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Renu Virmani

Publications and source records attributed to Renu Virmani.

At least 73 records · Page 4Linked to original sources
PubMed2004

Histology of in-stent restenosis in a transplanted heart.

We report the case of a 32-year-old heart transplant recipient who suffered several episodes of early Grade IIIA rejection and, on serial coronary angiography, demonstrated aggressive allograft vasculopathy. Severe lesions in the right coronary and left obtuse marginal arteries were stented; however, the disease was progressive and, almost 6 years after heart transplantation, she was retransplanted, providing us with the opportunity to examine the histology of transplant in-stent restenosis. She remains well 1 year after a second heart transplant operation.

Adult↗
PubMed2004

Superficial pseudoaneurysms: clinicopathologic aspects and involvement of extracellular matrix proteoglycans.

The distribution of proteoglycans in 21 temporal and two ulnar artery pseudoaneurysms was studied immunohistochemically. A history of trauma was elicited in six cases, and 16 of the lesions were pulsatile. The clinical diagnosis was aneurysm or cyst in 18 patients, possible arteritis in two patients, tumor in one patient, and unknown in the remaining patient. Histologically, there was a prominent myxoid neointimal response in the walls of each interrupted artery. The remnant arterial segment was often inconspicuous. Prominent smooth muscle cell proliferation and granulation tissue response with inflammation led to misdiagnosis of tumor or vasculitis, respectively, in 11 cases. Immunohistochemical staining for proteoglycans demonstrated abundant, diffuse versican in interrupted wall segments. Biglycan was confined to collagenized and vascularized areas. In some portions of medial disruption, in which angiogenesis was prominent, decorin was expressed within endothelial cells of neocapillaries. These findings demonstrate that superficial pseudoaneurysms may be mistaken clinically and pathologically for unrelated entities. The immunohistochemical studies confirm that versican is upregulated in areas of tensile stress. In addition, the presence of endothelial expression of decorin supports the concept of decorin's involvement in angiogenesis.

Adolescent↗
PubMed2004

Drug-eluting stents: caution and concerns for long-term outcome.

Recent publications on drug-eluting stents (DES) report a significant reduction in restenosis rates as compared to bare metal stents in patients mostly with single vessel disease. We have recently observed however, late stent thrombosis following CYPHER DES implantation. The patient developed a hypersensitivity reaction around stent struts limited to the polymer with aneurysmal dilatation and extensive inflammation of the arterial wall in the absence of vascular healing. This incidence promotes a cautionary view and perhaps supports the use of DES only in high-risk patients.

Animals↗
PubMed2004

The accumulation of specific types of proteoglycans in eroded plaques: a role in coronary thrombosis in the absence of rupture.

PURPOSE OF REVIEW: Although fibrous cap rupture is the primary cause of coronary thrombosis, plaque erosion is responsible for 30%-40% of acute thrombotic events. The interface of the eroded surface involves a denuded endothelium allowing direct contact of the platelet/fibrin thrombus with the underlying lesion. This review discusses the putative role of extracellular matrix molecules, in particular proteoglycans/hyaluronan, in the development of acute coronary thrombosis associated with erosion. RECENT FINDINGS: The plaque/thrombus interface in erosion presents a unique surface since it consists of predominantly SMCs and proteoglycans with minimal or no inflammation. The lack of significant inflammation raises the possibility that erosion represents chronic wounding rather than true atherogenesis. The abundance of proteoglycan and hyaluronan matrix suggests their potential role in the development of thrombosis. Matrix changes may contribute to endothelial loss, the magnitude of the thrombotic event, or both. Versican facilitates platelet adhesion at low shear and cooperates with collagen to promote platelet aggregation. Further, versican may, in part, regulate water content and in turn support coagulation because water-dependent functionality of anticoagulation molecules. Finally, experimental models of plaque erosion are currently being developed guided by the premise that the loss of surface endothelium together with other procoagulant factors may underlie the development of platelet-rich thrombi. SUMMARY: The loss of endothelium and exposure of a potentially procoagulant versican-hyaluronan matrix may be largely responsible for plaque erosion. The development of relevant animal models should allow further insight into the pathophysiology of coronary thrombosis in the absence of rupture.

Adult↗
PubMed2004

Drug-eluting stents: are they really safe?

Drug-eluting stents have reduced the frequency of in-stent restenosis. However, most of the results have been derived from simple lesions in noncomplex patients. In preclinical normal pig and rabbit studies, bare-metal stents show complete healing at 28 days, whereas drug-eluting stents show incomplete healing with persistence of fibrin and incomplete coverage of the stent struts by endothelial cells. In human beings similar delayed healing has been observed at 6 and 12 months in atherectomy specimens or at autopsy. The US Food and Drug Administration posted adverse event information for physicians regarding subacute thrombosis and hypersensitivity reaction following deployment of sirolimus-eluting stents in human beings. The authors have seen, at autopsy, late (18 months) stent thrombosis, aneurysm formation, and extensive inflammatory reaction limited to the arterial wall surrounding the stent that they interpret as a hypersensitivity reaction to the polymer. The authors advocate caution and aggressive use of nontoxic systemic drugs to prevent the complications of atherosclerosis along with better postmarket surveillance of patients and histologic examination of tissue from patients with drug-eluting stents.

Aneurysm↗
PubMed2004

Uptake of 111In-Z2D3 on SPECT imaging in a swine model of coronary stent restenosis correlated with cell proliferation.

UNLABELLED: Small targets such as cell proliferation in the coronary arteries may potentially be detected with single-photon imaging using high-radiotracer-specific activity. We hypothesized that an antibody linked to polymers to increase specific radioactivity can be visualized on SPECT images and that counts in the target will correlate with the strength of the biologic signal. METHODS: Twenty-four stents were placed using the balloon overexpansion technique in the coronary arteries of 14 juvenile domestic swine. One week later, the animals received 74 MBq of (111)In-diethylenetriaminepentaacetic acid-polylysine Z2D3-F(ab')(2), and SPECT imaging was performed at 24 h. The coronary vessels were removed, and the stented vessels were processed with plastic embedding and sectioning. Medial and neointimal areas, percentage of vessel stenosis, and cell proliferation indices were quantified using a 5-bromo-2-deoxyuridine (BrdU) labeling index. Reconstructed SPECT images were interpreted for tracer uptake in coronary vessels. RESULTS: Sixteen of the vessels were positive on SPECT imaging and 10 were negative. The percentage injected dose was 0.85 +/- 0.28 x 10(-3) in scan-positive vessels and 0.34 +/- 0.11 x 10(-3) in scan-negative vessels (P < 0.001). The medial-plus-neointimal proliferative index was 42 +/- 11 in scan-positive vessels and 11 +/- 11 in scan-negative vessels (P < 0.0001). The percentage stenoses were 21% +/- 22% versus 19% +/- 15% (not statistically significant). When individual values for the stented-to-control vessel counts were plotted against BrdU labeling index, a significant relationship was found (r(2) = 0.441; P = 0.0014). CONCLUSION: These data indicate that small targets relevant to human coronary vascular disease may be detected using polymer-modified radiolabeled antibodies.

Animals↗
PubMed2003

Targeting of apoptotic macrophages and experimental atheroma with radiolabeled annexin V: a technique with potential for noninvasive imaging of vulnerable plaque.

BACKGROUND: Apoptosis is common in advanced human atheroma and contributes to plaque instability. Because annexin V has a high affinity for exposed phosphatidylserine on apoptotic cells, radiolabeled annexin V may be used for noninvasive detection of apoptosis in atherosclerotic lesions. METHODS AND RESULTS: Atherosclerotic plaques were produced in 5 rabbits by deendothelialization of the infradiaphragmatic aorta followed by 12 weeks of cholesterol diet; 5 controls were studied without manipulation. Animals were injected with human recombinant annexin V labeled with technetium-99m before imaging. Aortas were explanted for ex vivo imaging, macroautoradiography, and histological characterization of plaque. Radiolabeled annexin V cleared rapidly from the circulation (T1/2, alpha 9 and beta 46 minutes). There was intense uptake of radiolabel within lesions by 2 hours; no uptake was seen in controls. The results were confirmed in the ex vivo imaging of the explanted aorta. Quantitative annexin uptake was 9.3-fold higher in lesion versus nonlesion areas; the lesion-to-blood ratio was 3.0+/-0.37. Annexin uptake paralleled lesion severity and macrophage burden; no correlation was observed with smooth muscle cells. DNA fragmentation staining of apoptotic nuclei was increased in advanced lesions with evolving necrotic cores, predominantly in macrophages; the uptake of radiolabel correlated with the apoptotic index. CONCLUSIONS: Because annexin V clears rapidly from blood and targets apoptotic macrophage population, it should constitute an attractive imaging agent for the noninvasive detection of unstable atherosclerotic plaques.

Animals↗
PubMed2003

Intraplaque hemorrhage and progression of coronary atheroma.

BACKGROUND: Intraplaque hemorrhage is common in advanced coronary atherosclerotic lesions. The relation between hemorrhage and the vulnerability of plaque to disruption may involve the accumulation of free cholesterol from erythrocyte membranes. METHODS: We stained multiple coronary lesions from 24 randomly selected patients who had died suddenly of coronary causes with an antibody against glycophorin A (a protein specific to erythrocytes that facilitates anion exchange) and Mallory's stain for iron (hemosiderin), markers of previous intraplaque hemorrhage. Coronary lesions were classified as lesions with pathologic intimal thickening, fibrous-cap atheromas with cores in an early or late stage of necrosis, or thin-cap fibrous atheromas (vulnerable plaques). The arterial response to plaque hemorrhage was further defined in a rabbit model of atherosclerosis. RESULTS: Only traces of glycophorin A and iron were found in lesions with pathologic intimal thickening or fibrous-cap atheromas with cores in an early stage of necrosis. In contrast, fibroatheromas with cores in a late stage of necrosis or thin caps had a marked increase in glycophorin A in regions of cholesterol clefts surrounded by iron deposits. Larger amounts of both glycophorin A and iron were associated with larger necrotic cores and greater macrophage infiltration. Rabbit lesions with induced intramural hemorrhage consistently showed cholesterol crystals with erythrocyte fragments, foam cells, and iron deposits. In contrast, control lesions from the same animals had a marked reduction in macrophages and lipid content. CONCLUSIONS: By contributing to the deposition of free cholesterol, macrophage infiltration, and enlargement of the necrotic core, the accumulation of erythrocyte membranes within an atherosclerotic plaque may represent a potent atherogenic stimulus. These factors may increase the risk of plaque destabilization.

Animals↗
PubMed2003

From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II.

Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document will focus on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.

Animals↗
PubMed2003

From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I.

Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document focuses on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.

Acute Disease↗
PubMed2003

Pathological mechanisms of fatal late coronary stent thrombosis in humans.

BACKGROUND: Coronary stent deployment is associated with a low incidence of acute thrombosis. However, late stent thrombosis (LST) has likely been underrecognized clinically, and pathological descriptions are lacking. METHODS AND RESULTS: LST was defined as an acute thrombus within a stent that had been in place > or =30 days. Cases of LST were selected from a registry of human coronary stents submitted for analysis. Thirteen cases of LST (9 men, 4 women) were identified. The mean duration from implantation to thrombosis was 3.6+/-3.5 months (range, 1 to 11.9 months). The causes of death were sudden cardiac death (n=10), acute myocardial infarction (n=2), and heart failure (n=1). The pathological mechanisms of LST were as follows: (1) stenting across ostia of major arterial branches (5 cases); (2) exposure to radiation therapy (3 cases); (3) plaque disruption in the nonstented arterial segment within 2 mm of the stent margin (2 cases); (4) stenting of markedly necrotic, lipid-rich plaques with extensive plaque prolapse (2 cases); and (5) diffuse in-stent restenosis (1 case). Twelve cases demonstrated a failure to form a completely healed neointimal layer overlying stent struts. Underlying in-stent restenosis was present in only 4 (31%) of 13 cases. CONCLUSIONS: LST is a potentially fatal complication of coronary stenting. Stenting across branch ostia, disruption of adjacent vulnerable plaques, radiation therapy, and extensive plaque prolapse can precipitate LST. Impaired intimal healing (ie, the failure to form a complete neointimal layer over stent struts) extends the window during which stents are prone to thrombosis.

Adult↗
PubMed2003

Collagenase plaque digestion for facilitating guide wire crossing in chronic total occlusions.

BACKGROUND: Chronic total occlusions (CTOs) are associated with significant angina, impaired left ventricular function, and worse long-term outcomes. Percutaneous coronary interventions in CTO are unsuccessful in up to 50% of cases, primarily because of inability to cross the lesion with a guide wire. Collagen is the predominant component of the atherosclerotic plaque. The objective of this study was to determine the efficacy and toxicity of local delivery of a collagen-degrading enzyme to facilitate guide wire crossing in CTO. METHODS AND RESULTS: Type IA collagenase (100 or 450 microg) or placebo was locally administered to 45 CTOs in a rabbit femoral artery model. Mean occlusion duration was 16+/-5 weeks. Attempts to cross the CTO (mean length, 28+/-9 mm) with conventional guide wires were assessed at 72 hours after treatment. An additional 3 arteries per group were assessed for collagenase effects at 24 hours after treatment. Successful guide wire crossings were significantly higher in collagenase-treated arteries (13 of 21, 62%) than in placebo-treated arteries (7 of 24, 29%) (P=0.028). No adverse effects on arterial structure were observed in collagenase-treated arteries. At 24 hours, collagenase-treated arteries demonstrated increased collagenase protein, gelatinase activity, and collagen fragments. CONCLUSIONS: Local delivery of collagenase can safely facilitate guide wire crossing of CTO. This novel approach could lead to higher percutaneous coronary intervention success rates in CTO.

Angiography↗
PubMed2003

Time course of stent endothelialization after intravascular radiation therapy in rabbit iliac arteries.

BACKGROUND: Late total occlusion after vascular brachytherapy (VBT) continues to be a serious complication. Delayed reendothelialization was suggested as a pivotal cause, but the time course for complete healing is unknown. METHODS AND RESULTS: Seventy-two rabbit iliac arteries underwent stent implantation and were treated with gamma-radiation using 192Ir. The prescribed doses were 0 Gy (controls, n=24 arteries), 15 Gy (n=24), or 30 Gy (n=24) at 2 mm. Animals were killed at 1 month (n=24), 3 months (n=24), or 6 months (n=24) and were analyzed for histomorphometry or scanning electron microscopy. Intimal area was reduced after VBT at 3 months with 15 and 30 Gy (0.66+/-0.07 and 0.66+/-0.04 mm2, respectively) compared with controls (1.01+/-0.11 mm2, P<0.05) and at 6 months with 30 Gy (0.75+/-0.09 versus 1.28+/-0.26 mm2 in controls, P<0.01). Intimal area was similar at 6 months between 15 Gy and controls. At 1 month, 92+/-4% of the control stented segment was covered with endothelial cells, whereas only 37+/-4% and 37+/-8% was covered in the 15- and 30-Gy arteries, respectively. Similarly, at 3 and 6 months, there was a difference in the extent of reendothelialized areas (at 3 months, 95+/-2%, 32+/-12%, and 29+/-13%; and at 6 months, 98+/-2%, 40+/-8%, and 35+/-12% in control, 15-Gy, and 30-Gy arteries, respectively). Excess platelets and leukocytes were seen in irradiated arteries without complete coverage of endothelium. CONCLUSIONS: Reendothelialization after VBT is not completed at 6 months after VBT. Special care with prolonged antiplatelet therapy should be considered beyond that time point.

Animals↗
PubMed2003

Wall tension is a potent negative regulator of in vivo thrombomodulin expression.

Thrombomodulin (TM), a key component of the anticoagulant protein C pathway, is a major contributor to vascular thromboresistance. We previously found that TM protein expression is dramatically reduced in autologous vein grafts during the first two weeks after implantation, coincident to a local inflammatory response, and remains suppressed for at least 6 weeks. To determine the proximate cause of TM loss, in vivo gene expression was quantified by real-time PCR. TM gene expression in vein grafts declined >85% during the first postoperative week and remained suppressed >55% at 6 weeks, accounting for the observed changes in protein expression. The effects of vein graft inflammation were evaluated in animals rendered leukopenic with vinblastine before graft implantation. Abrogating the local inflammatory response affected neither TM protein nor gene expression. To determine how hemodynamic forces might modulate TM expression, the surgical protocol was modified to alter blood flow and pressure-induced vessel distension. TM protein and gene expression did not correlate to changes in shear stress but highly correlated to changes in wall tension, both acutely and over time. We conclude that the primary stimulus for altered TM expression in vein grafts is the exposure to arterial pressure. Furthermore, these data identify strain as a novel and important pathway for in vivo TM gene regulation.

Animals↗
PubMed2003

Catheter-based coronary bypass: a development update.

Catheter-based coronary bypass has evolved since its origin in 1995. We present a status update of one version of catheter-based bypass, percutaneous in situ coronary venous arterialization (PICVA), its successes and failures, and the many questions and challenges that remain. Initial clinical experience with PICVA demonstrated promising mitigation of angina in no-option patients, but was complicated by a relatively low procedural completion rate and a high incidence of MACE. A great deal was learned in these initial cases. The system of devices is currently undergoing significant modification, and further clinical study is underway.

Cardiac Catheterization↗