A total of 61 patients who underwent both CCTA and LGE-CMR between January 2015 and December 2020 in our hospital were retrospectively enrolled. The exclusion criteria included: (1) high-intensity lesion in the anterior septum and lateral wall on LGE images that affects the observation of LLGE due to primary disease, or (2) poor LGE image quality on CCTA. Based on these criteria, three patients were excluded from the study, two of whom had obvious enhancement on LGE imaging (one with HCM and the other with cardiac amyloidosis) (Supplementary Fig. 1) and one who produced poor CMR image quality due to motion artifacts during image acquisition. Therefore, a total of 58 participants were included, of which forty patients (34 males, 45 ± 15 years of age) with LLGE + and eighteen patients (13 males, 45 ± 17 years of age) with LLGE- were studied. The study was approved by the Institutional Review Board of our hospital. This study was designed as a retrospective chart review, so written patient consent was waived.
Subjects were scanned with on 3-Tesla MRI scanner (Trio, Siemens Healthineers, Erlangen, Germany) using a 12-channel body array coil. Before scanning, the patient-specific CV shimming sequence was used to shimmer the heart region to improve field uniformity. A breath-hold, retrospective, electrocardiogram (ECG)-gated balanced steady state free-precision (bSSFP) cine sequence was used to obtain cine images, including the LV 2- and 4-chamber long-axis and short-axis stack covering the entire LV from base to apex. LGE images were acquired 10 minutes after injection of a 0.2 mmol/kg bolus of gadoteric acid meglumine (Dotarem, Guerbet, BP7400, F95943, Roissy CdG Cedex, France), with a Phase Sensitive Inversion Recovery (PSIR) sequence with the following parameters: FOV 400 × 300 mm2, matrix 256 × 166, TR/TE 301.7/1.09 ms, flip angle 35 degrees, 6 mm thickness, and slices including the LV 2- and 4-chamber long-axis and short-axis stack covering the entire LV from base to apex.
The CCTA was conducted using a 64-multidetector row scanner (SIEMENS; SOMETOM Definition, Germany). Metoprolol was used at 5 mg increments up to a total possible dose of 25 mg to reduce the heart rate if it was greater than 75 beats per minutes in the absence of any contraindications. A total of 40–50 ml of iohexol (350mg iodine/ml; Yangtze River Pharmaceutical Co., Ltd, Jiangsu) was injected for angiography into an antecubital vein at a flow rate of 5 ml/s followed by a 50 ml flush of normal saline at the same flow rate. The scan parameters were as follows: matrix, 512 × 512; collimation, 64 mm × 0.625 mm; tube rotation time, 350 ms; and tube current, 300–400 mA at 100–120 kV for subjects based on their body size. Retrospective ECG-gated mode (heart rate > 60 beats/min) or prospective ECG-gated mode (heart rate ≤ 60 beats/min).
Short-axis LGE images were analyzed by two radiologists with more than ten years of experience and who were blinded for clinical events. The definitions of LLGE + were as follows: (1) In the anterior septum or lateral wall, the linear high-intensity signal could be clearly seen in the epicardium or mid-wall of the myocardium, and (2) LLGE observable at 10 mm or more in the anterior septum and lateral wall. Based on previous studies, 15 mm was set as the cut-off value to exclude the possibility of artifacts. In this study, LGE images were obtained by the PSIR technique with higher resolution, so 10 mm was used as the criterion for determining LLGE. Other patients were regarded as LLGE-. In addition, the length of LLGE in the anterior septum and lateral wall was measured.
For nine patients with hypertrophic cardiomyopathy (HCM), LGE quantification was measured using CVI42 software (Circle Cardiovascular Imaging Inc., Calgary, Alberta, Canada). LV endocardial and epicardial borders on the LGE images were manually traced, taking care to avoid partial-volume effects from the blood pool and epicardial fat. LGE was defined as the signal intensity of the myocardium greater than or equal to 5 standard deviations above that of the remote myocardium, which has been shown to have the best accuracy with histology-verified fibrosis in HCM. LGE% was used to express the percentage of enhancement area mass in the total mass of the left ventricular myocardium. After manually removing the LLGE region, the LGE% was measured again.
The short-axis MIP images of the left ventricle were reconstructed on the diastolic images of the CCTA, and the slices corresponded to the LGE, with a slice thickness of 8 mm. The CCTA images were evaluated by another radiologist to determine whether there was a septal perforator artery or circumflex branch in the epicardium or mid-wall of the myocardium, and the lengths of the septal perforator artery and circumflex branch artery were measured. All the CCTA images were evaluated on a 3D image analysis workstation.
The Kolmogorov-Smirnov test was used to test the normality of the variables. Quantitative data with a normal distribution were expressed as the mean and standard deviation (SD), whereas the other measurement data were expressed as the median (first quartile, third quartile). The counting data were showed as the number of cases. Independent Student’s t tests were used to compare the differences in the continuous data, and the chi-squared test or Fisher’s exact test were used to evaluate the differences in proportions. For LLGE + patients, Pearson correlation coefficients were used to assess the correlation between LLGE length on CMR and the artery on CCTA. The LGE% between the original measurement and second measurement after removing the LLGE manually was compared using the paired t test among the HCM patients. Bland-Altman analysis was used to evaluate the consistency of lengths between LLGE and the artery on CCTA. P < 0.05 was considered to be statistically significant. Data were analyzed using SPSS (version 21.0, Statistical Package for the Social Sciences, International Business Machines, Inc., Armonk, New York, USA) and GraphPad Prism (version 6.01, GraphPad Software, Inc., La Jolla, California, USA).