Tsunekazu Kakuta

In vivo diagnosis of plaque erosion and calcified nodule in patients with acute coronary syndrome by intravascular optical coherence tomography.

OBJECTIVES The aim of this study was to characterize the morphological features of plaque erosion and calcified nodule in patients with acute coronary syndrome (ACS) by optical coherence tomography (OCT). BACKGROUND Plaque erosion and calcified nodule have not been systematically investigated in vivo. METHODS A total of 126 patients with ACS who had undergone pre-intervention OCT imaging were included. The culprit lesions were classified as plaque rupture (PR), erosion (OCT-erosion), calcified nodule (OCT-CN), or with a new set of diagnostic criteria for OCT. RESULTS The incidences of PR, OCT-erosion, and OCT-CN were 43.7%, 31.0%, and 7.9%, respectively. Patients with OCT-erosion were the youngest, compared with those with PR and OCT-CN (53.8 ± 13.1 years vs. 60.6 ± 11.5 years, 65.1 ± 5.0 years, p = 0.005). Compared with patients with PR, presentation with non-ST-segment elevation ACS was more common in patients with OCT-erosion (61.5% vs. 29.1%, p = 0.008) and OCT-CN (100% vs. 29.1%, p < 0.001). The OCT-erosion had a lower frequency of lipid plaque (43.6% vs. 100%, p < 0.001), thicker fibrous cap (169.3 ± 99.1 μm vs. 60.4 ± 16.6 μm, p < 0.001), and smaller lipid arc (202.8 ± 73.6° vs. 275.8 ± 60.4°, p < 0.001) than PR. The diameter stenosis was least severe in OCT-erosion, followed by OCT-CN and PR (55.4 ± 14.7% vs. 66.1 ± 13.5% vs. 68.8 ± 12.9%, p < 0.001). CONCLUSIONS Optical coherence tomography is a promising modality for identifying OCT-erosion and OCT-CN in vivo. The OCT-erosion is a frequent finding in patients with ACS, especially in those with non-ST-segment elevation ACS and younger patients. The OCT-CN is the least common etiology for ACS and is more common in older patients. (The Massachusetts General Hospital Optical Coherence Tomography Registry; NCT01110538).

Assessment of acute injuries and chronic intimal thickening of the radial artery after transradial coronary intervention by optical coherence tomography

AIMS Transradial coronary intervention (TRI) introduces a trauma to the radial artery (RA), possibly influencing quality as a bypass conduit if subsequently used. We sought to determine the acute and chronic effects of TRI on the RA by optical coherence tomography (OCT). METHODS AND RESULTS Immediately after TRI completion, 73 RAs in 69 patients were examined. The sheath was pulled back 2 cm distal to the puncture site, and OCT imaging was performed. The acute injuries and intimal thickening were compared between first-TRI RAs and repeat-TRI RAs. Intimal tears were observed in 49 RAs (67.1%) and were more frequent in the distal than in the proximal RA (P = 0.001). Medial dissections were not uncommon (26 RAs, 35.6%). The frequency of acute injury was significantly higher in repeat-TRI RAs (P < 0.001). Intima/medial area, the maximum intimal thickness/medial thickness ratio, and per cent narrowing were all significantly greater in repeat-TRI RAs in the distal and proximal RA. Multivariate analysis revealed that a repeated TRI procedure was the only independent predictor of intimal thickening. CONCLUSION Optical coherence tomography clearly demonstrated significant acute injuries and chronic intimal thickening of RA after TRI. Further study should evaluate the impact of these effects when TRI RAs are subsequently used as conduits, on long-term graft patency and on clinical outcomes after bypass surgery.

Predictors for Neoatherosclerosis A Retrospective Observational Study From the Optical Coherence Tomography Registry

Background—Recent studies have reported development of neoatherosclerosis (NA) inside the stents several years after stent implantation. The aim of this study was to determine the predictors for NA using optical coherence tomography. Methods and Results—From a total of 1080 patients who underwent optical coherence tomography, we identified 179 stents in 151 patients in which the mean neointimal thickness was >100 µm. The presence of lipid-laden neointima or calcification inside the stents was defined as NA in the present study. Patient characteristics, stent type, and time since stent implantation (stent age) were compared between stents with or without NA. Univariable and multivariable logistic regression analyses were used to assess the independent predictors. In univariate analysis, stent age ≥48 months (Odds ratio [OR], 4.48; [95% CI 2.68-9.65]; P<0.001), drug-eluting stents (OR, 2.66; [95% CI, 1.38–5.16]; P=0.004), age ≥65 years (OR, 1.91; [95% CI, 1.05–3.44]; P=0.032), current smoking (OR, 2.30; [95% CI, 1.10–4.82]; P=0.024), chronic kidney disease (OR, 4.17; [95% CI, 1.42–12.23]; P=0.009), and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockade use (OR, 0.42; [95% CI, 0.22–0.80]; P=0.008) were significant predictors. In multivariate analysis, stent age ≥48 months, all subtypes of drug-eluting stent, current smoking, chronic kidney disease, and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockade use remained independent predictors for NA. Conclusions—In addition to the stent type and the stent age, patient characteristics, including current smoking, chronic kidney disease, and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockade, were associated with the presence of NA. This result may support the importance of secondary prevention after stent implantation.Background— Recent studies have reported development of neoatherosclerosis (NA) inside the stents several years after stent implantation. The aim of this study was to determine the predictors for NA using optical coherence tomography. Methods and Results— From a total of 1080 patients who underwent optical coherence tomography, we identified 179 stents in 151 patients in which the mean neointimal thickness was >100 µm. The presence of lipid-laden neointima or calcification inside the stents was defined as NA in the present study. Patient characteristics, stent type, and time since stent implantation (stent age) were compared between stents with or without NA. Univariable and multivariable logistic regression analyses were used to assess the independent predictors. In univariate analysis, stent age ≥48 months (Odds ratio [OR], 4.48; [95% CI 2.68-9.65]; P <0.001), drug-eluting stents (OR, 2.66; [95% CI, 1.38–5.16]; P =0.004), age ≥65 years (OR, 1.91; [95% CI, 1.05–3.44]; P =0.032), current smoking (OR, 2.30; [95% CI, 1.10–4.82]; P =0.024), chronic kidney disease (OR, 4.17; [95% CI, 1.42–12.23]; P =0.009), and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockade use (OR, 0.42; [95% CI, 0.22–0.80]; P =0.008) were significant predictors. In multivariate analysis, stent age ≥48 months, all subtypes of drug-eluting stent, current smoking, chronic kidney disease, and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockade use remained independent predictors for NA. Conclusions— In addition to the stent type and the stent age, patient characteristics, including current smoking, chronic kidney disease, and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockade, were associated with the presence of NA. This result may support the importance of secondary prevention after stent implantation.

In vivo critical fibrous cap thickness for rupture-prone coronary plaques assessed by optical coherence tomography

AIMS The widely accepted threshold of <65 μm for coronary plaque fibrous cap thickness was derived from postmortem studies of ruptured plaques and may not be appropriate for in vivo rupture-prone plaques. We investigated the relationship between fibrous cap thickness and plaque rupture using optical coherence tomography (OCT). METHODS AND RESULTS We studied 266 lesions (103 from patients with acute coronary syndrome and 163 from patients with stable angina) before percutaneous coronary intervention using OCT. Ruptured and non-ruptured lipid-rich plaques were identified and the thinnest and most representative fibrous cap thickness were determined. Cap thickness was reliably measured in 71 ruptured and 111 non-ruptured plaques. From the ruptured plaques, the median thinnest cap thickness was 54 μm (50-60). The median most representative cap thickness was 116 μm (103-136). For non-ruptured plaques, the median thinnest cap thickness was 80 μm (67-104) and 182 μm (156-216) for most representative cap thickness. In 95% of ruptured plaques, the thinnest cap thickness and most representative cap thickness were <80 and <188 μm, respectively. The best cut-offs for predicting rupture were <67 μm (OR: 16.1, CI: 7.5-34.4, P < 0.001) for the thinnest cap thickness and <151 μm (OR: 35.6, CI: 15.0-84.3, P < 0.001) for most representative cap thickness. These two measures were modestly correlated (r(2) = 0.39) and both independently associated with rupture. CONCLUSION In vivo critical cap thicknesses were <80 μm for the thinnest and <188 μm for most representative fibrous cap thickness. Prospective imaging studies are required to establish the significance of these values.

Impact of Coronary Plaque Morphology Assessed by Optical Coherence Tomography on Cardiac Troponin Elevation in Patients With Elective Stent Implantation

Background—Mild elevations of cardiac troponin frequently occur after percutaneous coronary intervention (PCI), and patients with elevated post-PCI biomarkers have a worse prognosis. We used optical coherence tomography (OCT) to study the relationship between pre-PCI plaque morphology and post-PCI cardiac troponin I elevations. Methods and Results—One hundred thirty-one patients with normal pre-PCI cardiac troponin I levels underwent OCT before nonemergency stent implantation. Clinical and OCT findings were compared between patients with (n=31, 23.7%) and without (n=100, 76.3%) post-PCI cardiac troponin I of >3×upper reference limit (post-PCI myocardial infarction [MI]). After PCI, long-term follow-up data were collected. Post-PCI MI was associated with angiographic lesion length, type B2/C lesions, presence of thin-cap fibroatheroma, and fibrous cap thickness. In multivariable analysis, presence of thin-cap fibroatheroma (odds ratio, 10.47; 95% confidence interval, 3.74 to 29.28; P<0.001) and type B2/C lesions (odds ratio, 3.74; 95% confidence interval, 1.41 to 9.92; P=0.008) were predictors of post-PCI MI. At a median follow-up of 12 months, cardiac event-free survival was significantly worse in patients with post-PCI MI (log-rank test &khgr;2=8.9; P=0.003). Cox proportional hazards analysis showed that post-PCI MI (hazard ratio, 3.67; 95% confidence interval, 1.39 to 9.65; P=0.009) and ejection fraction (hazard ratio, 0.96; 95% confidence interval, 0.92 to 0.99; P=0.029) were independent predictors of adverse cardiovascular events during follow-up. Conclusions—Type B2/C lesions and the presence of OCT-defined thin-cap fibroatheroma can predict post-PCI MI in patients treated with elective stent implantation, who may require adjunctive therapy after otherwise successful PCI.

Increased QT dispersion in patients with vasospastic angina.

BACKGROUND The risk factors for ventricular arrhythmias in patients with coronary vasospasm have not been identified. We evaluated QT dispersion in patients with vasospastic angina and its relation to susceptibility to ventricular arrhythmias during myocardial ischemia and reperfusion. METHODS AND RESULTS We assessed the corrected QT (QTc) dispersion before induction of coronary artery spasm by intracoronary injection of acetylcholine (baseline) and 30 minutes after administration of isosorbide dinitrate in 50 patients with vasospastic angina and 50 patients with atypical chest pain. The baseline QTc dispersion was significantly greater in patients with vasospastic angina than in patients with atypical chest pain (mean+/-SD: 69+/-24 versus 44+/-19 ms, 95% confidence interval of mean difference [CI]: 16 to 33 ms; P<0.001). QTc dispersion decreased significantly, to 48+/-15 ms (CI: 15 to 26 ms; P<0.001 versus baseline), after administration of isosorbide dinitrate in patients with vasospastic angina but did not change significantly in patients with atypical chest pain (mean+/-SD: 41+/-17 ms, CI: -3 to 9 ms). During the provocation test, 24 of 50 patients with vasospastic angina experienced ventricular arrhythmias. The baseline QTc dispersion was significantly greater in patients with than without ventricular arrhythmias (mean+/-SD: 77+/-23 versus 61+/-19 ms, CI: 4 to 26 ms; P<0.05). CONCLUSIONS Patients with vasospastic angina exhibited an increased baseline QTc dispersion compared with patients with atypical chest pain, which suggests that inhomogeneity of repolarization and susceptibility to ventricular arrhythmias are increased in patients with vasospastic angina, even when asymptomatic. The association between increased QTc dispersion and ventricular arrhythmias during the provocation test suggests that measurement of QT dispersion may help predict which patients with vasospastic angina are at high risk for ventricular arrhythmias during ischemia.

Comparison of incidence and time course of neoatherosclerosis between bare metal stents and drug-eluting stents using optical coherence tomography.

Recent studies have reported the development of neoatherosclerosis inside stents and subsequent acute coronary syndrome secondary to disruption of neointimal hyperplasia. The aim of the study was to compare the characteristics of neointimal hyperplasia and its time course between bare metal stents (BMSs) and drug-eluting stents (DESs) using optical coherence tomography. A total of 138 stents were divided into 3 groups according to the follow-up period: early phase, <9 months (25 BMSs and 27 DESs); intermediate phase, ≥9 and <48 months (18 BMSs and 43 DESs); and delayed phase, ≥48 months (13 BMSs and 12 DESs). Optical coherence tomographic analysis included the presence of lipid-laden intima, percentage of lipid-rich plaque, and signal attenuation. The optical coherence tomographic findings were compared between the BMSs and DESs in each period, and the difference between the periods was also determined. In the early phase, a greater incidence of lipid-laden plaque (37% vs 8%, p = 0.02) and a greater percentage of lipid-rich plaque (12.9 ± 25.1% vs 1.2 ± 4.3%, p = 0.01) were found in the DESs than in the BMSs. In the intermediate phase, the DES group continuously showed a significantly greater incidence of lipid-laden plaque (63% vs 28%, p = 0.03) and greater percentage of lipid-rich plaque (24.8 ± 28.1% vs 4.1 ± 7.3%, p <0.01). In addition, signal attenuation was greater in the DES group, suggesting early changes in neointimal hyperplasia properties. In the delayed phase, lipid-laden plaque was the predominant type in both groups. In conclusion, lipid-rich neoatherosclerosis develops inside stents earlier in DESs than in BMSs. After 48 months, most restenotic stents will have developed lipid-laden neointima in both groups.

Inflammation and Atherosclerosis: Atherosclerotic Lesions in Takayasu Arteritis

Abstract: Takayasu arteritis is a chronic vasculitis, mainly involving the aorta and its main branches as well as the coronary and pulmonary arteries, causing stenosis and/or obstruction due to thrombus formation or dilatation due to aneurysmal formation and/or rupture of the involved arteries. These characteristic anomalies resulted from ischemia of retinal arteries due to the obstruction of cervical vessels. In Western countries this disease is also known as “pulseless disease,” because the pulse is frequently absent due to the obstruction of subclavian or brachial arteries. The pathogenesis of this morbid condition is still unknown. Epidemiologically, it is found mostly in female patients and is more prevalent in Asian and Latin American countries. Affected areas consist of a mixture of both active, productive inflammatory lesions, and old fibrous lesions. Autoimmune processes stimulated by viral infection and other unknown causative factors may play an important role under these pathophysiological conditions because HLA analysis revealed a statistically significant high frequency of haplotype A24‐B52‐DR2 in these patients in Japan. Documentation of atherosclerotic complications in young female patients with Takayasu arteritis who are generally free from traditional atherosclerosis risk factors may be clinical evidence that inflammation is indeed an important risk factor in atherogenesis.

Assessment of Echo-Attenuated Plaque by Optical Coherence Tomography and its Impact on Post-Procedural Creatine Kinase-Myocardial Band Elevation in Elective Stent Implantation

OBJECTIVES This study examined morphological characteristics of echo-attenuated plaques by optical coherence tomography (OCT) and evaluated their influence on creatine kinase-myocardial band (CK-MB) elevation after percutaneous coronary intervention (PCI) in patients with elective stent implantation. BACKGROUND Recent intravascular ultrasound studies have described atherosclerotic plaques with echo attenuation (EA) without associated bright echoes that are correlated with no-reflow phenomenon after PCI. METHODS We studied 135 native de novo culprit coronary lesions in 135 patients with normal pre-PCI CK-MB levels (28 with unstable angina; 107 with stable angina) who underwent intravascular ultrasound and OCT examinations before elective stent implantation. The lesions were divided into 2 groups based on the presence or absence of EA, and OCT findings were compared. We then determined predictors of post-PCI CK-MB elevation. RESULTS EA was found in 47 (34.8%) lesions and was associated with the presence of OCT-derived thin-capped fibroatheroma, ruptured plaques, greater lipid content, intravascular ultrasound-derived large reference and plaque area, lesion eccentricity, and microcalcification. Elevated CK-MB levels were observed in 36 (26.7%) lesions, and significantly more frequently in lesions with EA than without. In multivariable analysis, EA (odds ratio [OR]: 3.49; 95% confidence interval [CI]: 1.53 to 7.93; p = 0.003) and OCT-derived ruptured plaque (OR: 2.92; 95% CI: 1.21 to 7.06; p = 0.017) were independent predictors of post-PCI CK-MB elevation. CONCLUSIONS Atherosclerotic plaques with EA were associated with characteristics considered to be high risk or unstable. OCT examination showed an additive predictive value to the presence of EA for post-PCI CK-MB elevation.

Impact of plaque morphology on creatine kinase-MB elevation in patients with elective stent implantation

BACKGROUNDS The association between percutaneous coronary intervention (PCI) and subsequent myonecrosis has been widely recognized, and worse prognosis has been reported among patients with elevated post-PCI biomarkers. We used optical coherence tomography (OCT) to study the relationship between pre-PCI plaque morphology and post-PCI creatine kinase-MB (CK-MB) elevation. METHODS One hundred and twenty-five patients with normal pre-PCI CK-MB levels underwent OCT examination before nonemergency stent implantation. Patients were divided into two groups according to the presence (Group CK, n=35) or absence (Group NCK, n=90) of post-PCI CK-MB elevation ≥ upper limit of the normal range. Clinical and the OCT findings were compared between the two groups. RESULTS Elevated CK-MB levels was observed in 35 patients (28%). The CK-MB elevation was associated with elevated white blood cell count, type B2/C lesions, the presence of thin cap fibroatheroma (TCFA), plaque rupture, and lipid quadrants. In the multivariate analysis, the presence of TCFA (OR 4.68, 95% CI 1.88-11.64, p=0.001) and type B2/C lesions (OR 4.20, 95% CI 1.30-13.59, p=0.02) were independent predictors of post-PCI CK-MB elevation. CONCLUSIONS TCFA and angiographically complex lesion morphology can predict post-PCI CK-MB elevation in patients treated with elective stent implantation. OCT may be useful in stratifying the risk for nonemergency stent implantation.