Patient Population
This retrospective study was approved by the Institutional Review Board and did not require informed consent from patients. We retrospectively searched our hospital's database to select all patients who underwent simultaneous dynamic CT-MPI and CCTA. The clinical indication for the combination of CT-MPI and CCTA was to diagnose myocardial ischemia in symptomatic patients with known or suspected CAD, particularly those with an intermediate pretest probability of obstructive CAD [12]. Symptomatic patients aged ≥ 45 years with an intermediate pretest probability of obstructive CAD were included in this study. Exclusion criteria were as follows: 1) patients with history of myocardial infarction (MI); 2) patients with concomitant cardiomyopathies or significant other cardiovascular disease; 3) patients with history of revascularization including percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG); and 4) patients with impaired image quality of dynamic CT-MPI or CCTA. A total of 120 patients with dynamic CT-MPI plus CCTA were retrospectively reviewed.
Dynamic CT-MPI and CCTA Protocol
In all patients, a comprehensive imaging protocol integrating the coronary calcium score, dynamic stress CT-MPI, and CCTA was used. Dynamic CT-MPI was performed using third-generation dual-source CT (SOMATOM Force, Siemens Healthineers). The scan range of dynamic CT-MPI was determined based on the calcium score images to cover the left ventricle (LV) completely as well as all coronary arteries. Adenosine triphosphate (ATP) was intravenously infused over 3 minutes at 140 µg/kg/ min before triggering the MPI acquisition. A fixed volume of contrast media (40 mL, iopromide, 370 mg iodine/mL, Bayer AG) was given in a bolus injection at the rate of 5 mL/s in all patients, followed and followed by a 30 ml saline solution flushing (Dual shot GX7; Nemoto Kyorindo, Tokyo, Japan) continuously. Dynamic CT-MPI acquisition was started 4 seconds after the onset of contrast injection. The end-systolic phase (triggered at 250 ms after the R wave in all patients) was set for dynamic acquisition using a shuttle mode technique with coverage of 105 mm for complete imaging of the LV. Scans were launched every second or third heart cycle according to patient’s HR, resulting in a series of 10 to 15 phases acquired over a fixed period of 32 seconds. Nitroglycerin was given sublingually in all patients 10 minutes after dynamic CT-MPI, prior to the acquisition of CCTA. CCTA was performed using prospective electrocardiogram (ECG)-triggered axial scanning for patients with HR < 65 beats per minute and retrospective ECG-gated scanning with ECG pulse for patients with HR ≥ 65 beats per minute. A three-phase bolus at a rate of 4.5 mL/s was used for all CCTA examinations. For CCTA exam, a three-phase bolus was administered at a rate of 4.5 mL/s using a dual-head power injector (Dual Shot GX7; Nemoto Kyorindo, Tokyo, Japan). First, 0.9 mL/kg iopromide (Ultravist 370®; Bayer Healthcare, Berlin, Germany) was administered. Then, 45 mL of a 70-30% mixture of contrast medium and saline was administered. Finally, 30mL of saline solution was given (Fig. 1).
CT Data Reconstruction and Image Post-Processing
Dynamic CT-MPI images were reconstructed in the axial plane with 3-mm slice thickness and 2-mm overlap with a medium sharp convolution kernel (Qr40). The axial dynamic perfusion images were processed using commercial software (Syngo.CT Myocardial Perfusion, Siemens Healthineers). The data were then processed using prototype software (Cardiac Functional Analysis Prototype, Siemens Healthineers) to automatically segment the LV based on a heart model and generate 17-segment polar maps representing the myocardial blood flow (MBF) distribution within the subendocardial layer of the LV myocardium. All CCTA images were reconstructed with a medium soft convolutional kernel (Bv 40) using the 3rd generation iterative reconstruction technique (strength 3, ADMIRE, Siemens Healthineers). Data were transferred to an offline workstation and the dataset of optimal mid-diastolic and end-systolic phases was used for further analyses.
Image Analysis
Two readers (with 21 and 4 years of experience in cardiac imaging) who were blinded to the ICA and FFR results analyzed all data in consensus. The coronary diameter stenosis was defined as (reference diameter - minimal lumen diameter) / reference diameter. The coronary arteries were evaluated according to a 3-vessel and 16-segment coronary artery model modified from the American Heart Association classification. Each segment was classified as either non-significant (< 50% reduction in lumen diameter) or significant (≥ 50% reduction in lumen diameter) stenosis. Non-diagnostic segments were not evaluated because of cardiac or respiratory motion artifacts and severe calcification. We considered a non-diagnostic coronary segment as significant stenosis to avoid the risk of missing stenoses potentially present in non-diagnostic segments. A coronary vessel was considered as having a significant lesion if there was at least one segment that could not be evaluated or if the vessel had ≥ 50% lumen reduction.
CT-MPI maps were used to compare CCTA images side-by-side. The patient’s coronary anatomy on CCTA was used to assign myocardial perfusion defects to specific coronary vessels. A perfusion defect affecting two or more contiguous segments on CT-MPI is considered positive for ischemia. Based on the interpretation of available CCTA and CT-MPI images, the presence of hemodynamically significant CAD was determined per vessel territory. If CCTA and CT-MPI findings were discrepant, then myocardial perfusion overruled CCTA stenosis severity, unless CT-MPI image quality was compromised. The most severely affected coronary branch determined per-territory disease classification. For quantification of MBF, the round region of interest (ROI) that measured 1 to 2 cm2 were placed within each of the 16 myocardial segments, excluding an apex, in the short-axis view on the MBF map, at a minimal distance of 2 mm from the endocardial and epicardial borders to avoid contamination. Ischemic myocardium was defined as a segment with an absolute MBF < 100 mL/100 mL/min.