Laboratory studies
Laboratory investigations are directed toward defining the potential underlying etiologies as well as evaluating the complications of cor pulmonale. In specific instances, appropriate laboratory studies may include the following:
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Hematocrit for polycythemia, which can be a consequence of underlying lung disease but can also increase pulmonary arterial pressure by increasing viscosity
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Serum alpha1-antitrypsin, if deficiency is suspected
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Antinuclear antibody (ANA) level for collagen vascular disease, and anti-SCL-70 antibodies in scleroderma
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Coagulations studies to evaluate hypercoagulability states (eg, serum levels of proteins S and C, antithrombin III, factor V Leyden, anticardiolipin antibodies, hom*ocysteine)
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Arterial blood gas measurements may provide important information about the level of oxygenation and type of acid-base disorder.
Brain natriuretic peptide
Brain natriuretic peptide (BNP) is a peptide hormone that is released in response to volume expansion and the increased wall stress of cardiac myocytes. BNP helps to promote diuresis, natriuresis, vasodilation of the systemic and pulmonary vasculature, and reduction of circulating levels of endothelin and aldosterone. As a result, both congestive heart failure due to left ventricular (LV) failure and cor pulmonale due to noncardiac pulmonary hypertension can lead to elevations in plasma BNP. Although not specific, severe acute decompensated LV heart failure can result in higher levels of BNP.
Chest radiography
In patients with chronic cor pulmonale, the chest radiograph may show enlargement of the central pulmonary arteries with oligemic peripheral lung fields. Pulmonary hypertension should be suspected when the right descending pulmonary artery is larger than 16 mm in diameter and the left pulmonary artery is larger than 18 mm in diameter. Right ventricular enlargement leads to an increase of the transverse diameter of the heart shadow to the right on the posteroanterior view and filling of the retrosternal air space on the lateral view. These findings have reduced sensitivity in the presence of kyphoscoliosis or hyperinflated lungs.
Electrocardiography
Electrocardiographic (ECG) abnormalities in cor pulmonale reflect the presence of right ventricular hypertrophy (RVH), RV strain, or underlying pulmonary disease (see the image below). Such ECG changes may include the following:
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Right axis deviation
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R/S amplitude ratio in V1 greater than 1 (an increase in anteriorly directed forces may be a sign of posterior infarction)
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R/S amplitude ratio in V6 less than 1
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P-pulmonale pattern (an increase in P wave amplitude in leads 2, 3, and aVF)
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S1 Q3 T3 pattern and incomplete (or complete) right bundle branch block, especially if pulmonary embolism is the underlying etiology
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Low-voltage QRS because of underlying COPD with hyperinflation
Severe RVH may reflect as Q waves in the precordial leads that may be mistakenly interpreted as an anterior myocardial infarction (however, as electrical activity of the RV is significantly less than the left ventricle [LV], small changes in RV forces may be lost in the ECG). See the image below.
This ECG shows some typical abnormalities that may be seen in cor pulmonale and other chronic pulmonary diseases: (1) R/S ratio >1 in V1 and <1 in V6 suggestive of right ventricular hypertrophy/enlargement, (2) right superior axis deviation, (3) left atrial type of p wave with increased width of the p wave and biphasic p wave in V1, and (4) right bundle branch block pattern with wide QRS and RsR1 pattern in V1 and slurred s wave in V6.This ECG also presents a sinus bradycardia rhythm with first-degree AV block and left anterior fascicular block.
Additionally, many rhythm disturbances may be present in chronic cor pulmonale; these range from isolated premature atrial depolarizations to various supraventricular tachycardias, including paroxysmal atrial tachycardia, multifocal atrial tachycardia, atrial fibrillation, atrial flutter, and junctional tachycardia. These dysrhythmias may be triggered by processes secondary to the underlying disease, (eg, anxiety, hypoxemia, acid-base imbalance, electrolyte disturbances, excessive use of bronchodilators, heightened sympathetic activity). Life-threatening ventricular tachyarrhythmias are less common.
In selected cases, pulmonary function testing may be indicated to determine underlying obstructive or interstitial lung disease.
2-D and Doppler echocardiography
Two-dimensional (2-D) echocardiography usually demonstrates signs of chronic right ventricular (RV) pressure overload. As this overload progresses, increased thickness of the RV wall with paradoxical motion of the interventricular septum during systole occurs. At an advanced stage, RV dilatation occurs, and the septum shows abnormal diastolic flattening. In extreme cases, the septum may actually bulge into the left ventricular (LV) cavity during diastole, resulting in decreased LV diastolic volume and reduction of LV output.
Doppler echocardiography is used to estimate pulmonary arterial pressure, taking advantage of the functional tricuspid insufficiency that is usually present in pulmonary hypertension. This imaging modality is considered the most reliable noninvasive technique to estimate pulmonary artery pressure. However, the efficacy of Doppler echocardiography may be limited by the ability to identify an adequate tricuspid regurgitant jet, which may be further enhanced by using saline contrast. [17]
Several methods exist to assess RV function. One method includes tricuspid annular plane systolic excursion (TAPSE), which is measured by viewing the heart in the apical four-chamber view and using the M-mode function along the lateral tricuspid annulus. By measuring the distance traveled of this reference point during systole, the longitudinal shortening of the RV can be used as a surrogate for global RV function. Limitations include inadequate M-mode placement and the assumption that one segment of RV motion is representative of the entire RV.
Strain, which is distinct from measuring wall-motion abnormalities in traditional echocardiography, involves measuring myocardial deformation to quantitatively assess myocardial function. Two methods currently exist for measuring strain, including tissue Doppler imaging (TDI) and 2-D speckle tracking. TDI uses postprocessing to convert velocity to strain and strain rates, but it is significantly limited by the Doppler angle of incidence. 2-D speckle tracking uses greyscale to detect speckle patterns by tracking natural acoustic markers to calculate velocity vectors with 2-D ultrasonography. However, 2-D speckle tracking relies on high image quality. [18, 19]
Additionally, myocardial performance index (MPI) can also be used to measure RV function by calculating the isovolumetric relaxation time and contraction time divided by the ejection time. Higher MPI indicates greater RV dysfunction, and it is independent of RV chamber size and geometry.
Pulmonary thromboembolism imaging studies
Pulmonary thromboembolism has a wide range of clinical presentations—from massive embolism with acute and severe hemodynamic instability to multiple chronic peripheral embolisms—that may present with cor pulmonale. [20]
Pulmonary angiography was historically the gold standard for diagnosing acute pulmonary embolism. The injection of a radiocontrast dye under fluoroscopy allows for direct imaging of the pulmonary vasculature. This has been largely replaced by computed tomography pulmonary angiography (CTPA), which involves the injection of an iodinated contrast while obtaining CT scanning of the chest. CTPA is both sensitive and specific and only requires intravenous (IV) access; as a result, it is the first-line diagnostic imaging modality to diagnose a suspected pulmonary embolism.
Ventilation/perfusion (V/Q) scanning is often performed in cases in which the iodinated contrast agent used in CTPA is contraindicated (eg, pregnancy, renal insufficiency, contrast allergy). By comparing both ventilation and perfusion using a radionucleotide, perfusion deficits within areas of normal ventilation are highly suspicious of a pulmonary embolism. V/Q scanning is the test of choice in diagnosing chronic thromboembolic pulmonary hypertension (CTEPH), as it is more sensitive than CTPA. [21]
Ultrafast, ECG-gated CT scanning
Ultrafast, electrocardiographically (ECG)-gated computed tomography (CT) scanning has been evaluated to study right ventricular (RV) function. In addition to estimating RV ejection fraction (RVEF), this imaging modality can estimate RV wall mass. Although the use of ultrafast, ECG-gated CT scanning is still experimental, with further improvement, it may be used to evaluate the progression of cor pulmonale in the near future.
Magnetic resonance imaging
Cardiac magnetic resonance (CMR) imaging has been used as a method of providing high-quality images and diagnostic capabilities that are currently being explored. Electrocardiographic (ECG)-gated techniques and respiratory motion suppression have enabled protocols that can provide valuable information about right ventricular (RV) mass, septal flattening, and ventricular function. By incorporating gadolinium, myocardial scar and fibrosis can also be evaluated via CMR. Such a technique can be useful in determining the size and location of an infarction. Spin echo, which causes blood to appear black, can be used for anatomic imaging and identifying abnormal myocardium, and cine imaging, in which blood appears bright and the myocardium appears dark, can help in the assessment of wall motion abnormalities, valve function, and patterns of blood flow. As a result, CMR is being explored to better characterize and quantify pulmonary hypertension. [22, 23]
Nuclear imaging
Radionuclide ventriculography can noninvasively determine right ventricular ejection fraction. Myocardial perfusion may also show a permanent increase in brightness of the right ventricle. [24]
Ventilation/perfusion (V/Q) scanning can be particularly useful in evaluating patients with cor pulmonale, especially if pulmonary hypertension is due to chronic thromboembolic pulmonary hypertension (CTEPH). V/Q scans are performed by having the patient inhale a radionucleotide (typically xenon or technetium) to assess ventilation, whereas perfusion is evaluated by the intravenous injection of another radionucleotide. The two images are then analyzed to determine if there are any mismatched perfusion defects, which is suggestive of a pulmonary embolism.
V/Q scans are typically interpreted as being normal, or having a high, intermediate, or low probability for pulmonary embolism. In CTEPH, the V/Q scan typically demonstrates having a high probability for pulmonary embolism as well as having multiple mismatched perfusion defects which can be visualized.
Cardiac catheterization
Although high-resolution echocardiography and magnetic resonance imaging are accurate methods to measure pulmonary pressure, [25] right heart catheterization is considered the most precise method for diagnosis and quantification of pulmonary hypertension. This procedure is indicated when echocardiography cannot assess the severity of a tricuspid regurgitant jet, thus excluding an assessment of pulmonary hypertension.
In patients with cor pulmonale, right heart catheterization reveals evidence of right ventricular (RV) dysfunction without left ventricular (LV) dysfunction. Hemodynamically, this typically presents as a mean pulmonary artery pressure (PAP) above 25 mmHg, which leads to elevated RV systolic pressures and central venous pressures (CVP). However, these findings are also seen in LV dysfunction. One method of differentiating left-sided from right-sided disease includes measuring the pulmonary capillary wedge pressure (PCWP), which is an estimation of left atrial pressure. Thus, RV dysfunction is also defined as having a PCWP below 15 mmHg, because failure of the LV would result in elevated LV end diastolic pressures and, subsequently, left atrial pressures. [8]
Right heart catheterization is occasionally important for differentiating cor pulmonale from occult left ventricular dysfunction, especially when the presentation is confusing. Another indication is for evaluation of the potential reversibility of pulmonary arterial hypertension with vasodilator therapy or when a left-sided heart catheterization is indicated.
Lung biopsy
Lung biopsy may occasionally be indicated to determine the etiology of underlying lung disease. This is especially true if interstitial lung disease (ILD) is the suspected etiology for pulmonary hypertension resulting in cor pulmonale.
ILD encompasses a broad range of diagnoses, including but not limited to exposure-related causes (eg, asbestosis, silicosis), complications of connective tissue disorders (eg, rheumatoid arthritis, systemic lupus erythematosus, scleroderma), and idiopathic pneumonia (eg, usual interstitial pneumonia, acute interstitial pneumonia, nonspecific interstitial pneumonia, cryptogenic organizing pneumonia).
Typically, laboratory tests, pulmonary function tests, and imaging studies, including high-resolution computed tomography (HRCT) scanning, are performed before proceeding to invasive lung biopsy. Lung biopsy can sometimes be important in determining prognosis and management, depending on the diagnosis obtained via pathology. Biopsies can be obtained with the use of transbronchial biopsy, thoracotomy, or video-assisted thoracoscopic surgery (VATS).
