Relationship of Thrombus Healing to Underlying Plaque Morphology in Sudden Coronary Death

Kramer, Miranda C.A.; Rittersma, Saskia Z.H.; Winter, Robbert J. de; Ladich, Elena; Fowler, David; Liang, You-hui; Kutys, Robert; Carter‐Monroe, Naima; Kolodgie, Frank D.; Wal, Allard C. van der; Virmani, Renu

doi:10.1016/j.jacc.2009.09.007

Cited by 233 publications

(149 citation statements)

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“…Conversely, chronic thrombi showed the presence of spindle-shaped cells with or without macrophages that either lined the thrombus or infiltrated the thrombus, or had greater organization with matrix deposition interspersed between the fibrin. 12 Of a total of 21 thrombi, 13 had features of acute thrombi, whereas 8 had features that fulfilled the definition of chronic thrombi (organizing thrombus) Figure 6). In 9 patients, along with platelets, fibrin, and erythrocytes, some collagenous material was observed, but it was not possible to definitely identify whether this material was from the aortic valve or from the arterial wall ( Figure 4C and 4D).…”

Section: Downloaded Frommentioning

confidence: 99%

Histopathology of Embolic Debris Captured During Transcatheter Aortic Valve Replacement

Mieghem

Schipper

Ladich³

et al. 2013

Circulation

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220

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Background— Recent transcatheter aortic valve replacement studies have raised concerns about adverse cerebrovascular events. The etiopathology of the embolized material is currently unknown. Methods and Results— A total of 40 patients underwent transcatheter aortic valve replacement with the use of a dual filter–based embolic protection device (Montage Dual Filter System, Claret Medical, Inc). Macroscopic material liberated during the transcatheter aortic valve replacement procedure was captured in the device filter baskets in 30 (75%) patients and sent for histopathologic analysis. The captured material varied in size from 0.15 to 4.0 mm. Amorphous calcified material (size, 0.55–1.8 mm) was identified in 5 patients (17%). In 8 patients (27%), the captured material (size, 0.25–4.0 mm) contained valve tissue composed of loose connective tissue (collagen and elastic fibers) with focal areas of myxoid stroma, with or without coverage by endothelial cells and intermixed with fibrin. In another 13 (43%) patients, collagenous tissue, which may represent elements of vessel wall and valvelike structures, was identified. In 9 patients (30%), thrombotic material was intermixed with neutrophils (size, 0.15–2.0 mm). Overall, thrombotic material was found in 52% of patients, and tissue fragments compatible with aortic valve leaflet or aortic wall origin were found in 52% (21/40) of patients. Conclusions— Embolic debris traveling to the brain was captured in 75% of transcatheter aortic valve replacement procedures where a filter-based embolic protection device was used. The debris consisted of fibrin, or amorphous calcium and connective tissue derived most likely from either the native aortic valve leaflets or aortic wall.

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Section: Downloaded Frommentioning

confidence: 99%

Histopathology of Embolic Debris Captured During Transcatheter Aortic Valve Replacement

Mieghem

Schipper

Ladich³

et al. 2013

Circulation

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220

144

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“…Hearts of patients who had died suddenly with coronary artery disease (CAD) were obtained as previously described ( 13 ). Cases were identifi ed prospectively by the presence and type of CAD and included nonatherosclerotic intimal lesions, pathologic intimal thickening, early and late fi broatheroma, thin cap fi broatheroma (TCFA) and plaque rupture.…”

Section: Human Atherosclerotic Lesionsmentioning

confidence: 99%

Differential expression of oxidation-specific epitopes and apolipoprotein(a) in progressing and ruptured human coronary and carotid atherosclerotic lesions

Dijk

Kolodgie

Ravandi

et al. 2012

Journal of Lipid Research

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Oxidative pathways in the subendothelial space activate pro-infl ammatory, immunogenic, and atherogenic processes, resulting in endothelial dysfunction, plaque growth and destabilization, platelet activation, and thrombosis, ultimately leading to clinical events ( 1 ). A variety of oxidation-specifi c epitopes (OSE) are generated during oxidative modifi cation of plaque components. These epitopes are not only expressed on modifi ed lipoproteins but also on apoptotic cells and proteins in the extracellular matrix of atherosclerotic vessels ( 2 ).Extensive experimental data exists defi ning the role of oxidation in both progression and regression of atherosclerosis. Atherosclerotic lesions of hypercholesterolemic animal models, which represent primarily early and intermediate stage atherosclerosis, contain signifi cant amounts of OSE, often in proportion to plaque burden. OSE in the vessel wall of atherosclerotic animals can also be imaged with nuclear and magnetic resonance techniques using murine and human oxidation-specifi c antibodies, such as MDA2, E06, and IK17 ( 3-5 ). Dietary interventions in hypercholesterolemic animals that promote regression result in more rapid removal of OSE than apoB, which occurs prior to plaques diminishing signifi cantly in size, and is associated with markers of plaque stabilization, such Abstract The relationships between oxidation-specifi c epitopes (OSE) and lipoprotein (a) [Lp(a)] and progressive atherosclerosis and plaque rupture have not been determined. Coronary artery sections from sudden death victims and carotid endarterectomy specimens were immunostained for apoB-100, oxidized phospholipids (OxPL), apo(a), malondialdehyde-lysine (MDA), and MDA-related epitopes detected by antibody IK17 and macrophage markers. The presence of OxPL captured in carotid and saphenous vein graft distal protection devices was determined with LC-MS/MS. In coronary arteries, OSE and apo(a) were absent in normal coronary arteries and minimally present in early lesions. As lesions progressed, apoB and MDA epitopes did not increase, whereas macrophage, apo(a), OxPL, and IK17 epitopes increased proportionally, but they differed according to plaque type and plaque components. Apo(a) epitopes were present throughout early and late lesions, especially in macrophages and the necrotic core. IK17 and OxPL epitopes were strongest in late lesions in macrophagerich areas, lipid pools, and the necrotic core, and they were most specifi cally associated with unstable and ruptured plaques. Specifi c OxPL were present in distal protection devices. Human atherosclerotic lesions manifest a differential expression of OSEs and apo(a) as they progress, rupture, and become clinically symptomatic.

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“…Sato et al investigated the proportion of fibrin and platelets in thrombi of ruptured and eroded coronary atherosclerotic plaques obtained from patients who had died of acute MI within three days of onset and reported that fibrin was more abundant than platelets in the thrombi of ruptured plaques (74±19% vs. 35±20%, p＜0.01), whereas platelets tended to be more abundant than fibrin in the thrombi of eroded plaques (51±6% vs. 70±21%, p＜0.07) 16) . The second report was on the relationship between thrombus age (healing) and plaque morphology in sudden coronary death victims 82) . In that study, Kramer et al immunohistopathologically evaluated 111 sudden death victims who had coronary lesions (ruptures, n = 65; erosions, n = 50) with thrombi and determined the relationship between plaque morphology and thrombus healing classified as early (＜1 day) or late characterized in phases of lytic (1 to 3 days), infiltrating (4 to 7 days) or healing (＞7 days).…”

Section: Coronary Thrombus and Plaque Morphologymentioning

confidence: 99%

Thrombus Aspiration Therapy and Coronary Thrombus Components in Patients with Acute ST-Elevation Myocardial Infarction

Yunoki

Naruko

Sugioka

et al. 2013

JAT

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Inflammation and oxidative stress play key roles in atherosclerotic plaque instability, and plaque rupture/erosion and subsequent thrombus formation constitute the principal mechanisms of total vessel occlusion and acute ST-elevation myocardial infarction (STEMI). Plaque disruption triggers the formation of initial platelet aggregates that grow in association with an increase in fibrin formation, leading to persistent coronary flow obstruction and blood coagulation. The fibrin network may trap large numbers of erythrocytes and inflammatory cells to form an erythrocyte-rich thrombus. In fact, previous clinical studies have shown that not only platelet-rich white thrombi, but also erythrocyte-rich red thrombi can be visualized using angioscopy in patients with acute coronary syndrome. Recently, the development of thrombus aspiration and distal protection devices has significantly improved the clinical outcomes of percutaneous intervention in STEMI patients and has enabled the evaluation of antemortem coronary artery thrombi. This is important because previous autopsy studies were unable to differentiate coronary thrombi responsible for myocardial ischemia from postmortem clots. Using frozen samples of aspirated thrombi and specific monoclonal antibodies, we investigated the cellular components of thrombi (platelets, erythrocytes, fibrin and inflammatory cells, such as myeloperoxidase-positive cells) and pathologically evaluated the relationships between erythrocyterich thrombi and inflammation, oxidative stress and clinical outcomes in STEMI patients. Therefore, this review article focuses on the efficacy of thrombus aspiration therapy and the components of aspirated intracoronary thrombi in STEMI patients and presents the results of recent studies regarding the relationship between the composition of aspirated intracoronary thrombi and clinical outcomes.

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Relationship of Thrombus Healing to Underlying Plaque Morphology in Sudden Coronary Death

Abstract: Approximately two-thirds of coronary thrombi in sudden coronary deaths are organizing, particularly in young individuals-especially women, who perhaps might require a different strategy of treatment.

Cited by 233 publications

References 20 publications

Histopathology of Embolic Debris Captured During Transcatheter Aortic Valve Replacement

Histopathology of Embolic Debris Captured During Transcatheter Aortic Valve Replacement

Differential expression of oxidation-specific epitopes and apolipoprotein(a) in progressing and ruptured human coronary and carotid atherosclerotic lesions

Thrombus Aspiration Therapy and Coronary Thrombus Components in Patients with Acute ST-Elevation Myocardial Infarction

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