Detection of Ceramide, a Risk Factor for Coronary Artery Disease, in Human Coronary Plaques by Fluorescent Angioscopy.

BACKGROUND: The presence of ceramide in human coronary plaques is a risk factor for ischemic heart disease, but its visualization in the human vessel wall is currently beyond the scope of any available imaging techniques.Methods and Results:Deposition of ceramide was examined by fluorescent angioscopy (FA) and microscopy (FM) using golden fluorescence (Go) as a specific marker of ceramide in yellow plaques, which were obtained from 23 autopsy subjects and classified by conventional angioscopy and histology. Ceramide was observed by FM in 34 of the 41 yellow plaques with a necrotic core (NC) but rarely in the 28 without. Ceramide and macrophages/foam cells co-deposited mainly in the border zone of the NC and fibrous cap (FC). The Go of ceramide was seen when the fibrous cap thickness was ≤100 µm. FA was performed to detect coronary plaques exhibiting Go in patients with coronary artery disease. Ceramide was also detected by FA in 6 of 18 yellow plaques (33.3%) in 8 patients with stable angina and in 18 of 24 yellow plaques (75.0%, P<0.05 vs. stable angina) in 8 patients with old myocardial infarction. CONCLUSIONS: The Go of ceramide in human coronary plaques is detectable by FA and Go could be used as a marker of vulnerable plaque (i.e., thin FC with NC).

Human pericoronary adipose tissue as storage and possible supply site for oxidized low-density lipoprotein and high-density lipoprotein in coronary artery.

BACKGROUND: Thickening of the pericoronary adipose tissue (PCAT) is a proven risk factor for coronary artery disease, but it is poorly understood whether PCAT stores pro-atherogenic substances with oxidized low-density lipoprotein (oxLDL) and low-density lipoprotein (LDL), and an anti-atherogenic substance with high-density lipoprotein (HDL) and supply them to the coronary intima. METHODS: Using immunohistochemical techniques, the localization of oxLDL, LDL and HDL in PCAT and its adjacent coronary segments was examined in 30 epicardial coronary arteries excised from 11 human autopsy cases. RESULTS: PCAT stored oxLDL and HDL in all, but LDL rarely, in 77 specimens examined, irrespective of the presence or absence of coronary plaques and underlying disease. The percentage (%) incidence of oxLDL, HDL and LDL deposits in intima was, respectively, 28, 10, 35 in 29 normal segments, 80 (p<0.05 vs. normal segments), 12, 75 in 19 white plaques (growth stage), 57, 36, 90 in 15 yellow plaques without necrotic core (NC; mature stage), and 40, 21, 100 (p<0.05 vs. normal segments) in 14 yellow plaques with NC (end-stage of maturation) as classified by angioscopy and histology. In coronary intima, oxLDL deposited in either a dotted or diffuse pattern whereas HDL and LDL showed diffuse patterns. Dotted oxLDL deposits were contained in CD68(+)-macrophages traversing the border of PCAT and adventitia, external and internal elastic laminae. Diffuse oxLDL and HDL deposits colocalized with intimal vasa vasorum. CONCLUSIONS: The results suggested that, as a hitherto unrecognized supplying route, the human PCAT stores oxLDL and HDL and oxLDL is supplied to coronary intima either by CD68(+)-macrophages or vasa vasorum and HDL by vasa vasorum, and that deposition of oxLDL and HDL in the intima increased with plaque growth but the former decreased while the latter increased further with plaque maturation. Molecular therapy targeting PCAT before plaque maturation could be effective in preventing atherosclerosis.

Imaging of Triglycerides in Human Coronary Plaques by Color Fluorescent Angioscopy and Microscopy.

Native triglycerides (TG) deposited in the human vascular wall is not measurable or visible in vivo to date. We discovered that by exciting fluorescence at 345 nm and emitting at 420 nm, 3-amino-4-hydroxy-5-nitrobenzene sulfonic acid monohydrate (3-ANA) elicits a brown fluorescence that is characteristic of just TG. Therefore, localization of TG in coronary plaques and normal segments that were obtained from 19 human autopsy cases was examined by color fluorescent angioscopy (CFA) and microscopy using 3-ANA as a biomarker of TG. By CFA, the percentage (%) incidence of TG in 23 normal segments, 13 white plaques without lipid deposition, 18 white plaques (growth stage) with lipid deposition, 11 yellow plaques without necrotic core (mature stage), and 12 yellow plaques with necrotic core (advanced mature stage) was 95, 92, 50, 27, and 25, respectively. By color fluorescent microscopy, TG deposited mostly in the fibrotic area of the plaques. Contrary to the general belief that TG amount increases with plaque maturation, the results indicated that TG was deposited in most of the normal coronary segments, but the amount decreased with plaque maturation. If 3-ANA becomes applicable clinically, the CFA system could be used for imaging TG within coronary plaques in patients in vivo.

Pericoronary Adipose Tissue as Storage and Supply Site for Oxidized Low-Density Lipoprotein in Human Coronary Plaques.

OBJECTIVES: It is generally believed that low-density lipoprotein enters the vascular wall from its lumen and oxidized (oxLDL), after which it plays an important role in atherosclerosis. Because voluminous epicardial adipose tissue is a risk factor for coronary events, there is a possibility that the pericoronary adipose tissue (PCAT), which is a part of epicardial adipose tissue, acts as a risk factor by supplying oxLDL to the coronary arterial wall. The present study was performed whether PCAT stores and supplies oxLDL to the coronary wall. METHODS: Localization of oxLDL in PCAT and its relation to plaque morphology were examined by immunohistochemical techniques in 27 epicardial coronary arteries excised from 9 human autopsy cases. RESULTS: OxLDL deposited in all PCAT of the studied cases. The percent (%) incidence of oxLDL in the intima of 25 normal segment, 19 white plaques, 15 yellow plaques without necrotic core (NC) and 10 yellow plaques with NC, was 32, 84, 93 (p<0.05 vs normal segments and yellow plaques with NC), and 30, respectively. OxLDL deposited either in dotted or diffuse pattern. Double immunohistochemical staining revealed that the dotted oxLDL was that contained in CD68(+)-macrophages. The oxLDL-containing macrophages were observed in the interstitial space but not inside of the vasa vasorum, and they traversed PCAT, adventitia, external and internal elastic laminae, suggesting their migration towards the intima. Diffuse oxLDL deposits were observed in 17 preparations, the majority of which were co-localized with the vasa vasorum in outer or in both inner and outer halves of intima, and rarely in the inner half alone. CONCLUSIONS: The results suggested that PCAT is a supply source of oxLDL to coronary intima and acts as a risk factor for coronary events, that oxLDL increasingly deposits in the intima with plaque growth and decreases after plaque maturation, and therefore molecular therapies targeting the PCAT before plaque growth could be effective in preventing human coronary atherosclerosis.

Molecular Imaging of Native Low-Density Lipoprotein by Near-Infrared Fluorescent Angioscopy in Human Coronary Plaques.

Low-density lipoprotein (LDL) is an important risk factor for coronary artery disease, but its localization within the human coronary arterial wall is poorly understood. Imaging of LDL in 30 coronary arteries excised from 15 subjects who underwent autopsy was performed using near-infrared fluorescent angioscopy system and using indocyanine green dye as a biomarker of LDL. The percentage incidence of LDL in 28 normal segments, 24 white plaques (early stage of plaque growth), and 21 yellow plaques (mature stage of plaque) classified by conventional angioscopy, was 14.2, 79.1 (p <0.01 vs normal segments and p <0.05 vs yellow plaques), and 28.5, respectively. Coronary near-infrared fluorescent angioscopy showed similar results in 7 patients in vivo. Our results suggested that LDL begins to deposit in the human coronary arterial wall in the early stage of atherosclerosis, increasingly deposits with plaque growth and decreases in the mature stage; and therefore, molecular therapy targeting LDL should be started before plaque maturation.

Dye-Staining Angioscopy for Coronary Artery Disease.

Novel imaging techniques using biomarkers have clarified the mechanisms of hitherto unanswered or misunderstood phenomena of coronary artery disease and enabled evaluation of myocardial blood and tissue fluid flows in vivo. Dye-staining coronary angioscopy using Evans blue (EB) as the biomarker can visualize fibrin and damaged endothelial cells, revealing that the so-called platelet thrombus is frequently a fibrin-rich thrombus; occlusive transparent fibrin thrombus, but not platelet thrombus, is not infrequently a cause of acute coronary syndrome; "fluffy" coronary luminal surface is caused by fibrin threads arising from damaged endothelial cells and is a residue of an occlusive thrombus after autolysis in patients with acute coronary syndrome without angiographically demonstrable coronary stenosis; and web or membrane-like fibrin thrombus is a cause of stent edge restenosis. Fluorescent angioscopy using visual or near-infrared light wavelengths is now used clinically for molecular imaging of the substances such as lipoproteins and cholesterol that constitute coronary plaques. Dye-staining cardioscopy using EB or fluorescein enables direct and real-time visualization of subendocardial microcirculation.

Imaging of native high-density lipoprotein in human coronary plaques by color fluorescent angioscopy.

BACKGROUND: High-density lipoprotein (HDL) plays a key role in reverse cholesterol transport, and halts the progression of atherosclerosis. The aim of the present study was to visualize native HDL in the human coronary arterial wall. METHODS AND RESULTS: The fluorescence characteristics of HDL were investigated by color fluorescent microscopy (CFM) using excitation at 470 nm and emission at 515 nm with Fast green dye (FG) as the biomarker. HDL in 30 normal coronary segments, and in 25 white and 25 yellow plaques in excised human coronary arteries, was visualized by color fluorescent angioscopy (CFA) and CFM. Localization of HDL visualized by CFM was compared with that stained by immunostaining using an anti-HDL antibody. FG elicited a characteristic brown fluorescence of HDL. By CFA, the percent incidence of HDL in normal segments, white (early stage of plaque growth) and yellow (advanced stage of plaque growth) plaques was, respectively, 33%, 76% (P<0.05 vs. normal segments and yellow plaques) and 21%. Localization of HDL visualized by CFM did not differ from that stained by immunostaining. CONCLUSIONS: In the human coronary arterial wall, HDL deposits infrequently in normal segments, but increasingly deposits with plaque formation, and decreases in the advanced stage of plaque growth.

Localization of native high-density lipoprotein and its relation to plaque morphology in human coronary artery.

High-density lipoprotein (HDL) plays a key role in reverse cholesterol transport, and halts the progression of atherosclerosis. However, its localization in human vascular wall is not well understood. We discovered that by exciting at 470-nm and emitting at 515-nm light wavelengths, Fast green dye (FG) elicits brown fluorescence characteristic of HDL only. Therefore, the localization of native HDL in normal segments and plaques in excised human coronary artery was investigated by scanning their transected surface with color fluorescent microscopy (CFM) using FG as a biomarker, and the relationships between the localization of HDL and morphology of plaques and normal segments classified by conventional angioscopy and histology were examined. The % incidence of HDL in 13 normal segments (NS) with thin (≤ 200 µm) intima, 28 NS with thick (200 µm <) intima, 41 white plaques (early stage of plaque growth), 15 yellow plaques (Y) without necrotic core (NC), and 20 Y with NC (advanced stage of plaque growth), was 30, 71 (P < 0.05 versus NS with thin intima and Y with NC), 83 (P < 0.05 versus NS with thin intima and Y with NC), 60, and 35, respectively. HDL begins to deposit in human coronary arterial wall in the early stage of atherosclerosis and deposits increase with plaque growth, but HDL decreases in plaques at an advanced stage of growth.

Smooth muscle-like cells resident in the media participate in spasm-induced coronary intimal hyperplasia.

BACKGROUND: Coronary intimal hyperplasia occurs at the site of spasm in patients with vasospastic angina. The migration of vascular smooth muscle cells (VSMCs) from the media has been proposed as a potential mechanism; however, this has not been confirmed with supportive evidence. OBJECTIVE: To determine which cell types participate in spasm-induced coronary intimal hyperplasia. METHODS: Morphological changes in spastic coronary artery segments in beagles were examined using electron microscopy and immunohistochemical staining of cell markers at 1 h, 3 h and 6 h, and two and four weeks after spasm provocation. RESULTS: Small smooth muscle-like cells (SMLCs) were observed in the media of nonspastic coronary segments using electron microscopy. These cells attached side-to-side to large, known VSMCs. At 1 h to 6 h after spasm provocation, SMLCs separated from VSMCs, changed to an amoebic configuration and migrated through cleaved junctions or disrupted portions of the internal elastic lamina into the subendothelial space. The SMLCs expressed alpha-smooth muscle actin and N-cadherin, but not smooth muscle myosin heavy chain-1 and ß-actin, suggesting that they were myofibroblasts and not a synthetic phenotype of VSMCs. Intimal hyperplasia was observed in all preparations at two and four weeks after spasm provocation. Furthermore, alpha-smooth muscle actin-positive SMLCs, often amoebic in configuration, were observed in the hyperplastic intima. CONCLUSIONS: On coronary spasm provocation, SMLCs (ie, possible myofibroblasts) resident in the media migrate as a spearhead into the intima and play a role in coronary intimal hyperplasia.

Molecular imaging of apolipoprotein B-100 in human coronary plaques by color fluorescent angioscopy and microscopy.

Apolipoprotein B-100 (ApoB-100) is an important risk factor for coronary artery disease. However, its localization in human coronary plaques is not well understood. The present study was performed to visualize ApoB-100 in human coronary artery wall. Deposition of native ApoB-100 in excised human coronary plaques and normal segments classified by conventional angioscopy was investigated by color fluorescent angioscopy (CFA) and microscopy (CFM) using Nile blue dye (NB) which elicits a golden fluorescence characteristic of ApoB-100 as a biomarker. By CFA, the % incidence of ApoB-100 was 20 in 40 normal segments, 38 in 42 white, and 11 in 35 yellow plaques (P < 0.05 versus white plaques). There was no significant difference in detection sensitivity between CFA and luminal surface scan by CFM. By CFM transected surface scan, ApoB-100 deposited in superficial, deep, and/or in both layers. Deposition in both layers was frequently observed in white plaques and yellow plaques without necrotic core (NC), less frequently in normal segments, and rarely in yellow plaques with NC. (1) Taking into consideration the well known process of plaque growth, the results suggest that ApoB-100 begins to deposit before plaque formation, increasingly deposits with plaque growth, and disappears after necrotic core formation. (2) CFA is feasible for imaging of ApoB-100 in human coronary artery wall.

Impact of diabetes on long term follow-up of elderly patients with chronic total occlusion post percutaneous coronary intervention.

BACKGROUND: The prognosis of elderly patients with chronic total occlusion (CTO) and diabetes mellitus (DM) treated with percutaneous coronary intervention (PCI) is not known. OBJECTIVE: To investigate the effect of diabetes on long-term follow-up of CTO after PCI in elderly patients. METHODS: A total of 153 elderly patients (age > 65 years old) with CTO lesions which were successfully treated with PCI were enrolled. Fifty one patients with diabetes and 102 without diabetes were compared for long-term outcomes (mean follow up: 36 ± 12 months). Major adverse cardiac events (MACE) which include death, myocardial infarction or target lesion revascularization (TLR) were considered as a combined endpoint. RESULTS: The combined endpoint occurred in 29.4% of diabetes patients, and 11.3% of the patients without diabetes (P < 0.05). The Cox proportional hazards model identified: drug eluting stent (DES) or bare metal stent (BMS) (HR: 0.13, 95% confidence interval (95% CI): 0.03-0.62, P = 0.004), DM (HR: 6.69, 95% CI: 1.62-15.81, P = 0.01) and final minimal lumen diameter (MLD) (HR: 0.37, 95% CI: 0.13-0.90, P = 0.03 ) as independent predictors of MACE, DM with renal impairment (HR: 6.64, 95% CI: 1.32-33.36, P = 0.02), HBA1C on admission (HR: 1.79, 95% CI: 1.09-2.94, P = 0.02), as independent predictors of MACE at long term follow-up. CONCLUSIONS: The study demonstrates that DM is a predictive factor for MACE in elderly CTO patients treated with PCI, type of stent, final minimal lumen diameter and DM with renal impairment, and HBA1C level on admission are predictors of MACE.

Localization of oxidized low-density lipoprotein and its relation to plaque morphology in human coronary artery.

OBJECTIVES: Oxidized low-density lipoprotein (oxLDL) plays a key role in the formation of atherosclerotic plaques. However, its localization in human coronary arterial wall is not well understood. The present study was performed to visualize deposition sites and patterns of native oxLDL and their relation to plaque morphology in human coronary artery. METHODS: Evans blue dye (EB) elicits a violet fluorescence by excitation at 345-nm and emission at 420-nm, and a reddish-brown fluorescence by excitation at 470-nm and emission at 515-nm characteristic of oxLDL only. Therefore, native oxLDL in excised human coronary artery were investigated by color fluorescent microscopy (CFM) using EB as a biomarker. RESULTS: (1) By luminal surface scan with CFM, the % incidence of oxLDL in 38 normal segments, 41 white plaques and 32 yellow plaques that were classified by conventional angioscopy, was respectively 26, 44 and 94, indicating significantly (p<0.05) higher incidence in the latter than the former two groups. Distribution pattern was classified as patchy, diffuse and web-like. Web-like pattern was observed only in yellow plaques with necrotic core. (2) By transected surface scan, oxLDL deposited within superficial layer in normal segments and diffusely within both superficial and deep layers in white and yellow plaques. In yellow plaques with necrotic core, oxLDL deposited not only in the marginal zone of the necrotic core but also in the fibrous cap. CONCLUSION: Taken into consideration of the well-known process of coronary plaque growth, the results suggest that oxLDL begins to deposit in human coronary artery wall before plaque formation and increasingly deposits with plaque growth, exhibiting different deposition sites and patterns depending on morphological changes.

Molecular imaging of low-density lipoprotein in human coronary plaques by color fluorescent angioscopy and microscopy.

OBJECTIVES: Low-density lipoprotein (LDL) is an important risk factor for coronary artery disease. However, its localization in human coronary plaques is not well understood. The present study was performed to visualize LDL in human coronary artery wall. METHODS: (1) The fluorescence characteristic of LDL was investigated by color fluorescent microscopy (CFM) with excitation at 470-nm and emission at 515-nm using Nile blue dye (NB) as a biomarker. (2) Native LDL in 40 normal segments, 42 white plaques and 35 yellow plaques (20 with necrotic core) of human coronary arteries was investigated by color fluorescent angioscopy (CFA) and CFM. RESULTS: (1) NB elicited a brown, golden and red fluorescence characteristic of LDL, apolipoprotein B-100, and lysophosphatidylcholine/triglyceride, respectively. (2) The % incidence of LDL in normal segments, white, and yellow plaques was 25, 38 and 14 by CFA and 42, 42 and 14 by CFM scan of their luminal surface, respectively, indicating lower incidence (p<0.05) of LDL in yellow plaques than white plaques, and no significant differences in detection sensitivity between CFA and CFM. By CFM transected surface scan, LDL deposited more frequently and more diffusely in white plaques and yellow plaques without necrotic core (NC) than normal segments and yellow plaques with NC. LDL was localized to fibrous cap in yellow plaques with NC. Co-deposition of LDL with other lipid components was observed frequently in white plaques and yellow plaques without NC. CONCLUSIONS: (1) Taken into consideration of the well-known process of coronary plaque growth, the results of the present study suggest that LDL begins to deposit before plaque formation; increasingly deposits with plaque growth, often co-depositing with other lipid components; and disappears after necrotic core formation. (2) CFA is feasible for visualization of LDL in human coronary artery wall.

ß-actin-positive mononuclear cells participate in coronary microvascular medial hyperplasia by migrating through adventitia into media, with special reference to microvessel angina.

Coronary microvascular hyperplasia is a cause of microvessel angina, although the underlying cellular mechanisms remain unclear. We examined how mononuclear cells expressing ß-actin (ß-MNCs), which were identified in coronary vessels, induce coronary microvascular hyperplasia.The presence of ß-MNCs in coronary hyperplastic arterial (HAM) and venous microvessels (HVM) was examined by endomyocardial biopsy in 25 patients with suspected microvessel angina. ß-MNCs were identified in 14 HAMs obtained from 11 patients. Basic fibroblast growth factor and heparin sulfate were injected into the infarcted myocardium to induce HAM and HVM in 28 beagles, and then we examined the role of ß-MNCs in the onset of HAM and HVM. The following changes were observed after infarction induction in beagles: (a) migration of ß-MNCs from the existing microvessels into the interstitial space at 1-2 weeks; (b) those traversing the adventitia into the media, but not intima, of microvessels; (c) their transformation to smooth muscle cells (SMCs) and/or connective tissues (collagen and elastin fibers); (d) and medial hyperplasia without intimal hyperplasia. Medial hyperplasia was classified into SMC-proliferative and both SMC- and connective tissue-proliferative types. ß-MNCs expressed CD(34) but did not express other major vessel-related cell markers.ß-MNCs are a vascular progenitor, and migrate out of the adventitia into media, and participate in the etiology of coronary microvascular medial hyperplasia.

Migration of mononuclear cells expressing ß-actin through the adventitia into media and intima in coronary arteriogenesis and venogenesis in ischemic myocardium.

It was previously thought that arteriogenesis and venogenesis are induced not only by proliferation of vessel-resident smooth muscle cells (SMCs) and endothelial cells (ECs) but also by migration of their precursors. However, it is not well understood through what route(s) the precursors migrate into the existing vessels.We examined through what route or routes circulating mononuclear cells expressing ß-actin (ß-MNCs), which we identified in canine coronary vessels, migrate into coronary vessel walls and cause arteriogenesis and venogenesis at 1, 2, 4 and 8 weeks after induction of myocardial infarction.The following changes were observed: (1) The ß-MNCs migrated via coronary microvessels to the interstitial space at one week; (2) ß-MNCs traversed the adventitia into the media and settled in parallel with pre-existing smooth muscle cells (SMCs) in arterioles and arteries and lost ß-actin and acquired α-smooth muscle actin (α-SMA) to become mature SMCs at 2-4 weeks; (3) at the same time, other ß-MNCs migrated across the adventitia and media into the intima and settled in parallel with pre-existing endothelial cells (ECs) and lost ß-actin, while acquiring CD(31), to become mature ECs, resulting in arteriogenesis; (4) Similarly, ß-MNCs migrated into venular and venous walls and became SMCs or ECs, resulting in venogenesis.ß-MNCs in the interstitial space expressed CD(34) but not other major vascular cell markers.ß-MNCs, possibly a vascular progenitor, migrate not from the lumen but across the adventitia into the media or intima of coronary vessels and transit to SMCs or ECs, and participate in arteriogenesis and venogenesis in ischemic myocardium.

Nitroglycerin-induced heterogeneous subendocardial myocardial blood flow observed by cardioscopy in patients with coronary artery disease.

It is controversial as to whether or not nitroglycerin (NTG) increases subendocardial myocardial blood flow (SMBF), and if it does, whether arterial or venous blood flow is increased in patients with coronary artery disease. This study was performed to examine NTG-induced changes in SMBF.Changes in SMBF induced by NTG (200 µg, i.v.) were examined by cardioscopy in 58 left ventricular wall segments of 58 patients with coronary artery disease. NTG-induced red and purple endocardial colors were defined as increased arterial and venous SMBF, respectively. Endocardial color before NTG administration was classified into brown, light brown, pale and white. Endomyocardial biopsy of the observed portion and (201)Tl scintigraphy were performed in 40 of these patients immediately after cardioscopy and several days after cardioscopy, respectively.Upon administration of NTG, SMBF increased in 48 of 58 wall segments; arterial SMBF in 34 and venous SMBF in 12 wall segments; arterial SMBF in all 24 brown to light brown segments; venous SMBF, arterial SMBF and no change in 12, 10 and 5 of pale segments, respectively; and no change in all 10 white wall segments. (201)Tl-scintigraphy and endomyocardial biopsy revealed that brown, light brown, pale and white endocardial color represented no ischemia, mild ischemia, severe ischemia and fibrosis, respectively.NTG caused an increase in either arterial or venous SMBF depending on control endocardial color, wall motion and severity of coronary stenosis.

Cardioscopic observation of subendocardial microvessels in patients with coronary artery disease.

Coronary microvessels play a direct and critical role in determining the extent and severity of myocardial ischemia and cardiac function. However, because direct observation has never been performed in vivo, the functional properties of the individual microvesssels in patients with coronary artery disease remain unknown. Subendocardial coronary microvessels were observed by cardioscopy in 149 successive patients with coronary artery disease (81 with stable angina and 68 with old myocardial infarction). Twenty-four arterial microvessels (AMs) and 27 venous microvessels (VMs) were observed in the left ventricular subendocardium. All 12 AMs and 13 of 14 VMs that were located in normokinetic-to-hypokinetic left ventricular wall segments were filled with blood during diastole and were collapsed during systole. In contrast, 8 of 12 AMs and 9 of 13 VMs that were located in akinetic-to-dyskinetic wall segments were filled with blood during systole and were collapsed during diastole. There were no significant correlations between the timing of blood filling and the severity of coronary stenosis and collateral development. In patients with coronary artery disease, the timing of blood filling of AMs and VMs was dependent on the regional left ventricular contractile state; during diastole when contraction was preserved and during systole when it was not. It remains to be elucidated whether and how blood filling is disturbed in other categories of heart disease.

Cardioscopic detection of left ventricular thrombi. -With special reference to a comparison with left ventriculography and echocardiography-.

BACKGROUND: Thrombosis occurs in the left ventricle and causes ischemic cerebral attacks. However, differences in the incidence of left ventricular thrombi (LVT) among various categories of heart diseases are not known. METHODS AND RESULTS: From April 2000 to 31 March 2008, 258 patients (104 females and 154 males; age 63 ± 6 years) with a heart disease underwent cardioscopy of the left ventricle. LVT were detected by cardioscopy in 78 of 258 patients; 12.5% of 57 patients with stable angina, 0% of 9 with unstable angina, 45.2% of 42 with acute myocardial infarction, 23.2% of 43 with old myocardial infarction, 61.9% of 21 with idiopathic acute myocarditis, 44.3% of 68 with idiopathic chronic myocarditis, 33.3% of 6 with rheumatic valvular disease, 25.7% of 31 with idiopathic dilated cardiomyopathy and in 8.0% of 12 with idiopathic hypertrophic cardiomyopathy. Nine of 78 thrombi were globular and 69 were mural. The detection rate of LVT by cardioscopy, left venticulography, non-contrast and contrast echocardiography was 30.2%, 2.7%, 1.9% and 7.0%, respectively. CONCLUSIONS: LVT were frequently detected by cardioscopy in patients with heart diseases. Although invasive, cardioscopy was more sensitive in detecting LVT than left ventriculography, and non-contrast and contrast echocardiography.