Characterization of human atherosclerosis by optical coherence tomography.

BACKGROUND: High-resolution visualization of atherosclerotic plaque morphology may be essential for identifying coronary plaques that cause acute coronary events. Optical coherence tomography (OCT) is an intravascular imaging modality capable of providing cross-sectional images of tissue with a resolution of 10 micro m. To date, OCT imaging has not been investigated in sufficient detail to assess its accuracy for characterizing atherosclerotic plaques. The aim of this study was to establish objective OCT image criteria for atherosclerotic plaque characterization in vitro. METHODS AND RESULTS: OCT images of 357 (diseased) atherosclerotic arterial segments obtained at autopsy were correlated with histology. OCT image criteria for 3 types of plaque were formulated by analysis of a subset (n=50) of arterial segments. OCT images of fibrous plaques were characterized by homogeneous, signal-rich regions; fibrocalcific plaques by well-delineated, signal-poor regions with sharp borders; and lipid-rich plaques by signal-poor regions with diffuse borders. Independent validation of these criteria by 2 OCT readers for the remaining segments (n=307) demonstrated a sensitivity and specificity ranging from 71% to 79% and 97% to 98% for fibrous plaques, 95% to 96% and 97% for fibrocalcific plaques, and 90% to 94% and 90% to 92% for lipid-rich plaques, respectively (overall agreement, kappa=0.83 to 0.84). The interobserver and intraobserver reliabilities of OCT assessment were high (kappa values of 0.88 and 0.91, respectively). CONCLUSIONS: Objective OCT criteria are highly sensitive and specific for characterizing different types of atherosclerotic plaques. These results represent an important step in validating this new intravascular imaging modality and will provide a basis for the interpretation of intracoronary OCT images obtained from patients.

Quantification of macrophage content in atherosclerotic plaques by optical coherence tomography.

BACKGROUND: Macrophage degradation of fibrous cap matrix is an important contributor to atherosclerotic plaque instability. An imaging technology capable of identifying macrophages in patients could provide valuable information for assessing plaque vulnerability. Optical coherence tomography (OCT) is a new intravascular imaging modality that allows cross-sectional imaging of tissue with a resolution of approximately 10 micro m. The aim of this study was to investigate the use of OCT for identifying macrophages in fibrous caps. METHODS AND RESULTS: OCT images of 26 lipid-rich atherosclerotic arterial segments obtained at autopsy were correlated with histology. Cap macrophage density was quantified morphometrically by immunoperoxidase staining with CD68 and smooth muscle actin and compared with the standard deviation of the OCT signal intensity at corresponding locations. There was a high degree of positive correlation between OCT and histological measurements of fibrous cap macrophage density (r=0.84, P<0.0001) and a negative correlation between OCT and histological measurements of smooth muscle actin density (r=-0.56, P<0.005). A range of OCT signal standard deviation thresholds (6.15% to 6.35%) yielded 100% sensitivity and specificity for identifying caps containing >10% CD68 staining. CONCLUSIONS: The high contrast and resolution of OCT enables the quantification of macrophages within fibrous caps. The unique capabilities of OCT for fibrous cap characterization suggest that this technology may be well suited for identifying vulnerable plaques in patients.

Plaque erosion in the culprit lesion is prone to develop a smaller myocardial infarction size compared with plaque rupture.

BACKGROUND: Acute myocardial infarction (MI) stems from a disruption of the plaque in the coronary artery. Based on postmortem examinations, such plaque disruption has been classified as either a rupture or an erosion. Unfortunately, it has been difficult to clinically identify plaque ruptures and plaque erosions during the development of acute MI. To elucidate the relationships between clinical features and the morphological characteristics of the infarct-related lesions, we observed the culprit lesions in patients with acute MI by coronary angioscopy and intravascular ultrasound. METHODS: We examined culprit lesions in 107 patients with acute MI using coronary angioscopy and intravascular ultrasound immediately before performing percutaneous coronary intervention. The lesions were then classified as plaque ruptures or nonruptured erosions, and their clinical features were compared. RESULTS: Among the lesions studied, 44 were classified as plaque ruptures, 28 were classified as plaque erosions, and 35 were unclassified. Patients with nonruptured eroded plaques had more preinfarction angina before the onset of MI than those with ruptured plaques (53.6% vs 22.7%, P = .0074). They also had less ST-segment elevation MI (71.4% vs 93.2%, P = .0185), lower peak creatine kinase levels (2029 +/- 1517 vs 4033 +/- 2699 IU/L, P = .0009), less distal embolization after percutaneous coronary intervention (3.6% vs 36.4%, P = .0014), and less Q-wave MI 1 month after onset (40.7% vs 88.4%, P < .0001). CONCLUSION: Patients with eroded plaque lesions have smaller infarctions than those with ruptured plaque lesions, suggesting that an eroded plaque is less potently thrombogenic than a ruptured plaque.

Intravascular optical coherence tomography: cellular imaging.

The vast majority of acute coronary events are attributed to rupture or erosion of high-risk or vulnerable plaques. Novel imaging techniques are being actively sought that can detect quiescent vulnerable features within coronary plaque and thereby identify populations at risk, monitor plaque progression, and target therapy appropriately. Optical coherence tomography is an intravascular imaging modality capable of detecting and characterizing coronary plaque in vivo. Recently, optical coherence tomography quantification of macrophage infiltration within atherosclerotic plaque ex vivo was demonstrated. Application of this technique to clinical practice yields a hybrid image incorporating plaque morphology with a measure of biologic activity. In a recently conducted clinical study assessing macrophage distributions in patients, evidence supporting both the vulnerable plaque model and the hypothesis of multifocal inflammatory risk, linked by the common thread of increased macrophage infiltration, has been found. These results suggest that elevated multifocal coronary macrophage content, present both in culprit lesions and at remote sites, serves as a background for heightened risk. Superimposed on this inflammatory background, local increases in macrophage content, particularly at the cap surface and at areas at high risk for rupture, further promote the instability of individual lesions.

Recent decline in hospital mortality among patients with acute myocardial infarction.

BACKGROUND: Many patients with acute myocardial infarction will still die after admission. Recent trends in hospital mortality were analyzed to identify aspects that need improvement. METHODS AND RESULTS: A total of 1,247 patients admitted to Kinki University School of Medicine within 24 h of the onset of infarction were analyzed between 1975 and 2001. The percentage of patients discharged with 100% occlusion decreased gradually from 31.3% during 1975-1982 to 2.1% during 1998-2001, while those with 50% stenosis or less gradually increased from 12.5% to 82.5% during the same period (trends: p < 0.01). The cardiac death rate was 17.1% in 1975-1982, and 7.7% in 1998-2001, showing a significant decrease with time (p < 0.01). This decrease was particularly marked among those admitted within 6 h of the onset of infarction. Death due to cardiac rupture decreased significantly with time (p < 0.001). In contrast, the non-cardiac death rate, amounting to 2.2% on average, did not decline. CONCLUSIONS: Cardiac deaths due to acute myocardial infarction have decreased markedly of late. However, patients must be admitted within 6 h of the onset of infarction to benefit from this improvement. More effort should be made to improve the general care of patients in order to reduce the incidence of non-cardiac death.

Focal and multi-focal plaque macrophage distributions in patients with acute and stable presentations of coronary artery disease.

OBJECTIVES: This study was designed to utilize optical coherence tomography (OCT) images of coronary atherosclerotic plaque macrophages to investigate the relationship between macrophage distributions and clinical syndrome. BACKGROUND: The relative significance of focal macrophage infiltration and generalized coronary inflammation for predicting acute coronary events is a currently a source of considerable controversy in cardiology. Lack of a high-resolution cross-sectional imaging modality has limited macrophage evaluation in vivo. METHODS: Intracoronary OCT imaging was performed at culprit and non-culprit plaques in patients presenting with stable angina pectoris, unstable angina pectoris,and ST-segment elevation myocardial infarction. Macrophage densities were quantified from these images and analyzed with respect to the clinical presentations of the patients under investigation. RESULTS: A significantly greater macrophage density was found in unstable patients, both for fibrous and lipid-rich plaques (p = 0.025 and p = 0.002, respectively). Within each patient, the macrophage densities at culprit and non-culprit lesions correlated significantly (r = 0.66, y = 0.88x + 0.43, p = 0.01). Sites of plaque rupture demonstrated a greater macrophage density than non-ruptured sites (6.95 +/- 1.60%, 5.29 +/- 1.17%; p = 0.002). Surface macrophage infiltration was a stronger predictor of unstable clinical presentation than subsurface infiltration for culprit lesions (p = 0.035) but not for remote lesions (p = 0.80). CONCLUSIONS: Our results demonstrate that increases in both multi-focal and focal macrophage densities are highly correlated with symptom severity. By providing a means of detecting increases in plaque macrophage content before an acute event, this technique may aid in determining prognosis and guiding preventive therapy.