Patients
Consecutive treatment naive patients undergoing RHC and CMR for suspected PH were identified between January 2008 and March 2010 at a high volume nationally designated PH referral centre. All incident patients with suspected PH routinely undergo CMR as part of their diagnostic work-up. Inclusion criteria required the patients’ RHC and CMR to be within 48 h, and patients were excluded if the imaging was of non-diagnostic quality. Other exclusion criteria were as per standard criteria for patients undergoing CMR. Approval for retrospective analysis of imaging techniques was granted by the local research ethics committee.
CMR acquisition
CMR was performed on a 1.5 T whole body scanner GE HDx (GE Healthcare, Milwaukee, USA), using an 8 channel cardiac coil. 4 chamber and short axis cine images were acquired using a cardiac gated multi-slice balanced steady state free precession sequence (20 frames per cardiac cycle, slice thickness 8 mm, FOV 48, matrix 256 × 256, BW 125 KHz/pixel, TR/TE 3.7/1.6 ms). A stack of images in the short axis plane with slice thickness of 8 mm (2 mm inter-slice gap) were acquired fully covering both ventricles from base to apex. For short axis imaging end-systole was considered to be the smallest cavity area. End-systole was defined as maximal RV shortening on the 4 chamber slice images. End-diastole was defined as the first cine phase of the R-wave triggered acquisition for both short axis and four chamber imaging. Ten minutes following gadolinium contrast injection (0.1 mmol/kg of gadolinium-DTPA; Gadovist, Bayer, Germany), late-enhancement imaging was performed using a 3D-gradient spoiled echo sequence (repetition time 7.7 ms, echo time 3.6 ms, TI 180 ms, slice thickness 8 mm, FOV 45 × 40.5,matrix 256 × 224). Selective 180° inversion-recovery images were acquired in the short axis obtaining limited 3–5 slices through the ventricles. We have corrected our MR parameters where appropriate for body surface area, as previously reported in the literature [19]. Phase contrast imaging parameters were as follows: repetition time 5.6 ms, echo time 2.7 ms, slice thickness 10 mm, FOV 48 × 28.8, band-width 62.5 kHz, matrix = 256 × 128, 20 reconstructed cardiac phases and velocity encoding 150 cm/s in the slice direction. Phase contrast imaging was performed orthogonal to the pulmonary arterial (PA) trunk Studies were performed with patients in the supine position with a surface coil and with retrospective ECG gating.
Image analysis
Image analysis was performed on a GE Advantage Workstation 4.1 by a pulmonary vascular radiologist (AS) (with 2 years specialist experience in CMR) who was blinded to the patient clinical information, and cardiac catheter parameters. Patient’s scans were defined as non-diagnostic when image quality significantly affected cardiac measurements or volumetric analysis could not be accurately performed.
RV ejection fraction (RVEF), end-diastolic volume (RVEDVI), stroke volume (RVSVI)
Endocardial surfaces were manually traced from the stack of short-axis cine images, using our MR workstation software (GE Advantage Workstation ReportCard) to obtain RV end-diastolic and end-systolic volumes. From end-diastolic volume and end-systolic volumes, the RVEF and RVSV were calculated. RVSVI was defined as RVSV/body surface area (BSA) measured in ml/m2, see Figure 1.
RV mass index and ventricular mass index (VMI)
The RV epicardial and endocardial borders on each end-diastolic short axis slice image were outlined. The IVS was considered as part of the LV. The myocardial volume for each slice was calculated by multiplying the area of the RV wall by the slice thickness. The product of the sum total of the myocardial slice volumes for each ventricle and the density of myocardium (1.05 g/cm3) gave an estimate of RV mass[9]. RV mass index was defined as RV mass/body surface area (BSA) measured in g/m2. The LV epicardial and endocardial borders on each end-diastolic short axis slice were outlined, LV end diastolic mass was thus derived. VMI was defined as RV mass divided by LV mass, Figure 1.
RV relative area change (RVRAC)
The endocardial contours at end-diastole and end-systole were manually segmented. RVRAC expressed as a percentage was calculated from the 4 chamber plane images using the following formula: RAC = 100[(Diastolic area-Systolic area)/Diastolic area].
Longitudinal function
Longitudinal RV motion was assessed using Tricuspid Annular Plane Systolic Excursion (TAPSE), a measurement previously evaluated using echocardiography and MRI [20–22]. TAPSE was calculated manually from the change of the tricuspid annulus-apex distance between end-diastole and end-systole 4-chamber images. Fractional measure of longitudinal motion utilised the tricuspid annulus apex distance change (fractional- TAAD) and was calculated as TAPSE divided by the tricuspid annulus-apex dimension at end-diastole expressed as a percentage. This method was previously described by Kind et al. [22].
Transverse function
Transverse RV function was determined from the change of the septum-free-wall perpendicular distance (SFD) at the mid-point between the apex and the base. This was measured manually as the change between the SFD at end-diastole and SFD at end-systole on the 4-chamber images. Fractional-SFD was calculated as for fractional longitudinal function [22].
Left ventricular eccentricity
Left ventricular eccentricity measurements have been traditionally expressed as the ratio of the length of two LV perpendicular minor-axis diameters [23]. Systolic eccentricity index measurements were obtained from the mid-chamber SA end-systolic image, the ratio was calculated by the formula sEI = D2/D1, where D2 is the diameter parallel and D1 is perpendicular to the IVS. Abnormal values derived from echocardiography are considered to be > 1.2 [23]. dEI was calculated from the mid-chamber SA end-diastolic image using methods as described.
Phase contrast indices – PA (n = 106)
Phase contrast CMR was performed at our institution beginning May 2009. Phase contrast Q flow CMR was analysed using Reportcard software. The following indices were generated: average velocity (cm/s), retrograde flow (L/min) and percentage retrograde flow (%) Maximal and minimal pulmonary artery areas were recorded, and relative area change (RAC) was defined by the following: (maximal area-minimum area)/minimum area.
Late gadolinium enhancement CMR
Late enhancement images were qualitatively assessed for hyper-intensity at the inter-ventricular septal hinge points or along the septum as previously described. The presence or absence of delayed enhancement was recorded.
Echocardiography
Echocardiography was performed using Powervision 6000 and 8000 machines (Toshiba, Japan) by trained cardiac physiologists as part of routine clinical care at a high volume PH referral centre using a standard protocol for these patients. Multiple windows were used to obtain the optimal Doppler estimation of tricuspid regurgitant jet velocity (TRJV) and tricuspid gradient (TG) calculated using the modified Bernoulli equation, TG = 4 x TRJV2 . Saline agitation was not used. Right atrial pressure was estimated from the diameter and respiratory variation of the inferior vena cava. Estimates of right atrial pressure and TRJV were used to estimate PA systolic pressure (PA systolic pressure = tricuspid gradient + estimated right atrial pressure). For the purpose of comparison with right heart catheter measures of MPAP and CMRI estimates, MPAP was defined as 0.61 x PA systolic pressure + 2 mmHg [6].
RHC and clinical evaluation
RHC was performed using a balloon-tipped 7.5 Fr thermodilution catheter (Becton-Dickinson, USA). Patients referred for the investigation of suspected PH also underwent clinical evaluation including; blood testing, echocardiography, computed tomography scanning, lung function testing, exercise testing and perfusion lung imaging. Diagnostic classification of the form of PH was by standard criteria following multidisciplinary assessment [24].
Statistics
Comparisons of CMR measurements between ‘No PH’ and PH patients were analysed using the independent t-test for continuous data, the chi-square for categorical data and anova testing with bonferroni corrections for multiple variables. Pearson’s correlation coefficient was used to assess the correlations between CMR parameters and RHC values. Receiver operating characteristic (ROC) analysis was used to test the diagnostic strength of CMR parameters for the detection of the presence or absence of PH. ROC curve analysis results are presented as area under the curve (AUC). The sensitivity, specificity, negative and positive predictive values of CMR indices for determining the presence or absence of PH was assessed using Fisher’s exact test. A p-value < 0.05 was considered statistically significant. To perform and display the statistics, SPSS 18 (SPSS, Chicago, Ill) and GraphPad Prism 5.03 (GraphPad Software, San Diego, Calif) software were used.