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A 65-year-old man who underwent percutaneous coronary intervention with sirolimus-eluting stents (SESs) 2 years ago was admitted with recurrent acute chest pain. Coronary angiography showed thrombotic occlusion within the SESs. After aspiration thrombectomy, multi-focal peri-stent contrast staining (PSS) was observed. Optical frequency domain imaging (OFDI) showed intracoronary thrombus, incomplete stent apposition (ISA), and multiple inter-strut hollows. Intravascular ultrasound (IVUS) images showed positive vessel remodeling. We deployed bare-metal stents in the SESs. Follow-up angiography showed no in-stent restenosis or PSS. OFDI showed well-covered stent surface with homogeneous neointima, without ISA. Additionally, IVUS images showed that the vessel remodeling had not worsened.

Many investigators have reported that the total amount of coronary calcium correlates with the overall magnitude of atherosclerotic plaque burden in the entire coronary tree and is a powerful predictor of future cardiovascular events. However, the development and spatial distribution of coronary calcifications remain unclear. We investigated the spatial distribution of calcifications throughout the coronary tree during coronary artery evaluation using coronary computed tomography angiography (CTA). A further aim was to assess the progression of existing calcifications and the development of new deposits in a follow-up study. The study population consisted of 287 patients for the cross-sectional study using CTA to evaluate the spatial distribution of calcifications by parent coronary arteries. Next, we analyzed a CTA dataset of 57 patients who had undergone two CTA examinations. In this group, the two CTA images were used for assessing the progression of existing calcifications and the development of new deposits. The coronary calcifications tended to be clustered within the proximal and middle portions. Moreover, in the proximal left anterior descending coronary artery (LAD), small calcifications were located more toward the inner pericardial side. Finally, new calcium deposits developed within the proximal and middle portions of the LAD and left circumflex coronary artery, but those in the right coronary artery were likely to appear evenly from the proximal to the distal portion. This study shows the characteristic patterns of the longitudinal and circumferential distribution of calcifications by parent coronary arteries.

Objectives: This study sought to investigate the relationship between localization of high-intensity signals (HISs) on T1-weighted imaging (T1WI) with the noncontrast magnetic resonance technique and plaque morphology detected on optical coherence tomography, and the clinical severity of angina pectoris., Background: Since the introduction of the T1WI noncontrast magnetic resonance technique for plaque imaging, some groups have reported that HISs in the coronary artery on T1WI are associated with a vulnerable morphology and future cardiac events. However, the association between the localization of HISs, such as coronary intrawall or intraluminal, and plaque morphology has not been investigated., Methods: One hundred lesions with either stable or unstable angina were included and divided into 3 groups according to the following criteria using T1WI. First, the plaques with the ratio between the signal intensities of coronary plaque and cardiac muscle ≤1.0 were classified as non-HISs (n = 39). Then, HISs with the ratio between the signal intensities of coronary plaque and cardiac muscle >1.0 were classified into 2 types by using cross-sectional T1WI. Those localized within the coronary wall when the lumen was identified were defined as intrawall HISs (n = 37), whereas those occupying the lumen when the lumen was not, or even if only partly, identified, were defined as intraluminal HISs (n = 24)., Results: Multivariate analysis revealed that intrawall HISs were associated with macrophage accumulation and the absence of calcification assessed by using optical coherence tomography. In contrast, thrombus and intimal vasculature were independent factors associated with intraluminal HISs. Furthermore, 50% of patients with intraluminal HISs experienced rest angina, such as Braunwald class II or III., Conclusions: This study shows that intrawall and intraluminal HISs on T1WI in patients with angina are related to the different types of vulnerable plaque morphology and the clinical severity., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Cardiovascular (CV) diseases and chronic kidney disease (CKD) have common predisposing factors that subsequently cause microvascular dysfunction. In the absence of obstructive coronary artery disease, coronary flow reserve (CFR) represents the status of coronary microcirculation. This study aimed to investigate the prognostic importance of impaired CFR, as a marker of microvascular dysfunction, on long-term CV outcomes in patients with CKD. This study consisted of 139 patients with an estimated glomerular filtration rate of <60 ml/min/1.73 m(2) who had no obstructive narrowing of the left anterior descending artery. Transthoracic Doppler echocardiography was used to measure CFR in the left anterior descending artery. During the follow-up period (3.3 ± 1.6 years), CV events occurred in 26 patients (18.7%). Multivariate analysis that included CFR as a continuous value identified a serum level of C-reactive protein (hazard ratio 1.41, p = 0.03) and a value of CFR (hazard ratio 0.21, p = 0.009) as determinants for CV events, independent of traditional CV risk factors. Patients with a CFR of <2.0 had worse CV outcomes compared with those with a CFR of ≥2.0 (p <0.001). In conclusion, transthoracic Doppler echocardiographically derived CFR was useful for the risk stratification of CV outcomes in patients with CKD. The presence of microvascular dysfunction may play an important role in the association between CKD and future CV events., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to determine the predictive value of the napkin-ring sign on coronary computed tomography angiography (CTA) for future acute coronary syndrome (ACS) events in patients with coronary artery disease., Background: Recent studies have reported a close association between the napkin-ring sign on coronary CTA and thin-cap fibroatheroma., Methods: The subjects of this prospective study were 895 consecutive patients who underwent coronary CTA examination and were followed for >1 year. The primary endpoint was an ACS event (cardiac death, nonfatal myocardial infarction, or unstable angina pectoris). The coronary CTA analysis included the presence of obstructive plaque, positive remodeling (PR), low-attenuation plaque (LAP), and the napkin-ring sign. The napkin-ring sign was defined by the following criteria: 1) the presence of a ring of high attenuation around certain coronary artery plaques; and 2) attenuation of the ring presenting higher than those of the adjacent plaque and no >130 Hounsfield units., Results: Of the 12,727 segments, 1,174 plaques were observed, including plaques with PR in 130 segments (1.0%), LAP in 107 segments (0.8%), and napkin-ring signs in 45 segments (0.4%). Thirty-six of the 45 plaques with napkin-ring signs (80%) overlapped with those showing either PR or LAP. During the follow-up period (2.3 ± 0.8 years), 24 patients (2.6%) experienced ACS events, and plaques developed in 41% with a napkin-ring sign. Segment-based Cox proportional hazards models analysis showed that PR (p < 0.001), LAP (p = 0.007), and the napkin-ring sign (p < 0.0001) were independent predictive factors for future ACS events. Kaplan-Meier analysis demonstrated that plaques with napkin-ring signs showed a higher risk of ACS events compared with those without a napkin-ring sign., Conclusions: The present study demonstrated for the first time that the napkin-ring sign demonstrated on coronary CTA was strongly associated with future ACS events, independent of other high-risk coronary CTA features. Detection of the napkin-ring sign could help identify coronary artery disease patients at high risk of future ACS events., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Several coronary angiographic studies have reported that enlarged and tortuous epicardial coronary arteries are characteristic of patients with left ventricular concentric hypertrophy (LVCH). Recently, we showed that small volumes opacified by contrast medium can be accurately measured by 64-multislice computed tomography (MSCT) and that there is a direct relationship between the coronary artery volume and left ventricular (LV) mass. However, the relationship of coronary artery volume with LV mass in patients with dilated cardiomyopathy (DCM) is unknown. The present study was designed to investigate this issue. Thirteen patients with DCM and 18 patients with LVCH who underwent MSCT angiography were included in this analysis. The coronary arteries were segmented on a workstation, and the appropriate window settings obtained from the results of the phantom experiments were applied to the volume-rendered images to calculate the total coronary artery volume (right and left coronary arteries). The absolute coronary lengths and volumes in patients with LVCH and DCM were greater than those in controls. The coronary artery volumes adjusted for LV mass in patients with DCM were found to be smaller than those in patients with LVCH or in controls, and these values did not differ between patients with LVCH and controls (DCM 4.1 ± 0.9, LVCH 5.4 ± 1.4, controls 5.5 ± 2.3 ml/100 g of LV mass, P < 0.005; DCM vs LVCH, P < 0.01; and DCM vs control, P < 0.0005). This study showed that the increase in the coronary artery volume in patients with LVCH matched the increase in LV mass, but a decreased coronary volume with regard to LV mass was characteristic of patients with DCM.

Aims: Many investigators have speculated that hyperintense plaques (HIPs) of the carotid artery on non-contrast T1-weighted imaging (T1WI) in magnetic resonance indicate the presence of mural or intraplaque haemorrhage containing methemoglobin. Coronary plaque imaging with T1WI is challenging, and the clinical significance of coronary HIP on T1WI remains unknown. The aim of this study was to compare HIPs on T1WI with coronary plaque morphology assessed by optical coherence tomography (OCT), which allows us to identify not only plaque rupture, but also fibrous cap thickness and intracoronary thrombus in vivo, in patients with angina pectoris., Methods and Results: Twenty-six lesions from 26 patients with either stable or unstable angina pectoris were examined in this study. All patients underwent T1WI within 24 h before the day on which invasive coronary angiography was performed, and pre-interventional OCT was performed on a native atherosclerotic lesion, considered to be the culprit lesion. Of the 26 lesions studied, 16 (62%) were HIPs and 10 (38%) were non-HIPs. The signal intensity of the coronary plaque to cardiac muscle ratio in HIPs was significantly higher than that in non-HIPs. There were no significant differences in the frequency of lipid-rich plaque, thin-cap fibroatheroma, plaque rupture, and calcification between HIPs and non-HIPs. In contrast, the frequency of thrombus was significantly higher in HIPs than in non-HIPs (P = 0.004)., Conclusion: This study shows that the HIPs on T1WI in angina patients relate to the presence of intracoronary thrombus as detected by OCT imaging.

Objectives: The aim of this study was to investigate the conformational change of arterial structure in the vasospastic lesion with optical coherence tomography., Background: Coronary artery spasm plays an important role in the pathogenesis of ischemic heart diseases. The conformational change of each arterial layer during vasospasm has not been studied in detail., Methods: We assessed 19 coronary arteries (10 spasm and 9 nonspasm lesions) with optical coherence tomography during the provocation test for coronary spasm. An intimal bump was defined as 1 or more intimal projections into the lumen that disappeared after the administration of nitroglycerine (NTG). Intimal gathering was defined as a folding/gathering of the intima, resulting in multiple kinks in the luminal contour that resolved after the administration of NTG., Results: The spasm lesion more frequently showed an intimal bump at baseline and intimal gathering during spasm compared with the nonspasm lesion (spasm 80% vs. nonspasm 0%, p < 0.01, spasm 100% vs. nonspasm 0%, p < 0.01, respectively). The spasm lesion demonstrated a thicker maximum media thickness (spasm 0.24 ± 0.04 mm vs. nonspasm 0.12 ± 0.03 mm, p < 0.01) at baseline, whereas no differences were observed after the administration of NTG (spasm 0.13 ± 0.03 mm vs. nonspasm 0.13 ± 0.02 mm, p = 0.65)., Conclusions: Our results suggest that medial contraction occurs even in an asymptomatic state and facilitates the formation of an intimal bump in patients with vasospastic angina. Luminal narrowing during spasm is associated with intimal gathering without alteration of intimal area., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Optical coherence tomography (OCT) is a fiber-optic technology that enables high-resolution intracoronary imaging. The aim of this study was to evaluate the safety and feasibility of intracoronary imaging with OCT in the clinical setting; 76 patients with coronary artery disease from 8 centers were enrolled. The OCT imaging system (ImageWire, Light Imaging Inc., Westford, Massachusetts) consists of a 0.006 inch fiber-optic core that rotates within a 0.016 inch transparent sheath. OCT imaging was performed during occlusion of the artery with a compliant balloon and continuous flushing. Intravascular ultrasound (IVUS) imaging was performed in the same segments. We assessed the safety and feasibility of the OCT imaging, compared with IVUS. Vessel occlusion time was 48.3 +/- 13.5 seconds and occlusion-balloon pressure was 0.4 +/- 0.1 atmospheres. Flushing with lactated Ringer's solution was performed at a rate of 0.6 +/- 0.4 ml/s. No significant adverse events, including vessel dissection or fatal arrhythmia, were observed. Procedural success rates were 97.3% by OCT and 94.5% by IVUS. The OCT image wire was able to cross 5 of 6 tight lesions that the IVUS catheter was unable to cross. Of the 98 lesions in which both OCT and IVUS were successfully performed, OCT imaging had an advantage over IVUS for visualization of the lumen border. Minimum lumen diameter and area measurements were significantly correlated between OCT and IVUS imaging (r = 0.91, p <0.0001 and r = 0.95, p <0.0001, respectively). In conclusion, this multicenter study demonstrates the safety and feasibility of OCT imaging in the clinical setting.

Recent epidemiologic, pathologic, and intravascular ultrasound (IVUS) studies have shown that there are differences in coronary risk factors or plaque morphology between younger and older patients with acute myocardial infarctions (AMIs). This study examined clinical background and plaque morphology using IVUS in younger and older adults with AMIs in Japan. The study population consisted of 96 patients with AMIs, for whom preinterventional IVUS images were obtained. Patients were classified into 3 groups: a young group (aged < or =55 years), a middle-aged group (aged 56 to 69 years), and an old group (aged > or =70 years). The remodeling index was defined as the ratio of the external elastic membrane area at the culprit lesion to the external elastic membrane area at the proximal reference site. Expansive remodeling was defined as a remodeling index >1.05 and constrictive remodeling as a remodeling index <0.95. The frequency of hypercholesterolemia was significantly different among the 3 age groups. Total cholesterol (p <0.001), low-density lipoprotein cholesterol (p <0.005), and triglyceride (p <0.05) levels and body mass index (p <0.001) in the young group were significantly higher than in the old group. On IVUS images, constrictive remodeling was most common in the young group, whereas expansive remodeling occurred most commonly in the middle-aged and old groups. In conclusion, this study demonstrated that patients with AMIs in the young group had higher levels of hypercholesterolemia, obesity, and constrictive remodeling compared with those in the old group. The differences in arterial remodeling of the culprit lesions between younger and older patients with AMIs may reflect different biologic mechanisms of plaque activation and destabilization.

Objectives: To investigate the impact of arterial remodelling on long-term clinical outcome after stent implantation in patients with acute coronary syndrome (ACS)., Methods: 134 patients with ACS were enrolled. External elastic membrane (EEM) cross-sectional area (CSA) and lumen CSA were measured. Plaque and media CSA was calculated as EEM minus lumen CSA. Final minimal stent area (MSA) was also measured after stenting. Positive remodelling (PR) was defined as the ratio of the EEM CSA at the target lesion to that at the proximal reference of >1.05, and intermediate or negative remodelling (IR/NR) was defined as that of < or =1.05., Results: Although final MSA was similar, target lesion revascularisation (TLR) rates at 2 years were significantly higher in patients with PR (33.7%) than in those with IR/NR (13.7%; p = 0.01). In addition, non-TLR rates were also significantly higher in patients with PR (42.2%) than in those with IR/NR (23.5%; p = 0.03). Cardiac event-free survival (for events such as death, myocardial infarction, TLR and non-TLR) was significantly lower in patients with PR than in those with IR/NR (log rank, p = 0.001). By multivariate logistic regression analysis, PR (chi2 6.57, OR 2.70; 95% CI, 1.27 to 5.78; p = 0.01) and plaque rupture (chi2 4.17, OR 2.38; 95% CI, 1.04 to 5.45; p = 0.04) were independent predictors of cardiac events., Conclusion: In patients with ACS, PR and intravascular ultrasound findings that may correspond with plaque rupture predict cardiac events including both TLR and non-TLR at 2 years.

Objective: Accelerated atherosclerosis is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Altered coronary microvascular function may act as a marker of changes that predispose to the development of significant coronary vascular disease. The purpose of this study was to compare coronary flow reserve (CFR) in a group of premenopausal women with SLE and a group of age-, sex-, and race-matched healthy control subjects., Methods: Coronary flow velocity in 18 premenopausal women with SLE (mean +/- SD age 29.4 +/- 5.9 years) and 19 matched healthy controls (mean +/- SD age 28.2 +/- 4.3 years) was assessed by transthoracic Doppler echocardiography after an overnight fast. The CFR was calculated as the ratio of hyperemic to baseline coronary blood flow velocity in the left anterior descending coronary artery. Hyperemia was induced by intravenous administration of adenosine triphosphate., Results: The mean +/- SD duration of SLE was 8.2 +/- 7.2 years (range 0.25-25 years), and the mean +/- SD score on the Systemic Lupus Erythematosus Disease Activity Index was 11.0 +/- 5.3 (range 4.0-21.0). Adequate recordings of flow velocity in the left anterior descending artery under both conditions were obtained using an ultrasound procedure in all study subjects. CFR was significantly lower in SLE patients as compared with control subjects (mean +/- SD 3.4 +/- 0.8 versus 4.5 +/- 0.5; P < 0.0001)., Conclusion: These findings provide evidence that coronary vasomotor function is impaired in patients with SLE and support the notion that many of these young patients have subclinical coronary artery disease.

To evaluate the usefulness of adenosine triphosphate stress strain imaging for detecting significant coronary artery disease in the left anterior descending coronary artery (LAD), 34 patients underwent coronary flow velocity reserve measurement in the distal LAD and adenosine triphosphate stress strain imaging simultaneously. Time to peak strain (TPS) was measured in the apical septal segment. TPS ratio was obtained as the ratio between TPS at adenosine triphosphate stress and at baseline. TPS ratio in 11 patients with LAD lesions was significantly greater than that in 23 patients without LAD lesions (1.24 +/- 0.17 vs 0.92 +/- 0.12, respectively, P < .0001). With a cut-off value greater than or equal to 1.1 for the TPS ratio and less than 2.0 for the coronary flow velocity reserve, diagnostic accuracy for the presence of significant LAD lesions were 88% and 82%, respectively. In conclusion, strain imaging can differentiate ischemic and nonischemic myocardium accurately comparable with coronary flow velocity reserve measurement.

Atherosclerosis is a diffuse process and can be evaluated in the distal part of the left anterior descending coronary artery (LAD). We evaluated whether 2-dimensional high-frequency transthoracic echocardiography could detect changes in coronary wall thickness and size associated with coronary risk factors. In all, 312 patients without a history of coronary artery disease and 40 patients with LAD disease proven by coronary angiography underwent transthoracic echocardiography evaluation of the distal LAD using high-frequency transducer. LAD wall thickness, luminal diameter, external diameter, and coronary flow velocity were measured, and these values were compared according to the number of coronary risk factors (hypertension, hypercholesterolemia, diabetes, smoking, and family history). The feasibility of measuring coronary thickness and coronary flow velocity was 86% and 90%, respectively. LAD wall thickness and external diameter significantly increased according to the increase in the number of risk factors. Patients with 3 or more coronary risk factors showed similar LAD wall thickness (0.82 +/- 0.2 vs 0.89 +/- 0.2 mm) and external diameter (3.4 +/- 0.8 vs 3.3 +/- 0.9 mm) compared with those obtained in patients with LAD disease. High-frequency transthoracic echocardiography is feasible to measure coronary artery wall thickness and external diameter in the distal LAD. This approach has a potential for noninvasive evaluation of the arterial remodeling and the changes in these variables after risk factor modification and intensive drug therapy.

We evaluated the influence of collateral circulation on a donor left anterior descending artery and an appropriate cut-off value of coronary flow velocity reserve for the diagnosis of significant donor left anterior descending artery stenosis. Measurement of coronary flow velocity reserve by transthoracic Doppler echocardiography provides noninvasive assessment of significant left anterior descending artery stenosis. The cut-off value of coronary flow velocity reserve for the diagnosis of significant donor left anterior descending artery stenosis has not been well studied. We retrospectively examined 64 patients who had no significant left anterior descending artery stenosis and who had other coronary artery stenosis. Seventeen patients had collaterals from the left anterior descending artery (group A) and 47 patients did not have collaterals (group B). We prospectively examined 23 consecutive patients who had collaterals from the left anterior descending artery to other coronary arteries. Eight patients had a significant donor left anterior descending artery stenosis. Coronary flow velocity reserve assessment was performed by transthoracic Doppler echocardiography in the 2 protocols. Coronary flow velocity at baseline in group A was significantly higher than that in group B. Coronary flow velocity reserve in group A was significantly lower than that in group B (2.6 +/- 0.8 vs 3.2 +/- 0.9, p < 0.05). Coronary flow velocity during hyperemia and coronary flow velocity reserve were significantly lower in patients with significant stenosis. A cut-off value of 2.0 of coronary flow velocity reserve had a sensitivity of 88% and a specificity of 93% for the diagnosis of significant donor left anterior descending artery stenosis. In conclusion, coronary flow velocity reserve of a donor left anterior descending artery was decreased by the presence of collaterals. However, a cut-off value < 2.0 was appropriate for the diagnosis of significant donor left anterior descending artery stenosis in a population that included patients with collaterals.

Objectives: The purpose of this study was to assess the feasibility and usefulness of coronary flow velocity measurements of the left anterior descending coronary artery (LAD) by transthoracic Doppler echocardiography (TTDE) to differentiate ischemic cardiomyopathy (ICM) from non-ICM in patients., Background: ICM and non-ICM have similar 2-dimensional echocardiographic features, left ventricular dilatation, and diffuse wall-motion abnormalities. TTDE may be useful to differentiate ICM from non-ICM by detecting significant LAD stenosis based on LAD flow signal analysis., Methods: TTDE was performed in 52 consecutive patients with left ventricular dilatation and diffuse wall-motion abnormalities of unknown origin. Peak and averaged systolic and diastolic flow velocities of the distal LAD flow could be recorded and measured from 44 patients (85%). Peak and mean diastolic/systolic velocity ratio (DSVR) were calculated., Results: By coronary angiogram, 13 patients were given the diagnosis of ICM and 31 of non-ICM. Left ventricular end-diastolic and end-systolic volumes and ejection fraction were similar between ICM and non-ICM. On the other hand, peak DSVR (1.47 +/- 0.38 vs 2.34 +/- 0.67, P < .0001) and mean DSVR (1.40 +/- 0.42 vs 2.24 +/- 0.61, P < .0001) were significantly lower in patients with ICM than non-ICM. Either peak DSVR less than 1.8 or mean DSVR less than 1.8 had a sensitivity of 77% and a specificity of 77% for detecting the presence of severe LAD stenosis and, therefore, the diagnosis of ICM., Conclusion: TTDE is a useful noninvasive method to differentiate ICM from non-ICM.

Objective: The repair process at the site of injury after percutaneous coronary intervention (PCI) is dominated by neointimal formation composed mainly of smooth muscle cells (SMC). Endothelin-1 (ET-1) is a powerful vasoconstrictor and SMC mitogen. Endothelin-converting enzyme (ECE) is the final key enzyme of endothelin processing. The effects of ET-1 are mediated by binding to endothelin type A (ETA) and endothelin type B (ETB) receptors. The ligand/receptor/ligand-producing system (ET system) could be involved in the pathogenesis of neointimal formation in humans., Methods: Fifteen post-PCI sites obtained at autopsy and eight atherectomy specimens obtained from restenotic sites were investigated using immunohistochemical single and double staining techniques. Frozen sections were stained with antibodies against ECE, ET-1, ETA and ETB receptors, SMC, macrophages and endothelial cells., Results: At the early stage, less than 3 months after PCI, neointimal SMC were positive for ECE, ET-1, ETA and ETB receptors. The expression of ECE, ET-1, ETA and ETB receptors in these neointimal SMC decreased markedly from 6 months onwards. The ECE, ET-1, ETA and ETB receptor-positive cell areas were significantly (P < 0.005) greater in the first 3 months after PCI compared with 6 months or more after PCI. Atherectomy specimens also showed similar positivity., Conclusions: These observations strongly suggest that the expression of ECE, ET-1, ETA and ETB receptors is enhanced in neointimal SMC at early stages after PCI injury in human coronary arteries. The increased expression of the ET system may contribute to SMC proliferation/migration and vasoconstriction in human post-PCI coronary lesions.

Background: Measurement of the coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography (TTDE) has been reported to be useful for the noninvasive assessment of significant coronary artery stenosis or myocardial ischemia. The purpose of this study was to evaluate the value of this method in three major coronary arteries for detecting myocardial ischemia in the clinical setting., Methods: We studied 89 consecutive patients who were referred to our outpatient clinic because of chest pain. We measured CFVR using TTDE in three major coronary arteries. We defined CFVR<2.0 in at least one vessel as being positive for myocardial ischemia. The accuracy of CFVR measurements for detecting myocardial ischemia was determined in comparison with exercise thallium-201 (Tl-201) single photon emission computed tomography (SPECT) as a reference standard., Results: CFVR in at least one vessel was successfully measured in 87 of 89 patients (98%). The sensitivity and specificity of CFVR<2.0 in at least one coronary vessel, in any of the coronary territories, was 86% and 89%, respectively. In terms of assessing myocardial ischemia in each coronary artery territory, the agreement between CFVR<2.0 and Tl-201 SPECT for the left anterior descending coronary artery, the posterior descending coronary artery, and the left circumflex coronary artery territories was 95%, 81%, and 73%, respectively., Conclusion: Noninvasive CFVR measurement by TTDE may be useful for detecting myocardial ischemia, as well as for identifying ischemic territories in the clinical setting.

We evaluated the significance of the diastolic-to-systolic blood flow velocity ratio (DSVR) determined by transthoracic Doppler echocardiography, for a physiologic assessment of the severity of coronary stenosis without stress tests, as compared with thallium 201 single photon emission computed tomography. In 95 patients undergoing thallium 201 single photon emission computed tomography for coronary artery disease, the flow velocity in the distal left anterior descending coronary artery was obtained with transthoracic Doppler echocardiography. The mean and peak DSVR values were calculated using mean and peak coronary flow velocity. DSVR was successfully measured for 82 patients (86.3%), including 33 patients with reversible perfusion defects in the left anterior descending coronary artery territories. For predicting reversible perfusion defects in thallium 201 single photon emission computed tomography, the best cut-off points were 1.5 for mean DSVR (sensitivity 81.8%, specificity 85.7%) and 1.6 for peak DSVR (sensitivity 75.7%, specificity 83.6%). Noninvasive measurement of DSVR with transthoracic Doppler echocardiography provides physiologic estimation of the left anterior descending coronary artery stenosis severity at high success rate, without stress tests.

Background: We hypothesized that detection of reverse flow in the distal right coronary artery (d-RCA) and the inferior septal branches (ISB) by transthoracic Doppler echocardiography (TTDE) would be useful for noninvasive diagnosis of the occluded right coronary artery (RCA)., Methods: Coronary angiography and TTDE were performed on 129 patients. Antegrade flows in the d-RCA and the ISB were defined as directions from the base to the apex in the posterior sulcus and from anterior to inferior in the inferior septum, respectively. Retrograde flow was defined as an inverse direction., Results: Retrograde flow was obtained by TTDE in 14 patients (d-RCA:11, ISB:3) of 18 patients with occluded RCA. The sensitivity and the specificity for identification of occluded RCA were 100% and 97.8%, respectively., Conclusion: Detection of reverse flow in the d-RCA and the ISB using TTDE is a useful method for the noninvasive diagnosis of occluded RCA.

Background: Transthoracic Doppler echocardiography (TTDE) assessment of coronary flow velocity reserve (CFVR) has been validated in Asian and European centers. This methodology has not gained acceptability in the United States due to the bias that coronary flow velocity (CFV) by TTDE might be difficult in an obese population with relatively poor acoustic windows., Methods: Baseline CFV in the left anterior descending coronary artery (LAD) by TTDE was obtained in 67 nonselected American patients. A subset of 38/67 received adenosine infusion for measuring CFVR of the LAD., Purpose: The aim of this study was twofold: (1) to determine the feasibility of measuring CFV and CFVR in the LAD by TTDE in a relatively obese American population, and (2) to compare CFV and CFVR values in this population with those previously obtained in a group of Japanese patients., Results: The mean body mass index (BMI) of the American population (28 +/- 6 kg/m2, range: 18-46 kg/m2) was significantly higher than that of the Japanese group (23 +/- 4 kg/m2, range: 15-37 kg/m2). Twenty-five American patients were classified as obese (BMI >30 kg/m2). Baseline CFV was obtained in 60/67 patients (feasibility: 90%) with a 10% need for intravenous contrast agent to enhance the delineation of the CFV envelope. The success rate in recording CFVR in American patients (92%) was nearly identical to that of a Japanese group (99%). The time-averaged peak diastolic coronary flow velocity increased from 15.6 +/- 5.5 cm/sec at baseline to 47.1 +/- 17.9 cm/sec during adenosine infusion, and CFVR was calculated to be 3.22 +/- 1.15 (range: 0.94-5.69). Intraobserver and interobserver variability for the CFV recording was 4.7 and 6.2%, respectively., Conclusions: These results suggest that the noninvasive measurement of CFV and CFVR of the LAD is feasible even in a relatively obese American population. Furthermore, the success rates for recording CFV and CFVR are similar to those measured in a Japanese population. This methodology has the potential to provide useful physiological information on the coronary circulation in American patients.

Background: Several studies have demonstrated the benefit of the patency of infarct-related artery (IRA) in acute myocardial infarction (AMI). However those studies have not been concerned with myocardial viability in the region-at-risk. In the present study the effect of the patency of IRA was investigated in the setting of anterior AMI with poor viable myocardium in the risk region., Methods and Results: From 1993 to 1996 patients with a first time anterior AMI and poor viable myocardium in the region-at-risk at 1 month after onset were identified and enrolled. Patients with a totally occluded IRA were included in the Non-Open group (n=44), and patients with a reperfused IRA were included in the Open group (n=49). At 5 years after onset, left ventricular function was better preserved in the Open group than in the Non-Open group (p<0.05). Kaplan-Meier survival curves for cardiac mortality and event-free survival curves revealed poor prognoses in the Non-Open group over a 5-year period (p<0.05, respectively). The advantages of a patent IRA were further seen in health-related quality-of-life outcomes (p<0.05)., Conclusions: Even in patients with poor myocardial viability after an anterior AMI, the patency of the IRA is strongly associated with improved long-term survival, independent of residual myocardium viability.

Background: HMG-CoA reductase inhibitors (statin) have been reported to decrease coronary artery events in several angiographic studies. However, the mechanism by which statin achieve this is still unclear. The purpose of this study was to identify the effect of statin on coronary plaque using serial intravascular ultrasound analysis., Methods and Results: In this study, 48 patients with 48 lesions were divided into the prescribed group (statin group, n = 22) or the non-prescribed group (control group, n = 26) after successful coronary artery stenting. IVUS images were obtained at consecutive 5 mm segments, 5 mm from the proximal stent edge, immediately after stenting and at 6 months follow up. External elastic membrane volume (EEMV), lumen volume (LV) and plaque volume (PV) were measured using Simpson's method. The control group revealed no significant serial change in EEMV, PV, and LV during 6 months. On the other hand, the statin group revealed significant reductions of PV (35.5 +/- 12.7 mm3 vs 30.9 +/- 15.6 mm3, p = 0.001), resulting in increase of LV (47.7 +/- 19.8 mm3 vs 52.5 +/- 22.2 mm3, p = 0.003) without EEMV change (82.8 +/- 21.8 mm3 vs 83.9 +/- 25.7 mm3, p = NS). Although percent EEMV and percent LV changes showed no differences between the two groups, a larger percent PV change was observed in the statin group compared to the control group (control; 5.8 +/- 20.3% vs statin; -20.4 +/- 21.8%, p = 0.02)., Conclusion: The results of this study suggest that statin administration for 6 months reduces coronary plaque without positive vessel remodeling.

Measurement of endothelial function in patients has emerged as a useful tool for cardiovascular research. Although no gold standard for the measurement of endothelial function exists, the measurement of flow-mediated dilation in the brachial artery, assessed with Doppler ultrasonography, is the most studied method. However, the assumption that endothelial dysfunction detected in brachial arteries is a manifestation of systemic endothelial dysfunction including the coronary circulation may not be entirely valid. Brachial and myocardial circulations differ in terms of the microvascular architecture, the pattern of blood flow and vascular resistance (e.g. shunt vessels occur in the hand but not in the myocardium), their metabolic regulation, type of receptors that contribute to humoral regulation and the pathways that are activated to induce hyperaemia. In this context, measuring coronary vasomotor function may be more useful than brachial artery measures to predict and assess potential myocardial damage related to limited vascular responsiveness. This review aims to provide an overview of the basic concept of coronary flow reserve and its different modalities of measurement, as well as its utility in cardiovascular research.

Background: Nicorandil, a potassium channel opener, is used for the treatment of angina pectoris and has a pharmacologic preconditioning effect. This study evaluated whether intravenous nicorandil reduces QT dispersion and prevents bradyarrhythmia during percutaneous transluminal coronary angioplasty (PTCA) of the right coronary artery., Methods: A historical cohort study on the effect of nicorandil on QT dispersion and bradyarrhythmia was conducted. Fifty patients who underwent PTCA of the right coronary artery were enrolled. The patients were divided into a nicorandil (n = 25) group and control group (n = 25). Nicorandil was injected at 4 mg/h continuously 1 hour before PTCA in the nicorandil group. QT dispersion was measured at 1 hour before PTCA (baseline), immediately before PTCA, and 1 minute after the initiation of the first balloon inflation., Results: QT dispersion at 1 minute after the initiation of the first balloon inflation in the control group increased significantly (QT dispersion: 37.1 +/- 17.8 msec and 21.7 +/- 12.2 msec, respectively, P < .001 vs baseline in the control group), and this was larger than at 1 minute after the initiation of the first balloon inflation in the nicorandil group (QT dispersion: 37.1 +/- 17.8 msec and 20.8 +/- 9.4 msec, respectively, P < .001). By two-way repeated measures analysis of variance, there were significant interactions between the time factor and the grouping factor in QT dispersion (P < .001). Bradyarrhythmia was observed in 6 patients in the control group, but none was observed in the nicorandil group., Conclusions: Intravenous nicorandil reduces QT dispersion and prevents bradyarrhythmia during PTCA of the right coronary artery.

Objectives: The usefulness of coronary flow reserve measurement in the left circumflex coronary artery by transthoracic Doppler echocardiography to detect myocardial ischemia was compared with exercise thallium-201 single photon emission computed tomography (SPECT)., Methods: Transthoracic Doppler echocardiography was performed in 110 patients with suspected coronary artery disease. Color Doppler signals of the left circumflex coronary artery flow in the apical four-chamber view were identified, and the velocities at rest and during hyperemia recorded for calculation of coronary flow reserve by the pulsed Doppler method. All patients underwent SPECT within 1 week of the transthoracic Doppler echocardiographic study., Results: Coronary flow reserve in the left circumflex coronary artery was measured in 79 (72%) of 110 patients. SPECT revealed reversible perfusion defect in the left circumflex coronary artery territories in 12 of 69 patients excluding those with multivessel disease. Coronary flow reserve < 2.0 had a sensitivity of 92% and specificity of 96% for reversible perfusion defect detected by SPECT., Conclusions: Noninvasive coronary flow reserve measurement in the left circumflex coronary artery by transthoracic Doppler echocardiography can estimate myocardial ischemia in the left ventricular lateral regions.

Background: Microvascular damage immediately after reperfusion therapy is an independent predictor of left ventricular function in patients with acute myocardial infarction (AMI). However, its recovery may vary among individuals and the relationship between convalescent stage microvasculature and late myocardial morphologic change is unclear., Methods and Results: Patients treated with coronary angioplasty within 12 h of their first anterior AMI were enrolled in this study. Coronary flow reserve (CFR) was measured 3 weeks post AMI, in both branches of the left coronary artery: culprit (left anterior descending artery: LAD) and non-culprit (left circumflex artery: LCX). Left ventriculography was performed at 3 weeks and 6 months post AMI and compared. Seventeen patients showed abnormal CFR in the LAD (Group 1: CFR<2), whereas 20 patients showed normal CFR (Group 2: CFR >/=2). Percent changes of end-diastolic volume tended to be higher in Group 1 than in Group 2 (11.8+/-21.6% vs -1.3+/-14.4%, p=0.056), and %changes of end-systolic volume was significantly smaller in Group 2 (11.8+/-22.1% vs -8.7+/-25.1%, p<0.05). A statistically significant correlation was found between absolute and relative CFR in the LAD and %change of end-systolic volume (r=-0.58: p<0.001, and r=0.40: p<0.05, respectively)., Conclusions: Microvascular function in the convalescent stage may be related to these favorable changes.

Objectives: The study was done to determine potential utility of measuring coronary flow velocity (CFV) by transthoracic Doppler echocardiography (TTDE) during intra-aortic balloon pumping (IABP)., Background: Use of IABP has been shown to increase CFV assessed by an invasive technique. The CFV in the left anterior descending coronary artery (LAD) can be measured by TTDE., Methods: Coronary flow velocity in the distal LAD by TTDE was measured in 40 critically ill patients requiring IABP. All patients received emergency coronary angiography. Both CFV and pressure data were obtained during 1:2 balloon pumping., Results: Adequate diastolic CFV recording was obtained in all patients. The IABP decreased systolic pressure and increased diastolic pressure. Average peak diastolic flow velocity and diastolic velocity time integral was 19 +/- 11 cm/s and 7.7 +/- 4.4 cm with non-augmented beat. These values were increased significantly (61 +/- 38%, 59 +/- 35%, p < 0.001) with augmented beat. Significant correlation was noted between % diastolic pressure augmentation and % increase in diastolic CFV (r = 0.62 to 0.69, p < 0.001). There was no significant difference in flow enhancement during IABP, irrespective to the proximal LAD stenosis severity (severe stenosis: 73 +/- 70%; intermediate stenosis: 61 +/- 29%; no significant stenosis: 58 +/- 29%; p = NS, analysis of variance). By continuous recording of CFV, the optimal timing of balloon control could be adjusted to maximize flow velocity during augmentation., Conclusions: Use of TTDE can be employed in monitoring CFV augmentation during IABP. The IABP produced significant distal flow enhancement even in patients with critical proximal stenosis. This totally noninvasive approach may help to optimize the benefits of IABP for coronary flow augmentation.

Background: We hypothesized that coronary flow assessment by transthoracic Doppler echocardiography (TTDE) for both intramyocardial collateral channel and epicardial channels would be useful for identifying occluded left anterior descending coronary artery (LAD)., Methods: We assessed flow direction in the LAD and the septal branch (SEP) by TTDE in 302 consecutive patients who were suggested to have ischemic heart disease. We defined antegrade LAD flow as a direction from the base to the apex of the left ventricle in the anterior groove area, and antegrade SEP flow as a direction from anterior to inferior in the anterior interventricular septum. By contrast, we defined retrograde LAD and SEP flow as an inverse direction. We performed angiography on all patients., Results: Retrograde flow was detected in 22 (LAD, 16 patients; SEP, 6 patients) of 23 patients with occluded LAD, and antegrade flow was detected in all patients without occluded LAD. The sensitivity and specificity for identification of occluded LAD by TTDE were 96% and 100%, respectively., Conclusions: Assessment of flow direction in both LAD and SEP by TTDE is a useful method in identification of occluded LAD.

Objectives: The aim of this study was to investigate the relationship between circulating monocytes and in-stent neointimal volume at six-month follow-up., Background: In-stent neointimal hyperplasia is the main contributing factor to in-stent restenosis. There is increasing evidence that white blood cells (WBCs), especially monocytes, play a central role in restenosis after stent implantation., Methods: We performed coronary stent implantation in 107 patients (107 lesions). Peripheral blood was obtained from all patients immediately before coronary angiography and every day for seven days after the intervention, and each WBC fraction count was analyzed. At scheduled six-month follow-up, all patients received angiographic and volumetric intravascular ultrasound analysis., Results: The circulating monocyte count increased and reached its peak two days after stent implantation (from 350 +/- 167 to 515 +/- 149/mm3, p < 0.01). The maximum monocyte count after stent implantation showed a significant positive correlation with in-stent neointimal volume at six-month follow-up (r = 0.44, p < 0.0001). Other fractions showed neither significant serial changes nor a correlation with in-stent neointimal volume. Multiple regression analysis revealed that in-stent neointimal volume was independently correlated with stent volume immediately after implantation (r = 0.45, p < 0.0001) and maximum monocyte count (r = 0.35, p < 0.001). Angiographic restenosis, defined as percent diameter stenosis >50%, was observed in 22 patients (21%), and these patients showed a significantly larger maximum monocyte count than patients without restenosis (642 +/- 110 vs. 529 +/- 77/mm3, p < 0.01)., Conclusions: Circulating monocytes increased after coronary stent implantation, and the peak monocyte count related to in-stent neointimal volume. Our results suggest that circulating monocytes play a role in the process of in-stent neointimal hyperplasia.

Background: Although the measurement of coronary flow velocity (CFV) reserve (CFVR) in the left anterior descending coronary artery (LAD) by transthoracic Doppler echocardiography has been established, its success rate in the posterior descending coronary artery (PD) is still limited., Objective: This study reports the feasibility and diagnostic accuracy of measuring CFVR in the PD by transthoracic Doppler echocardiography., Methods: CFVR in both the distal LAD and the PD was measured in 151 consecutive patients before coronary angiography. PD flow was investigated under the guidance of a nondirectional Doppler color flow map with harmonic imaging in the modified apical 2-chamber view. Intravenous contrast agent, Levovist, was injected to enhance the CFV envelope at baseline and during hyperemia., Results: CFVR was obtained in 145 patients in the LAD and 126 patients in the PD (P <.001). The success rate of CFVR measurement in the PD was significantly higher in the last 50 patients (88%) than it was in the first 50 patients (72%) (P <.05). CFVR in the PD was significantly lower for patients with significant stenosis of the artery supplying the PD than it was in those without stenosis (1.58 +/- 0.59 vs 2.45 +/- 0.72, P <.001). CFVR in the distal LAD was 1.40 +/- 0.62 in patients with significant LAD stenosis and 2.45 +/- 0.80 in those without stenosis (P <.001). If a cut-off value of CFVR < 2 was used, sensitivity, specificity, and accuracy for the diagnosis of significant (>50%) stenosis of the artery supplying the PD were 84%, 83%, and 83%, respectively, whereas for the LAD they were 91%, 75%, and 80%, respectively., Conclusions: Noninvasive measurement of CFVR in the PD could be obtained in the majority of unselected patients using a nondirectional Doppler color flow map and contrast-enhanced harmonic imaging. The diagnostic accuracy of CFVR in the PD is similar to that of the LAD and, hence, has a potential clinical use.

Background: Neutrophils in unstable atherosclerotic lesions have not received much consideration, despite accumulating evidence suggesting a link between systemic inflammation and acute coronary syndromes., Methods and Results: Coronary artery segments were obtained at autopsy from 13 patients with acute myocardial infarction (AMI); 8 had a ruptured and 5 an eroded plaque. Patients (n=45) who had died of noncardiovascular diseases served as reference. Atherectomy specimens were obtained from 35 patients with stable angina pectoris (SAP) and from 32 patients with unstable angina pectoris (UAP). Antibodies against CD66b, elastase, myeloperoxidase, and CD11b identified neutrophils; CD10 identified neutral endopeptidase (NEP). CD66b-positive and NEP-positive neutrophils were counted and expressed as a number per square millimeter of tissue. All specimens with plaque rupture or erosion showed distinct neutrophil infiltration; the number did not differ between ruptured and eroded plaques. However, the number of NEP-positive neutrophils was significantly higher (P<0.0001) in ruptured plaques than in eroded plaques. UAP patients showed neutrophils in 14 of 32 culprit lesions; in SAP only 2 of 35 lesions contained neutrophils. The number of neutrophils and NEP-positive cells in patients with UAP was significantly higher (neutrophils, P<0.0005; NEP-positive cells, P<0.005) than in patients with SAP., Conclusions: The observations suggest that neutrophil infiltration is actively associated with acute coronary events. The high number of NEP-positive neutrophils in ruptured plaques, compared with eroded plaques, may reflect differences in the underlying pathophysiological mechanisms.

The purpose of this study was to determine the relationship between coronary flow velocity (CFV) measured by transthoracic Doppler echocardiography (TTDE) and wall motion during dobutamine stress echocardiography (DSE) in patients with resting wall motion abnormalities (WMAs). One hundred fifty patients with resting WMA in the left anterior descending coronary artery (LAD) territory underwent CFV recording in the distal LAD by TTDE during contrast-enhanced DSE. Regional wall motion, CFV, and CFV ratio, defined as a ratio of CFV at each stage of dobutamine stress to basal CFV, were obtained. Patients were divided into 4 groups (sustained improvement, biphasic response, worsening response, and no change). CFV was successfully recorded in 129 patients during DSE (86%). The mean value of basal CFV did not differ among the 4 groups. Although CFV ratio during DSE progressively increased in patients with sustained improvement, this increase was blunted with biphasic response and almost lost with worsening or no change response (P <.001, ANOVA). CFV ratio at peak stress was significantly higher in patients with sustained improvement (2.73 +/- 0.69) than that with the other 3 groups (P <.001). The value with biphasic response (1.68 +/- 0.56) was also higher than that with worsening (0.98 +/- 0.15, P <.005) and no change (1.28 +/- 0.38, P <.08). The simultaneous assessment of CFV and function in the LAD territory is feasible, and flow and function are closely correlated. TTDE provides flow information that may complement conventional echocardiographic assessment of myocardial viability.

Coronary flow velocity recordings were obtained in three patients with ampulla (Takotsubo) cardiomyopathy using Doppler guide wire. Immediately after admission, coronary angiography demonstrated no significant stenosis and normal coronary flow in the epicardial coronary artery. Left ventriculography showed abnormal wall motion of the left ventricle mimicking ampulla shape in all patients. The coronary flow velocity pattern was normal, but coronary flow reserve of the left anterior descending coronary artery was decreased by adenosine administration in all patients. The coronary flow reserve in the left circumflex and right coronary artery also decreased. Cardiac catheterization was performed during the follow-up period in two patients. Left ventriculography revealed almost normal wall motion of the left ventricle. The coronary flow reserve normalized in one patient.

The cellular mechanisms by which hypertension enhances atherosclerosis are still not known in detail. Recently, evidence has been obtained that oxidative stress plays a role in the pathogenesis of pressure-induced atherosclerosis. We examined the effects of pressure on oxidative stress in cultured human coronary smooth muscle cells (SMCs). Application of increased pressure (+100 mmHg) with He gas for 48 h increased oxidative stress of measured by flow cytometry by 71% and F2-isopretane by 77%. Increased pressure also increased the activities of phospholipase D (PLD), and particulate protein kinase C (PKC). The PLD inhibitor suramin 100 micromol/l, 1-butanol 40 mmol/l, and the PKC inhibitors chelerythrine 1 micromol/l and calphostin C 100 nmol/l and completely blocked the increase in oxidative stress induced by pressure. Carvedilol 1 micromol/l but not propranolol 1 micromol/l blocked pressure-induced increases in oxidative stress in cultured SMCs. These findings suggest that pressure increases oxidative stress and that carvedilol significantly inhibits pressure-induced increase in oxidative stress in cultured human coronary smooth muscle cells.