Treatment Of Vulnerable Plaques Research Articles

Aiming at early-stage vulnerable plaques: A nanoplatform with dual-mode imaging and lipid-inflammation integrated regulation for atherosclerotic theranostics

The vulnerable plaques in atherosclerosis can cause severe outcome with great danger of acute cardiovascular events. Thus, timely diagnosis and treatment of vulnerable plaques in early stage can effectively benefit the clinical management of atherosclerosis. In this work, a targeting theranostic strategy on early-stage vulnerable plaques in atherosclerosis is realized by a LAID nanoplatform with X-CT and fluorescent dual-mode imaging and lipid-inflammation integrated regulation abilities. The iodinated contrast agents (ICA), phenylboronic acid modified astaxanthin and oxidized-dextran (oxDEX) jointly construct the nanoparticles loaded with the lipid-specific probe LFP. LAID indicates an active targeting to plaques along with the dual-responsive disassembly in oxidative stress and acidic microenvironment of atherosclerosis. The X-CT signals of ICA execute the location of early-stage plaques, while the LFP combines with lipid cores and realizes the recognition of vulnerable plaques. Meanwhile, the treatment based on astaxanthin is performed for restraining the progression of plaques. Transcriptome sequencing suggests that LAID can inhibit the lipid uptake and block NF-κB pathway, which synergistically demonstrates a lipid-inflammation integrated regulation to suppression the plaques growing. The in vivo investigations suggest that LAID delivers a favorable theranostics to the early-stage vulnerable plaques, which provides an impressive prospect for reducing the adverse prognosis of atherosclerosis.

P42 ACUTE STENT THROMBOSIS IN CATH LAB DURING OPTIMIZED PCI: HOW TO RECOGNIZE IT AND POSSIBLE TREATMENT

Abstract Angiographic Acute Stent Thrombosis occur in 0.5%–2% of procedures.OCT–PCI or Optimized PCI represents a new approach particularly indicated in complex high thrombotic risk lesions, in patients at high bleeding risk with need for short DAPT and in the treatment of vulnerable plaques. Post–stent OCT thrombus finding was defined in previous studies as mass with diameter ≥250μm attached to the stent struts, was present until 40% of cases and is associated with definite angiographic thrombosis. Outcome of OCT thrombus is generally favorable although in about 25% there may be a progression. Case 1: 75–y smoker female with hypertension and atrial fibrillation on NOAC therapy presented in ICU with NSTEMI. At angiography: 75% stenosis focal plaque at proximal circumflex (Fig1A). At OCT vulnerable plaque: ulcerated with intimal flap < 90°, thin fibrous cap 20 µm, MLA 2.17mm² and AS 63%, intimal micro–calcifications and cholesterol crystals (Fig1C). We implanted DES with post–dilatation. Treatment was Cangrelor, heparin 100 IU/kg and ASA 250 mg ev. OCT showed acute 660 µm thrombosis of the stent body although there was perfect angiographic result (Fig1D+B). Further multiple balloon dilatation of the stent was carried out with thrombosis persistence on OCT control (Fig1E) and new appearance of multiple thromboses adhering to the intravascular side stent struts (Fig1F–G). Switch from Cangrelor to Tirofiban was done. Patient‘s clinical course was uneventful with discharge after six days on triple antithrombotic therapy with low–dose NOAC, ASA and clopidogrel.Case 2: 63–y smoker man arrived in cath lab for anterior STEMI. He had already taken ASA 300 mg ev and Ticagrelor 180 mg oral bolus about 60 minutes earlier in the ambulance. In Cath Lab was done heparin 100 IU/kg. P–PCI was performed for acute sub–occlusion (Fig2A) of the ostial DA treated by pre–dilation, DES implantation on Left Main–DA and multiple post–dilations according to the POT technique. OCT control showing extensive stent malapposition (860 µm) with evidence of multiple thromboses adhering to the stent struts on Left Main (diameter 410 µm) although there was perfect angiographic result (Fig2B–E). Procedure was optimized by adequate post–dilatation of the LM and administration of Abciximab. Patient‘s clinical course was uneventful with discharge after five days on ASA and Ticagrelor. Conclusions Post–stent OCT thrombus may guide the choice of use of Glicoprotein IIb/IIIA Inhibitors in Cath Lab.

HPDA/Zn as a CREB Inhibitor for Ultrasound Imaging and Stabilization of Atherosclerosis Plaque†

Comprehensive SummaryThrombosis, secondary to rupture of unstable plaque, is a fatal risk factor for myocardial infarction and ischemic stroke. At present, more novel methods are needed for the diagnosis and treatment of vulnerable plaque. Here, we report a hollow polydopamine/Zn (HPDA/Zn) ultrasound contrast agent. Through western‐blot, Elisa, and other experiments, we found that in addition to having a good contrast‐enhancement capability in ultrasound imaging in vitro and in vivo, HPDA/Zn also has the effect of reducing the expression of CREB. CREB protein and its downstream‐regulated proteins and factors are closely related to the stability of plaque. HPDA/Zn has the effect of reducing the expression of CREB protein, which leads to the decrease of expression of MMP‐9, the regulatory protein downstream of the CREB protein. In addition, it also reduces the secretion of inflammatory factors hs‐CRP and IL‐17A. Thus, HPDA/Zn can stabilize plaque by inhibiting CREB and reducing plaque vulnerable markers and inflammatory factors. In a word, HPDA/Zn is a kind of ultrasound contrast agent, which can stabilize plaques by inhibiting CREB protein.

Treatment of vulnerable plaque using combined high-density lipoprotein and pentostatin- loaded microbubbles- mediated shock wave sonoporation therapy: Evaluation with positron emission tomography imaging and histopathology

Background and Aims : The rupture of vulnerable atherosclerosis and the subsequent formation of thrombi are the main factors responsible for myocardial infarctions. Macrophages are responsible for the prevalence of inflammation in atherosclerotic lesions. In the present study, we developed a shock wave sonoporation therapy system and investigated its effect on advanced atherosclerosis regression using Positron Emission Tomography (PET) imaging.

High-Risk Coronary Plaque Features: A Narrative Review.

Advances in coronary plaque imaging over the last few decades have led to an increased interest in the identification of novel high-risk plaque features that are associated with cardiovascular events. Existing practices focus on risk stratification and lipid monitoring for primary and secondary prevention of cardiac events, which is limited by a lack of assessment and treatment of vulnerable plaque. In this review, we summarize the multitude of studies that have identified plaque, haemodynamic and patient factors associated with risk of acute coronary syndrome. Future progress in multi-modal imaging strategies and in our understanding of high-risk plaque features could expand treatment options for coronary disease and improve patient outcomes.

GW27-e0930 New-style nanoparticles in detection and treatment of vulnerable plaques

Cardiovascular disease is the leading cause of death in the world. The most manifest contributor to cardiovascular morbidity and mortality is atherosclerosis. When atherosclerotic plaques rupture, it can cause clinical events such as myocardial infarction and stroke. The plaques prone to rupture are

Methods of producing high specific activity Sn-117m with commercial cyclotrons

Sn-117m is a theragnostic isotope of increasing interest. It has ideal imaging and therapeutic properties for many applications. Production of high specific activity Sn-117m can only be achieved with accelerators and the Sb(p,x) and Cd-116(α,3n) reactions provide the highest yields for this isotope. This paper describes the production and a new purification method for obtaining commercial quantities of Sn-117m via the Cd-116(α,3n) reaction. The purified Sn-117m has subsequently been chelated with an aminobenzyl derivative of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and then conjugated with annexin V-128 to produce an agent for the diagnosis and treatment of vulnerable plaque.

Intravascular ultrasound: Virtual histology IVUS, integrated backscatter IVUS, and palpography

The concept of the vulnerable plaque is the focus of much research, although our knowledge of the histology, pathobiology, natural history, and therapy of vulnerable plaque remains incomplete. The evolving intravascular ultrasound technologies of virtual histology, integrated backscatter, and palpography have yielded complementary information to traditional grayscale intravascular ultrasound, and advanced our understanding of vulnerable plaque. Although each of these techniques has enjoyed success in the academic arena, none of these techniques has been sufficiently validated to the extent that would allow it to play a part in clinical decision-making. Their future role, both in regard to risk stratification and identification of vulnerable plaque, will depend upon additional rigorous studies of the natural history and treatment of vulnerable plaque.

Distribuição espacial da placa vulnerável na árvore coronária: avaliação angiográfica de uma coorte consecutiva e não-selecionada de pacientes submetidos a angioplastia primária

FUNDAMENTOS: A gênese do infarto agudo do miocárdio (IAM) está intimamente relacionada à ruptura de "placas vulneráveis". Estudos anatomopatológicos sugerem uma distribuição não-homogênea dessas placas ao longo da árvore coronária. Neste estudo, visamos a estabelecer as "zonas vulneráveis", no sentido de obter um mapa do risco de maior probabilidade de ocorrência de IAM. MÉTODO: Neste estudo, foram analisados 82 pacientes consecutivos tratados com angioplastia primária em um centro terciário de referência, no período de janeiro a setembro de 2007. Somente foram incluídos pacientes com IAM com elevação do segmento ST, com fluxo coronário TIMI 0/1. Após definir o segmento de oclusão, utilizando a segmentação coronária do Coronary Artery Surgery Study (CASS), mensuramos a distância do ponto de oclusão do vaso culpado até seu óstio, com software dedicado (CMS-Medis). O modelo de regressão de Poisson foi utilizado para determinar o risco de IAM, baseado na distância da oclusão a partir do óstio coronário. RESULTADOS: A média das idades foi de 60 anos e 73,1% dos pacientes eram homens. A artéria descendente anterior foi o vaso culpado mais prevalente (46,3%). O diâmetro médio de referência do vaso foi de 2,8 ± 0,6 mm. Para cada segmento de 10 mm a partir do óstio do vaso-alvo, foi observada, pela regressão de Poisson, redução de 36,9% no risco de oclusão aguda do vaso. Nesta coorte notou-se distribuição não homogênea das placas vulneráveis, com maior prevalência nos segmentos proximais dos vasos epicárdicos. CONCLUSÕES: Os achados desta análise in vivo estão em concordância com os estudos anatomopatológicos prévios. Identificação das "zonas vulneráveis" na árvore coronária pode ajudar a selecionar dispositivos diagnósticos e de prevenção/tratamento das placas vulneráveis.

Detection and Treatment of Vulnerable Plaques and Vulnerable Patients

There is growing interest in the possibility that identification and treatment of vulnerable plaques and vulnerable patients can enhance the progress made against coronary artery disease. Innovations in medical therapy—statins and other agents—and novel interventional cardiology techniques—eg, drug-eluting stents—have significantly decreased the morbidity and mortality caused by coronary atherosclerosis. However, coronary events continue to be the leading cause of death in the United States, accounting for >479 000 deaths (1 in 5) in 2003.1 Improved preventive measures are needed because, for many individuals, sudden coronary death is the first sign of the disorder. And even those who survive an acute coronary syndrome remain at high risk. After successful treatment of the initial culprit lesion by a percutaneous coronary intervention (PCI), the risk of a coronary event from a new lesion is ≈10% in the following year and 5% in each of the subsequent 4 years2,3 (Figure 1). Figure 1. Occurrence of coronary events (revascularization, death, MI, acute coronary syndromes, or congestive heart failure) after PCI in 4 studies of bare-metal stents. In addition to events resulting from stented lesions (solid line), many events are caused by nontarget (vulnerable) plaques (dashed line). Modified from Cutlip et al2 with permission from the American Heart Association. Copyright 2004. These substantial levels of ongoing morbidity and mortality have led to heightened interest in new methods to prevent coronary events. For primary prevention, the effort has focused on plasma markers and noninvasive testing to identify vulnerable individuals. For secondary prevention, interest has focused on vulnerable patients and the vulnerable plaques they may possess that might be identified and treated during the catheterization for their initial event. ### Definitions of the Vulnerable Plaque and the Vulnerable Patient The terminology to describe vulnerability has become relatively standardized.4–10 The term “vulnerable plaque” is used to designate a plaque at high risk of disruption leading …

Cardiología intervencionista 2005

Drug-eluting stents have been shown to reduce the rate of restenosis significantly in all types of lesion, patient and clinical context without increasing thrombotic complications. Although their high cost limits the extent to which they can replace bare-metal stents, their use will increase inexorably in coming years. In addition to stents containing sirolimus and paclitaxel, which have already been approved, two additional drug-eluting stents have appeared on the market this year: one elutes tacrolimus and the other, ABT578 (a rapamycin analogue). Now that the restenosis rate has been dramatically reduced, the main limitations on percutaneous coronary intervention (PCI) stem from problematic lesions such as those at bifurcations and chronic total occlusions. Although these lesions can be tackled more often and more successfully than in the past, the results obtained are very different from those achieved with other types of lesion. With improvements in safety and long-term efficacy, the number of indications for PCI has expanded to include patients with multivessel disease, left main coronary artery disease, left ventricular dysfunction, and diabetes, conditions in which surgical revascularization was thought necessary only a few years ago. Acute coronary syndromes now make up an increasing proportion of indications for PCI, both in absolute and relative terms. One future challenge is the early identification and treatment of vulnerable plaques before they manifest clinically in the form of irreversible complications such as sudden death or acute myocardial infarction. The use of multislice computed tomography, such as 64-slice detector systems, has considerably increased the sensitivity, specificity, and positive and negative predictive values of diagnosis to around 90%, though diagnostic accuracy may be considerably less in patients with severe coronary calcification, stents, or cardiac arrhythmias. Although the technique is straightforward for patients, the image reconstruction process is time-consuming, few centers currently offer the technique, and radiation exposure is several times that with conventional invasive coronary angiography. It appears that the main application of the technique is in ruling out coronary disease in low-risk patients rather than being part of the diagnostic work-up in those with a high probability of coronary artery disease.

Thoughts on the role of the healing professions and the events of September 11, 2001.

On October 5 and 6, 2001, less than a month after the terrorist attacks on the United States, a conference on the Pathophysiology, Detection, and Treatment of Vulnerable Plaque was held in Boston, Mass. Nineteen scientists from around the world came together, despite the uncertainty of air travel, to continue the work against this important cause of cardiovascular disease. After the faculty dinner, Dr James Muller, Co-Director of the Vulnerable Plaque Program of the Center for the Integration of Medicine and Innovative Technology (CIMIT) and Director of Clinical Research in Cardiology at the Massachusetts General Hospital and Harvard Medical School, offered the following thoughts on cardiovascular research and the September 11, 2001, terrorist attacks. Dr Muller was one of the co-founders of International Physicians for Prevention of Nuclear War, the organization awarded the 1985 Nobel Peace Prize. The terrible violence of September 11, a day of mass murder of innocent civilians, had many consequences, some of which directly affected our collective effort to prevent death from vulnerable plaque. Specifically, I refer to the irony that September 11 started as a day to celebrate progress for the vulnerable plaque research community. Over 10 000 individuals congregated at the Transcatheter Cardiovascular Therapeutics (TCT) Conference in Washington, DC. The program included a town meeting on vulnerable plaque, one of those wonderful occasions when the scientists working in isolation come together to share progress and ideas. The event was a rare moment when one could actually feel a massive human problem slowly giving way to organized, dedicated human effort. At 8:00 AM, I gave the opening lecture, which included an overview of the topic of vulnerable and invulnerable plaques. At 8:45, while Dr Peter Fitzgerald described the use of ultrasound and OCT for the diagnosis and treatment …