Extraction of Pulmonary Vascular Compliance, Pulmonary Vascular Resistance, and Right Ventricular Work From Single-Pressure and Doppler Flow Measurements in Children With Pulmonary Hypertension: a New Method for Evaluating Reactivity

Abstract

Background-Current evaluation of pulmonary hypertension (PH) in children involves measurement of pulmonary vascular resistance (PVR); however, PVR neglects important pulsatile components. Pulmonary artery (PA) input impedance and ventricular power (VP) include mean and pulsatile effects and have shown promise as alternative measures of vascular function. Here we report the utility of pulsed-wave (PW) Doppler-measured instantaneous flow and pressure measurements for estimation of input impedance and VP and use this method to develop a novel parameter: reactivity in compliance. Methods and Results-An in vitro model of the general pulmonary vasculature was used to obtain impedance and VP, measured by PW Doppler and a reference flow meter. The method was then tested in a preliminary clinical study in subjects with normal PA hemodynamics (nϭ4) and patients with PH undergoing reactivity evaluation (8 patients; 23 data points). In vitro results showed good agreement between the impedance spectra computed from both flowmeasurement methods. Excellent correlation was seen in vitro between actual resistance and the zero-frequency (Z o ) impedance value (r 2 ϭ0.984). Excellent agreement was also found between Z o and PVR in the clinical measurements (yϭ1.075xϩ0.73; rϭ0.993). Furthermore, total VP and VP/cardiac output increased significantly with hypertension (128.73 to 365.91 mW and 2.42 to 6.69 mW · mL Ϫ1 · s Ϫ1 , respectively). The first-harmonic value of impedance (Z 1 ) was used as a measure of compliance reactivity; older patients exhibited markedly less compliance reactivity than did younger patients. Conclusions-Input impedance and VP calculated from Doppler measurements and a single-catheter pressure measurement provide comprehensive characterization of PH and reactivity.

Pulmonary vascular input impedance is a combined measure of pulmonary vascular resistance and stiffness and predicts clinical outcomes better than pulmonary vascular resistance alone in pediatric patients with pulmonary hypertension

“…Representative impedance curves for each Group are shown in Figures 3A and 3B. As seen in the figures, the hypertensive patients typically displayed both larger values of Z 0 , indicating higher PVR [1][2][3][4]8], and larger values of the first several harmonics of impedance. Differences in Z 0 and Z 1 +Z 2 between the normotensive and hypertensive patients were significant (p< 0.05).…”

“…Cumulative logistic regression between these parameters and the ordinal outcomes categories was performed with the PROC LOGISTIC procedure in SAS (SAS Institute Inc, Cary, NC) and goodness-of-fit statistics were computed as described in [11]. Finally, uncertainties for each measurement were obtained as described previously [4].…”

“…Here, we measure pressure and flow at the entrance to the main pulmonary artery, which yields the input impedance of the whole pulmonary vasculature. In an earlier study on a smaller number of patients we showed that this input impedance is both easily measured during a routine catheterization study and provides information on both steady and dynamic components of right ventricular afterload [4]. The importance of including dynamic (stiffness) components in evaluation of PAH has since been confirmed as a better predictor of mortality [5].…”

Molecular pathogenesis of pulmonary arterial hypertension

“…Although the focus in understanding the mechanism of PAH has been on the small PAs (less than 500 μM), changes in impedance (140) resulting from stiffening of the more proximal as well as the distal PAs may also be a critical determinant of RV function (141). BMPR2 mutations associated with PAH may also influence the remodeling pathology of proximal PAs and of cardiac myocytes and fibroblasts.…”

Molecular pathogenesis of pulmonary arterial hypertension

“…The proximal pulmonary arteries and the right ventricle Although the focus in understanding the mechanism of PAH has been on the small pulmonary arteries (<500 μM), there is evidence that changes in impedance (124), resulting from stiffening of the more proximal pulmonary arteries, may also be a critical determinant not only of the pressure but of the ability of the right ventricle to function (125). These studies also raise questions as to how BMP-RII mutations associated with PAH influence the remodeling pathology of the proximal PAs and of cardiomyocytes and fibroblasts.…”