Ultrasound Assessment of Pulmonary Artery Stiffness in Pulmonary Hypertension due to Left Heart Disease (PH-LHD)

Background: Diagnosis of pulmonary hypertension (PH) in patients with left heart disease (LHD) is commonly late in the disease, as right heart catheterization is not routinely performed in LHD patients due to its inherent adverse effects. As such, noninvasive techniques to detect and monitor PH-LHD are an unmet clinical need. Recently, pulmonary artery (PA) stiffening has emerged as a diagnostic and prognostic parameter in PH. Using a translational bench-to-bedside approach based on noninvasive echocardiography, we aimed to develop a non-invasive stiffness index to estimate PA stiffness as a diagnostic parameter in PH due to LHD.

Method: A rat model of congestive heart failure secondary to aortic banding was used to induce PH-LHD and PA stiffening. PA diameter, radial strain (PA-RS), and stroke volume (SV) were determined by 2D transthoracic echocardiography and a stiffness index (Echo-SI) was calculated as ratio of SV multiplied by PA diameter relative to PA-RS. Echo SI was correlated to ex vivo measured “true” PA stiffness. Next, the developed Echo SI was validated in a prospective cohort of 24 LHD patients with or without PH prior to heart transplantation. Echo-SI in patients was measured by 2D transesophageal echocardiography and again compared with “true” PA stiffness assessed ex vivo in intraoperatively collected PA specimens. To determine the clinical significance of pulmonary vascular stiffness in heart transplant recipients, we assessed the incidence of right heart dysfunction after transplantation.

Results: In a rat model of PH-LHD PA stiffening correlated with invasive pulmonary hemodynamics and RV hypertrophy. Echocardiography-derived PA-RS and Echo-SI correlated with ex vivo measured “true” PA stiffness. In PH-LHD patients, either right PA radial strain (rPA-RS) or Echo-SI detected “true” PA stiffness with 76.9% sensitivity and 90.9% specificity. However, in comparison to PA-RS, Echo-SI performed better in detecting non-stiff PAs in LHD patients without PH. A combination of both parameters yielded 90.0% sensitivity and 92.8% specificity. None of the patients with an ex vivo stiffness index of <5 revealed right heart dysfunction with tricuspid regurgitation (TR) >2, while 25% of the patients with an index >5 developed right heart dysfunction and TR >2.

Conclusion: Echocardiographic PA-RS and Echo-SI were developed and validated as measures of PA stiffness. As such, non-invasive assessment of PA stiffness by echocardiography may improve the clinical diagnosis and longitudinal monitoring of PH-LHD.

This research was supported by the DZHK, BMBF, and DSHF.

Publication History

Article published online:
28 January 2023