IMproving PULmonary hypertension Screening by Echocardiography: IMPULSE

Abstract

Background: The world symposium on pulmonary hypertension (PH) has proposed that PH be defined as a mean pulmonary artery pressure (mPAP) > 20 mmHg as assessed by right heart catheterisation (RHC). Transthoracic echocardiography (TTE) is an established screening tool used for suspected PH. International guidelines recommend a multi-parameter assessment of the TTE PH probability although effectiveness has not been established using real world data.

Study aims: To determine accuracy of the European Society of Cardiology (ESC) and British Society of Echocardiography (BSE) TTE probability algorithm in detecting PH in patients attending a UK PH centre. To identify echocardiographic markers and revised algorithms to improve the detection of PH in those with low/intermediate BSE/ESC TTE PH probability.

Methods: TTE followed by RHC (within 4 months after) was undertaken in patients for suspected but previously unconfirmed PH. BSE/ESC PH TTE probabilities were calculated alongside additional markers of right ventricular (RV) longitudinal and radial function, and RV diastolic function. A refined IMPULSE algorithm was devised and evaluated in patients with low and/or intermediate ESC/BSE TTE PH probability.

Results: Of 310 patients assessed, 236 (76%) had RHC-confirmed PH (average mPAP 42.8 ± 11.7). Sensitivity and specificity for detecting PH using the BSE/ESC recommendations was 89% and 68%, respectively. 36% of those with low BSE/ESC TTE probability had RHC-confirmed PH and BSE/ESC PH probability parameters did not differ amongst those with and without PH in the low probability group. Conversely, RV free wall longitudinal strain (RVFWLS) was lower in patients with vs. without PH in low BSE/ESC probability group (- 20.6 ± 4.1% vs - 23.8 ± 3.9%) (P < 0.02). Incorporating RVFWLS and TTE features of RV radial and diastolic function (RVFAC and IVRT) within the IMPULSE algorithm reduced false negatives in patients with low BSE/ESC PH probability by 29%. The IMPULSE algorithm had excellent specificity and positive predictive value in those with low (93%/80%, respectively) or intermediate (82%/86%, respectively) PH probability.

Conclusion: Existing TTE PH probability guidelines lack sensitivity to detect patients with milder haemodynamic forms of PH. Combining additional TTE makers assessing RV radial, longitudinal and diastolic function enhance identification of milder forms of PH, particularly in those who have a low BSE/ESC TTE PH probability.

Keywords: Echocardiography; Pulmonary hypertension; RV free wall longitudinal strain.

Fig. 1

Flow chart to assess the probability of pulmonary hypertension using parameters identified from within ≥ 2 categories (the ventricles, pulmonary artery or the inferior vena cava and right atrium) in conjunction with tricuspid regurgitation velocity. Adapted from [3]

Fig. 2

Proposed additional algorithm for those with low or intermediate TTE probability to help identify those with PH and low TTE probability. RVFAC normal cut-off values taken from (Harkness et al., 2020). RVFWLS (right ventricular free wall longitudinal strain); RVFAC (right ventricular fractional area change); IVRT TDI (isovolumetric relaxation time by tissue Doppler imaging); IMPULSE (improving pulmonary hypertension screening by echocardiography)

Fig. 3

Comparison of the frequency of WHO Classification of PH in those with an low echocardiographic probability of PH (N = 78)

Fig. 4

Kaplan–Meier survival curve analysis in 127 PH patients for RVFWLS over a follow-up period of 29 [19–40] months. RVFWLS was categorised into low risk (blue line, n = 73) and high risk (red line, n = 54). ROC derived cut-off RVFWLS value was used to categorise those at low (> − 15%) or high (≤ − 15.5%) risk of all-cause mortality. Kaplan–Meier survival curve analysis demonstrated a significant difference in survival between those with low risk RVFWLS scores and high risk RVFWLS scores (P < 0.01)

Fig. 5

a Comparison of mPAP (mmHg) relative to TTE probability of PH. Kruskal–Wallis analysis demonstrated mPAP values were significantly different across TTE PH probability groups; Kruskal–Wallis H = 138.2 (2) (P < 0.0001). Pairwise analysis with adjusted P-values demonstrated mPAP was significantly higher in those with either high or intermediate TTE probability compared to low (both P < 0.0001). mPAP was also significantly higher in those with intermediate compared to low TTE probability (P < 0.0001). mPAP (mean pulmonary artery pressure). b Comparison of PVR (woods units) relative to TTE probability of PH. Kruskal–Wallis analysis demonstrated PVR was significantly different across TTE PH probability groups; H = 138.3(2) (P < 0.0001). Pairwise analysis with adjusted P-values demonstrated PVR was significantly higher in those with high or intermediate TTE probability compared to low probability (both P < 0.0001). PVR was also significantly elevated in those with intermediate compared to low TTE probability (P < 0.0001). PVR (pulmonary vascular resistance)