Pulmonary pulse wave transit time is associated with right ventricular-pulmonary artery coupling in pulmonary arterial hypertension

Abstract

Pulmonary pulse wave transit time (pPTT), defined as the time for the systolic pressure pulse wave to travel from the pulmonary valve to the pulmonary veins, has been reported to be reduced in pulmonary arterial hypertension (PAH); however, the underlying mechanism of reduced pPTT is unknown. Here, we investigate the hypothesis that abbreviated pPTT in PAH results from impaired right ventricular-pulmonary artery (RV-PA) coupling. We quantified pPTT using pulsed-wave Doppler ultrasound from 10 healthy age- and sex-matched controls and 36 patients with PAH. pPTT was reduced in patients with PAH compared with controls. Univariate analysis revealed the following significant predictors of reduced pPTT: age, right ventricular fractional area change (RV FAC), tricuspid annular plane excursion (TAPSE), pulmonary arterial pressures (PAP), diastolic pulmonary gradient, transpulmonary gradient, pulmonary vascular resistance, and RV-PA coupling (defined as RV FAC/mean PAP or TAPSE/mean PAP). Although the correlations between pPTT and invasive markers of pulmonary vascular disease were modest, RV FAC (r = 0.64, P < 0.0001), TAPSE (r = 0.67, P < 0.0001), and RV-PA coupling (RV FAC/mean PAP: r = 0.72, P < 0.0001; TAPSE/mean PAP: r = 0.74, P < 0.0001) had the strongest relationships with pPTT. On multivariable analysis, only RV FAC, TAPSE, and RV-PA coupling were independent predictors of pPTT. We conclude that shortening of pPTT in patients with PAH results from altered RV-PA coupling, probably occurring as a result of reduced pulmonary arterial compliance. Thus, pPTT allows noninvasive determination of the status of both the pulmonary vasculature and the response of the RV in patients with PAH, thereby allowing monitoring of disease progression and regression.

Keywords: echocardiography; pulse wave velocity; right ventricular–pulmonary artery coupling.

Figure 1

Reduced pulmonary pulse wave transit time (pPTT) in patients with pulmonary arterial hypertension (PAH) determined using echocardiography. Shown are examples of determination of pPTT from a control patient (A) and a patient with PAH (B). Pulse wave Doppler interrogation of right ventricular outflow track (RVOT; upper boxes) and pulmonary veins (PVs; lower boxes). C, Quantification of pPTT (mean ± standard error of the mean) from 10 control patients and 36 patients with PAH. Asterisk indicates P < 0.0001. R-PVs2: time interval between the R-wave in the electrocardiogram and the corresponding peak late-systolic PV flow velocity; R-RVOT: time interval between the R-wave in the electrocardiogram and the corresponding onset of RVOT pulse Doppler flow velocity.

Figure 2

Distribution of pulmonary pulse transit time (pPTT) in controls and patients with pulmonary arterial hypertension (PAH). Most patients with PAH had lower pPTT when compared with the median pPTT of the age- and sex-matched control group. pPTT in the X-axis has no units, because it is normalized to the cardiac cycle length in seconds using the formula (time from R-wave to peak S-wave on pulmonary vein Doppler − time from R-wave to onset of right ventricular outflow track Doppler)/cardiac cycle length.

Figure 3

Moderate correlation between pulmonary pulse transit time (pPTT) and invasively measured markers of pulmonary vascular disease. Scatterplots showing moderate negative correlations between pPTT and diastolic pulmonary gradient (DPG; r = −0.61, P = 0.0002; Fig. 3A), transpulmonary gradient (TPG; r = −0.55, P = 0.001; Fig. 3B), pulmonary vascular resistance (PVR; r = −0.38, P = 0.04; Fig. 3C), and mean pulmonary arterial pressure (mPAP; r = −0.45, P = 0.006; Fig. 3D).

Figure 4

Pulmonary pulse transit time (pPTT) is most strongly associated with markers of right ventricular–pulmonary artery (RV-PA) coupling in pulmonary arterial hypertension (PAH). Scatterplots showing correlation between pPTT and right ventricular fractional area change (RV FAC; r = 0.64, P < 0.0001; Fig. 4A), tricuspid annular plane systolic excursion (TAPSE; r = 0.64, P < 0.0001; Fig. 4B), RV-PA coupling as defined by RV FAC/mean pulmonary arterial pressure (mPAP; r = 0.72, P < 0.0001; Fig. 4C), and RV-PA coupling as defined by TAPSE/mPAP (r = 0.74, P < 0.0001).

Figure 5

Forest plot of multivariate analysis of pulmonary pulse transit time (pPTT) in pulmonary arterial hypertension (PAH). Right ventricular fractional area change (RVFAC; A), tricuspid annular plane systolic excursion (TAPSE; B), and RV-PA coupling defined as RV FAC/mean pulmonary artery pressure (mPAP; C) and TAPSE/mPAP (D) were significantly associated with pPTT after correcting for pulmonary vascular resistance (PVR), diastolic pulmonary gradient (DPG), transpulmonary gradient (TPG), mPAP, presence of diabetes, and age. P values are listed to the right. Data are presented as coefficient with 95% confidence interval.

Figure S1

Method of pulmonary pulse wave transit time (pPTT) measurement. pPTT was calculated as time from R-wave to peak S-wave on pulmonary vein Doppler (R-PVs2) minus time from R-wave to onset of right ventricular outflow tract Doppler (R-RVOT) divided by cardiac cycle length. EKG: electrocardiogram.