This document discusses approaches to cardiovascular disease (CVD) and the need for new approaches. It summarizes that the emphasis is shifting from high risk plaques to high risk symptomatic patients, and from high risk asymptomatic to intermediate and low risk patients. It discusses diagnostic tools like magnetic resonance imaging to identify high risk asymptomatic patients and computed tomography to identify intermediate risk patients using coronary artery calcium scoring and biomarkers. It also discusses prevention and treatment strategies like polypills and improving time to reperfusion for heart attacks.
The document discusses the role of imaging coronary calcium using electron beam tomography (EBT) scans. It provides evidence that EBT calcium scores are strongly correlated with the amount of atherosclerotic plaque buildup. It also shows that higher EBT calcium scores are associated with significantly higher risks of future cardiovascular events, with risk increasing progressively as calcium scores rise. EBT calcium scoring more accurately predicts cardiovascular risk than traditional risk models like Framingham and can reclassify a person's risk level in about half of intermediate-risk individuals.
This document summarizes key points from a task force report on identifying and treating asymptomatic patients vulnerable to heart attack. It introduces a new paradigm focused on outcomes studies, measuring disease activity, and identifying the vulnerable plaque and patient. The report was chaired by Morteza Naghavi and had writing contributions from experts in cardiovascular imaging, risk assessment, and prevention. It aims to advance the field beyond traditional risk factor assessment alone.
This study analyzed data from the Heinz Nixdorf Recall Study to evaluate whether measuring coronary artery calcification (CAC) improves risk prediction of cardiovascular events beyond traditional risk factors. The study found that higher CAC scores were associated with significantly higher risks of cardiovascular events over 5 years of follow up. CAC scoring reclassified some individuals' risk and improved prediction, especially among those at intermediate risk by traditional measures. Measuring CAC provides additional prognostic information beyond traditional risk factors and may help guide prevention efforts.
1. Peripheral arterial disease (PAD) is a marker for increased risk of myocardial infarction and ischemic stroke, as it often co-exists with atherosclerosis in other arteries.
2. PAD is more common than diagnosed, so proper diagnosis using ankle-brachial pressure index is important. A low index reliably predicts increased risk of ischemic events.
3. Lifestyle changes and antiplatelet drugs like clopidogrel, which provides greater benefit than aspirin, are key for managing PAD patients and reducing cardiovascular risks.
Ohio State's 2016 ASH Review - BEST OF ASH 2015 MULTIPLE MYELOMA AND PLASMA C...OSUCCC - James
This randomized clinical trial compared autologous stem cell transplantation (ASCT) versus continued therapy without transplantation in newly diagnosed multiple myeloma patients. 389 patients received induction with lenalidomide-dexamethasone (Rd) or cyclophosphamide-lenalidomide-dexamethasone (CRD). Patients were then randomized to receive ASCT or continued Rd or CRD therapy. The primary endpoint was progression-free survival (PFS). Results showed ASCT improved PFS compared to continued therapy without transplantation. However, overall survival was not significantly different between the two groups, suggesting continued therapy without ASCT may be sufficient for some patients.
The document summarizes a study that compared the effects of aggressive atorvastatin therapy (80 mg) versus conventional simvastatin therapy (40 mg) on markers of inflammation in patients with familial hypercholesterolemia. The study found that atorvastatin reduced levels of hs-CRP and other inflammatory markers to a greater extent than simvastatin after 2 years. Patients with the largest reductions in hs-CRP also showed greater reductions in carotid intima-media thickness. However, about one-third of patients in both treatment groups experienced increases in hs-CRP levels. The study suggests more aggressive statin therapy may be more effective at reducing atherosclerosis by its anti-inflammatory effects.
1) The document reports on the current status of acute myeloid leukemia (AML) in China, including characteristics and prognosis factors of different AML subtypes. It also describes results from clinical trials comparing induction therapies using homoharringtonine (HHT) and high-dose cytarabine.
2) HHT-based induction therapies achieved higher complete remission rates compared to standard daunorubicin and cytarabine, especially in patients with favorable/intermediate-risk disease. HHT regimens also showed improved survival outcomes in these patient groups.
3) For patients aged ≤55 years old, induction with high-dose idarubicin and high-dose cytarabine
The document discusses the role of imaging coronary calcium using electron beam tomography (EBT) scans. It provides evidence that EBT calcium scores are strongly correlated with the amount of atherosclerotic plaque buildup. It also shows that higher EBT calcium scores are associated with significantly higher risks of future cardiovascular events, with risk increasing progressively as calcium scores rise. EBT calcium scoring more accurately predicts cardiovascular risk than traditional risk models like Framingham and can reclassify a person's risk level in about half of intermediate-risk individuals.
This document summarizes key points from a task force report on identifying and treating asymptomatic patients vulnerable to heart attack. It introduces a new paradigm focused on outcomes studies, measuring disease activity, and identifying the vulnerable plaque and patient. The report was chaired by Morteza Naghavi and had writing contributions from experts in cardiovascular imaging, risk assessment, and prevention. It aims to advance the field beyond traditional risk factor assessment alone.
This study analyzed data from the Heinz Nixdorf Recall Study to evaluate whether measuring coronary artery calcification (CAC) improves risk prediction of cardiovascular events beyond traditional risk factors. The study found that higher CAC scores were associated with significantly higher risks of cardiovascular events over 5 years of follow up. CAC scoring reclassified some individuals' risk and improved prediction, especially among those at intermediate risk by traditional measures. Measuring CAC provides additional prognostic information beyond traditional risk factors and may help guide prevention efforts.
1. Peripheral arterial disease (PAD) is a marker for increased risk of myocardial infarction and ischemic stroke, as it often co-exists with atherosclerosis in other arteries.
2. PAD is more common than diagnosed, so proper diagnosis using ankle-brachial pressure index is important. A low index reliably predicts increased risk of ischemic events.
3. Lifestyle changes and antiplatelet drugs like clopidogrel, which provides greater benefit than aspirin, are key for managing PAD patients and reducing cardiovascular risks.
Ohio State's 2016 ASH Review - BEST OF ASH 2015 MULTIPLE MYELOMA AND PLASMA C...OSUCCC - James
This randomized clinical trial compared autologous stem cell transplantation (ASCT) versus continued therapy without transplantation in newly diagnosed multiple myeloma patients. 389 patients received induction with lenalidomide-dexamethasone (Rd) or cyclophosphamide-lenalidomide-dexamethasone (CRD). Patients were then randomized to receive ASCT or continued Rd or CRD therapy. The primary endpoint was progression-free survival (PFS). Results showed ASCT improved PFS compared to continued therapy without transplantation. However, overall survival was not significantly different between the two groups, suggesting continued therapy without ASCT may be sufficient for some patients.
The document summarizes a study that compared the effects of aggressive atorvastatin therapy (80 mg) versus conventional simvastatin therapy (40 mg) on markers of inflammation in patients with familial hypercholesterolemia. The study found that atorvastatin reduced levels of hs-CRP and other inflammatory markers to a greater extent than simvastatin after 2 years. Patients with the largest reductions in hs-CRP also showed greater reductions in carotid intima-media thickness. However, about one-third of patients in both treatment groups experienced increases in hs-CRP levels. The study suggests more aggressive statin therapy may be more effective at reducing atherosclerosis by its anti-inflammatory effects.
1) The document reports on the current status of acute myeloid leukemia (AML) in China, including characteristics and prognosis factors of different AML subtypes. It also describes results from clinical trials comparing induction therapies using homoharringtonine (HHT) and high-dose cytarabine.
2) HHT-based induction therapies achieved higher complete remission rates compared to standard daunorubicin and cytarabine, especially in patients with favorable/intermediate-risk disease. HHT regimens also showed improved survival outcomes in these patient groups.
3) For patients aged ≤55 years old, induction with high-dose idarubicin and high-dose cytarabine
The document discusses cardiovascular risk factors and management. It summarizes that most heart attacks are caused by low-grade coronary artery blockages rupturing and triggering blood clots. Several risk factors can make plaques more vulnerable to rupture, such as inflammation, thin fibrous caps, and lipid-rich cores. Lifestyle changes and statin drugs are effective at reducing cardiovascular risks by lowering cholesterol levels and having additional anti-inflammatory effects. More aggressive lowering of LDL cholesterol is associated with greater reduction in heart attack risk.
12 ème journée-Actualités sur la metformineall-in-web
This document summarizes a study that analyzed the risk and benefits of metformin use in diabetic patients undergoing secondary cardiovascular prevention. The study found that among 28,700 diabetic patients, those taking metformin had a 25% lower risk of all-cause mortality over 2 years compared to those not taking metformin, even after adjusting for differences in patient characteristics. Metformin use was associated with reduced mortality risk across most patient subgroups, with the largest benefits seen in those with a history of heart failure or those using insulin. The results suggest metformin may provide unexpected survival benefits in high-risk diabetic patients.
Changing Landscape of Treatment for Multiple Myelomaspa718
1) Treatment for multiple myeloma has improved significantly over time, with median overall survival increasing from 30 months in 1971-1996 to 45 months in 1996-2006.
2) Newer proteasome inhibitors like carfilzomib have shown effectiveness in heavily pre-treated multiple myeloma patients, with overall response rates of 15-24% and median durations of response around 7-8 months. Dose escalation studies indicate carfilzomib is generally well-tolerated.
3) Other novel agents in clinical trials for relapsed/refractory multiple myeloma include second-generation proteasome inhibitors (e.g. oprozomib), immunomodulatory drugs (e
This study aimed to determine the epidemiological characteristics and outcomes of lymphomas in HIV-positive patients in Russia. The study analyzed data from 73 patients treated between 2006-2016 at several medical centers. It found that diffuse large B-cell lymphoma was most common, comprising 34% of cases. The 2-year overall survival was 64% and was improved with chemotherapy combined with antiretroviral therapy. Poor prognostic factors included elevated LDH levels and B symptoms. Rituximab improved outcomes for CD20-positive lymphomas. Autologous stem cell transplantation was found to be a safe treatment for relapsed/refractory cases. Genome editing of stem cells may provide a cure for HIV by generating HIV-resistant immune
VTE and Cancer Healthcare Professional Educationvtesimplified
Cancer patients are at increased risk of developing blood clots (venous thromboembolism or VTE) due to factors such as tumour infiltration of blood vessels, immobility, and cancer treatments. VTE is a leading cause of death in cancer patients and the risk is highest in the first months after diagnosis. Guidelines recommend thromboprophylaxis for hospitalized cancer patients without bleeding risk, but evidence for routine outpatient prophylaxis is limited to certain high risk groups. Risk assessment tools can help identify those at highest risk who may benefit most from prophylaxis.
Hemostatic markers and atrial fibrillation in ARICalonso1976
Association of hemostatic markers with the risk and prognosis of atrial fibrillation in the ARIC Study. Slides presented at the 50th AHA EPI/NPAM meeting, San Francisco, March 2010
This document summarizes the risk of thrombosis/deep vein thrombosis (DVT) associated with multiple myeloma and its treatments. It finds that the risk of DVT is increased by certain drugs like thalidomide, lenalidomide, and dexamethasone, especially when combined with chemotherapy. Studies show aspirin, low molecular weight heparin, and warfarin can effectively prevent DVT when used as prophylaxis, with aspirin and heparin posing a lower bleeding risk than warfarin. A phase III trial compared aspirin, low dose warfarin, and low molecular weight heparin for DVT prevention in newly diagnosed multiple myeloma patients on thalidomide-containing regimens
Nstemi invasive treatment rationale and timingoptimacardio
1. Invasive treatment is superior to conservative management for patients with NSTEMI based on multiple randomized controlled trials.
2. For high-risk patients based on risk scores like TIMI and GRACE, an immediate invasive approach within 2 hours is recommended to reduce death and myocardial infarction rates.
3. Biomarkers, recurrent ischemia, ECG changes, and hemodynamics help determine which patients should undergo early invasive treatment versus delayed invasive treatment.
This document summarizes studies evaluating immune checkpoint inhibitors for the treatment of Hodgkin lymphoma. It discusses pivotal trials that led to FDA approval of nivolumab and pembrolizumab for relapsed/refractory HL after stem cell transplant and brentuximab vedotin. It also reviews mechanisms of action of PD-1 blockade in HL and efforts to combine checkpoint inhibitors with other agents or incorporate them into frontline treatment for high-risk patients.
This document discusses moving beyond the traditional Framingham Risk Score for assessing individual coronary heart disease risk. It outlines three areas showing promise: (1) biomarkers like hsCRP and LpPLA2 that can identify pre-clinical disease, (2) vascular imaging like CIMT and CACS that provide more direct measures of atherosclerosis, and (3) genomics though the effects of common gene variants on risk are small and replication has been difficult. Biomarkers and imaging allow refining risk assessment, especially for those at intermediate Framingham risk, while challenges remain in applying genetics to individual risk prediction.
SOLACI Chile Congress 2011. Dr.Ajay Kirtane. Drug-Eluting Stents for Multivessel PCI: Indications and Outcomes. Find more presentations on the web site: www.solaci.org/
The LANCELOT-ACS trial investigated the safety and tolerability of the PAR-1 inhibitor atopaxar in 603 patients with acute coronary syndrome. The trial found that atopaxar achieved potent platelet inhibition through PAR-1 without significantly increasing bleeding risk compared to placebo. There were favorable trends for reduced major cardiac events but dose-dependent increases in liver enzymes and QTc interval prolongation at higher doses. Further studies are still needed to fully establish the safety and efficacy of atopaxar.
1) The IMPROVE-IT trial investigated whether adding ezetimibe to simvastatin therapy provides additional cardiovascular benefit compared to simvastatin monotherapy in 18,144 high-risk patients who recently had an acute coronary syndrome.
2) Patients receiving ezetimibe/simvastatin had a lower rate of major cardiovascular events (32.7% vs 34.7%) over a median follow-up of 6 years, demonstrating the additional clinical benefit of further lowering LDL-C with ezetimibe.
3) Ezetimibe/simvastatin also reduced the rate of the composite endpoint of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke compared to
This document discusses the diagnostic and treatment approaches to venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). It provides details on evaluating patients using Wells criteria and D-dimer testing to determine pre-test probability and decide between imaging with CT pulmonary angiogram or VQ scan. For confirmed VTE, treatment options include warfarin, novel oral anticoagulants (NOACs), inferior vena cava filters or thrombolytics. The document reviews best practices for treating isolated distal DVT, catheter-related thrombosis, and selecting appropriate long-term anticoagulation therapy.
This document provides an overview of immunotherapy and how it works to treat cancer. It discusses the different types of T cells like CD4+ helper T cells and CD8+ cytotoxic T cells. It describes antigen presenting cells and their role in activating T cells. It explains how tumors evade immune surveillance and the factors that allow this. It discusses different immunotherapy approaches like blocking the CTLA-4 and PD-1 pathways with drugs like ipilimumab and nivolumab. Clinical trial results are summarized that show improved survival with these immunotherapies compared to chemotherapy in cancers like melanoma. Combination approaches are also discussed.
Transplant Updates on donor and conditioning for Aplastic Anemia.spa718
Here are a few things to consider regarding the clinical course:
- Onset of aplasia after day 100 could indicate graft failure or rejection, even though chimerism is 99% donor. Consider repeat bone marrow biopsy.
- CMV reactivation is common after transplant but prolonged antigenemia could indicate resistant infection and may require adjustment of antiviral therapy.
- EBV-LPD also develops commonly after transplant but persistent viremia increases risk of progression to lymphoma - consider preemptive rituximab.
- Continued transfusion support and G-CSF use beyond day 100 suggests inadequate hematopoietic recovery and graft dysfunction. May need to consider augmenting immunosuppression, donor lymphocyte infusion
1) Out-of-hospital sudden cardiac death (SCD) remains a major public health challenge, with over 400,000 cases per year in the United States.
2) While there is evidence of slight declines in pre-hospital delay times and more in-hospital treatment, over 60% of cardiac deaths continue to be sudden and outside of a hospital setting.
3) Improving early recognition of heart attack symptoms and rapid intervention through public health initiatives focused on out-of-hospital screening and treatment of patients with cardiac chest discomfort could help reduce the number of sudden cardiac deaths.
A 71-year-old man with a history of diabetes, coronary artery disease status post myocardial infarction times three, and hypercholesterolemia was found to have an accidental left carotid stenosis and was scheduled for a left carotid endarterectomy. MRI of the carotid arteries was performed using SPIO contrast to better evaluate the extent of disease prior to surgery.
This document discusses using measurements of carotid intima-media thickness (CIMT) and coronary artery calcium (CAC) to monitor atherosclerosis and cardiovascular risk. It finds that progression in these measures is associated with increased risk of cardiovascular events. However, accurately detecting progression with CIMT is challenging due to measurement reproducibility. While CAC progression over 15% per year also indicates higher risk, determinants are uncertain and statins may paradoxically increase CAC while reducing events. More research is still needed to clarify using progression of atherosclerosis to monitor risk.
This document summarizes the capabilities of LightLab OCT technology for plaque characterization and precision imaging and therapy. LightLab OCT uses near-infrared light to provide ultra high-resolution imaging down to 12 micrometers. In addition to morphological imaging, it enables spectroscopic, polarization, Doppler, and elastography imaging. These advanced imaging modes allow for a better understanding of microanatomic plaque characteristics such as composition, structure, and orderliness. LightLab OCT technology has applications in selecting appropriate therapies, guiding targeted delivery, and developing new therapeutic approaches.
The document discusses several studies related to atherosclerosis and cardiovascular disease:
1) A study finds that a polymorphism in the Fas gene promoter region is a genetic risk factor for myocardial infarction by modulating Fas expression.
2) Immunoglobulin treatment suppresses atherosclerosis in mice via its Fc portion by reducing macrophage accumulation in lesions.
3) Inhibition of NF-kB reduces inflammatory molecule expression and attenuates atherosclerosis in mice.
4) MMP-8 may represent a new collagenolytic pathway in acute plaque disruption based on its levels in carotid plaques from patients.
The document discusses cardiovascular risk factors and management. It summarizes that most heart attacks are caused by low-grade coronary artery blockages rupturing and triggering blood clots. Several risk factors can make plaques more vulnerable to rupture, such as inflammation, thin fibrous caps, and lipid-rich cores. Lifestyle changes and statin drugs are effective at reducing cardiovascular risks by lowering cholesterol levels and having additional anti-inflammatory effects. More aggressive lowering of LDL cholesterol is associated with greater reduction in heart attack risk.
12 ème journée-Actualités sur la metformineall-in-web
This document summarizes a study that analyzed the risk and benefits of metformin use in diabetic patients undergoing secondary cardiovascular prevention. The study found that among 28,700 diabetic patients, those taking metformin had a 25% lower risk of all-cause mortality over 2 years compared to those not taking metformin, even after adjusting for differences in patient characteristics. Metformin use was associated with reduced mortality risk across most patient subgroups, with the largest benefits seen in those with a history of heart failure or those using insulin. The results suggest metformin may provide unexpected survival benefits in high-risk diabetic patients.
Changing Landscape of Treatment for Multiple Myelomaspa718
1) Treatment for multiple myeloma has improved significantly over time, with median overall survival increasing from 30 months in 1971-1996 to 45 months in 1996-2006.
2) Newer proteasome inhibitors like carfilzomib have shown effectiveness in heavily pre-treated multiple myeloma patients, with overall response rates of 15-24% and median durations of response around 7-8 months. Dose escalation studies indicate carfilzomib is generally well-tolerated.
3) Other novel agents in clinical trials for relapsed/refractory multiple myeloma include second-generation proteasome inhibitors (e.g. oprozomib), immunomodulatory drugs (e
This study aimed to determine the epidemiological characteristics and outcomes of lymphomas in HIV-positive patients in Russia. The study analyzed data from 73 patients treated between 2006-2016 at several medical centers. It found that diffuse large B-cell lymphoma was most common, comprising 34% of cases. The 2-year overall survival was 64% and was improved with chemotherapy combined with antiretroviral therapy. Poor prognostic factors included elevated LDH levels and B symptoms. Rituximab improved outcomes for CD20-positive lymphomas. Autologous stem cell transplantation was found to be a safe treatment for relapsed/refractory cases. Genome editing of stem cells may provide a cure for HIV by generating HIV-resistant immune
VTE and Cancer Healthcare Professional Educationvtesimplified
Cancer patients are at increased risk of developing blood clots (venous thromboembolism or VTE) due to factors such as tumour infiltration of blood vessels, immobility, and cancer treatments. VTE is a leading cause of death in cancer patients and the risk is highest in the first months after diagnosis. Guidelines recommend thromboprophylaxis for hospitalized cancer patients without bleeding risk, but evidence for routine outpatient prophylaxis is limited to certain high risk groups. Risk assessment tools can help identify those at highest risk who may benefit most from prophylaxis.
Hemostatic markers and atrial fibrillation in ARICalonso1976
Association of hemostatic markers with the risk and prognosis of atrial fibrillation in the ARIC Study. Slides presented at the 50th AHA EPI/NPAM meeting, San Francisco, March 2010
This document summarizes the risk of thrombosis/deep vein thrombosis (DVT) associated with multiple myeloma and its treatments. It finds that the risk of DVT is increased by certain drugs like thalidomide, lenalidomide, and dexamethasone, especially when combined with chemotherapy. Studies show aspirin, low molecular weight heparin, and warfarin can effectively prevent DVT when used as prophylaxis, with aspirin and heparin posing a lower bleeding risk than warfarin. A phase III trial compared aspirin, low dose warfarin, and low molecular weight heparin for DVT prevention in newly diagnosed multiple myeloma patients on thalidomide-containing regimens
Nstemi invasive treatment rationale and timingoptimacardio
1. Invasive treatment is superior to conservative management for patients with NSTEMI based on multiple randomized controlled trials.
2. For high-risk patients based on risk scores like TIMI and GRACE, an immediate invasive approach within 2 hours is recommended to reduce death and myocardial infarction rates.
3. Biomarkers, recurrent ischemia, ECG changes, and hemodynamics help determine which patients should undergo early invasive treatment versus delayed invasive treatment.
This document summarizes studies evaluating immune checkpoint inhibitors for the treatment of Hodgkin lymphoma. It discusses pivotal trials that led to FDA approval of nivolumab and pembrolizumab for relapsed/refractory HL after stem cell transplant and brentuximab vedotin. It also reviews mechanisms of action of PD-1 blockade in HL and efforts to combine checkpoint inhibitors with other agents or incorporate them into frontline treatment for high-risk patients.
This document discusses moving beyond the traditional Framingham Risk Score for assessing individual coronary heart disease risk. It outlines three areas showing promise: (1) biomarkers like hsCRP and LpPLA2 that can identify pre-clinical disease, (2) vascular imaging like CIMT and CACS that provide more direct measures of atherosclerosis, and (3) genomics though the effects of common gene variants on risk are small and replication has been difficult. Biomarkers and imaging allow refining risk assessment, especially for those at intermediate Framingham risk, while challenges remain in applying genetics to individual risk prediction.
SOLACI Chile Congress 2011. Dr.Ajay Kirtane. Drug-Eluting Stents for Multivessel PCI: Indications and Outcomes. Find more presentations on the web site: www.solaci.org/
The LANCELOT-ACS trial investigated the safety and tolerability of the PAR-1 inhibitor atopaxar in 603 patients with acute coronary syndrome. The trial found that atopaxar achieved potent platelet inhibition through PAR-1 without significantly increasing bleeding risk compared to placebo. There were favorable trends for reduced major cardiac events but dose-dependent increases in liver enzymes and QTc interval prolongation at higher doses. Further studies are still needed to fully establish the safety and efficacy of atopaxar.
1) The IMPROVE-IT trial investigated whether adding ezetimibe to simvastatin therapy provides additional cardiovascular benefit compared to simvastatin monotherapy in 18,144 high-risk patients who recently had an acute coronary syndrome.
2) Patients receiving ezetimibe/simvastatin had a lower rate of major cardiovascular events (32.7% vs 34.7%) over a median follow-up of 6 years, demonstrating the additional clinical benefit of further lowering LDL-C with ezetimibe.
3) Ezetimibe/simvastatin also reduced the rate of the composite endpoint of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke compared to
This document discusses the diagnostic and treatment approaches to venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). It provides details on evaluating patients using Wells criteria and D-dimer testing to determine pre-test probability and decide between imaging with CT pulmonary angiogram or VQ scan. For confirmed VTE, treatment options include warfarin, novel oral anticoagulants (NOACs), inferior vena cava filters or thrombolytics. The document reviews best practices for treating isolated distal DVT, catheter-related thrombosis, and selecting appropriate long-term anticoagulation therapy.
This document provides an overview of immunotherapy and how it works to treat cancer. It discusses the different types of T cells like CD4+ helper T cells and CD8+ cytotoxic T cells. It describes antigen presenting cells and their role in activating T cells. It explains how tumors evade immune surveillance and the factors that allow this. It discusses different immunotherapy approaches like blocking the CTLA-4 and PD-1 pathways with drugs like ipilimumab and nivolumab. Clinical trial results are summarized that show improved survival with these immunotherapies compared to chemotherapy in cancers like melanoma. Combination approaches are also discussed.
Transplant Updates on donor and conditioning for Aplastic Anemia.spa718
Here are a few things to consider regarding the clinical course:
- Onset of aplasia after day 100 could indicate graft failure or rejection, even though chimerism is 99% donor. Consider repeat bone marrow biopsy.
- CMV reactivation is common after transplant but prolonged antigenemia could indicate resistant infection and may require adjustment of antiviral therapy.
- EBV-LPD also develops commonly after transplant but persistent viremia increases risk of progression to lymphoma - consider preemptive rituximab.
- Continued transfusion support and G-CSF use beyond day 100 suggests inadequate hematopoietic recovery and graft dysfunction. May need to consider augmenting immunosuppression, donor lymphocyte infusion
1) Out-of-hospital sudden cardiac death (SCD) remains a major public health challenge, with over 400,000 cases per year in the United States.
2) While there is evidence of slight declines in pre-hospital delay times and more in-hospital treatment, over 60% of cardiac deaths continue to be sudden and outside of a hospital setting.
3) Improving early recognition of heart attack symptoms and rapid intervention through public health initiatives focused on out-of-hospital screening and treatment of patients with cardiac chest discomfort could help reduce the number of sudden cardiac deaths.
A 71-year-old man with a history of diabetes, coronary artery disease status post myocardial infarction times three, and hypercholesterolemia was found to have an accidental left carotid stenosis and was scheduled for a left carotid endarterectomy. MRI of the carotid arteries was performed using SPIO contrast to better evaluate the extent of disease prior to surgery.
This document discusses using measurements of carotid intima-media thickness (CIMT) and coronary artery calcium (CAC) to monitor atherosclerosis and cardiovascular risk. It finds that progression in these measures is associated with increased risk of cardiovascular events. However, accurately detecting progression with CIMT is challenging due to measurement reproducibility. While CAC progression over 15% per year also indicates higher risk, determinants are uncertain and statins may paradoxically increase CAC while reducing events. More research is still needed to clarify using progression of atherosclerosis to monitor risk.
This document summarizes the capabilities of LightLab OCT technology for plaque characterization and precision imaging and therapy. LightLab OCT uses near-infrared light to provide ultra high-resolution imaging down to 12 micrometers. In addition to morphological imaging, it enables spectroscopic, polarization, Doppler, and elastography imaging. These advanced imaging modes allow for a better understanding of microanatomic plaque characteristics such as composition, structure, and orderliness. LightLab OCT technology has applications in selecting appropriate therapies, guiding targeted delivery, and developing new therapeutic approaches.
The document discusses several studies related to atherosclerosis and cardiovascular disease:
1) A study finds that a polymorphism in the Fas gene promoter region is a genetic risk factor for myocardial infarction by modulating Fas expression.
2) Immunoglobulin treatment suppresses atherosclerosis in mice via its Fc portion by reducing macrophage accumulation in lesions.
3) Inhibition of NF-kB reduces inflammatory molecule expression and attenuates atherosclerosis in mice.
4) MMP-8 may represent a new collagenolytic pathway in acute plaque disruption based on its levels in carotid plaques from patients.
This document discusses the use of coronary CT angiography (CTA) to detect and characterize coronary atherosclerosis beyond just detecting coronary stenoses. CTA can identify calcified plaques, non-calcified plaques, and mixed plaques. It can detect atheromas and characterize plaque density. CTA can also identify intracoronary thrombi and myocardial infarction scars. The document outlines the CTA scanning parameters and techniques used to minimize motion artifacts and optimize image quality for plaque detection and characterization.
The document summarizes the sessions from the Congress of European Society of Cardiology that focused on vulnerable plaque. Several sessions discussed ongoing research into the mechanisms of plaque inflammation and new markers of vulnerability. Emerging diagnostic techniques for detecting vulnerable plaque, such as thermography and elastography, were presented. The cardiology field is awaiting large clinical studies to evaluate the predictive value of these new diagnostic devices and provide guidance on risk stratification and treatment. The field of vulnerable plaque research is rapidly expanding and increasing understanding of plaque vulnerability mechanisms and markers while also developing new detection technologies.
1) A Mexican family with familial hypercholesterolemia (FH) linked to chromosome 1p32 was found to also have elevated HDL-C (high-density lipoprotein cholesterol) linked to chromosome 6p, which protected against atherosclerosis despite FH.
2) The FH trait mapped to chromosome 1p32, a region previously linked to FH, while the elevated HDL-C trait mapped to chromosome 6p, a region not previously linked to FH.
3) This family provides evidence that a locus on chromosome 6p confers an anti-atherogenic effect exceeding its effect on cholesterol levels, and may protect against risk factors beyond FH like hypertension and smoking.
1) The document discusses using protein structures as targets for ligand design in drug development. It provides examples of targeting matrix metalloproteinase 9 (MMP9), cellulases, and a serine protease from fire ants.
2) Specific protein structures discussed include truncated forms of MMP9, cellulases from Aspergillus niger and a wood-eating termite, and a C3 serine protease from fire ants. Key structural features of these proteins are highlighted.
3) Structure-based drug design is discussed as a method to use determined protein structures to identify small molecule ligands through docking simulations and molecular dynamics calculations.
Statins are associated with a reduced incidence of perioperative mortality in patients undergoing major vascular surgery. In a retrospective case-control study of 2816 patients, statin use was associated with a 78% reduced risk of perioperative mortality. Patients taking statins had over a four-fold lower risk of death compared to non-users. The protective effect of statins was consistent regardless of cardiac risk factors or beta-blocker use.
This study investigated the effects of exercise training on vascular dysfunction in hypercholesterolemic rabbits. Rabbits were fed either a normal or high-cholesterol diet, with some receiving exercise training. The high-cholesterol diet led to increased lipid deposition, impaired vasorelaxation, and elevated inflammatory markers in the aortas. However, exercise training reduced lipid deposition, improved vasorelaxation, and decreased inflammatory marker expression in the high-cholesterol diet rabbits. The results suggest that regular exercise can ameliorate vascular damage caused by hypercholesterolemia.
This document discusses several studies on the relationship between stenosis severity and risks of coronary occlusion and acute coronary syndrome:
1) Two studies found that coronary segments with 50-80% stenosis at baseline had higher risks of total occlusion at follow-up than segments with less severe stenosis.
2) Another study found that prior to myocardial infarction, 29% of culprit lesions showed 0-50% stenosis, while 4.1-7.9% showed 50-90% stenosis.
3) A review concluded that the majority of infarcts evolve from angiographically mild to moderate stenoses, not severe stenoses.
4) A study on plaque rupture found that two-thirds of acute coronary disease
The document discusses that less obstructive plaques pose a greater risk of coronary occlusion than severely obstructed plaques due to their greater numbers. It also states that the aggregate risk of rupture from many non-significant lesions exceeds that of fewer significant lesions, so a myocardial infarction is more likely to originate from a non-significant lesion. Additionally, while electron beam tomography (EBT) cannot identify vulnerable plaques directly, it can identify vulnerable patients based on their coronary artery calcium (CAC) scores and percentiles, as risk increases with higher scores. EBT is also useful for estimating prognosis and tracking changes in plaque burden in response to treatment over time.
1. Isolated-low HDL levels in ABCA1 heterozygotes is associated with impaired basal and stimulated endothelial nitric oxide synthase activity.
2. A single rapid infusion of reconstituted HDL completely restored both basal and stimulated endothelial nitric oxide synthase activity in ABCA1 heterozygotes.
3. Impaired lipid trafficking and caveolar disruption caused by dysfunctional ABCA1 profoundly affects endothelial nitric oxide synthase activity.
This document summarizes findings from the Heart Outcomes Prevention Evaluation (HOPE) study regarding the relationship between various infections and subsequent cardiovascular events. The study analyzed antibodies to Chlamydia pneumoniae, H. Pylori, CMV, and hepatitis A virus in 3,168 patients over 4.5 years of follow up. While C. pneumoniae and H. Pylori antibodies did not correlate with cardiovascular risk, the presence of CMV antibodies was associated with a slightly higher risk. A total pathogen score based on levels of antibodies to all four infections predicted a higher risk of cardiovascular events compared to a score of zero or one.
This document discusses the potential for non-invasive coronary angiography using computed tomography (CT) techniques such as electron beam CT (EBCT) and multi-slice CT (MSCT). It provides an overview of the history and technological developments of CT as well as results of studies evaluating the diagnostic accuracy of EBCT and MSCT for detecting coronary artery disease compared to invasive angiography. The document concludes that with improvements in rotation speed and larger detector arrays, fast MSCT is becoming the leading screening technique for non-invasive detection of coronary stenosis without radiation or contrast exposure of invasive methods.
This document discusses vascular interventions guided by MRI, including:
1) Early experiments with intravascular MRI to image arteries and plaques.
2) The technical challenges of MRI-guided balloon angioplasty and stent placement, such as developing MRI-compatible devices and monitoring procedures.
3) Examples of MRI-guided balloon angioplasty, stent placement, and plaque imaging in human studies.
4) The potential for MRI to guide new treatments like gene therapy delivery to diseased arteries.
This document discusses the use of C-reactive protein (CRP) and low-density lipoprotein (LDL) cholesterol levels to predict cardiovascular risk. It summarizes a study that found CRP to be a stronger predictor of future cardiovascular events than LDL, with CRP and LDL providing complementary and non-correlated information. The document concludes that measuring both CRP and LDL provides superior risk detection compared to either marker alone, and that patients with high CRP but low LDL (<160 mg/dl) should be considered at increased risk.
This study examined the accumulation of superparamagnetic iron oxide (SPIO) nanoparticles in vulnerable atherosclerotic plaques. In vitro experiments demonstrated that human macrophages actively take up fluorescent-labeled SPIO particles over 24 hours in a time- and concentration-dependent manner. In vivo studies in mice and rabbit models of atherosclerosis found SPIO particles in macrophage-rich areas of plaques, with a strong correlation between iron staining and foam cell density. Cytokine treatment increased SPIO uptake in plaques. The results suggest MRI using SPIO has potential for noninvasively assessing monocyte recruitment in vulnerable plaques.
This document summarizes research on biochemical and imaging markers for cardiovascular disease. It includes 3 sections:
1. It discusses several major risk factors for cardiovascular events and how biomarkers like CRP, fibrinogen, and homocysteine can provide additional predictive value beyond traditional risk factors.
2. It reviews studies on emerging biomarkers for inflammation, thrombosis, and oxidative stress, and their association with future cardiovascular outcomes in prospective studies.
3. It presents data on imaging markers like carotid intimal thickness, echocardiography, and electron beam computed tomography and their ability to track disease severity and response to treatment.
The document concludes by discussing features of an ideal cardiovascular biomarker and potential surrogate markers of endothelial function
Ponencia realizada por el Prof. Alberto Zambon en la segunda sesión de CardioVascular Virtual Topic 2022, titulada Residual cardiovascular risk. What is the role of icosapent ethyl?
1. The document discusses acute coronary syndrome and its pathophysiology including plaque rupture and thrombosis leading to dynamic obstruction.
2. It summarizes several studies on outcomes of invasive versus conservative treatment strategies for acute coronary syndrome patients, finding reduced mortality and myocardial infarction with invasive approaches.
3. Biomarkers like troponin and homocysteine are discussed as risk factors for adverse outcomes in acute coronary syndrome.
1. The document discusses acute coronary syndrome and its pathophysiology including plaque rupture and thrombosis leading to dynamic obstruction.
2. It summarizes several studies on outcomes of invasive versus conservative treatment strategies for acute coronary syndrome patients, finding reduced mortality and myocardial infarction with invasive approaches.
3. Biomarkers like troponin and homocysteine are discussed as risk factors for adverse outcomes in acute coronary syndrome.
This document summarizes the cardiovascular risk of patients with type 2 diabetes mellitus (T2DM) in India and the potential benefits of SGLT2 inhibitor treatment. It finds that:
1) The majority of Indian outpatients with T2DM have at least moderate cardiovascular disease (CVD) risk, and over 35% have known CVD.
2) T2DM confers 2-4 times greater CVD risk regardless of duration, and risk increases with longer duration.
3) Empagliflozin treatment consistently reduces the risk of cardiovascular death and heart failure hospitalizations in clinical trials of patients with T2DM and atherosclerotic CVD.
4) Empagliflozin may provide additional benefits
This document discusses how coronary artery calcium scoring using computed tomography (CT) and levels of the inflammatory marker C-reactive protein (CRP) can be used together to predict cardiovascular risk. It finds that higher calcium scores and CRP levels each indicate greater risk of future heart attacks and cardiac deaths. The combination of an intermediate calcium score and elevated CRP may identify patients who would benefit from more aggressive prevention treatment and closer follow-up. The document recommends using calcium scoring and CRP testing together in asymptomatic individuals to help refine clinical decision making and prevention strategies.
This document discusses how coronary artery calcium scoring using computed tomography (CT) and levels of the inflammatory marker C-reactive protein (CRP) can be used together to predict cardiovascular risk. It finds that higher calcium scores and CRP levels each indicate greater risk of future heart attacks and cardiac deaths. The combination of an intermediate calcium score and elevated CRP may identify those at intermediate risk who could benefit from more aggressive prevention efforts like closer follow-up or treatment targeting both inflammation and plaques. Together, calcium scoring and CRP testing provide complementary information that can refine clinical decision making for asymptomatic individuals.
214 how can calcium score improve your practiceSHAPE Society
This document discusses how coronary artery calcium scoring using computed tomography (CT) and levels of the inflammatory marker C-reactive protein (CRP) can be used together to predict cardiovascular risk. It finds that higher calcium scores and CRP levels each indicate greater risk of future heart attacks and cardiac deaths. The combination of an intermediate calcium score and elevated CRP may identify patients who would benefit from more aggressive prevention treatment and closer follow-up. The document recommends using calcium scoring and CRP testing together in asymptomatic individuals to help refine clinical decision making and prevention strategies.
This document provides an overview of systemic lupus erythematosus (SLE), an autoimmune disorder characterized by inflammation of multiple organ systems. It discusses the epidemiology, etiology, clinical manifestations, diagnostic criteria, treatment approaches, and new developments for SLE. Key points include that SLE affects multiple organ systems, is associated with various autoantibodies, and treatment involves managing symptoms, preventing flares and organ damage through immunosuppression and addressing traditional cardiovascular risk factors.
This document discusses various biomarkers for coronary artery disease and myocardial infarction. It begins by outlining existing diagnostic and prognostic biomarkers, and then describes several new biomarkers under investigation. These include biomarkers of biomechanical stress like BNP, biomarkers of neurohormonal activation like copeptin, and biomarkers of plaque instability like CRP. The document also discusses newer technologies like metabolomics and genetic biomarkers. Throughout, it provides details on each biomarker and their clinical significance.
Marc Penn, MD, PhD, FACC - Trials and Tribulations of Assessing CVD Risk in ...Cleveland HeartLab, Inc.
This document discusses the importance of assessing cardiovascular risk through inflammatory markers in addition to traditional lipid markers. It provides evidence that atherosclerosis is driven by inflammation and markers like hsCRP and MPO can help identify patients at higher risk of events. The document also discusses how statins work through multiple anti-inflammatory pathways beyond just lowering lipids. A multimarker inflammation approach is presented as a way to better stratify risk and identify high-risk patients within populations that may otherwise appear low risk based on traditional metrics alone.
This document summarizes contemporary management of pulmonary embolism (PE). It discusses that PE is a common cause of death in the US, killing 50,000-200,000 people annually. Massive PE has a much higher mortality than non-massive PE. The document reviews risk factors, diagnostic testing including D-dimer, V/Q scan, CT, and echocardiography. Treatment options discussed include anticoagulation with heparin, thrombolysis for unstable patients or those with RV dysfunction, and percutaneous interventions.
Multidisciplinary approach to the management of leukemias amlmadurai
The document discusses the multidisciplinary approach to managing leukemias like AML and MDS. It presents the case of a 68-year old male patient presenting with fever and fatigue, and details the diagnostic workup showing features consistent with acute myeloid leukemia. The document then reviews classification, prognostic factors, recent treatment trials, and the role of allogeneic stem cell transplantation for AML patients.
Dr. maryalice stetler stevenson lymphoma mrdHitham Esam
Flow cytometry can be used to detect minimal residual disease (MRD) in plasma cell neoplasms such as multiple myeloma. It provides both prognostic information and a way to measure response to drug therapies. Several factors are important for obtaining high quality flow cytometry results, including using bone marrow aspirates within 24 hours of collection, lysing red blood cells, acquiring sufficient events, and using standardized staining and gating strategies. Detection of MRD by flow post-treatment is predictive of patient outcomes and can guide clinical decision making.
The JUPITER trial was stopped early due to clear evidence of benefit from rosuvastatin treatment. The trial aimed to test whether rosuvastatin could reduce cardiovascular events in apparently healthy people with normal LDL cholesterol but high hsCRP. Over 17,000 participants were randomized to rosuvastatin 20mg or placebo. After almost 2 years, rosuvastatin showed a highly significant 44% reduction in the primary cardiovascular endpoint compared to placebo, demonstrating its benefit in primary prevention. This clear benefit led to the trial being stopped early.
This document summarizes molecular genetics guiding treatment of acute myeloid leukemia (AML). Over 100 genetic lesions have been identified in AML. New molecular markers do not currently impact clinical practice due to heterogeneity, study design limitations, and lack of predictive value. Genomic profiling of over 1,500 AML patients identified 11 non-overlapping molecular classes and over 5,000 driver mutations involving 77 loci. Certain mutations like FLT3, KIT, IDH1/2 inform targeted therapy approaches in clinical trials. Phase III trials are investigating chemotherapy with or without targeted agents like midostaurin, dasatinib and quizartinib in genetically defined AML patient subgroups.
The document discusses various types of thyroid tumors including cancer. It describes the normal anatomy and microscopic picture of the thyroid gland. The primary types of thyroid cancer are papillary, follicular, medullary, and anaplastic originating from the follicular epithelium or parafollicular cells. Risk factors include radiation exposure, family history, iodine deficiency, and thyroiditis. Evaluation involves history, examination, FNAC, ultrasound, and radiological investigations. Treatment depends on cancer type and involves surgery, radioactive iodine, and thyroxine therapy. Prognosis depends on age, tumor size and spread.
This document discusses developing an artificial intelligence system to predict short-term cardiovascular disease (CVD) events. The goal is to eradicate unexpected heart attacks by predicting risk similar to hurricane forecasts. Existing studies are cited that show over 50% of heart attacks are first symptoms of underlying disease. The document outlines previous work by SHAPE to define vulnerable patients and release guidelines. It proposes using machine learning on existing cohort data to develop algorithms predicting heart attacks within 12 months, and validate the system. The hope is this can trigger preventative actions and add over 10 years to life expectancy. Funding is needed to implement the proposed "Machine Learning Vulnerable Patient Project".
Triggers of cardiovascular events can include physical and emotional stress. Stress from events like earthquakes, blizzards, intense sporting games, and overexertion from activities like snow shoveling have been shown to increase the risk of acute cardiovascular outcomes like myocardial infarction. While modern therapies have improved cardiovascular health, research continues to show temporary increases in cardiovascular mortality associated with highly emotional sporting events even in recent years. Managing risk factors, reducing stress, and utilizing preventative therapies may help reduce the impact of triggers on cardiovascular health.
The document introduces the All of Us Research Program, which aims to collect health data from one million Americans to advance precision medicine research. It was announced by President Obama in 2015. The program receives funding from the federal government and private partners. It collects various types of health data from participants through surveys, health records, samples, and devices. The data is stored and shared securely while protecting privacy. The goal is to generate new medical discoveries and more personalized healthcare through collaboration between researchers and participants.
A machine learning model outperformed the ACC/AHA Pooled Cohort Equations Risk Calculator in detecting high-risk asymptomatic individuals and recommending statin treatment for cardiovascular disease prevention in the Multi-Ethnic Study of Atherosclerosis. The machine learning model used support vector machines and data augmentation to derive a CVD risk predictor from nine variables in the MESA study population. It demonstrated higher sensitivity, specificity, and AUC compared to the ACC/AHA risk calculator, recommending statin treatment for fewer individuals while missing fewer cardiovascular events.
This document discusses machine learning applications in cardiac imaging presented by Piotr Slomka. It describes how machine learning can improve image analysis, diagnosis, and risk prediction. Machine learning combines multiple data points like imaging and clinical data to predict outcomes. Deep learning can perform tasks like image segmentation. Machine learning provides quantitative scores that predict disease, need for intervention, or patient outcomes to help clinicians. The goal is to integrate machine learning into clinical decision making.
This document summarizes a post-mortem study examining the prevalence of inflammatory cells in non-ruptured atherosclerotic plaques. The study found that moderate or heavy staining for macrophages was present in 45% of femoral artery cross-sections and 84% of femoral arteries had at least one cross-section with moderate/heavy inflammation. There was no observed relationship between the degree of inflammation in the left and right coronary arteries within individuals, indicating the level of local inflammation is locally determined with little predictive value for other arteries.
The document provides guidelines for defining vulnerable plaque and vulnerable patients from the Association for Eradication of Heart Attack. It outlines major and minor histopathological and clinical criteria for vulnerable plaque including active inflammation, thin fibrous cap with large lipid core, endothelial denudation, and stenosis. Potential screening and diagnostic methods are discussed at the plaque, systemic, and blood levels ranging from non-invasive imaging to intravascular techniques. Different types of vulnerable plaque that can cause acute coronary events are also categorized.
Vulnerable plaque refers to dangerous forms of atherosclerotic plaques that can rupture or induce thrombosis, disrupting blood flow. The document discusses the history and research around vulnerable plaque, including pioneers in the field and emerging techniques to detect vulnerable plaque such as intravascular ultrasound, optical coherence tomography, and magnetic resonance imaging. It summarizes that vulnerable plaques are typically characterized by a thin fibrous cap, large lipid core, and presence of macrophages.
The document summarizes research on vulnerable plaques and markers of vulnerability. It finds that ruptured plaques are the most common type of culprit lesion, accounting for around 70% of cases. Major criteria for defining vulnerable plaque include outward remodeling, endothelial dysfunction, and a thin fibrous cap with a large lipid core. Both plaque morphology and activity need to be assessed to identify vulnerability.
This document contains a summary of a presentation on vulnerable patient syndrome. It includes PowerPoint slides and videos on defining and identifying vulnerable plaques and patients. It thanks sponsors for their support of the educational event. The slides define vulnerable plaques as those likely to rupture in the future, causing heart attacks, and provide criteria for identifying them based on morphology and activity. Biomarkers and conditions that increase plaque and myocardial vulnerability are also summarized. The presentation outlines a pyramid approach for screening, diagnosing, and treating vulnerable patients annually to help reduce heart attacks and their high costs.
This document discusses triggers for sudden cardiac arrest (SCA) and death (SCD). It notes that over 2/3 of SCD cases are unable to be predicted due to a lack of well-established risk factors. While population risk factors can identify at-risk groups, they cannot predict risk for individuals. The document explores various biological, anatomical, and environmental factors that can precipitate fatal arrhythmias and discusses how the timing of transient initiating events is critical for the development of ventricular tachyarrhythmias. It emphasizes that myocardial electrophysiological processes likely determine the onset or lack of VT/VF/SCD and that immediate access to automated external defibrillators is needed to save lives.
This document summarizes presentations from symposia on vulnerable plaque and discusses the relationship between plaque, blood, and patients in atherothrombosis. It notes that multiple factors like diabetes, smoking, and hyperlipidemia can make blood more thrombogenic and moderate the severity of acute events after plaque rupture. Statins, aspirin, and other drugs that target tissue factor or thrombin pathways may be promising antithrombotic agents by inhibiting thrombosis initiation and propagation.
The document discusses vulnerable plaque and challenges in detecting and treating it. It describes various imaging techniques for detecting vulnerable plaque such as thermography, MRI, CT angiography, and optical coherence tomography. However, it notes that while these can identify high-risk features, it remains unclear what exactly defines vulnerable plaque and whether imaging findings truly correlate with risk. The document also notes that while statins reduce events, the relationship between plaque burden and events is unclear, and better defining and detecting the disease is still needed before new therapies can be developed.
1) The study examined 92 hearts from patients with severe coronary artery disease who died suddenly. The hearts were sectioned and plaque types were classified.
2) The number of "vulnerable" plaques, particularly thin cap atheromas, was highest in hearts of patients who died from acute plaque rupture and lowest in those with incidental disease.
3) Thin cap atheromas and other unstable plaque types were concentrated in the proximal coronary segments, similar to the distribution of plaque ruptures. The study suggests vulnerable plaques contribute to acute coronary syndromes and are non-uniformly distributed within the coronary arteries.
1) Drug-coated stents, particularly those coated with sirolimus, have shown promise in reducing restenosis compared to bare metal stents. Sirolimus inhibits cell proliferation and has been shown in studies to reduce intimal hyperplasia and restenosis in animal models by 50% or more.
2) A study by Suzuki et al. found that a sirolimus-coated stent reduced restenosis by 50% through inhibiting cellular proliferation in a dose-dependent manner compared to a bare metal stent. Adding dexamethasone to the coating did not provide additional benefit.
3) If results of the RAVEL clinical trial showing "zero" restenosis out to 5 years
This document discusses drug-coated stents for preventing restenosis. It summarizes a study showing that stents coated with sirolimus via a polymer matrix reduced restenosis by 50% by inhibiting cell proliferation. Adding dexamethasone provided no additional benefit. Other studies also showed sirolimus inhibits smooth muscle cell proliferation. If results of the RAVEL trial showing "zero" restenosis at 210 days hold true long-term, sirolimus-coated stents may become the standard therapy for coronary revascularization. Questions are raised about whether coating vulnerable plaques could be a primary treatment and if multiple vulnerable plaques would all be stented.
1) Drug-coated stents, particularly those coated with sirolimus, have shown promise in reducing restenosis compared to bare metal stents. Sirolimus inhibits cell proliferation and has been shown in studies to reduce intimal hyperplasia and restenosis in animal models by 50% or more.
2) A study by Suzuki et al. found that a sirolimus-coated stent reduced restenosis by 50% through inhibiting cellular proliferation in a dose-dependent manner compared to a bare metal stent. Adding dexamethasone to the coating did not provide additional benefit.
3) If results of the RAVEL clinical trial showing "zero" restenosis out to 5 years
I. This document discusses various animal models that have been used to study atherosclerosis and plaque rupture, including quail, pigeons, chickens, dogs, monkeys, pigs, rats, rabbits, and mice. It provides details on the types of lesions developed and similarities to human disease for each model.
II. The double knockout LDL/apoE mice are highlighted as offering improvements in studying clinical complications of atherosclerosis like human heart disease. However, it is unclear how closely they model vulnerable plaques.
III. Questions are raised about how closely the coagulation systems of these animal models resemble humans and whether any model fully captures repeated plaque ruptures and the role of aging in natural history as seen in humans.
Trans-Blood Vision is a patented infrared technique that uses short-wave infrared wavelengths to see directly through blood. It has the potential to find vulnerable plaque lesions without first entering them, determine their size and surface characteristics in high resolution, and look at their material constituents both on and below the surface. While it cannot provide direct visual guidance for therapy or penetrate as deeply as ultrasound, combining it with augmentative technologies could allow for real-time multi-mode detection, analysis, and therapy guidance of vulnerable plaque lesions. The document concludes that Trans-Blood Vision warrants significant investigation, possibly in combination with other emerging technologies.
This study used intravascular ultrasound to examine arterial remodeling and plaque characteristics in 131 patients with either stable angina or recent unstable symptoms. Patients with unstable presentations had greater plaque burden at the culprit lesion despite similar luminal narrowing, and a greater extent of positive arterial remodeling compared to those with stable angina. The culprit lesions in unstable patients also showed a higher rate of echolucent plaque morphology. This suggests that bulky, remodeled plaques may be more vulnerable to rupture, leading to acute coronary syndromes. Further prospective study is needed to better understand the relationship between clinical presentation and plaque features.
More from Society for Heart Attack Prevention and Eradication (20)
Our backs are like superheroes, holding us up and helping us move around. But sometimes, even superheroes can get hurt. That’s where slip discs come in.
Hiranandani Hospital in Powai, Mumbai, is a premier healthcare institution that has been serving the community with exceptional medical care since its establishment. As a part of the renowned Hiranandani Group, the hospital is committed to delivering world-class healthcare services across a wide range of specialties, including kidney transplantation. With its state-of-the-art facilities, advanced medical technology, and a team of highly skilled healthcare professionals, Hiranandani Hospital has earned a reputation as a trusted name in the healthcare industry. The hospital's patient-centric approach, coupled with its focus on innovation and excellence, ensures that patients receive the highest standard of care in a compassionate and supportive environment.
One health condition that is becoming more common day by day is diabetes.
According to research conducted by the National Family Health Survey of India, diabetic cases show a projection which might increase to 10.4% by 2030.
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxwalterHu5
In some case, your chronic prostatitis may be related to over-masturbation. Generally, natural medicine Diuretic and Anti-inflammatory Pill can help mee get a cure.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
1. THE EPIDEMIC OF CVD – NEED FOR NEW APPROACHES
Epidemiology and Change in Emphasis
- From the High Risk Plaque to the High Risk Symptomatic Patient
- From the High Risk Asymptomati to the Intermediate and Low Risk Patient
HRSP - Therapeutic Polypill & Single Pill
HRAP - BAD, Diagnostic MR Imaging
- BAD, Diagnostic & Rx - MR Plaque Composition
- BAD, Diagnostic Molecular MR Contrast Enhanced,
IRAP - Diagnostic CACS & CRP Biomarkers
LRAP - Government, Polymeal, Children
SHAPE & AEHA.
Orlando, March 05, 2005
3. Prevalence of Obesity & Diabetes in the U.S.
1990/19911990/1991 20002000
ejt 0901–120
Mokdad et al., JAMA 286:1195–1200, 2001Mokdad et al., JAMA 286:1195–1200, 2001
No DataNo Data < 4%< 4% 4%-6%4%-6% > 6%> 6%
No DataNo Data < 10%< 10% 10%-14%10%-14% 15%-19%15%-19% ≥≥ 20%20%
ObesityObesity
DiabetesDiabetes
5. THE EPIDEMIC OF CVD – NEED FOR NEW APPROACHES
Epidemiology and Change in Emphasis
- From the High Risk Plaque to the High Risk Symptomatic Patient
- From the High Risk Asymptomati to the Intermediate and Low Risk Patient
HRSP - Therapeutic Polypill & Single Pill
HRAP - BAD, Diagnostic MR Imaging
- BAD, Diagnostic & Rx - MR Plaque Composition
- BAD, Diagnostic Molecular MR Contrast Enhanced,
IRAP - Diagnostic CACS & CRP Biomarkers
LRAP - Government, Polymeal, Children
SHAPE & AEHA. Within This Context
Orlando, March 05, 2005
6.
7. ATHEROTHROMBOSIS: APPROACH IN 2005
Aggressive
Intervention3
Effective
Prevention1
2.Chronic Atherothrombosis
2. CAD Equivalents
HRAP- Subclinical
MRI / CT
Low
Risk
Modified from V Fuster, Circulation 1999; 99:1132
IRAP – Risk Frs
CACS / CRP
1.Acute Coronary Syndromes
Early
Detection 2
HRAP: High Risk Asymptomatic Patient - >2% y - >20% 10y
IRAP: Intermediate Risk Asymptomatic Patient – 0.5-2% y - 5-20% 10y
LOW RISK: FRS - < 0.5%y - < 5% 10 y
9. HIGH RISK PLAQUES - HRP
HIGH RISK BLOOD - HRB
BURDEN OF ATHEROTHROMBOSIS DISEASE - BAD
a) HRP / HRB / BAD - Systemic
b) HRP – Abundant
c) HRP AND HRB – Regionally Different
Maseri A, Fuster V, Circulation 2003; 107: 2068
Fuster V, Kim RJ, Circulation 2005 (In Press)
10. ACS (N=198) & SYSTEMIC ENDOTHELIAL DYSFUNCTION (FBF) – 5 DAYS 1
ADJUSTED RISK FACTORS, CV EVENTS (DEATH, MI, STROKE)- Av 4 YRS
Fichtlscherer et al., Circ 2004; 110:1926 (Frankfurt)
70
80
90
100
0 365 730 1095 1460 1825
days of follow up
Proportionofpatients
withouCVevents(%)
Logrank test p<0.03
Acetylcholine - dose - response
70
80
90
100
0 365 730 1095 1460 1825
days of follow up
Proportionofpatients
withouCVevents(%)
Logrank test p<0.08
Sodium nitroprusside - dose - response
≥ 35.0 (1. quartile)
< 34.9 (2. quartile)
< 24.3 (3. quartile)
< 15.6 (4. quartile)
≥ 31.6 (1. quartile)
< 31.5 (2. quartile)
< 18.7 (4. quartile)
< 24.1 (3. quartile)
1
Improved response at 8 weeks adds to the prediction (ACH)
11. CAD (ACS 54%) - CULPRIT VESSEL / LESION – N=843
NON-STENOTIC YELLOW PLAQUES / THROMBUS – N=1253
0
20
40
60
80
100
1 2 3
Color Grade of Plaque
PrevalenceofThrombosis
*
† ‡
(%)
*P=.0003 vs grade 1. †P<.0001 vs grade 1. ‡P<.0001 vs grade 2
Y Ueda et al., AHJ 2004; 148:842 (Osaka)
12. CAROTID ACTIVE PLAQUES (ENDARTERECTOMY)
CAP RUPTURE AND CAP EROSION BY STUDY GROUP
ICTB (LG Spagnoli et al.) JAMA 2004; 292:1895 (Rome, Mineapolis, Mayo)
C Yuan et al Circ 2002;105:181 (Seattle) – MRI – Several Plaques
No. of Plaques (%) P Val
Ipsilat. Stroke With TIA Asymptom. Stroke vs Stroke vs TIA vs
(n=96) (n=91) (n=82) TIA Asympt. Asympt.
Thromb. active % 74.0 35.2 14.6 <.001 <.001 .002
Cap rupture 66.7 23.1 13.4 <.001 <.001 .004
Cap erosion 7.3 12.1 1.2 .51 .09 .03
13.
14. THE EPIDEMIC OF CVD – NEED FOR NEW APPROACHES
Epidemiology and Change in Emphasis
- From the High Risk Plaque to the High Risk Symptomatic Patient
- From the High Risk Asymptomatic to the Intermediate and Low Risk Patient
HRSP - Therapeutic Polypill & Single Pill
HRAP - BAD, Diagnostic MR Imaging
- BAD, Diagnostic & Rx - MR Plaque Composition
- BAD, Diagnostic Molecular MR Contrast Enhanced,
IRAP - Diagnostic CACS & CRP Biomarkers
LRAP - Government, Polymeal, Children
SHAPE & AEHA.
Orlando, March 05, 2005
15. ATHEROTHROMBOSIS: APPROACH IN 2005
Aggressive
Intervention3
Effective
Prevention1
Chronic Atherothrombosis
CHD Equivalents
HRAP- Subclinical
CT / MRI
Low
Risk
Modified from V Fuster, Circulation 1999; 99:1132
IRAP – Risk Frs
CACS / CRP
Acute Coronary Syndromes
Early
Detection 2
HRAP: High Risk Asymptomatic Patient - >2% y - >20% 10y
IRAP: Intermediate Risk Asymptomatic Patient – 0.5-2% y - 5-20% 10y
LOW RISK: FRS - < 0.5%y - < 5% 10 y
16. THE EPIDEMIC OF CVD – NEED FOR NEW APPROACHES
Epidemiology and Change in Emphasis
- From the High Risk Plaque to the High Risk Symptomatic Patient
- From the High Risk Asymptomati to the Intermediate and Low Risk Patient
HRSP - Therapeutic Polypill & Single Pill
HRAP - BAD, Diagnostic MR Imaging
- BAD, Diagnostic & Rx - MR Plaque Composition
- BAD, Diagnostic Molecular MR Contrast Enhanced,
IRAP - Diagnostic CACS & CRP Biomarkers
LRAP - Government, Polymeal, Children
SHAPE & AEHA.
Orlando, March 05, 2005
17. ATHEROTHROMBOSIS: APPROACH IN 2005
Aggressive
Intervention3
Effective
Prevention1
2.Chronic Atherothrombosis
2. CAD Equivalents
HRAP- Subclinical
MRI / CT
Low
Risk
Modified from V Fuster, Circulation 1999; 99:1132
IRAP – Risk Frs
CACS / CRP
1.Acute Coronary Syndromes
Early
Detection 2
HRAP: High Risk Asymptomatic Patient - >2% y - >20% 10y
IRAP: Intermediate Risk Asymptomatic Patient – 0.5-2% y - 5-20% 10y
LOW RISK: FRS - < 0.5%y - < 5% 10 y
18. x
Patient Transport In-hospital Reperfusion
2004
2014
0 1 2 3
A B C D
Hours
Methods of Speeding Time to Reperfusion:
A B C D
Media Campaign 911 Expansion Regionalization PCI-Eluted Stents
Patient Education Pre-hosp. Rx MI protocol New devices / demand
1. MI - TIME TO REPERFUSION – 2005, 2015
X New antithrombotics, Myoc-Imaging., AICD, RF modification
x
X
19. 1. ACS – A PRE-HOSPITAL POLYPILL
V Fuster 2005
Definite ACS with
Possible ACS Definite ACS High risk/intervention
Tx R Bl. Tx R Bl. Tx R Bl
+ +
Clopidogrel - Like Clopidogrel - Like
+ +
Oral Fr Xa Inhib Oral Fr Xa Inhib
+ +
Statin Statin
+
Oral Antithrombin
20. 2. CAD EQUIVALENTS, CHRONIC ATHEROTHROMBOSIS
AND A POLYPILL
• ASA
• CLOPIDOGREL
• STATINS / LDL- C (HDL- C)
• ACE INHIBITORS
• BEHAVIOR MODIFICATION
• INTERVENTION (PCI VS CABG): LIFE QUALITY VS QUANTITY
CHALLENGES: COMPLIANCE, COSTS
21. THE EPIDEMIC OF CVD – NEED FOR NEW APPROACHES
Epidemiology and Change in Emphasis
- From the High Risk Plaque to the High Risk Symptomatic Patient
- From the High Risk Asymptomati to the Intermediate and Low Risk Patient
HRSP - Therapeutic Polypill & Single Pill
HRAP - BAD, Diagnostic MR Imaging
- BAD, Diagnostic & Rx - MR Plaque Composition
- BAD, Diagnostic Molecular MR Contrast Enhanced,
IRAP - Diagnostic CACS & CRP Biomarkers
LRAP - Government, Polymeal, Children
SHAPE & AEHA.
Orlando, March 05, 2005
22. ATHEROTHROMBOSIS: APPROACH IN 2005
Aggressive
Intervention3
Effective
Prevention1
Chronic Atherothrombosis
CHD Equivalents
HRAP- Subclinical
CT / MRI
Low
Risk
Modified from V Fuster, Circulation 1999; 99:1132
IRAP – Risk Frs
CACS / CRP
Acute Coronary Syndromes
Early
Detection 2
HRAP: High Risk Asymptomatic Patient - >2% y - >20% 10y
IRAP: Intermediate Risk Asymptomatic Patient – 0.5-2% y - 5-20% 10y
LOW RISK: FRS - < 0.5%y - < 5% 10 y
24. Longitudinal View
Ca++
BAD (Fayad ZA, Mani V, Fuster V et al.) 2005
Multi Slice Black Blood Imaging
Rapid Extended Coverage (REX) Turbo Spin Echo Technique
Mid heart Aorta- 12 slices
25. Descriptive
StatisticsParameter No Mean St dev Min Max Range
Age 100 54.3 20.55 9 87 78
Framingham
Score
44 7.27 3.99 1 20 19
10-Year Risk 42 0.118 0.069 0.03 0.31 0.28
Total Chol 84 199.9 57.3 105 366 261
LDL 83 120.7 54.5 46 303 257
HDL 84 53.2 16.8 20 100 80
TGC 83 139.3 122.9 32 891 859
HbA1C 20 6.75 1.57 4.7 10.9 6.2
BMI 82 25.98 5.2 15.1 42.5 27.3
BSA (m2
) 80 1.89 0.30 1.13 2.85 1.72
BAD (Fayad ZA, Mani V, Fuster V et al.) 2005
26. Comparing Framingham Risk Factor Score and
Coronary Artery Disease (CAD)
0
2
4
6
8
10
12
14
NO YES
CAD
FraminghamScore
p = 0.447
BAD (Fayad ZA, Mani V, Fuster V et al.) 2005
27. Comparing Wall Area (mm2
) and
Coronary Artery Disease (CAD)
Wall Area Aorta - CAD
100
150
200
250
300
NO YES
CAD
WADA
p <
0.001
*
BAD (Fayad ZA, Mani V, Fuster V et al.) 2005
28. CAD (N=167) – STATIN vs NIACIN / STATIN
CIMT
-0.01
0
0.01
0.07
0.02
0.03
0.04
0.05
0.06
Placebo PlaceboER Niacin ER Niacin
No DM / MS DM / MS Present
ChangeinCIMT(mm±SEM)
ARBITER 2 (AJ Taylor et al.) Circ 2004; 110:3510
29. THE FREEDOM TRIAL
FUTURE REVASCULARIZATION EVALUATION
IN PATIENTS WITH DIABETES MELLITUS:
OPTIMAL MANAGEMENT OF MULTIVESSEL DISEASE
Risk Factor modification and Rx are critical.
1) BAD-MRI: Diabetics vs Non Diabetics
NHLBI 2005 (PI V Fuster)
30. THE EPIDEMIC OF CVD – NEED FOR NEW APPROACHES
Epidemiology and Change in Emphasis
- From the High Risk Plaque to the High Risk Symptomatic Patient
- From the High Risk Asymptomati to the Intermediate and Low Risk Patient
HRSP - Therapeutic Polypill & Single Pill
HRAP - BAD, Diagnostic MR Imaging
- BAD, Diagnostic & Rx - MR Plaque Composition
- BAD, Diagnostic Molecular MR Contrast Enhanced,
IRAP - Diagnostic CACS & CRP Biomarkers
LRAP - Government, Polymeal, Children
SHAPE & AEHA.
Orlando, March 05, 2005
31. 0
10
20
30
40
50
60
70
80
90
100
MRI (1st) Histology
Percent
66.3 64
23.7
5.1 5
20.3
6.3 9.4
CAROTID PLAQUE COMPOSITION
(AS PERCENTAGE OF THE WALL)
Fibrous Tissue
Lipid Necrotic Core
Loose Matrix
Calcification
T Saam et al., ATVB 2005; 25:234 – In Vivo (Seattle, Wash)
M Shinnar et al., ATVB 1999; 19:2756 - Ex Vivo (New York)
32. MRI (no fat sat)
MRI (fat sat)
LAD
Lumen
LV
RV
RVOT
LAD WallX-ray angiogram
LAD
~6 mm max wall thickness
Fayad ZA et al.
Circ. 2000;102;506-510
Eccentric (“lipid-rich”)
MRI - Plaque Composition
33. Baseline 24 months follow up
R Corti, J J Wentzel, Z A Fayad, J J Badimon, V Fuster 2005 (Subm)
A ) MRI-LIPID LOWERING (SIMVASTATIN 20 or 80 mg/d)
AND REGRESSION OF ATHEROSCLEROSIS
R Corti, ZA Fayad, V Fuster, et al. Circ. 2001;104:249-252
R Corti, V Fuster, ZA Fayad, JJ Badimon et al. Circ 2002;106:2884
34. Independent of dose, LDL-C < 100 mg/dl had more regresion
Corti, J J Wentzel, Z A Fayad, J J Badimon, V Fuster 2005 (Subm)
35. R Corti, J J Wentzel, Z A Fayad, J J Badimon, V Fuster 2005 (Subm) PROVE IT
- TIMI 22 (C Cannon et al.), NEJM 2004; 350:15 - Clinical
36. Abdominal
Aorta
Thoracic
Aorta Baseline MRI Repeat MRI
after 12 months
treatment
3 contiguous slice
(no interslice gap
Lower corner
of Th9
Upper corner
of L4
Total vascular area
Lumen area
Maximal
vessel wall thickness
Minimal
vessel wall thickness
Yonemura A; Momiyama Y; Fayad ZA et al. JACC 2005;45:733-42
MRI - ATHEROSCLEROSIS AORTA – ATORVASTATIN (12mo,N=40)
39. B) MRI - HDL-Cholesterol
Rabbit / IV HDL, Apo E / HDL, Rabbit / PPAR-y /
Fenofibrate
1
10
J.X. Rong et al. Circ 2001;104:2447
High-chol. Diet
Simv. + PPAR-y
Badimon JJ, Badimon L, Fuster V, JCI 1990; 85:1234, 1990
Rong JX et al Circ 2001;104:2447
40. PPARs in Atherosclerosis:
Castrillo A et. al. J Clin Invest. 2004;114:1538.
A C Li et al. J Clin Invest 2004;114:1564
PPAR signaling pathways influence
macrophage gene expression and
foam cell formation
42. THE FREEDOM TRIAL
FUTURE REVASCULARIZATION EVALUATION
IN PATIENTS WITH DIABETES MELLITUS:OPTIMAL
MANAGEMENT OF MULTIVESSEL DISEASE
2) MRI-Diabetics: Reversibility, Statins-PPAR
NHLBI 2005 (PI V Fuster)
43. THE EPIDEMIC OF CVD – NEED FOR NEW APPROACHES
Epidemiology and Change in Emphasis
- From the High Risk Plaque to the High Risk Symptomatic Patient
- From the High Risk Asymptomati to the Intermediate and Low Risk Patient
HRSP - Therapeutic Polypill & Single Pill
HRAP - BAD, Diagnostic MR Imaging
- BAD, Diagnostic & Rx - MR Plaque Composition
- BAD, Diagnostic Molecular MR Contrast Enhanced,
IRAP - Diagnostic CACS & CRP Biomarkers
LRAP - Government, Polymeal, Children
SHAPE & AEHA.
Orlando, March 05, 2005
45. Targeted Contrast Agent - Approaches
Choudhury RP; Fuster V; Fayad ZA Nature Drug Disc. 2004;3:1
46. Lipid Rich Atherosclerotic Rabbit 24h
Post Gadofluorine
n=10 NZW
Atherosclerotic rabbits
No Enhancement in
Controls (n=6)
Pre Contrast
24 H Post
Gadofluorine
Sirol, M et. al. Circulation 2004; 109: 2890 – AHA 2004 -
48. In Vivo Detection of Macrophages
in Human Carotid Atheroma
Use of Post-Ultrasmall Superparamagnetic Particles of Iron (USPIO) MRI
Pre-USPIO
Post-USPIO
24h
Post-USPIO
36h
Areas of USPIO accumulation (Pearls staining, b)
colocalizing with
areas of high macrophage content (MAC 387 stain, c)
in the fibrous cap region
Trivedi AR et al. Stroke 2004; 35: 1631
49. Pre Contrast
Post Contrast
3 day old thrombus
Crush injured left
carotid artery
30 minutes
P.I.
60 minutes P.I.
Molecular Imaging of Fibrin with MR
Chronic Rabbit Model
Thrombus
in Left CCA
fibrin MRA
Fayad ZA
Imaging Science Laboratories
Control
H&E
Sirol M. et al. Circulation 2005 (In Press)
50. Diabetes and PAD - Proposed Sequence for an
Integrated Plaque (IP)-MRI Diagnostic Protocol
Combination of multi-weighted, post-Gadolinium and post-USPIO imaging
Dellegrottaglie S, Mani V, Fayad Z, Moreno P, Fuster V, Rajagopalan S. 2005
PDW MRI of the
Superficial femoral
artery
51. THE FREEDOM TRIAL
FUTURE REVASCULARIZATION EVALUATION
IN PATIENTS WITH DIABETES MELLITUS:
OPTIMAL MANAGEMENT OF MULTIVESSEL DISEASE
3) MRI - Contrast Enhanced PAD
NHLBI 2005 (PI V Fuster)
52. THE EPIDEMIC OF CVD – NEED FOR NEW APPROACHES
Epidemiology and Change in Emphasis
- From the High Risk Plaque to the High Risk Symptomatic Patient
- From the High Risk Asymptomati to the Intermediate and Low Risk Patient
HRSP - Therapeutic Polypill & Single Pill
HRAP - BAD, Diagnostic MR Imaging
- BAD, Diagnostic & Rx - MR Plaque Composition
- BAD, Diagnostic Molecular MR Contrast Enhanced,
IRAP - Diagnostic CACS & CRP Biomarkers
LRAP - Government, Polymeal, Children
SHAPE & AEHA.
Orlando, March 05, 2005
53. ATHEROTHROMBOSIS: APPROACH IN 2005
Aggressive
Intervention3
Effective
Prevention1
Chronic Atherothrombosis
CHD Equivalents
HRAP- Subclinical
CT / MRI
Low
Risk
Modified from V Fuster, Circulation 1999; 99:1132
IRAP- Risk Frs
CACS / CRP
Acute Coronary Syndromes
Early
Detection 2
HRAP: High Risk Asymptomatic Patient - >2% y - >20% 10y
IRAP: Intermediate Risk Asymptomatic Patient – 0.5-2% y - 5-20% 10y
LOW RISK: FRS - < 0.5%y - < 5% 10 y
55. 0 5 10 20 30 40
10
20
30
40
Initial Probability (%)
Posterior
Probability(%)
40% 25%35%
Identity Line
TRADITIONAL RISK PROBABILITY – IRAP & HRAP (FRS)
AND POSTERIOR NON-INVASIVE PROBABILITY
PWF Wilson et al., JACC 2003; 41:1898
NAHNES III (TA Jacobson et al.) Arch Int Med 2000; 160:1361
5
56. 1) PREDICTED 7-YEAR EVENT RATES FOR CHD DEATH OR
NONFATAL MI FOR CATEGORIES OF FRS OR CACS
P Greenland et al., JAMA 2004; 291:210
0-9 10-15 16-20 ≥ 21
Framingham Risk Score, %
CoronaryDeathor
NonfatalMI,%
0
4
8
12
16
20
CACS
0
1-100
101-300
≥ 301
58. THE EPIDEMIC OF CVD – NEED FOR NEW APPROACHES
Epidemiology and Change in Emphasis
- From the High Risk Plaque to the High Risk Symptomatic Patient
- From the High Risk Asymptomati to the Intermediate and Low Risk Patient
HRSP - Therapeutic Polypill & Single Pill
HRAP - BAD, Diagnostic MR Imaging
- BAD, Diagnostic & Rx - MR Plaque Composition
- BAD, Diagnostic Molecular MR Contrast Enhanced,
IRAP - Diagnostic CACS & CRP Biomarkers
LRAP - Government, Polymeal, Children
SHAPE & AEHA.
Orlando, March 05, 2005
59. ATHEROTHROMBOSIS: APPROACH IN 2005
Aggressive
Intervention3
Effective
Prevention1
Coronary Atherothrombosis
CHD Equivalents
HRAP- Subclinical
CT / MRI
Low
Risk
Modified from V Fuster, Circulation 1999; 99:1132
IRAP - Risk Frs.
CACS / CRP
Acute Coronary Syndromes
Early
Detection 2
HRAP: High Risk Asymptomatic Patient - >2% y - >20% 10y
IRAP: Intermediate Risk Asymptomatic Patient – 0.5-2% y - 5-20% 10y
LOW RISK: FRS - < 0.5%y - < 5% 10 y
60. 1) RISK FACTORS FOR WHICH INTERVENTION
IS PROVEN TO LOWER RISK –
GOVERNMENT ?
Cessation1
↓ 10%2
DP ↓ 6 mmHg3
↓
Cigarette Smoking1
50% ↓ CHD ------ ------
Cholesterol2
------ 30% ↓ CHD ------
Hypertension3
------ ------ 16% ↓ CHD
42% ↓ Stroke
CH Hennekens, Circ 1998; 97:1095
61. 2) EFFECT OF INGREDIENTS OF POLYMEAL
IN REDUCING RISK OF CVD
% Reduction (95% CI)
Ingredients in Risk of CVD Source
Wine (150 ml/d) 32 (23 to 41) DiCastelnuovo, 2002 (MA)
Fish (114 g x 4 w) 14 (8 to 19) Whelton, 2004 (MA)
Dark Chocolate (100 g/d) 21 (14 to 27) Taubert, 2003 (RCT)
Fruit/Vegetables (400 g/d) 21 (14 to 27) John, 2002 (RCT)
Garlic (2.7 g/d) 25 (21 to 27) Ackerman, 2001 (MA)
Almonds (68 g/d) 12.5 (10.5 to 13.5) Jenkins, Sabate. 2002,03 (RCT)
Combined Effect 76 (63 to 84)
MA = meta-analysis; RCT = randomized controlled trial
OH Franco et al., BMJ 2004; 329:1447
Polypill - NJ Wald et al., BMJ 2003; 326:1419
Statin, ASA, Folic Acid, BP (ACE-I, β-blocker, Thiazide) - % Reduction 85%
62. 3) NIH Launches Study of 100,000 U.S. Kids 2.7 Billion
Kaiser, J Science 2004;306:1883.
Random sampling across the US to follow the health of children from birth to age 21.
63. THE EPIDEMIC OF CVD – NEED FOR NEW APPROACHES
Epidemiology and Change in Emphasis
- From the High Risk Plaque to the High Risk Symptomatic Patient
- From the High Risk Asymptomati to the Intermediate and Low Risk Patient
HRSP - Therapeutic Polypill & Single Pill
HRAP - BAD, Diagnostic MR Imaging
- BAD, Diagnostic & Rx - MR Plaque Composition
- BAD, Diagnostic Molecular MR Contrast Enhanced,
IRAP - Diagnostic CACS & CRP Biomarkers
LRAP - Preventive - Government, Polymeal, Children
SHAPE & AEHA. Innovative, Feasible (RF)?, Simple?, Preventive?, Polyauthor?
Orlando, March 05, 2005
64.
65.
66.
67.
68.
69.
70.
71. 2) C-Reactive Protein
Structure Affects Function
Dissociation from pentameric to monomeric form of CRP to exert
proatherosclerotic effects
Verma, S et. al. Circulation 2004;109:1914.
73. Wyttenbach R……..Corti R. Circ 2004;110:1156
EFFECTs OF PTA & EVBT ON VASCULAR REMODELING
HUMAN FEMOROPOPLITEAL ARTERY - MRI
74. 1) ROLE FOR GOVERNMENTS ON PREVENTION
TA Pearson et al., Circ 2003; 107:645
Diet
Sedentary
Lifestyle
Tobacco
Hyperlipidemia
Hypertension
Earlyrecognition
ofSymptomatic
Disease
Risk Factor/Risk Behavior
Community
Setting
Essential Public
Health Services
Policy/Legislation
Assuring Personal Health Services
Religious
Organizations
Organizational Partnerships
Education/media
Surveillance
Whole
communities
Schools
Worksites
Healthcare
Facilities
75. Descriptive Statistics: Image Parameters
Parameter Count Mean Stdev Min Max Range
Average Wall
AreaCarotids
(mm2
)
100 29.28 11.45 13.14 60.81 47.67
Normalized
Plaque Index
Carotid
100 4.98 1.89 2.19 14.56 12.37
Average Wall
Area Aorta
(mm2
)
100 144.78 62.41 36.43 309.91 273.47
Normalized
Plaque Index
Aorta
100 7.20 2.21 3.60 13.18 9.58
Max Wall
Thickness
Carotid (mm)
100 5.82 2.63 1.41 16.27 14.86
Max Wall
Thickness
Aorta (mm)
100 5.97 3.18 2.83 18.44 15.61
77. T1W PDW T2W
RGB
Fibrous cap
Lipid Core
Clustered
Itskovich VV, Samber D, Mani V, et al Magn Reson Med 2004; 52: 515
In-Vivo Cluster Analysis for Plaque Characterization
78. X
x
Patient Transport In-hospital Reperfusion
2004
2014
0 1 2 3 4
A B C D
Hours
Methods of Speeding Time to Reperfusion:
A B C D
Media Campaign 911 Expansion Regionalization PCI-Eluted Stents
Patient Education Pre-hosp. Rx MI protocol New devices / demand
3a) MI - TIME TO REPERFUSION – 2005, 2014
79. CORONARY CALCIUM AND CORONARY DISEASE EVENTS
Calcium Score Threshold
> 0 ≥ 100 ≥ 200 ≥ 600
Subjects above threshold (%) 64 19 12 4
Sensitivity (%) 91 71 54 26
Specificity (%) 36 82 89 96
Positive predictive value (%) 3.2 8.6 10.5 14.1
Negative predictive value (%) 99.5 99.2 98.8 98.2
Relative risk 5.9 10.7 8.9 8.0
(95% CI) (3.0-11.6) (7.1-16.3) (6.1-12.9) (5.3-12.1)
St. Francis Study (AD Guerci et al.) 2005 (Submitted)
83. CT AND MR IMAGING OF MAIN COMPONENTS
OF ATHEROTHROMBOTIC PLAQUE
Modality CT MR
Unit HU SI*
Sequence 200† T1W PDW T2W TOF
Thrombus 20 +/- +/- +/- +
Lipid 50 + + - +/-
Fibrous 100 +/- + +/- +/-
Calcium > 300 - - - -
Z.A. Fayad, V.Fuster., Circ Res 2001;89:305
ZA Fayad, V Fuster, K Nikolaou, C Becker. Circ 2002;106:2026
RP Choudhury, V Fuster, JJ Badimon et al., ATVB 2002; 22:1065
† Vessel contrast enhancement - * Signal intensity (SI) relative to adjacent muscle
+ = hyperintense; +/- = isointense; - = hypointense
84. COMPARISON OF SOFT, INTERMEDIATE, AND CALCIFIED PLAQUES
BY MDCT (PLAQUE MAP) AND IVUS
S Komatsu et al., Circ J 2005; 69:72
IVUS
Soft Intermediate Calcified
MDCT-positive 144 134 84
MDCT-negative 12 19 10
Sensitivity (%) 92 87 89
85. 0 5 10 15 20
0
1
0.1
0.8
0.4
0.6
Years
Survival
ST Depression
0 5 10 15 20
0
1
0.1
0.8
0.4
0.6
Years
Failure THR
0 5 10 15 20
0
1
0.1
0.8
0.4
0.6
Years
Low METs
Absent Present
SURVIVAL FREE OF CHD IN HIGH-RISK MEN
CJ Balady et al., Circ 2004; 110:1920 (Framingham)
86. CAD (N=167) – STATIN vs NIACIN / STATIN
CIMT
-0.01
0
0.01
0.07
0.02
0.03
0.04
0.05
0.06
Placebo PlaceboER Niacin ER Niacin
No DM / MS DM / MS Present
ChangeinCIMT(mm±SEM)
ARBITER 2 (AJ Taylor et al.) Circ 2004; 110:3510
87. CVMR-ISL
Zahi Fayad, PhD
Gilbert Aguinaldo, MD
Robin P Choudhury, MD
Vitalii Itskovich, PhD
Michael J Lipinski
Teresa Rius, MD
Frank Macalusso, RT
Karen Metroka, RT
Javier Sanz, MD
M.Sirol,MD
Cardiology
Valentin Fuster, MD, PhD
Juan Badimon, PhD
Michael Poon, MD
Stella Palentia, RN
Don Smith, MD
Meir Shinnar, MD, PhD
Pedro R Moreno MD
Pathology
John Fallon, MD, PhD
KR Purushothaman,MD
Molecular Biology
Yale Nemerson, MD
Mark Taubman, MD
Edward Fisher, MD, PhD
Ernane Reis, MD
K-R Purushothaman
Funding
NIH-HL 94013
NIH-HL 61801
NIH-HL 07208
BMS Inv. Award
Merck, GSK,
Schering AG
CV Research Fellows
Ursula Rauch MD
Roberto Corti, MD
Julio Osende, MD
Antonia Sambola, MD
Stephen Worthley, MD
Juan F Viles MD
Randolph Hutter MD
The Mount Sinai Medical Center
The Cardiovascular Institute
Radiology
Burton Drayer, MD
Jeff Goldman, MD
Neurology
Jessey Weinberger, MD
88. 15
16
17
18
19
20
21
22
23
Baseline End of Follow-up
TREATMENT
CONTROL
Total Vessel Area (mm2
) Vessel Wall Area (mm2
)
The Selective TP Receptor Antagonist S18886 has
Anti-atherosclerotic and Plaque Stabilizing Effects
S18886 induces regression of advanced atherosclerotic plaques
Viles-Gonzalez JF, Fuster V, Corti R, Badimon JJ.Viles-Gonzalez JF, Fuster V, Corti R, Badimon JJ. European Heart JournalEuropean Heart Journal, 2005, 2005
89. The Selective TP Receptor Antagonist S18886 has
Anti-atherosclerotic and Plaque Stabilizing Effects
Viles-Gonzalez JF, Fuster V, Corti R, Badimon JJ.Viles-Gonzalez JF, Fuster V, Corti R, Badimon JJ. European Heart JournalEuropean Heart Journal, 2005, 2005
90. Detection of Occlusive thrombus in the Rabbit
Using Fibrin-Targeted MR Contrast Agent
Pre Contrast Post Contrast
T1-Weighted
sequence
2D BB FSE
Sirol M. et al. Circ 2004 (In Press) - AHA 2004
91. Chronic Thrombus Detection
Age Characterization Using Fibrin-Targeted MR Contrast
Agent
N=14 NZW Rabbits
Acute 1 Week 2 Weeks 4 Weeks 6 Weeks 8 WeeksNormal
Artery
Pre
Post
contrast
Sirol M. et al. Circ 2004 (In Press) - AHA 2004
92. Descriptive Statistics: Image Parameters
Parameter Count Mean Stdev Min Max Range
Average Wall
AreaCarotids
(mm2
)
100 29.28 11.45 13.14 60.81 47.67
Normalized
Plaque Index
Carotid
100 4.98 1.89 2.19 14.56 12.37
Average Wall
Area Aorta
(mm2
)
100 144.78 62.41 36.43 309.91 273.47
Normalized
Plaque Index
Aorta
100 7.20 2.21 3.60 13.18 9.58
Max Wall
Thickness
Carotid (mm)
100 5.82 2.63 1.41 16.27 14.86
Max Wall
Thickness
Aorta (mm)
100 5.97 3.18 2.83 18.44 15.61
93. In vivo MR evaluation of aortic
Atherosclerosis, risk factors and CAD at angiography
MRI slices of aorta and
plaque scores
Taniguchi H, ZA Fayad et. al. Am Heart J 2004;148:137 (Japan).
BAD (Fayad ZA, Mani V, Fuster V et al.) 2005
95. PREVENTING CARDIOVASCULAR DISEASE,
DIABETES AND CANCER
AHA, ADA, ACS – Circulation 2004;109:3244
Eat right - Mediterranean, serving size
Get active - >30min, >3days/week
Do not smoke - Advocacy, programs …
96. GENERAL PREVENTION GUIDELINES FOR CANCER, CVD AND
DIABETES IN ADULTS
20 30 40 50+AGETEST
BMI
Blood Pressure
Lipid Profile
Blood Glucose test
Clinical Breast Exam (CBE)
and Mammography
Pap test
Colorectal Screening
Prostate specific antigen
test and/digital rectal exam
Each regular health care visit
Each regular health care visit (or at least
once every 2 years if BP < 120/80 mm Hg)
Every 5 years
Every 3 years
CBE every 3 yrs
Yearly CBE and
Mammography
Yearly
Every 1-3 years; depends on
type of test and past results.
Frequency depends
on test preferred
Offer yearly, assist
informed decisions
ACS/ADA/AHA - Circ 2004; 109:3244
97. 3) CARDIOVASCULAR HEALTH IN CHILDHOOD
CHALLENGES 20021
1
Multidisciplinary - Schools
2
Above 10 years and less demanding levels than in adults
AHA Statement (CL Williams et al.) Circ 2002; 106:143
1. Physical Activity Promotion methods
2. Obesity (< IR Type II Diabetes) Prevention methods
Nutrition
3. Hypertension Identification
4. Cholesterol Identification
Nutrition
Statins2
LDL > 190
LDL > 160 + FU
5. Cigarette Smoking Prevention methods
98. Lipid-Rich Atherosclerotic Plaques Detected by
Gadofluorine-Enhanced In Vivo Magnetic Resonance Imaging
Sirol, M et. al. Circulation 2004; 109: 2890.
In vivo T1W MR image of the rabbit abdominal aorta
24-hours post-gadofluorine injection
99. -1 0 1 2 3 4 5Years
Cardiovascular disease
Perinatal disease
Injuries
Cancer
Chronic obstructive
pulmonary disease
HIV infection or AIDS
Other causes
Coronary heart
disease
Stroke
Other heart
disease
U.S. LIFE EXPECTANCY 1970 & 2000 – SUCCESS OF RESEARCH ON THERAPIES
C Lenfant et al., NEJM 2003; 349:9
NCHS and AHA 2002 - Leading cause of death -
101. HIGH RISK PLAQUES - HRP
HIGH RISK BLOOD - HRB
BURDEN OF ATHEROTHROMBOSIS DISEASE - BAD
a) HRP / HRB / BAD - Systemic
b) HRP – Abundant
c) HRP AND HRB – Regionally Different
Maseri A, Fuster V, Circulation 2003; 107: 2068
Fuster V, Kim RJ, Circulation 2005 (In Press)
102. HIGH RISK PLAQUES - HRP
HIGH RISK BLOOD - HRB
BURDEN OF ATHEROTHROMBOSIS DISEASE - BAD
a) HRP / HRB / BAD - Systemic
b) HRP – Abundant
c) HRP AND HRB – Regionally Different
Maseri A, Fuster V, Circulation 2003; 107: 2068
Fuster V, Kim RJ, Circulation 2005 (In Press)
103. CAD (N=167) – STATIN vs NIACIN / STATIN
CIMT
-0.01
0
0.01
0.07
0.02
0.03
0.04
0.05
0.06
Placebo PlaceboER Niacin ER Niacin
No DM / MS DM / MS Present
ChangeinCIMT(mm±SEM)
ARBITER 2 (AJ Taylor et al.) Circ 2004; 110:3510
104. BAA 62 HU
DC
Despite the increasedDespite the increased spatial resolutionspatial resolution of the new generation ofof the new generation of
MDCTMDCT scanners,scanners, MRIMRI is better foris better for plaqueplaque characterization (Rabbitcharacterization (Rabbit
model)model)
Viles JF, Poon M, Sanz J, Rius T, Fuster V, Badimon JJ.Viles JF, Poon M, Sanz J, Rius T, Fuster V, Badimon JJ. Circ.Circ. 20042004
(In Press)(In Press)
106. C ) Selective TP Receptor Antagonist S18886 has
Anti-atherosclerotic and Plaque Stabilizing Effects
Baseline End of Treatment
Follow-up With Serial High Resolution Magnetic Resonance
Viles-Gonzalez JF, Fuster V, Corti R, Badimon JJ.Viles-Gonzalez JF, Fuster V, Corti R, Badimon JJ. EHJEHJ,, 20052005 (In(In
107. THE EPIDEMIC OF CVD – NEED FOR NEW APPROACHES
Epidemiology and Change in Emphasis
- From the High Risk Plaque to the High Risk Symptomatic Patient
- From the High Risk Asymptomati to the Intermediate and Low Risk Patient
HRSP - Therapeutic Polypill & Single Pill
HRAP - BAD, Diagnostic MR Imaging
- BAD, Diagnostic & Rx - MR Plaque Composition
- BAD, Diagnostic Molecular MR Contrast Enhanced,
IRAP - Diagnostic CACS & CRP Biomarkers
LRAP - Government, Polymeal, Children
SHAPE & AEHA. Within This Context
Orlando, March 05, 2005
108. FROM GENES TO HEALTH AND HEALTH TO GENES 1,2
TRAINING / MENTORS
Imaging: Non Inv. Molec.
Clinical Proteinomics
Inform. / Science / Techn.
Behav. Instrum./ Technol.
Clinical Trials Infrastr.
TRANSLATIONAL
GENES ⇔ CELL ⇔ TISSUE ⇔ PHYSIOL. ⇔ PHENOTYPE ⇔ POPUL. ⇔HEALTH
ENVIROMENT
Regenerative Biol./ Replac.Therapy.
.
Embryogenesis / Development
Immunobiol./ Inflammation / Thromb.
Public Health / Genom.Protein.
Health Promotion
1
NHLBI SPARK I 1998-2002
Circ 1999; 99:1132 & 2064 - Defined
Circ 2002;106:162 - Update
2
1
42
ClinicalTrials
ENABLING APPROACHES3
SPECIFIC AIMS
Editor's Notes
DLMP
.
Post-USPIO MRI can be used to identify macrophages accumulation within the plaque in vivo
Pre- and post-contrast (Omniscan) enhanced images show regional variation in contrast enhancement
A region of strong enhancement adjacent to the lumen (arrow 1) indicates neovasculature
Also indicated are a necrotic core with minor enhancement (arrow 2) and an enhancing region of neovasculature near the outer wall (arrow 3)
The presence of neovessels was confirmed in the correpsonding histological slice
Vascular disease is the result of a generalized process that affects multiple vascular beds, including the cerebral, coronary, and peripheral arteries. Coexistence of vascular disease in multiple beds increases the risk for developing ischemic events such as MI and stroke.[1]
Vascular disease in cerebral arteries may precipitate a transient ischemic attack (TIA) or an ischemic stroke. A TIA, by definition, lasts for fewer than 24 hours, but the majority clear within 1 hour. A TIA may be a warning of an impending stroke, with the risk for a stroke being 4% to 8% during the first month following a TIA and 24% to 29% during the next 5 years.[2]
Vascular disease in coronary arteries produces a spectrum of ischemic coronary syndromes that include stable angina, unstable angina, non–ST-segment elevation myocardial infarction (NSTEMI; also known as non–Q-wave MI), and ST-segment elevation (STEMI; also known as Q-wave MI). Cardiovascular disease is the single largest cause of death in the United States.[3]
Vascular disease in peripheral vessels, peripheral arterial disease (PAD), produces a variety of symptoms ranging from intermittent claudication to pain at rest.[4] Patients with the most serious PAD have critical limb ischemia that produces pain at rest and threatens the viability of the limb by increasing the risk for gangrene and necrosis.[4] PAD is a strong marker for cardiovascular disease. Over a 10-year period, PAD increases risk for death due to cardiovascular disease approximately 6-fold.[5]
Note: Plavix® (clopidogrel) is not indicated for all the conditions listed on this slide.