Shuang Leng1, Yang Dong2, Xiaoke Shang3, Xiaodan Zhao1, Ru-San Tan1,4, Wen Ruan1, Gangcheng Zhang5, John C. Allen4, Angela S. Koh1,4, Bryant Jennifer1, Lynette Teo6,7, Ping Chai7,8, James W. Yip7,8, Jonathan Yap1, Soo Teik Lim1,4, Marielle V Fortier4,9, Teng Hong Tan4,9, Ju Le Tan1,4, Yucheng Chen2, and Liang Zhong1,4
1National Heart Centre Singapore, Singapore, Singapore, 2West China Hospital, Chengdu, China, 3Wuhan Union Hospital, Wuhan, China, 4Duke-NUS Medical School, Singapore, Singapore, 5WuHan Asia Heart Hospital, Wuhan, China, 6National University Hospital, Singapore, Singapore, 7National University of Singapore, Singapore, Singapore, 8National University Heart Centre, Singapore, Singapore, 9KK Women's and Children's Hospital, Singapore, Singapore
Synopsis
Survival of patients
with pulmonary arterial hypertension (PAH) is closely related to right
ventricular (RV) function. This study aims to introduce a fast global
longitudinal strain (GLS) measurement for RV function assessment by
automatically tracking the distance variation between tricuspid annular
insertion points and the RV apical epicardium. The intra- and inter-observer
variation of coefficients range from 3.9% to 5.7% with processing time averaging
32
± 8 seconds per subject. Results demonstrate that lower fast GLS measurements are
closely related to impaired RV function and higher risks in PAH.
Background and Purpose
Pulmonary arterial
hypertension (PAH) is characterized by progressive elevation of pulmonary
artery pressure (PAP) and pulmonary vascular resistance (PVR). Although changes
in the pulmonary vasculature are the primary cause of PAH, survival of patients
with PAH is closely related to right ventricular (RV) function.1 The
assessment of RV function is challenging due to the complex geometric shape of
the RV and existence of prominent trabeculations. The aim of this study is to assess
the RV global longitudinal strain (GLS) in PAH using a fast semi-automated strain
measurement approach with cine cardiovascular magnetic resonance (CMR) images. Methods
Sixty-one patients (38
± 16 years, female/male: 49/12) with clinically diagnosed PAH and 61 age- and
gender-matched normal controls were enrolled. PAH is defined hemodynamically as
having1 1) mean PAP ≥ 25 mmHg; 2) pulmonary artery wedge pressure
(PAWP) ≤ 15 mmHg; and (3) PVR > 3 Wood units. Patients
were classified as low risk, intermediate risk or high risk according to
cut-off values for World Health Organization functional class, six-minute
walking distance, N-terminal pro-brain natriuretic peptide (NT-proBNP) level,
right atrial area, right atrial pressure (RAP), and cardiac index.1 All
subjects underwent CMR scan on a 3T system (Ingenia, Philips Healthcare).
End-expiratory breath hold cine images were acquired in multiple standardized
planes including the short-axis (SA) views and long-axis 4-chamber view. RV
end-diastolic and end-systolic volumes (EDV, ESV) and ejection fraction (EF)
were calculated with Simpson’s rule in all SA planes. The fast RV longitudinal
strain parameters were measured using an in-house semi-automated algorithm2-7 that tracked, on long-axis 4-chamber view, the distance ($$$L$$$) between the
tricuspid valve insertion points (septal and free wall) and the RV apical
epicardium (Fig. 1A). The strain of each
wall at time point ($$$t$$$) relative to RV
end-diastole (time 0) was measured based on the distance variation: $$$\frac{\left(L(t)-L_{0}\right)\times100}{L_{0}}$$$. Peak systolic RV
GLS was obtained at $$$t$$$ equal to RV end-systole, and the corresponding
peak GLS rate (GLSR) was derived (Fig. 1B).
GLS and GLSR measurements from the RV septal and free wall were then averaged
to obtained mean results for analysis. In addition, peak systolic tricuspid annular
velocity (Sm) and displacement (TAPSE) were calculated based on the tracking of
tricuspid annular points.2 Student’s t test was used for comparison between groups; p < 0.05 denotes statistical significance. Results
The fast RV GLS
assessment was feasible in all subjects. Average processing time per subject
was 32
± 8 seconds. Intra-observer coefficient of variation (CV) was 3.9% and 5.3% for GLS and GLSR, with corresponding
inter-observer CVs of 4.4% and 5.7%, respectively. RV longitudinal strain and strain rate were
significantly impaired in PAH group compared with the normal controls (GLS: -14.1 ± 4.4% vs -23.4 ± 3.3%; GLSR: -0.87 ± 0.28 s-1 vs. -1.18 ± 0.25 s-1,
both p < 0.001). Furthermore,
patients in the high-risk group had much lower RV GLS and GLSR measurements
compared with those in the low- and intermediate-risk groups (Table 1). Receiver operating
characteristics (ROC) analysis demonstrated that the fast GLS had higher
diagnostic accuracy to differentiate PAH from normal controls compared to
conventional parameter such as RVEF. The following cut-off values could be defined to identify diseased states: -20.3% for GLS (area under the ROC curve (AUC)
= 0.951, sensitivity = 93%, specificity = 83%); -1.01 s-1 for GLSR
(AUC = 0.806, sensitivity = 76%, specificity = 75%); 50% for RVEF (AUC = 0.837,
sensitivity = 70%, specificity = 90%). In the PAH patient group, lower RV GLS
correlated with higher RAP (r =
-0.39, p < 0.05), RV EDV index (r = -0.33, p < 0.05) and NT-proBNP (r
= -0.46, p < 0.001). Reduced RV
GLS was also associated with lower RVEF (r
= 0.51, p < 0.001), Sm velocity (r = 0.50, p < 0.001) and TAPSE (r
= 0.68, p < 0.001) in PAH
patients.Conclusion
The fast
semi-automated RV longitudinal strain enables a reproducible and accurate
evaluation of RV function. RV GLS was markedly reduced as the PAH risk class
progressed from low to high. This finding suggested that the fast GLS may represent
a more useful non-invasive imaging index of RV function than standard RV
indices and may be applied clinically for earlier detection and monitoring of
RV dysfunction in PAH.Acknowledgements
This study received funding support from the
National Medical Research Council of Singapore (NMRC/OFIRG/0018/2016; NMRC/TA/0031/2015),
Hong Leong Foundation, Duke-NUS Medical School and the Estate of Tan Sri Khoo
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