Table 11: Hemodynamics during Chronic Administration of Epoprostenol in Patients with Idiopathic or Heritable PAH

• At 8 weeks: Epoprostenol N = 10, conventional therapy N = 11 (N is the number of patients with hemodynamic data). At 12 weeks: Epoprostenol N = 38, conventional therapy N = 30 (N is the number of patients with hemodynamic data) † Denotes statistically significant difference between Epoprostenol and conventional therapy groups. CI = cardiac index, PAPm = mean pulmonary arterial pressure, PVR = pulmonary vascular resistance, SAPm = mean systemic arterial pressure, SV = stroke volume, TPR = total pulmonary resistance Baseline Mean Change from Baseline at End ofTreatment Period* Hemodynamic Parameter Epoprostenol(N = 52) StandardTherapy(N = 54) Epoprostenol(N = 48) StandardTherapy(N = 41) CI (L/min/m2) 2 2 0.3†† -0. 1 PAPm (mmHg) 60 60 -5† 1 PVR (Wood U) 16 17 -4† 1 SAPm (mmHg) 89 91 -4 -3 SV (mL/beat) 44 43 6† -1 TPR (Wood U) 20 21 -5† 1

The laboratory findings in Pulmonary Arterial Hypertension (PAH) include:

• Hemodynamic changes:
  • Increases in cardiac index (CI) and stroke volume (SV)
  • Decreases in pulmonary vascular resistance (PVR), total pulmonary resistance (TPR), and mean systemic arterial pressure (SAPm)
  • Variable and minor effects on mean pulmonary arterial pressure (PAPm)
• Chronic hemodynamic effects:
  • Increases in CI, SV, and arterial oxygen saturation
  • Decreases in PAPm, mean right atrial pressure (RAPm), TPR, and systemic vascular resistance (SVR) 2

From the Research

Laboratory Findings in Pulmonary Arterial Hypertension (PAH)

The laboratory findings in PAH include various biomarkers and tests that help in diagnosing and assessing the severity of the disease. Some of the key findings are:

• Elevated levels of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the blood, which correlate with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) 3, 4, 5, 6
• Abnormal proteomic signatures, including upregulation of extracellular matrix (ECM) proteins, which are associated with poor outcomes and RV vulnerability 4
• Distinct metabolomic profiles, including alterations in polyamine, histidine, and sphingomyelin pathways, which are associated with RV dilation, mortality, and disease severity 5
• Elevated levels of endothelin-1, uric acid, and troponin, which are useful in predicting outcome and monitoring response to therapy 7
• Right ventricular expression of NT-proBNP, which adds predictive value to REVEAL score in patients with PAH 6

Biomarkers in PAH

Biomarkers play a crucial role in the diagnosis and management of PAH. Some of the key biomarkers include:

• BNP and NT-proBNP, which are elevated in PAH and correlate with disease severity 3, 4, 5, 6
• ECM proteins, which are upregulated in PAH and associated with poor outcomes 4
• Polyamine, histidine, and sphingomyelin pathways, which are altered in PAH and associated with disease severity 5
• Endothelin-1, uric acid, and troponin, which are useful in predicting outcome and monitoring response to therapy 7

Diagnostic Tests in PAH

Diagnostic tests are essential in the diagnosis and assessment of PAH. Some of the key tests include:

• Right heart catheterization (RHC), which is necessary to establish the diagnosis and document pulmonary hemodynamics 7
• Acute vasoreactivity testing, which is used to determine the appropriate therapy for an individual patient 7
• Echocardiography, which is used to assess RV function and estimate pulmonary arterial pressure 7
• Laboratory tests, including complete blood count, blood chemistry, and coagulation studies, which are used to assess disease severity and monitor response to therapy 7