David Poch and Jess Mandel
The main challenges in the diagnosis of pulmonary hypertension are: (1) including pulmonary hypertension in the initial differential diagnosis and (2) completing a thorough diagnostic evaluation that establishes its presence. Historical information is usually nonspecific and patients frequently are misdiagnosed with more common conditions, such as asthma or heart failure. As an example, dyspnea on exertion is present in virtually all patients with pulmonary hypertension and may be the only presenting symptom. Other common symptoms include cough (30%), easy fatigability (25%), chest pain (21%), and hemoptysis (10%). These nonspecific symptoms often appropriately suggest other, more common, diagnostic considerations (asthma, coronary artery disease, psychogenic dyspnea) rather than pulmonary hypertension. More specific historical information, such as a history of anorectic drug use or childhood heart murmurs, should arouse suspicion for a specific pulmonary hypertensive disorder.
Findings on physical examination can be relatively subtle. Signs of pulmonary hypertension can include murmurs of tricuspid regurgitation or pulmonic insufficiency, accentuation of the pulmonic component of the second heart sound (P2), fixed splitting of S2, and a left parasternal lift, indicative of right ventricular hypertrophy. With more advanced disease, pedal edema, hepatomegaly, and jugular venous distension may be appreciated. One notable physical examination finding observed in some patients with chronic thromboembolic pulmonary hypertension (CTEPH) is the presence of pulmonary artery flow murmurs. These are bruits auscultated over the lung fields, heard best during breath holding at mid-inspiration. These sounds indicate flow through partially occluded central pulmonary arteries and are highly suggestive of chronic large-vessel pulmonary embolic disease.
Chest radiography frequently is unrevealing. If pulmonary hypertension is severe, enlargement of the right ventricle and pulmonary arteries is apparent. Chest radiography, however, can be useful in documenting secondary causes of pulmonary hypertension such as interstitial lung disease or chronic obstructive pulmonary disease (COPD). One notable radiographic finding is the presence of interstitial edema (Kerley B lines) in the setting of right ventricular failure and pulmonary artery enlargement. This constellation of x-ray findings should raise suspicion for pulmonary veno-occlusive disease.
In patients in whom pulmonary hypertension is suspected, echocardiography is a very useful initial test that is likely to be abnormal in the presence of moderate or severe pulmonary hypertension. Two-dimensional echocardiography demonstrates varying degrees of right atrial and right ventricular enlargement. Paradoxical movement of the interventricular septum indicates right ventricular pressure overload. Doppler echocardiography can also estimate the pulmonary artery systolic pressure (PASP) using the velocity of a tricuspid regurgitant jet (almost always present) and the formula PASP = 4 × v2 + right atrial pressure.
The 2008 Dana Point classification of pulmonary hypertension includes five major categories:
1. Pulmonary arterial hypertension (PAH)
a. Idiopathic
b. Heritable
c. Drug and toxin associated (e.g., fenfluramine, cocaine)
d. Associated with collagen vascular disease, congenital systemic to pulmonic shunts, portal hypertension, HIV, drugs and toxins, schistosomiasis, and others
e. Associated with significant venous or capillary involvement: pulmonary veno-occlusive disease, pulmonary capillary hemangiomatosis
2. Pulmonary hypertension due to left-sided heart disease
3. Pulmonary hypertension associated with lung diseases or hypoxemia (e.g., COPD, interstitial lung disease, sleep-disordered breathing, alveolar hypoventilation disorders, chronic exposure to high altitude, developmental abnormalities)
4. Pulmonary hypertension caused by chronic thromboembolic disease (CTEPH)
5. Pulmonary hypertension with unclear multifactorial mechanisms (e.g., sarcoidosis, histioytosis X, lymphangiomatosis, Gaucher disease).
Once a patient is identified as having a reasonable likelihood of pulmonary hypertension, additional tests are required to establish the diagnosis and determine which type of disease is present. These tests include: (1) echocardiography to exclude the presence of congenital heart disease (atrial septal defect, ventricular septal defect, patent ductus arteriosus) and left-sided heart disease (valvular or ventricular dysfunction), (2) pulmonary function testing to determine if significant obstructive or restrictive lung disease is present, (3) ventilation–perfusion scanning and possibly pulmonary angiography to identify CTEPH, (4) arterial blood gas analysis to evaluate for a hypoventilation syndrome, (5) polysomnography, if clinically indicated, and (6) chest radiography and high-resolution computed tomography scanning if the diagnosis of interstitial lung disease–associated pulmonary hypertension is contemplated.
With these noninvasive studies, multiple disorders can be excluded and patients with PAH can be identified. Further studies to identify conditions associated with PAH include liver function tests, HIV serology, and antinuclear antibody titer (collagen vascular disease). Patients should also be questioned regarding a family history of pulmonary hypertension, a history of anorexigen use, or a history of use of stimulant drugs (e.g., methamphetamines, cocaine). Right heart catheterization should be done to confirm the diagnosis and exclude an elevated pulmonary capillary wedge pressure indicative of left atrial hypertension, assess disease severity, and determine whether vasoreactivity is present.
The outcome of patients with untreated idiopathic PAH is quite unfavorable. In the National Institutes of Health Registry of such patients before modern treatments were available, median survival from the time of recognition was 2.9 years. Factors associated with a worse prognosis include severity of right ventricular failure (high right atrial pressure, low cardiac index), poor functional class, and poor exercise capacity as assessed by a 6-minute walk test.
Because the subset of patients with PAH that is responsive to vasodilators has a much better prognosis, it is critical to determine the ability of the pulmonary vascular bed to vasodilate in response to pharmacologic agents such as epoprostenol, inhaled nitric oxide, or adenosine; longer acting agents should not be used. An acute fall in mean pulmonary arterial pressure of at least 10 mmHg and to a final value less than 40 mmHg without reduction in cardiac output identifies a subgroup that may do well on long-term calcium channel blockers. Unfortunately, less than 10% of patients fall into this acute “vasoreactive” subgroup.
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
