Smartscore 4

All cardiac computed tomography (CT) scans were performed using a 64-channel detector scanner (LightSpeed VCT; General Electric (GE) Healthcare, Milwaukee, WI, USA) in cine mode. Scans were ECG-gated and a standard non-contrast protocol was used with a tube voltage of 100 kV, tube current of 200 mA, 350 ms rotation time, 2.5 mm slice thickness and displayed field of 25 cm. Calcium deposits in the coronary arteries were identified by a radiologist with Level 2 competence and extensive experience of cardiac CT interpretation. Data were subsequently processed and analysed using an Advantage Workstation (GE Healthcare). Smartscore 4.0 (GE Healthcare) was used to assess CAC scores. Calcified plaques were considered to be present if values exceeded the standard threshold of 130 Hounsfield units. The CAC scores were expressed in Hounsfield units (HU) as previously described in detail [45 (link)]. Total CAC score was defined as the sum of the CAC scores in the left main artery, the left anterior descending artery, the left circumflex artery and the right coronary artery.

Most patients have clinical symptoms such as chest pain and the ischemic change in electrocardiogram, which are suspecting symptoms of coronary arteriosclerosis. Thus, CCTA, an accurate non-invasive approach, was carried out twice to diagnose whether fatty deposits or calcium deposits were present in the coronary arteries. CAC was assessed by CT performed on a 64-channel detector scanner (SOMATOM Definition Flash 128, Siemens, Germany; SCENARIA 128) in the cine and straight mode. Scans were assessed by the electrocardiogram (ECG)-gated method, and a standard non-contrast protocol was used with a tube voltage of 120 kV, tube current of 50–80 mA, rotation time of 280 ms, slice thickness of 3 mm, and display field of view (DFOV) of 20 × 20 cm. CAC data were processed and analyzed using SYNAPSE VINCENT (FUJIFILM). These CAC data were blinded and evaluated by a single radiologist. SMARTSCORE 4.0 (GE Healthcare) was used to assess the CAC scores. Plaque measurement software automatically recognized the plaques and lumens, and vessel walls and plaque edges were then manually modified where needed in order to define both ends of the plaques.

The coronary calcium score was calculated using semi-automatic software (SmartScore 4.0, GE Healthcare, Milwaukee, WI, USA) on the Advantage Workstation 4.4 (GE Healthcare, Milwaukee, WI, USA). The total calcium burden of the coronary arteries was reported in terms of AJ-130 score, based on the scoring algorithm of Agatston et al. [25] (link).

Images were transferred to a dedicated workstation (Advantage AW 4.4, GE Healthcare) with a dedicated CACS software (SmartScore 4.0, GE Healthcare). All pixels with an attenuation equal or above the lowest threshold (e.g., ≥ 130 HU for 120-kV scans) having an area ≥ 1 mm² are automatically color marked, and lesions are manually selected by creating a region of interest around all lesions found in a coronary artery. The software then calculates the CAC score, as previously described.^{20 (link)} In brief, a score for each region of interest is calculated by multiplying the density score (i.e., the thresholds) and the area of calcifications. A total CAC score is then determined by adding up the scores for each CT slice. Importantly, the software computes an overall CAC score and vessel-wise CAC scores. Of note, the thresholds for CACS are only applied to pixels with a density equal or larger than the lowest threshold and an area of ≥ 1 mm². This eliminates single pixels with a density above the thresholds due to noise. All datasets were analyzed by two experienced readers in random order, and measurements from both readers were averaged.^{8 (link)} CAC risk categories were defined according to the following CAC score boundaries: 0, 1-100, 101-400, > 400.

Agatston score[7 (link)] was derived from CAC CT datasets using SmartScore 4.0 ™ (AW server 3.2, GE Healthcare). The entire coronary arterial tree was inspected and interrogated for the presence of calcified plaques by a CT technologist with 17 years of experience (CCC) under the supervision of a thoracic radiologist with 25 years of experience (MTW). A calcified plaque was defined as an area of 3 connected voxels with a CT attenuation ≥ 130 Hounsfield unit (HU) applying 3D connectivity criteria. Agatston score of each calcification was calculated[7 (link)], summed up, and converted into three ranks (1-100, 101–400, and > 400).
Radiomics analyses were performed using the LIFEx (version 6.1) package [19 (link)]. A semi-automated segmentation with the same ROI used for Agatston scoring was used to analyze radiomics parameters. Shape features, first-order histogram features, were extracted from the 77 1:2 propensity-matched group, which is composed of volume, mean, median, standard deviation, covariance, kurtosis, and skewness. Kurtosis is the peakedness of the pixel histogram, and a Gaussian distribution histogram has a kurtosis value of 3. Skewness is the measure of the asymmetry of a distribution, and a Gaussian distribution histogram has a skewness value of zero. [20 (link)].

Participants underwent the scans of HDCT (Discovery CT 750 HD, GE Healthcare, Wisconsin, USA). All scans were performed in the same room using the same equipment, and analyzed by the consensus of two radiologists with more than two years of experience blinded to all participants and prior information. For defining the quantity of coronary calcium, the Agatston, volume and mass scores were calculated using the software (Smart Score 4.0, GE Healthcare, Wisconsin, USA) on the three-dimensional workstation (Advantage Windows Workstation 4.5, GE Healthcare, Wisconsin, USA), according to the following equations: 1) Agatston score = slice increment/slice thickness × ∑(area × cofactor); 2) volume score = ∑(area × slice increment); and 3) mass score = ∑(area × slice increment × mean CT density) × calibration factor [13 (link), 14 (link)]. The sum of all scores for each coronary artery including left main artery, left anterior descending artery, left circumflex artery and right coronary artery was used to generate the total CAC scores (Fig. 1).Fig. 1

Flow chart of study participants with inclusion and exclusion criteria

To obtain the CAC score, a non-enhanced scan was performed, using a prospectively ECG-triggered scan protocol: detector configuration 64 x 0.625 mm, rotation time 350 ms, tube potential 120 kV, tube current 200 mA.
The CAC score was calculated using semi-automatic software (SmartScore 4.0, GE Healthcare, Milwaukee, WI, USA) on the Advantage Workstation 4.4 (GE Healthcare, Milwaukee, WI, USA). The total calcium burden of the coronary arteries was reported in terms of AJ-130 score, based on the scoring algorithm of Agatston et al [26 (link)].