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Pulmonary Hypertension, Primary: Differential Diagnoses & Workup
Updated: Aug 13, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Other Problems to Be Considered
Anorexigen-associated pulmonary hypertension
Workup
Laboratory Studies
- Antinuclear antibody (ANA): When performing a workup of a patient with possible primary pulmonary hypertension (PPH), excluding autoimmune disorders is important. However, up to 40% of patients with idiopathic pulmonary arterial hypertension (IPAH) have been reported to have a positive ANA and have no other clinical manifestations of autoimmune disease. Most connective-tissue diseases associated with pulmonary artery hypertension are diagnosed based on clinical results, with serology results used as adjunctive confirmation of the disease.
- Thyrotropin: Screen for thyroid abnormalities during the initial workup for IPAH because these abnormalities are common in patients with IPAH. Thyroid abnormalities may be the cause of or contribute to symptoms similar to IPAH. In addition, hyperthyroidism itself may lead to an elevation in pulmonary artery pressure.
- HIV testing: HIV-positive patients have a higher rate of IPAH compared with the general population; therefore, include an HIV test as part of the routine evaluation.
Imaging Studies
- Chest radiography: Chest radiography may be the first diagnostic step in the evaluation of a patient with dyspnea; however, for many patients with pulmonary artery hypertension, the findings do not help reveal the underlying etiology of the pulmonary hypertension. Chest radiography is useful for excluding interstitial and alveolar processes that may cause hypoxia-mediated pulmonary vasoconstriction.
- Echocardiography: This is extremely useful for assessing right and left ventricular function, estimating pulmonary systolic arterial pressure, and excluding congenital anomalies and valvular disease. Findings from echocardiography may demonstrate right-to-left shunting across a patent foramen ovale in approximately 33% of patients.
Two-dimensional short-axis echocardiogram image. Note the flattened interventricular septum due to right ventricular overload.
- High-resolution chest CT scanning and ventilation-perfusion lung scanning: These are frequently obtained to help exclude interstitial lung disease and thromboembolic disease.
- Pulmonary angiography: This test is occasionally required to help definitively exclude thromboembolic disease. While considered a high-risk procedure in patients with elevated pulmonary arterial pressures and/or right ventricular failure, a carefully performed study is generally safe.
Other Tests
- ECG: Results are often abnormal in patients with PPH, revealing right atrial enlargement, right axis deviation, right ventricular hypertrophy, and characteristic ST depression and T-wave inversions in the anterior leads. Some patients have few or no abnormal ECG findings; thus, normal ECG results do not exclude a diagnosis of PPH.
- Exercise testing: Six-minute walk testing is commonly used as a surrogate for aerobic capacity and IPAH severity. It is a simple and relatively easy test to perform; however, it lacks specificity in that it cannot discern between several causes of an impaired ability to walk.3
- Cardiopulmonary exercise testing: Assessment of aerobic capacity and ventilatory efficiency can help identify a pulmonary vascular limit to exercise and can differentiate intrinsic pulmonary vascular disease from cardiac deconditioning and restrictive or obstructive lung disease or left-sided cardiac dysfunction. In patients with IPAH, values for peak exercise oxygen consumption, oxygen pulse, and ventilator equivalents (ratio of expired volume to carbon dioxide output at the anaerobic threshold) during exercise are abnormal to varying degrees.
- Pulmonary function testing: Assessment of mechanical lung function can also help differentiate intrinsic pulmonary vascular disease from restrictive or obstructive lung disease. The diffusing capacity of the lung for carbon dioxide (DLCO) is known to decrease in proportion to the degree of IPAH severity.
- Diagnostic algorithms: Several diagnostic algorithms have been proposed in the literature that are useful for helping complete a thorough workup, which may be necessary to exclude all reasonable causes of secondary pulmonary hypertension. In 2004, an American College of Chest Physicians (ACCP) consensus statement was published, with diagnostic and treatment recommendations.4,5 In 2009, a joint American Heart Association (AHA)/American College of Cardiology (ACC) Guideline was published with extensive coverage of PAH diagnosis and management.6
- Sleep study: Sleep apnea must be excluded as a contributor or cause of pulmonary hypertension if the patient's history suggests this diagnosis.
Procedures
- Cardiac catheterization: This is the criterion standard test to definitively confirm a PPH diagnosis. Excluding left-sided heart disease, including diastolic dysfunction, is especially important in these patients because of major treatment implications. Catheterization is also performed to determine vasoreactive status, which may have implications in the initiation and titration of high-dose calcium channel blocker (CCB) therapy.
- Catheter placement for long-term therapy: The initiation of intravenous therapy with epoprostenol (EPO) requires placement of a central venous catheter and detailed instruction on the long-term use of vasodilator therapy.
- Lung biopsy: When the etiology of pulmonary hypertension is still in doubt, a lung biopsy may be necessary.
Histologic Findings
Several histologic subtypes are associated with pulmonary arteriopathy in PPH, one of which involves in situ thrombosis. Thrombotic pulmonary arteriopathy may be observed, with or without plexiform lesions. It is characterized by in situ thrombosis of small muscular arteries of the pulmonary vasculature. Thrombotic pulmonary arteriopathy is often present at earlier stages of PPH (ie, before the development of plexogenic pulmonary arteriopathy) or as an irreversible lesion in later stages. Platelet activation and increased circulating procoagulant factors are observed.
Staging
Traditionally, New York Heart Association/World Health Organization functional classification is used to grade PPH disease severity. This grading system has obvious limitations because it is subjective.
Other means to characterize disease severity include hemodynamic findings after right-sided heart catheterization, exercise capacity (eg, peak exercise oxygen consumption, 6-min walk distance), and clinical severity of heart failure signs found during the physical examination. More recent studies show that the echocardiographically determined eccentricity index, a marker of interventricular septum flattening, is a prognostic indicator. Positive findings for serum troponin and the presence of a pericardial effusion are also of prognostic utility, indicating a worse prognosis.7
More on Pulmonary Hypertension, Primary |
| Overview: Pulmonary Hypertension, Primary |
 Differential Diagnoses & Workup: Pulmonary Hypertension, Primary |
| Treatment & Medication: Pulmonary Hypertension, Primary |
| Follow-up: Pulmonary Hypertension, Primary |
| Multimedia: Pulmonary Hypertension, Primary |
| References |
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References
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Further Reading
Keywords
primary pulmonary hypertension, idiopathic pulmonary arterial hypertension, IPAH, idiopathic pulmonary hypertension, elevated pulmonary artery pressure, thrombotic pulmonary arteriopathy, TPA, plexogenic pulmonary arteriopathy, PPH, precapillary pulmonary hypertension, endothelin receptor antagonists, ERAs, endothelin-receptor antagonists, pulmonary hypertension, portal hypertension, pulmonary arteriopathy, pulmonary artery hypertension, PAH, pulmonary arterial hypertension, portopulmonary hypertension, CREST syndrome
