Study patients
Using two-dimensional (2D) echocardiography, we retrospectively enrolled 50 patients with NICM having LVEF of < 50% in whom both STE and CMR were performed between January 2014 and June 2017 and who did not fit the exclusion criteria. All patients had experienced chronic cardiac failure of at least 12 months, with the typical onset symptoms of this condition, including gradually progressive breathlessness, fatigue, and palpitation. None of the patients in the present study exhibited clinical symptoms or signs of ongoing myocarditis. The presence of severe coronary artery disease (CAD; > 50% diameter luminal stenosis in any coronary artery) was ruled out in all patients using coronary angiography. Moreover, patients with cardiogenic shock, unstable hemodynamic status, severe renal dysfunction (glomerular filtration rate < 30 ml/min/1.73 m2), CMR contraindications (e.g., metal implants), moderate or severe mitral and aortic valve regurgitation or stenosis [15, 16], hypertrophic cardiomyopathy, any infiltrative heart disease, atrial fibrillation, and postcardiac operation were carefully excluded. The present study was approved by the Committee for the Protection of Human Subjects in Research at Wakayama Medical University.
Echocardiographic measurements
Standard transthoracic echocardiographic examinations were performed in all patients using a Vivid E9 or Vivid 7 digital ultrasound system (GE Medical Systems, Horten, Norway). Echocardiography was performed within 1 week of performing CMR. Images were recorded with > 40 frames per second. Two cardiac cycles were stored in cineloop format for offline analysis. LV end-diastolic volume index (LVEDVI), LV end-systolic volume index (LVESVI), LVEF, and left atrial volume index (LAVI) were measured using biplane Simpson’s rule from the apical four- and two-chamber views, according to the criteria established by the American Society of Echocardiography [17]. The E and A waves were measured based on the mitral inflow profile, assessed in the apical four-chamber view using pulsed-wave Doppler echocardiography, with the sample volume placed at the tips of mitral leaflets during diastole. The e’ velocity from the septal and lateral mitral valve annuli was measured in the apical four-chamber view using Doppler tissue imaging of the mitral annulus. The systolic transtricuspid pressure gradient (TR-PG) was calculated from the maximal continuous-wave Doppler velocity of the tricuspid regurgitant jet, calculated using the modified Bernoulli equation.
STE-GLS was determined using 2D speckle-tracking strain analysis using an EchoPAC version 113 workstation (GE Medical Systems, Horten, Norway), as described previously [18–20]. This speckle-tracking software tracks the frame-to-frame movement of speckles (natural acoustic markers) in standard 2D echocardiographic images. The percentage change in length/initial length of the speckle pattern over the cardiac cycle was calculated as the longitudinal strain.
Two-dimensional speckle-tracking strain analysis was performed using standard 2D images of the apical two-chamber, four-chamber, and long-axis view by a certified and experienced cardiologist blinded to the CMR data. After defining the mitral annulus and apex at the end-systolic frame in each view, the software automatically traced the endocardial border, mid-myocardial layer, and epicardial border, including the entire myocardium. The width of the region of interest (ROI) was manually adjusted to ensure accurate tracking of the myocardial wall. The software automatically tracked speckles throughout the cardiac cycle; it accepted segments of good tracking quality and rejected poorly tracked segments. The tracking algorithm facilitates further manual adjustment of ROI for ensuring that all myocardial segments were included throughout the cardiac cycle. After completion of 2D speckle tracking in the three apical views, the results of the LV longitudinal strain analysis were automatically combined in a single bull’s eye summary provided the peak systolic longitudinal strain for each LV segment, with the mean peak systolic longitudinal strain value for each view and mean global longitudinal peak systolic strain value for the entire left ventricle (STE-GLS).
A total of 15 patients was randomly selected for assessment of intra- and interobserver reliability of speckle-tracking echocardiographic measurements. The intraobserver analysis was performed by the same observer at two different time points; the observer was blinded to the clinical information and investigation results of the other time point. The interobserver analysis was performed by two observers who were blinded to the clinical information and investigation results. We evaluated the intra- and interobserver reliability of speckle-tracking echocardiographic measurements using intraclass correlation coefficient (ICC).
CMR
All CMR examinations were performed using a 1.5-T clinical scanner (Intera Achieva; Philips Medical Systems, Best, the Netherlands), equipped with a 32-element cardiac phased-array coil for signal reception, as previously described. During the examination, patients were continuously monitored using single-lead electrocardiography, repeated blood pressure measurements, and pulse oximetry. With the patient in the supine position, contiguous short-axis cine images encompassing the left ventricle from base to apex were acquired using a standard steady-state free precession sequence. LGE imaging covering the entire ventricle was performed 10–15 min after the intravenous injection of 0.1 mmol/kg gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA; Magnevist, Schering, Berlin, Germany). We used a three-dimensional inversion recovery turbo gradient echo sequence, and images were obtained during an end-expiratory breath hold. Scan parameters were as follows: TR, 4.1 ms; TE, 1.25 ms; flip angle, 15°; FOV, 350 × 350 mm; partial echo; matrix, 224 × 256; and spatial resolution, 1.56 × 2.24 × 10 mm3 reconstructed to 0.68 × 0.68 × 5 mm3. The inversion time was adjusted to nullify the signal from viable myocardium [21].
All analyses were performed by consensus of the certified and experienced cardiologists blinded to the echocardiographic data on an offline workstation (View Forum, Philips Medical System). According to the previous studies [22, 23], the area of LGE was defined as the area with a signal intensity of 5 SDs above the mean signal obtained in the normal myocardium on LGE images.
Statistical analysis
All statistical analyses were conducted using JMP Pro 13 (SAS Institute Inc., Cary, NC, USA). Categorical variables, presented as frequency counts and percentages, were compared using the Fsher’s exact test. Distribution of the continuous data was assessed using the Shapiro–Wilk test. Normally distributed variables were analyzed using the Student’s t-test, whereas abnormally distributed variables were analyzed using the Wilcoxon test. Receiver operating characteristic (ROC) curve analysis was performed to establish STE-GLS as a predictor of the presence of CMR-LGE. The resulting sensitivity, specificity, and the area under the curve (AUC) were calculated. The best threshold value was determined by the maximum sum of sensitivity and specificity. A p value of < 0.05 was considered statistically significant.