A comparison of echocardiography to invasive measurement in the evaluation of pulmonary arterial hypertension in a rat model

Abstract

Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by progressive elevation in pulmonary artery pressure (PAP) and total pulmonary vascular resistance (TPVR). Recent advances in imaging techniques have allowed the development of new echocardiographic parameters to evaluate disease progression. However, there are no reports comparing the diagnostic performance of these non-invasive parameters to each other and to invasive measurements. Therefore, we investigated the diagnostic yield of echocardiographically derived TPVR and Doppler parameters of PAP in screening and measuring the severity of PAH in a rat model. Serial echocardiographic and invasive measurements were performed at baseline, 21 and 35 days after monocrotaline-induction of PAH. The most challenging echocardiographic derived TPVR measurement had good correlation with the invasive measurement (r = 0.92, P < 0.001) but also more simple and novel parameters of TPVR were found to be useful although the non-invasive TPVR measurement was feasible in only 29% of the studies due to lack of sufficient tricuspid valve regurgitation. However, echocardiographic measures of PAP, pulmonary artery flow acceleration time (PAAT) and deceleration (PAD), were measurable in all animals, and correlated with invasive PAP (r = -0.74 and r = 0.75, P < 0.001 for both). Right ventricular thickness and area correlated with invasive PAP (r = 0.59 and r = 0.64, P < 0.001 for both). Observer variability of the invasive and non-invasive parameters was low except in tissue-Doppler derived isovolumetric relaxation time. These non-invasive parameters may be used to replace invasive measurements in detecting successful disease induction and to complement invasive data in the evaluation of PAH severity in a rat model.

Fig. 1

Progression of PAH demonstrated by echocardiography at baseline, and 21 and 35 days after MCT induction. Columns represent temporal phases (baseline, day 21, and day 35) and rows five different imaging windows: (1) high parasternal short-axis view is used to detect pulmonary artery flow by pulsed-wave Doppler, right ventricular remodeling by (2) apical four-chamber view, (3) parasternal long-axis, (4) parasternal short-axis views using B-mode (all end-diastolic), and right ventricular thickness by (5) parasternal long-axis through aortic valve using M-mode. Upper row demonstrates different types of pulmonary artery flow profiles regarding to the severity of pulmonary hypertension. Normal, round-shaped flow profile (baseline), intermediate type flow profile with a sharp peak at early systole, decreased acceleration time and increased deceleration (day 21) and triangular flow profile with mid-systolic notching (day 35). Apical four-chamber and both parasternal views show progressive right ventricular dilatation with concomitant decrease of left ventricle. Parasternal long-axis images through aorta using M-mode show progressing right ventricular hypertrophy

Fig. 2

Correlations between TPVR by right heart catheterization and two different echocardiographic techniques. Echo-TPVR (formula-1) was calculated by dividing tricuspid regurgitation velocity from pulmonary artery velocity time integral (a), Echo-TPVR (formula-2) was calculated by the following formula (Echo TPVR = 80 * mean PAP in mmHg/cardiac output in liters) (b). Invasive TPVR was calculated using the previous formula and the mean PAP was derived from systolic PAP using previously validated formula [24], and Bland–Altman plot between Echo-TPVR formula-2 and invasive TPVR measurement (c)

Fig. 3

Correlation between invasive (right heart catheterization) measurement of PAP and its estimation from echocardiographically derived pulmonary artery acceleration time (a) and pulmonary artery deceleration (b)