Cardiogenic Pulmonary Edema Workup

Lab studies used in the evaluation of patients with cardiogenic pulmonary edema (CPE) include the following:

• Complete blood count - The complete blood count (CBC) with differential helps in assessing for severe anemia and may suggest sepsis or infection if a markedly elevated white blood cell (WBC) count or bandemia is present
• Serum electrolyte measurements - Patients with chronic CHF often use diuretics and are therefore predisposed to electrolyte abnormalities, especially hypokalemia and hypomagnesemia; patients with chronic renal failure are at high risk for hyperkalemia, especially when they are noncompliant with hemodialysis sessions
• Blood urea nitrogen (BUN) and creatinine determinations - These tests help in assessing patients for renal failure and the anticipated response to diuretics; in low-output states, such as systolic dysfunction, decreased BUN and creatinine levels may be secondary to hypoperfusion of the kidneys
• Pulse oximetry - Pulse oximetry is useful in assessing hypoxia and, therefore, the severity of CPE; it is also useful for monitoring the patient's response to supplemental oxygenation and other therapies
• Arterial blood gas analysis - This test is more accurate than pulse oximetry for measuring oxygen saturation; the decision to start mechanical ventilation is based mainly on clinical findings, but in rare instances, arterial blood gas results are taken into account

Electrocardiography

LA enlargement and LV hypertrophy are sensitive, although nonspecific, indicators of chronic LV dysfunction. The electrocardiogram (ECG) may suggest acute tachydysrhythmia or bradydysrhythmia or acute myocardial ischemia or infarction as the cause of CPE.

Brain-type natriuretic peptide (BNP) and N -terminal proBNP (NT-proBNP) are derived from pre-proBNP, a 134 ̶ amino acid precursor synthesized by cardiac myocytes. A number of triggers including wall stretch, ventricular dilation, and/or increased pressures, stimulate a 26 ̶ amino-acid signal peptide sequence to be cleaved from the precursor’s N -terminus to produce proBNP (which has a 108 ̶ amino acid sequence). This hormone is further cleaved by a membrane-bound serine protease (corin) into the inactive NT-proBNP fragment and the active BNP (32 ̶ amino acid sequence) fragment.^[1]

NT-proBNP and BNP testing are clinically available and have exhibited parallel changes across broad ranges of patient age, ejection fraction, diastolic CHF, and renal function.

BNP testing

CHF is the most common form of CPE. Several observational studies and clinical trials have shown the important diagnostic value of BNP measurements in differentiating heart failure from pulmonary causes of dyspnea.

Characteristics of BNP and points to consider in BNP testing include the following:

• BNP testing decreases the total cost of treatment and the length of hospitalization; this is a cost-effective diagnostic test in this setting
• Although reports differ, a cutoff value of 100 pg/mL is generally accepted; by using this cutoff value, measurement of BNP has a high negative predictive value; that is, in patients with BNP value of under 100 pg/mL, heart failure is unlikely
• The level of BNP increases with age and is slightly higher in women than in men; BNP levels also tend to be lower in obese patients
• In one study, a cutoff point of 250 pg/mL was the most accurate for elderly patients (mean age, 80 y)
• Renal dysfunction may be associated with a significantly increased level of BNP
• In the Breathing Not Properly Multinational Study, the mean BNP level in patients without heart failure and with a glomerular filtration rate (GFR) below normal was 300 pg/mL
• One study of intensive care unit (ICU) patients who required invasive hemodynamic monitoring showed that they had markedly elevated BNP values, but the correlation between BNP values and pulmonary capillary wedge pressure (PCWP) was weak

Although the predictive value of a BNP measurement with a cutoff value of 100 pg/mL is high, its positive predictive value is not as high as its negative predictive value. This means that mildly to moderately elevated levels of BNP should be interpreted in accordance with the patient's clinical status and other diagnostic results.

Values of 100-400 pg/mL may be related to various pulmonary conditions, such as cor pulmonale, COPD, and pulmonary embolism. Atrial fibrillation is another factor that may mildly increase the BNP cutoff value in diagnosing heart failure. It is important to know the patient's baseline heart function. Patients with chronic heart failure and BNP values of less than or equal to 400 pg/mL may have pulmonary causes of dyspnea without exacerbation of their CHF.

Until additional studies establish the precise cutoff values for different conditions, the threshold of 100 pg/mL is recommended, with the exceptions noted above. This cutoff value has an accuracy of 80-85%, a sensitivity of 90%, and a specificity of about 75% along with other appropriate clinical and laboratory findings.

NT-proBNP testing

Ventricular myocytes secrete proBNP in response to muscle-wall tension. NT-proBNP has a longer half-life (120 min) than that of BNP (20 min). Although NT-proBNP is less studied than BNP, its levels are well correlated with BNP levels.

The cutoff value for NT-proBNP of greater than 450 pg/mL in patients younger than 50 years correlates to BNP values of greater than 100 pg/mL. NT-proBNP is less accurate than BNP in patients older than 65 years.

Chest radiography is helpful in distinguishing CPE from other pulmonary causes of severe dyspnea. Features that suggest CPE rather than NCPE and other lung pathologies include the following (see the images below):

• Enlarged heart
• Inverted blood flow
• Kerley lines
• Basilar edema (vs diffuse edema)
• Absence of air bronchograms
• Presence of pleural effusion (particularly bilateral and symmetrical pleural effusions)Radiograph shows acute pulmonary edema in a patient known to have ischemic cardiomyopathy. Findings are Kerley B lines (1mm thick and 1cm long) in the lower lobes and Kerley A lines in the upper lobes. Radiograph shows interstitial pulmonary edema, cardiomegaly, and left pleural effusion presenting at an earlier stage of pulmonary edema. Radiograph demonstrates cardiomegaly, bilateral pleural effusions, and alveolar opacities in a patient with pulmonary edema. Lateral chest radiograph shows prominent interstitial edema and pleural effusions.

Chest radiography is somewhat limited in patients with CPE of abrupt onset, because the classic radiographic abnormalities may not appear for as long as 12 hours after dyspnea begins.

A bedside echocardiogram in a patient with decompensated CHF is an important diagnostic tool in determining the etiology of pulmonary edema. Echocardiography can be used to evaluate LV systolic and diastolic function, as well as valvular function, and to assess for pericardial disease. It is especially helpful in identifying a mechanical etiology for pulmonary edema, such as the following:

• Acute papillary muscle rupture
• Acute ventricular septal defect
• Cardiac tamponade
• Contained LV rupture
• Valvular vegetation with resulting acute severe mitral, aortic regurgitation

PCWP can be measured with a pulmonary arterial catheter (Swan-Ganz catheter). This method helps in differentiating CPE from NCPE; NCPE occurs secondary to injury to the alveolar-capillary membrane rather than from alteration in Starling forces.

A PCWP exceeding 18 mm Hg in a patient not known to have chronically elevated LA pressure indicates CPE. In patients with chronic pulmonary capillary hypertension, capillary wedge pressures exceeding 30 mm Hg are required to overcome the pumping capacity of the lymphatics and produce pulmonary edema.

Large V waves are sometimes observed in the PCWP tracing with acute mitral regurgitation, because large volumes of blood regurgitate into a poorly compliant left atrium. This condition raises pulmonary venous pressure and causes acute pulmonary edema. The pulmonary artery waveform appears falsely elevated because of the large V wave reflected back from the left atrium through the compliant pulmonary vasculature. The Y descent of the waveform is rapid, as the overdistended left atrium quickly empties.

Cardiogenic shock is the result of a severe depression in myocardial function. Cardiogenic shock is hemodynamically characterized by a systolic blood pressure of less than 80mm Hg, a cardiac index of less than 1.8 L/min/m², and a PCWP of more than 18 mm Hg. This form of shock can occur from a direct insult to the myocardium (large acute MI, severe cardiomyopathy) or from a mechanical problem that overwhelms the functional capacity of the myocardium (acute severe mitral regurgitation, acute ventricular septal defect).

Although the pulmonary artery catheter is commonly used in ICU patients with severe acute decompensated CHF, it is not clear whether this technique improves mortality rate and clinical outcome.

The results of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial showed no mortality benefit or decrease in the number of hospitalized days in the group of patients who underwent PAC insertion.^[2] This matter needs further investigation.