The Site of Plaque Rupture in Native Coronary Arteries

A Three-Vessel Intravascular Ultrasound Analysis

Methods

IVUS imaging and analysis

The IVUS examinations of all three major epicardial arteries were performed before intervention and after intra-coronary administration of 0.2 mg nitroglycerin with motorized transducer pullback system (0.5 mm/s) and a commercial scanner (Boston Scientific Corp./SCIMED, Natick, Massachusetts) consisting of a rotating 30 MHz transducer within a 3.2-F imaging sheath. After successful pre-interventional imaging and treatment of the culprit/target lesion, pre-intervention IVUS examinations of the remaining non-culprit/non-target arteries and lesions were performed before any additional treatment.

Qualitative and quantitative analyses were performed according to criteria of the Clinical Expert Consensus Document on IVUS (6).

The IVUS criteria for plaque rupture were a plaque containing a cavity that communicated with the lumen with an overlying residual fibrous cap fragment (7). A typical example of plaque rupture is shown in Figure 1.The diagnosis of plaque rupture required independent review and agreement by two of the authors (M-K.H. and Y-H.K.). Confirmation of the initial 279 plaque ruptures by a second reader and repeat evaluation by the first reader resulted in 6 plaque ruptures being excluded from this study.

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Figure 1

Angiographic and intravascular ultrasound image of a typical ruptured plaque (arrow)in a right coronary artery are shown.

In all three coronary arteries in each of the patients studied, the transducer was advanced into the distal coronary artery; and an imaging run was performed back to the aorto-ostial junction. With motorized transducer pullback, we measured the distance from each plaque rupture back to the respective coronary ostium (pullback speed multiplied by number of seconds).

Quantitative IVUS analysis was performed with computerized planimetry at the plaque rupture site. Quantitative measurements included external elastic membrane and lumen cross-sectional area (CSA). The intraplaque cavity CSA was measured (8).

Results

Baseline clinical characteristics of the 206 patients are shown in Table 1.Multiple plaque ruptures (≥2 plaque ruptures) were observed in 53 patients (40 ACS patients and 13 SAP patients). Thus, a total of 273 plaque ruptures were detected in 247 coronary arteries: 143 ruptures in 128 left anterior descending arteries (LAD), 40 ruptures in 38 left circumflex arteries (LCX), and 90 ruptures in 81 right coronary arteries (RCA) (Fig. 2).In these 247 arteries with at least one plaque rupture, the total length of the coronary artery imaged by IVUS was 83 ± 14 mm in the LAD, 77 ± 12 mm in the LCX, and 101 ± 22 mm in the RCA.

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Figure 2

The frequency of 273 plaque ruptures according to distance from each coronary ostium is shown for the left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA).

As illustrated in Figure 3,at least the proximal 50 mm of each of the three arteries was imaged in each patient. The frequency of plaque ruptures located in segments 0 to 30 mm, 30 to 60 mm, 60 to 90 mm, and >90 mm from the coronary ostium when these corresponding segments were actually imaged(thereby, excluding segments that could not be reached with the IVUS catheter) were 61% (150 of 247), 35% (86 of 247), 13% (29 of 233), and 8% (8 of 102), respectively (p <0.001).

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Figure 3

The length of coronary artery containing each plaque rupture imaged with intravascular ultrasound is shown. Abbreviations as in Figure 2.

A LAD plaque rupture was predominantly located in the segment between 10 and 40 mm from the LAD ostium (83%, 119 of 143). The LCX plaque ruptures were evenly distributed throughout the length of the LCX that was imaged. Most RCA plaque ruptures were located in the segments between 10 and 40 mm (48%, 43 of 90) and in the segments beyond 70 mm from the RCA ostium (32%, 29 of 90). This is also illustrated in Figure 2.

There were 197 culprit/target lesion plaque ruptures and 76 non-culprit/non-target lesion plaque ruptures (Fig. 4).The clustering of the plaque ruptures was similar in culprit/target lesions compared with non-culprit/non-target lesions. Quantitative IVUS measurements at ruptured plaque sites comparing culprit/target lesions and non-culprit/non-target lesions are shown in Table 2.Thrombi were found in 129 culprit/target (66%) versus 21 non-culprit/non-target lesions (28%) (p < 0.001).

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Figure 4

The frequency of plaque ruptures according to distance from each coronary ostium is shown for the LAD, LCX, and RCA. Culprit/target lesions and non-culprit/non-target lesions are shown separately. Abbreviations as in Figure 2.

There were 206 plaque ruptures in ACS patients and 67 plaque ruptures in SAP patients. The clustering of plaque ruptures, similar to the total cohort, was also similar between ACS and SAP patients.Table 3shows quantitative IVUS ruptured plaque segment measurements, comparing ACS and SAP patients.

Angiographic appearance was normal in 16 lesions (6%), hazy in 8 (3%), and revealed aneurysm/ulceration in 26 (10%), simple stenosis in 44 (16%), and complex stenosis in 179 (65%). Plaque ruptures were located at areas of high shear stress: 136 lesions (50%) near a branch point and 31 lesions (11%) on an angulated point.

Discussion

With three-vessel IVUS imaging, we evaluated the geographic distribution of both culprit/target lesion plaque rupture as well as non-culprit/non-target lesion plaque ruptures in native coronary arteries in 395 patients with both ACS and SAP. Plaque ruptures—especially culprit/target lesion plaque ruptures—were clustered mainly in the proximal segments of the LAD, in the proximal and distal segments of the RCA, and in the entire LCX.

In a recent angiographic study, Wang et al. (1) analyzed 208 consecutive patients with ST-segment elevation MI to determine the location of epicardial thrombosis. These occlusions tended to cluster within the proximal third of each coronary artery. The current study agrees with Wang et al. regarding the proximal distribution of LAD (83%) and RCA (48%) plaque ruptures; however, in the current study, 32% of RCA plaque ruptures were >70 mm from the RCA ostium, and there was no predilection for LCX plaque rupture to develop at any one specific location. The reasons for the differences between the current IVUS study and the previous angiographic study are unclear, but the study populations were different, and the number of LCX plaque ruptures or acute occlusions was small in both studies. The angiographic study enrolled patients with acute vessel occlusion regardless of the underlying plaque pathology (plaque rupture vs. erosion), whereas we included any plaque rupture regardless of clinical consequences. Therefore, especially in the RCA, which has few branches, the initial event may be more distal and the angiographic occlusion more proximal, following retrograde thrombus propagation.

In addition, the current study extends the findings of the angiographic study of Wang et al. (1) by also studying patients with stable angina as well as by studying secondary (non-culprit and non-target lesion) plaque ruptures. While a minority of SAP target lesions contained plaque ruptures, the locations were similar to those of ACS patients, confirming the importance of plaque rupture clustering. Multi-focal plaque instability has been reported in previous studies (5,7,8). The current study showed that proximal segments of the LAD and RCA were also the most common sites of secondary plaque ruptures.

There are several possible explanations for the distribution of plaque ruptures. First, plaque rupture distribution seems to follow the distribution of coronary atherosclerosis as assessed with IVUS (9–11) as well as the larger arterial dimensions present in the proximal LAD and LCX and throughout the RCA. Second, within segments of higher plaque burden, plaque ruptures seem to occur at sites of increased stress (i.e., 50% occurred near a branch point).