A New Method to Quantify Coronary Calcification by Intravascular Ultrasound

The Different Patterns of Calcification of Acute Myocardial Infarction, Unstable Angina Pectoris and Stable Angina Pectoris

ABSTRACT: Background. Intravascular ultrasound (IVUS) enables the identification of calcification with more details and quantification of calcification, but there is not a proper method to quantify the calcification with IVUS. Previous IVUS studies used arc or length of calcium, respectively, to quantify calcification, but calcium is determined by a combination of arc and length. We devised a new method to quantify calcium as arc area (AA) in the present study, and AA is two-dimensional and irrelevant to vessel size. Methods and Results. We selected 201 patients with stable angina pectoris (SAP), unstable angina pectoris (UAP), or acute myocardial infarction (AMI) who underwent IVUS imaging of a de novo native atherosclerotic lesion considered to be the culprit lesion before percutaneous coronary intervention between December 2001 and December 2007. The culprit lesion site for analysis was the 10-mm-long segment including the smallest lumen cross-sectional area. The arc of each calcium deposit in each image was measured with a protractor centered on the lumen and the length of each calcium deposit was calculated with the number of images containing the calcium deposit minus 1, then multiplying 0.5 mm (the images were 0.5 mm apart). Finally, the AA was calculated by arc (degree) multiplying length (mm). The average number of calcium deposits in the culprit lesions of patients with acute myocardial infarction (AMI) was significantly larger than patients with SAP or UAP, and the number of calcium deposits of patients with SAP or UAP was almost the same (mean ± SD, AMI 2.21 ± 1.98, SAP 1.15 ± 1.01, UAP 1.20 ± 1.15, AMI versus SAP or UAP; p Methods Patient selection. We selected 201 consecutive patients with SAP, UAP, or AMI who gave informed consent to undergo IVUS imaging before the study between December 2001 and December 2007. These patients underwent IVUS imaging of a de novo native atherosclerotic lesion considered to be the culprit lesion before percutaneous coronary intervention. We excluded patients with cardiac arrest, cardiogenic shock, severe heart failure or whose culprit vessel or lesion cannot be identified. Of the 201 patients, 55 patients had SAP, 75 had UAP and 71 had AMI. SAP was defined as chest pain typical of cardiac ischemia on exertion. UAP was defined either as new-onset angina within 2 months after a previous bout, angina with a progressive crescendo pattern (with anginal episodes increasing in frequency or duration), angina that occurred at rest, or angina that occurred in the immediate postinfarction period. AMI was diagnosed based on a history of prolonged ischemic chest pain, characteristic ECG changes, and elevated creatine kinase (greater than twice the upper limit of normal) within 24 hours after the onset of pain. IVUS imaging. All IVUS studies were performed after 0.2 mg intracoronary nitroglycerin and before intervention. IVUS studies were performed using a commercially available system (Boston Scientific Corp./Cardiovascular Imaging Systems, Inc., with a 30 MHz transducer). The IVUS catheter was carefully advanced distal to the culprit lesion under fluoroscopic guidance, and was then withdrawn automatically at 0.5 mm/sec to perform the imaging sequence, which started at least 10 mm distal to the culprit lesion and ended at least 10 mm proximal to the culprit lesion. Repeated injections of saline solution were performed to facilitate the identification of the lumen. IVUS studies were recorded on super VHS videotape for offline analysis. Quantitative assessment of calcification within the culprit lesion segment. Quantitative measurements were performed offline with a computer-assisted IVUS analysis system by a single experienced observer who was blinded to the clinical data. The culprit lesion was identified on the basis of clinical, ECG and angiographic stenosis ≥ 70%. The culprit lesion site for analysis was the 10-mm-long segment including the smallest lumen cross-sectional area. Calcium was defined by the presence of a bright echogenic signal with acoustic shadowing. In each patient, the calcium deposits within the 10-mm-long segment were quantified using serial cross-sectional IVUS images 0.5 mm apart. If a calcium deposit was visible beyond the segment, we followed it to the end. The arc of each calcium deposit in each image was measured with a protractor centered on the lumen and the length of each calcium deposit was calculated with the number of images containing the calcium deposit minus 1, then multiplying by 0.5 mm. Finally, the AA was calculated by arc (degree) multiplied by length (mm). The study was approved by the hospital ethics committee, and written informed consent was obtained from all patients before the study. Statistical analysis. Results are expressed as mean ± standard deviation (SD). Two-sample t-tests were used to compare the means of continuous variables and Chi square analysis was used to compare categorical variables. A p-valueResults Patient characteristics. Clinical characteristics of all patients are shown in Table 1. There were no statistically significant differences in age, gender, clinical history, drug treatment and culprit vessel among patients with SAP, UAP, or AMI. Calcifications. The results of calcium measurements are shown in Table 2. Ten, one, and three patients had calcium extending beyond 10 mm in the SAP group, UAP group and AMI group respectively; two patients with SAP had two calcifications extending beyond 10 mm. The average number of calcium deposits in the culprit lesions of patients with AMI was significantly larger than patients with SAP or UAP, and the number of calcium deposits in patients with SAP or UAP was almost the same (mean ± SD, AMI 2.21 ± 1.98, SAP 1.15 ± 1.01, UAP 1.20 ± 1.15, AMI versus SAP or UAP; p Discussion Quantifying calcification of coronary arteries has been a big problem, and quantifying total calcification burden or each calcium deposit is still challenging. IVUS offers a better method for quantifying calcification because it enables the identification of calcification with more details than either EBCT or MSCT. Previous methods of quantifying calcification with IVUS were varied, but they were all based on the arc or length, respectively.9–13 In our study, we combined the arc and length and devised a new method to quantify calcium as AA; AA = arc × length. AA is a two-dimensional parameter, while arc or length is only one-dimensional. The depth of the calcium deposit cannot be detected with IVUS to make a three-dimensional parameter, though calcium is three-dimensional. On the other hand, AA is a relative parameter and irrelevant to vessel size, so calcium can be compared in vessels of different size. AA is able to reflect the extent and degree of calcification more accurately than arc or length, respectively. Scott et al15 quantified calcium as the percentage of the coronary luminal surface, a method which is close to AA as a relative two-dimensional parameter, but more complicated than AA. Using AA, we found the culprit lesions of patients with SAP had the greatest calcification burden (greatest total AA per patient) due to the larger calcium deposits (larger average AA per calcium deposit) and fewer deposits of calcium. The culprit lesions of patients with AMI had less calcification burden (less total AA per patient) due to smaller calcium deposits (less average AA per calcium deposit) and a larger number of calcium deposits, the culprit lesions of patients with UAP had the least calcification burden (least total AA per patient) due to smaller calcium deposits (less average AA per calcium deposit) and a lower number of calcium deposits. The culprit lesions of patients with SAP had larger calcium deposits than patients with UAP or AMI and the culprit lesions of patients with AMI had a larger number of calcium deposits than patients with SAP or UAP. The culprit lesions of patients with SAP had fewer but bigger calcium deposits, patients with AMI had smaller but a larger number of calcium deposits, and patients with UAP had smaller and fewer calcium deposits. The explanation for why patients with SAP, UAP and AMI had different calcium burdens and a different number and size of calcium deposits is yet to be found. Previous studies11,12 and our present finding based on IVUS analysis concluded that the pattern of calcium deposits in SAP, UAP and AMI patients was different. The small or spotty calcification detected by IVUS, even cellular microcalcification detected by optical coherence tomography (OCT),16 is a characteristic of vulnerable plaque which can cause UAP or AMI. Extensive calcifications are associated with stable plaque and are found in SAP patients. Huang et al17 demonstrated that calcium is a stabilizing force for coronary plaques using large-strain finite-element analysis, and this calcium is identified in a histological cross-section of each coronary artery, thus it is a large calcium deposit. For the small, spotty calcium, it may have the opposite effect on the stability of coronary plaque, which could explain why the culprit lesion of a patient with SAP has larger but fewer calcifications; a patient with AMI has smaller calcification deposits, but larger in size; and the calcification of patients with UAP is just between them in size and number. Study limitations. Occasionally, it was difficult to identify culprit lesions, especially when there were more than one with severe stenoses (≥ 70%) in one coronary artery or in the right coronary artery and left circumflex artery, while ischemia appeared on the inferior wall on electrocardiography. In these situations, we selected the most severe stenosis as the culprit lesion, however, the culprit lesion was not always the most severe lesion. Acoustic shadowing caused by calcification made identification of the external elastic membrane difficult, so it was challenging to identify the center of the vessel, especially when the arc of calcification was > 90 degrees. We used two types of extrapolation (according to Mintz et al18), but this meant some deviation in arc measurement. Performing IVUS of culprit lesions in patients with AMI was difficult when the flow in the culprit vessel was below thrombolysis in myocardial infarction (TIMI) 2, or the IVUS catheter obstructed the vessel. In these cases, we usually used a balloon to cross the lesion or dilated the lesion before performing IVUS to deform the plaque and make the IVUS measurement change. In the present study, there were 39 patients in whom the lesion could not be crossed with an IVUS catheter, or the coronary arteries were obstructed by the IVUS catheter prior to intervention in the three groups. However, we were able to complete an IVUS study on most of them after low-pressure balloon dilatation, and only 5 of those who failed the IVUS procedure were excluded from the study; 2 of the 5 were patients with AMI. Seventeen patients with AMI were excluded because of cardiac arrest, cardiogenic shock or severe heart failure. Conclusions The culprit lesions of patients with SAP, AMI or UAP had greatest, less, or least calcification burden, respectively. The culprit lesions of patients with SAP had larger and fewer calcium deposits, patients with AMI had smaller and more numerous calcium deposits, and patients with UAP had smaller and fewer calcium deposits.

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