Ryotaro Yamada

Assessment of the coronary calcification by optical coherence tomography

AIMS Optical coherence tomography (OCT) can delineate calcified plaque without artefacts. The aim of this study was to evaluate the ability of OCT to quantify calcified plaque in ex vivo human coronary arteries. METHODS AND RESULTS Ninety-one coronary segments from 33 consecutive human cadavers were examined. By intravascular ultrasound (IVUS), 32 superficial calcified plaques, defined as the leading edge of the acoustic shadowing appears within the most shallow 50% of the plaque plus media thickness, were selected and compared with corresponding OCT and histological examinations. The area of calcification was measured by planimetry. IVUS significantly underestimated the area of calcification compared with histological examination (y = 0.39x + 0.14, r = 0.78, p < 0.001). Although OCT slightly underestimated the area of calcification (y = 0.67x + 0.53, r = 0.84, p < 0.001), it showed a better correlation with histological examination than IVUS. CONCLUSIONS Both OCT and IVUS underestimated the area of calcification, but OCT estimates of the area of calcification were more accurate than those estimated by IVUS. Thus, OCT may be a more useful clinical tool to quantify calcified plaque.

Plaque Characteristics of Thin-Cap Fibroatheroma Evaluated by OCT and IVUS

OBJECTIVES The purpose of this study was to assess plaque characteristics of optical coherence tomography (OCT)-derived thin-cap fibroatheroma (TCFA) by integrated backscatter intravascular ultrasound (IB-IVUS). BACKGROUND Radiofrequency signal-derived IVUS tissue characterization technology has become clinically available and provided objective and quantitative plaque characteristics of the coronary vessel wall. Integrated backscatter IVUS is one of the tissue characterization methods that can possibly provide quantitative plaque characteristics of the OCT-derived TCFA. METHODS Eighty-one coronary lesions with plaque burden >40% were selected and analyzed with both IB-IVUS and OCT. The OCT-derived TCFA was defined as a presence of thin fibrous cap (<65 μm) overlying a signal-poor lesion with diffuse border representing a lipid-rich plaque. By conventional gray-scale IVUS, external elastic membrane (EEM) cross-sectional area (CSA), lumen CSA, plaque plus media (P+M) CSA, plaque burden and remodeling index were measured. By IB-IVUS, plaque characteristics were further classified as fibrosis, dense fibrosis, calcification, or lipid pool. RESULTS Optical coherence tomography identified 40 TCFAs (49%) and 41 non-TCFAs. The EEM CSA, P+M CSA, plaque burden, and remodeling index were significantly larger in OCT-derived TCFA than non-TCFA. By IB-IVUS, percentage lipid pool area (= lipid pool area/P+M CSA × 100) was significantly higher (62.4 ± 12.8% vs. 38.4 ± 13.1%, p<0.0001) and percentage fibrosis area (= fibrosis area/P+M CSA × 100) was significantly lower (34.6 ± 11.4% vs. 50.5 ± 8.7%, p<0.0001) in OCT-derived TCFA than non-TCFA. By receiver-operator characteristic curve analysis, percentage lipid pool area ≥55%, percentage fibrosis area ≤41%, and remodeling index ≥1.0 were predictors of OCT-derived TCFA. CONCLUSIONS The OCT-derived TCFA had larger plaque burden and positive remodeling with predominant lipid component and less fibrous plaque assessed by IB-IVUS.

C-Reactive protein predicts severity, progression, and prognosis of asymptomatic aortic valve stenosis

BACKGROUND C-Reactive protein (CRP) has been shown to play a pivotal role in the pathogenesis of atherosclerosis progression. The aim of this study was to assess whether CRP predicts severity, progression, and prognosis of aortic valve stenosis (AS). METHODS One hundred and thirty-five patients with asymptomatic AS were studied. Patients were diagnosed as mild (n = 18, aortic valve area [AVA] > or =1.5 cm(2)), moderate (n = 57, AVA 1.0-1.49 cm(2)), or severe AS (n = 60, AVA <1.0 cm(2)) by Doppler echocardiography. Patients with serial (baseline and at 1 year) echocardiographic examination (n = 47) were grouped as either slow (n = 22, DeltaAVA <-0.15 cm(2)/y) or rapid progression group (n = 25, DeltaAVA > or =-0.15 cm(2)/y). In addition, long-term prognosis was compared between patients with low CRP (n = 68, CRP <0.15 mg/dL) and those with high CRP (n = 67, CRP > or =0.15 mg/dL). RESULTS Baseline CRP was significantly higher in patients with severe AS than in those with mild or moderate AS (mild AS 0.17 +/- 0.43, moderate AS 0.22 +/- 0.28, severe AS 0.53 +/- 0.66 mg/dL, P = .001). By multivariate logistic regression analysis, CRP was an independent predictor of severe AS (odds ratio 3.51, P = .015). Similarly, CRP was significantly higher in the rapid progression group than in the slow progression group (0.56 +/- 0.76 vs 0.19 +/- 0.25 mg/dL, P = .004). Furthermore, long-term survival was significantly lower in the high CRP group than in the low CRP group (log rank: P < .001). CONCLUSION C-Reactive protein predicts severity, progression, and prognosis in patients with asymptomatic AS.

Usefulness of CHADS2 Score to Predict C-Reactive Protein, Left Atrial Blood Stasis, and Prognosis in Patients With Nonrheumatic Atrial Fibrillation

The CHADS2 score (congestive heart failure, hypertension, age >75 years, diabetes, and previous stroke/transient ischemic attack) is used for embolic risk stratification in patients with atrial fibrillation (AF). Although systemic inflammation is a known predictor of left atrial thrombus formation in patients with nonrheumatic AF, the relation between the CHADS2 score and systemic inflammation is unknown. A total of 165 patients with nonrheumatic AF were enrolled and analyzed. According to the CHADS2 score, the study patients were grouped into low- (score 0 to 1), intermediate- (score 2 to 3), or high- (score 4 to 6) risk categories. The plasma C-reactive protein levels, transesophageal echocardiographic findings, and cardiovascular events (death, stroke, and heart failure) were compared. Patients in the high-risk group had significantly greater C-reactive protein levels than those in the intermediate- and low-risk groups (0.80 mg/dl, range 0.21 to 1.50, vs 0.16 mg/dl, range 0.06 to 0.50, vs 0.08 mg/dl, range 0.04 to 0.21, p <0.01). Using transesophageal echocardiography, the incidence of left atrial spontaneous echo contrast and left atrial thrombus increased with an increasing CHADS2 score. During the follow-up period, the cardiovascular event-free survival was significantly lower in the high-risk group than in the intermediate- or low-risk groups. In conclusion, in patients with nonrheumatic AF, CHADS2 score is related to systemic inflammation, left atrial thrombus formation, and prognosis.

Systemic inflammation and left atrial thrombus in patients with non-rheumatic atrial fibrillation

BACKGROUND There is an apparent link between thrombogenesis and inflammation. We hypothesized that systemic inflammation [as indicated by C-reactive protein (CRP)] would be related to the presence of left atrial (LA) thrombus in patients with atrial fibrillation (AF). To test this hypothesis, we evaluated the relationship between CRP and LA thrombus in patients with non-rheumatic AF. METHODS AND RESULTS Between October 2004 and December 2008, 190 patients with non-rheumatic AF (122 males, age 71+/-10 years) who underwent transesophageal echocardiography (TEE) were enrolled and analyzed. All patients were examined for presence or absence of LA thrombus by TEE. CRP was measured within 1 week before the TEE examination. LA thrombus was detected in 19 patients (10%). Hypertension, hypertensive heart disease (HHD), valvular heart disease, ticlopidine, and CRP were univariate correlates of LA thrombus. By multivariate analysis, HHD (p<0.01), ticlopidine (p=0.01), and CRP (p=0.03) were independently associated with LA thrombus. A cut-off CRP value for identifying LA thrombus was 0.21mg/dl (sensitivity: 84%, specificity: 60%, positive predictive value: 19%, and negative predictive value: 97%). CONCLUSION A high CRP is related to LA thrombus in patients with non-rheumatic AF.

Impact of right ventricular involvement on the prognosis of takotsubo cardiomyopathy

BACKGROUND Previous studies showed that patients with takotsubo cardiomyopathy had a higher long-term mortality rate than the general population and the incidence of in-hospital complications was higher in takotsubo cardiomyopathy with than without right ventricular (RV) involvement. This study was performed to investigate the long-term prognostic impact of RV involvement in takotsubo cardiomyopathy. METHODS AND RESULTS The clinical data of 113 patients (72.7 ± 11.4 years old, 84 females) with takotsubo cardiomyopathy were studied retrospectively. The patients were divided into two groups according to the presence (biventricular group, n = 21, 18.6%) or absence (classical group, n = 92, 81.4%) of RV involvement assessed by initial echocardiography. The end point was a composite of all-cause death, re-hospitalization due to heart failure, and recurrence of takotsubo cardiomyopathy. The in-hospital mortality rate was significantly higher in the biventricular group than the classical group (14.3 vs. 1.1%, respectively, P = 0.02). Kaplan-Meier analysis indicated a significantly lower event-free survival rate in the biventricular group than the classical group (log-rank, P < 0.001). On multivariate analysis, RV involvement was the only independent predictor of the end point (HR: 2.73, P = 0.026). CONCLUSION The rates of in-hospital and long-term events were significantly higher in takotsubo cardiomyopathy with than without RV involvement, and RV involvement was the independent predictor of the poor prognosis.

A comparison between 40 MHz intravascular ultrasound iMap imaging system and integrated backscatter intravascular ultrasound.

BACKGROUND iMap is a newly developed intravascular ultrasound (IVUS) tissue characterization system based on pattern recognition of the radio frequency (RF) signals. PURPOSE The purpose of this study was to compare tissue characterization between iMap and another previously validated tissue characterization system, integrated backscatter (IB)-IVUS in vivo and to clarify similarities and differences between these two methods. METHODS A total of 31 lesions from 16 patients with ischemic heart disease were studied. IVUS imaging was performed using 40 MHz IVUS catheter. RF signals from each lesion were then exported to analyze tissue characterization using both iMap and IB-IVUS. By iMap, coronary plaque was classified into four categories, fibrotic, lipidic, necrotic, or calcified. By IB-IVUS, coronary plaque was classified into four categories, fibrosis, lipid pool, dense fibrosis, or calcification. After the images were acquired, IB-IVUS and iMap images were compared at exactly the same cross-sections. Because severe calcification is a perfect reflector, dense calcification lesions (>20%) were excluded. RESULTS Both fibrotic and calcified by iMap correlated well with fibrosis and calcification by IB-IVUS (fibrotic vs. fibrosis: r(2)=0.522, p<0.001, calcified vs. calcification: r(2)=0.560, p<0.001). Although lipidic by iMap did not correlate with lipid pool by IB-IVUS, necrotic by iMap correlated well with lipid pool by IB-IVUS (r(2)=0.480, p<0.001). CONCLUSION Although tissue types classified by iMap correlated well with corresponding tissue type by IB-IVUS, some discrepancy presented between the two systems. These results may call for careful interpretation of the tissue types obtained by the different IVUS tissue characterization systems.

Quantitative measurement of mitral valve coaptation in functional mitral regurgitation: In vivo experimental study by real-time three-dimensional echocardiography

BACKGROUND The degree of mitral valve (MV) coaptation should be an important parameter in the assessment of functional mitral regurgitation (MR). This study aimed to quantify the degree of MV coaptation in experimental models of functional MR caused by acute left ventricular (LV) pressure overload, using real-time three-dimensional (3D) echocardiography. METHODS AND RESULTS Using canine models, LV pressure overload was induced by staged ascending aortic banding. Echocardiographic examinations were performed before and during the aortic banding. By using a novel software system for 3D quantification (REALVIEW®), the annulus and leaflet were traced manually both at the onset of MV closure and at the maximum MV closure. The coaptation index was calculated by the following formula: [(3D tenting surface area at the onset of MV closure-3D tenting surface area at the maximum MV closure)/3D tenting surface area at the onset of MV closure] x 100. MR area gradually increased with the decrease in coaptation index during progressively exacerbated aortic banding. MR area was significantly correlated with the coaptation index. A coaptation index < 12 had a high sensitivity and specificity in the presence of significant MR. CONCLUSIONS The degree of MV coaptation can be quantified using 3D echocardiography. The coaptation index should be a useful parameter in the assessment of functional MR.

Relationship Between Arterial and Fibrous Cap RemodelingClinical Perspective

Background—Positive arterial remodeling and thin fibrous cap are characteristics of rupture-prone or vulnerable plaque. The natural course of the fibrous cap thickness and the relationship between serial arterial remodeling and changes in fibrous cap thickness are unknown. Therefore, the purpose of this study was to evaluate the relationship between changes in fibrous cap thickness and arterial remodeling by using optical coherence tomography (OCT) and intravascular ultrasound (IVUS) during 6-month follow-up. Methods and Results—Both IVUS and OCT examinations were performed on 108 vessels from 36 patients with ischemic heart disease who underwent percutaneous coronary intervention. Fifty-eight fibroatheromas were selected from 82 nonsignificant, nonculprit lesions (angiographic diameter stenosis, 25% to 75%; plaque burden, >40% by IVUS). Fibroatheroma was defined by OCT as lipid-rich plaque in >1 quadrant that has lipid. Thickness of the fibrous cap was measured by OCT. IVUS and OCT examinations were repeated at 6-month follow-up. Serial changes and relationships between IVUS indices and fibrous cap thickness were investigated. Overall, fibrous cap thickness (98.1±38.9 to 96.9±44.5 &mgr;m) as well as IVUS indices did not change significantly within 6 months. The percent changes in fibrous cap thickness correlated negatively and significantly (r=−0.54; P<0.0001; generalized estimating equation adjusted, r=−0.42; P=0.001) with the percent changes in external elastic membrane cross-sectional area. Conclusions—Arterial remodeling is related to changes in fibrous cap thickness. Positive arterial remodeling is not only an adaptive process, but also related to thinning of the fibrous cap.Background— Positive arterial remodeling and thin fibrous cap are characteristics of rupture-prone or vulnerable plaque. The natural course of the fibrous cap thickness and the relationship between serial arterial remodeling and changes in fibrous cap thickness are unknown. Therefore, the purpose of this study was to evaluate the relationship between changes in fibrous cap thickness and arterial remodeling by using optical coherence tomography (OCT) and intravascular ultrasound (IVUS) during 6-month follow-up. Methods and Results— Both IVUS and OCT examinations were performed on 108 vessels from 36 patients with ischemic heart disease who underwent percutaneous coronary intervention. Fifty-eight fibroatheromas were selected from 82 nonsignificant, nonculprit lesions (angiographic diameter stenosis, 25% to 75%; plaque burden, >40% by IVUS). Fibroatheroma was defined by OCT as lipid-rich plaque in >1 quadrant that has lipid. Thickness of the fibrous cap was measured by OCT. IVUS and OCT examinations were repeated at 6-month follow-up. Serial changes and relationships between IVUS indices and fibrous cap thickness were investigated. Overall, fibrous cap thickness (98.1±38.9 to 96.9±44.5 μm) as well as IVUS indices did not change significantly within 6 months. The percent changes in fibrous cap thickness correlated negatively and significantly ( r =−0.54; P <0.0001; generalized estimating equation adjusted, r =−0.42; P =0.001) with the percent changes in external elastic membrane cross-sectional area. Conclusions— Arterial remodeling is related to changes in fibrous cap thickness. Positive arterial remodeling is not only an adaptive process, but also related to thinning of the fibrous cap.

In-stent neointimal characteristics and late neointimal response after drug-eluting stent implantation: A preliminary observation

BACKGROUND Progressive neointimal proliferation may lead to late restenosis and/or neoatherosclerosis after drug-eluting stent (DES) implantation. Late neointimal response may be different among different tissue characteristics. The aim of this study was to assess impact of in-stent neointimal characteristics on late neointimal response following DES implantation. METHODS Serial (median 270 days and median 551 days after stent implantation) optical coherence tomography (OCT) examinations were performed in 42 stented lesions from 26 patients. In-stent neointimal tissue was categorized as either homogeneous or heterogeneous neointima based on the OCT appearance at 1st follow-up. Serial changes in neointimal area (NIA) were compared between lesions with homogeneous neointima and those with heterogeneous neointima. RESULTS At first follow-up, homogeneous neointima was observed in 22 (52%) and heterogeneous neointima in 20 (48%) lesions, respectively. During follow-up, NIA in lesions with homogeneous neointima decreased significantly (1.8±0.93 mm(2) to 1.5±0.88 mm(2), p<0.001). On the other hand, NIA in lesions with heterogeneous neointima did not change significantly (2.7±1.8 mm(2) to 2.8±1.6 mm(2), p=0.658). Homogeneous neointima was the only predictor of late neointimal regression (late neointimal regression defined as NIA at first follow-up - NIA at second follow-up <0) by multivariable analysis (odds ratio=7.591, 95% confidence interval: 1.616-35.67, p=0.010). CONCLUSIONS OCT characteristics of neointima after DES implantation may be related to late neointimal progression or regression.