Contrast-enhanced Ultrasound and Non-invasive Pulmonary Artery Pressure Measurement

Background Pulmonary hypertension (PH), defined as a mean pulmonary arterial pressure ≥ 25 mmHg at rest as assessed by right heart catheterization (RHC), is present in several clinical conditions1. While considered the gold standard for the measurement of pulmonary pressure, RHC is an invasive procedure and is associated with a small risk of morbidity (1.1%) and mortality (0.055%) even when performed at experienced centers2. Therefore, alternative diagnostic approaches are often employed. Doppler echocardiography is non-invasive, relatively inexpensive and widely available technique. It is potentially suitable not only as a screening tool for PH but also as a method for serial monitoring of disease progression. Among the echocardiographic methods introduced to indirectly measure pulmonary arterial pressure, the tricuspid valve regurgitant jet method and the pulmonary artery regurgitant jet method have been widely adopted3. By measuring with Doppler ultrasound the maximum velocity of the tricuspid regurgitant jet (v), the transtricuspid pressure gradient (Pg) can be calculated using the modified Bernoulli equation: Pg = 4v2. Right ventricular systolic pressure (RVSP) can then be estimated by adding the transtricuspid pressure gradient to the right atrial pressure (RAP), indirectly estimated by the diameter of the inferior vena cava (IVC) and the degree of its collapse during spontaneous respiration4. In the absence of pulmonary valve stenosis, the RVSP can be equated to the pulmonary arterial systolic pressure (PASP). Measurements of PASP by Doppler echocardiography show a very high correlation (r=0.93) with values obtained by RHC 5. However, the accuracy of Doppler echocardiography appears to be limited in the assessment of patients with suspected PH, in whom the difference in PASP determined by echo and by RHC may be overestimated or underestimated by greater than 10 mmHg6. To improve the performance of Doppler echocardiography, particularly in the presence of an inadequate jet of tricuspid regurgitation, it is common practice to use maneuvers such as the injection of agitated saline and/or echo contrast media such as Optison® (Perflutren Protein-Type A Microspheres Injectable Suspension, USP) to augment the tricuspid regurgitant velocity profile4. However, whether these maneuvers increase the accuracy of Doppler echocardiography in the assessment of right ventricular and pulmonary arterial pressures compared to standard Doppler echocardiography has not been investigated.

2. Research Methods Study Design Cross-sectional investigation to assess: 1) the correlations between right sided (right ventricular, pulmonary artery, and right atrial) pressures measured by RHC and by Doppler echocardiography in the absence of contrast and during the intravenous administration of agitated saline or Optison®; and 2) to compare such measures by assessment modality. The investigators hypothesize that the correlations between right sided pressures measured by Doppler echo during agitated saline or Optison® will be higher than those measured in the absence of a contrast agent, and that the correlations between right sided pressures measured by Doppler echo during Optison® will be higher than those measured during agitated saline.

The main correlations explored in the study will be:

Correlation between right atrial pressure measured by RHC and by Doppler echocardiography in the absence of a contrast agent.

Correlation between right ventricular pressure measured by RHC and by Doppler echocardiography in the absence of a contrast agent and during the intravenous administration of agitated saline or Optison®.