ABSTRACT
Aims: To derive and validate a readily useable risk score to identify patients at high-risk of in-hospital ST-segment elevation myocardial infarction (STEMI)-related cardiogenic shock (CS). Methods and results: In all, 6838 patients without CS on admission and treated by primary percutaneous coronary intervention (pPCI), included in the Observatoire Régional Breton sur l'Infarctus (ORBI), served as a derivation cohort, and 2208 patients included in the obseRvatoire des Infarctus de Côte-d'Or (RICO) constituted the external validation cohort. Stepwise multivariable logistic regression was used to build the score. Eleven variables were independently associated with the development of in-hospital CS: age >70 years, prior stroke/transient ischaemic attack, cardiac arrest upon admission, anterior STEMI, first medical contact-to-pPCI delay >90 min, Killip class, heart rate >90/min, a combination of systolic blood pressure <125 mmHg and pulse pressure <45 mmHg, glycaemia >10 mmol/L, culprit lesion of the left main coronary artery, and post-pPCI thrombolysis in myocardial infarction flow grade <3. The score derived from these variables allowed the classification of patients into four risk categories: low (0-7), low-to-intermediate (8-10), intermediate-to-high (11-12), and high (≥13). Observed in-hospital CS rates were 1.3%, 6.6%, 11.7%, and 31.8%, across the four risk categories, respectively. Validation in the RICO cohort demonstrated in-hospital CS rates of 3.1% (score 0-7), 10.6% (score 8-10), 18.1% (score 11-12), and 34.1% (score ≥13). The score demonstrated high discrimination (c-statistic of 0.84 in the derivation cohort, 0.80 in the validation cohort) and adequate calibration in both cohorts. Conclusion: The ORBI risk score provides a readily useable and efficient tool to identify patients at high-risk of developing CS during hospitalization following STEMI, which may aid in further risk-stratification and thus potentially facilitate pre-emptive clinical decision making.
Subject(s)
Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction/surgery , Shock, Cardiogenic/epidemiology , Age Factors , Aged , Aged, 80 and over , Female , France/epidemiology , Heart Arrest/epidemiology , Humans , Hypertension/epidemiology , Logistic Models , Male , Middle Aged , Peripheral Arterial Disease/epidemiology , Prognosis , Registries , Risk Assessment , ST Elevation Myocardial Infarction/epidemiology , Stroke/epidemiologyABSTRACT
OBJECTIVES: The use of summed planar images generated from single-photon emission computed tomography (SPECT) ventilation/perfusion (V/Q) scintigraphy has been proposed as a substitute for planar V/Q scans in order to use the revised PIOPED interpretation criteria when only SPECT acquisition is performed in patients with suspected pulmonary embolism. The aim was to evaluate the accuracy of angular summed planar scans in comparison with true planar images. METHODS: Patients included in the 'SPECT study' assessing the diagnostic performance of V/Q SPECT were analysed. Angular summed planar images were generated from SPECT acquisition data and compared with true planar scans. RESULTS: Angular summed planar images were successfully generated for 246 patients. Regarding interobserver variability, the interpretation result was different for 15 (6%) summed planar scans with an excellent degree of agreement (κ=0.92; 95% confidence interval 0.88-0.96). With regard to intermodality interpretation variability between conventional planar and angular summed images, the result was different for 63 (26%) of 246 patients with an intermodality degree of agreement of κ=0.66 (95% confidence interval 0.58-0.73). CONCLUSION: Planar images generated from SPECT V/Q scintigraphy are not a reliable substitute for true planar V/Q images.
Subject(s)
Image Interpretation, Computer-Assisted/methods , Pulmonary Embolism/diagnostic imaging , Tomography, Emission-Computed, Single-Photon/methods , Ventilation-Perfusion Ratio/physiology , Adolescent , Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Prospective Studies , Reproducibility of Results , Young AdultABSTRACT
BACKGROUND: Planar ventilation/perfusion (V/Q) lung scintigraphy is a validated tool for the diagnosis of pulmonary embolism (PE). Nevertheless, given the high rate of nonconclusive V/Q, further investigation is often necessary. V/Q single-photon emission CT (SPECT) scan could improve V/Q performance, but sparse data are available on its accuracy. This study assessed the diagnostic performance of V/Q SPECT scan in a cohort of consecutive patients with suspected PE. METHODS: Three hundred twenty-one consecutive patients with a clinical suspicion of PE were prospectively included. Patients suspected of having PE were managed according to a reference diagnostic strategy validated by a 3-month follow-up. In addition to the reference strategy, patients had a V/Q SPECT scan, the results of which were compared with the initial work-up results. RESULTS: Prevalence of PE was 0 of 41 (0%; 95% CI, 0%-9%), six of 134 (4%; 95% CI, 2%-9%),15 of 36 (42%; 95% CI, 27%-58%), and 28 of 32 (88%; 95% CI, 72%-95%) in the normal, low,intermediate, and high V/Q SPECT scan probability groups, respectively. The combination of V/Q SPECT scan with clinical probability was diagnostic in 88% of patients. CONCLUSIONS: V/Q SPECT scan results show satisfactory accuracy for PE diagnosis. Validation of dedicated interpretation criteria is required, followed by outcome studies that use V/Q SPECT scan as part of a diagnostic strategy to rule out PE. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01183026; URL: www.clinicaltrials.gov
Subject(s)
Pulmonary Embolism/diagnostic imaging , Tomography, Emission-Computed, Single-Photon , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prevalence , Prospective Studies , Pulmonary Embolism/epidemiologyABSTRACT
Medicalized high sea rescue is very different from prehospital medical evacuation. It requires specifically trained medical teams because the difficulties are marine, aerial, and medically related. The French Navy provides medical evacuations by helicopter on the Atlantic coast, up to 320 km offshore and under all weather conditions. The epidemiology of acute chest pain in the high seas has been poorly described. Therefore, in this retrospective study, we aimed to assess the prevalence and constraints found in the management of these emergencies. From January 1, 2000, to April 30, 2009, 286 medical evacuations by helicopter were performed, 132 of which were due to traumatological emergencies, and 154 to medical emergencies. Acute chest pain, with 36 missions, was the leading cause of medical evacuation. All evacuated patients were men who were either professional sailors or ferry passengers. The median age was 48 years (range, 26-79). The most common prehospital diagnosis was coronary chest pain in 23 patients (64%), including 11 patients with acute coronary syndrome with ST-segment elevation. Thirty-two patients were airlifted by helicopter. All patients benefited from monitoring, electrocardiogram, peripheral venous catheter, and medical management as soon as the technical conditions allowed it.
Subject(s)
Air Ambulances , Chest Pain/therapy , Emergencies , Naval Medicine , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/therapy , Adult , Aged , Atlantic Ocean , Chest Pain/diagnosis , Emergency Medical Services , France , Humans , Male , Middle Aged , Myocardial Infarction/diagnosis , Myocardial Infarction/therapy , Retrospective StudiesABSTRACT
BACKGROUND: Extracranial internal carotid artery stenosis is a risk factor for perioperative stroke in patients undergoing coronary artery bypass surgery (CAB). Although selective and non-selective methods of preoperative carotid screening have been advocated, it remains unclear if this screening is clinically relevant. AIM: To test whether selective carotid screening is as effective as non-selective screening in detecting significant carotid disease. METHODS: The case records of patients consecutively undergoing CAB were reviewed. Patients were stratified retrospectively into high- or low-risk groups according to risk factors for significant carotid stenosis and perioperative stroke: peripheral vascular disease (PVD), carotid bruit, diabetes mellitus, age >70 years and/or history of cerebrovascular disease. Prevalence of carotid stenosis detected by ultrasonography, surgical management and perioperative stroke rates were determined in each group. RESULTS: Overall, 205 consecutive patients underwent preoperative carotid screening. The prevalence of significant carotid stenosis was 5.8%. Univariate analysis confirmed that PVD (P=0.005), carotid bruit (P=0.003) and diabetes mellitus (P=0.05) were significant risk factors for stenosis. Carotid stenosis was a risk factor for stroke (P=0.03). Prevalence of carotid stenosis was higher in the high-risk group (9.1%) than the low-risk group (1.2%) (P<0.05). All concomitant or staged carotid endarterectomies/CAB (5/205) and all patients who had perioperative strokes (5/205) were in the high-risk group (P=0.01). CONCLUSION: In our cohort, selective screening of patients aged >70 years, with carotid bruit, a history of cerebrovascular disease, diabetes mellitus or PVD would have reduced the screening load by 40%, with trivial impact on surgical management or neurological outcomes.
Subject(s)
Carotid Stenosis/diagnostic imaging , Coronary Artery Bypass , Coronary Artery Disease/surgery , Ultrasonography, Doppler, Duplex , Aged , Algorithms , Carotid Stenosis/complications , Carotid Stenosis/epidemiology , Carotid Stenosis/surgery , Chi-Square Distribution , Coronary Artery Disease/complications , Coronary Artery Disease/epidemiology , Endarterectomy, Carotid , Female , France/epidemiology , Humans , Male , Patient Selection , Predictive Value of Tests , Preoperative Care , Prevalence , Retrospective Studies , Risk Assessment , Risk Factors , Severity of Illness Index , Stroke/etiologyABSTRACT
BACKGROUND: We designed a simple and integrated diagnostic algorithm for acute pulmonary embolism (PE). Diagnosis was based on clinical probability assessment, plasma D-dimer testing, then sequential testing to include lower limb venous compression ultrasonography, ventilation perfusion lung scan, and chest multidetector CT (MDCT) imaging. METHODS: We included 321 consecutive patients presenting at Brest University Hospital in Brest, France, with clinically suspected PE and positive d-dimer or high clinical probability. Patients in whom VTE was deemed absent were not given anticoagulants and were followed up for 3 months. RESULTS: Detection of DVT by ultrasonography established the diagnosis of PE in 43 (13%). Lung scan associated with clinical probability was diagnostic in 243 (76%) of the remaining patients. MDCT scan was required in only 35 (11%) of the patients. The 3-month thromboembolic risk in patients not given anticoagulants, based on the results of the diagnostic protocol, was 0.53% (95% CI, 0.09-2.94). CONCLUSIONS: A diagnostic strategy combining clinical assessment, d-dimer, ultrasonography, and lung scan gave a noninvasive diagnosis in the majority of outpatients with suspected PE and appeared to be safe.
Subject(s)
Pulmonary Embolism/diagnosis , Aged , Aged, 80 and over , Algorithms , Angiography , Cohort Studies , Enzyme-Linked Immunosorbent Assay , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Middle Aged , Perfusion Imaging , Prognosis , Pulmonary Embolism/blood , Pulmonary Embolism/therapy , Tomography, X-Ray Computed , Ventilation-Perfusion RatioABSTRACT
AIMS: P947 is a gadolinium-based magnetic resonance imaging (MRI) contrast agent with high affinity for several matrix metalloproteinases (MMPs) involved in arterial wall remodelling. We tested whether the intensity of enhancement detected in vivo in the arterial wall with P947 and MRI correlates with actual tissue MMP-related enzymatic activity measured in a rabbit atherosclerotic model subjected to dietary manipulations. METHODS AND RESULTS: Aortas of 15 rabbits in which atherosclerotic lesions were induced by balloon angioplasty and 4 months of hypercholesterolaemic diet were imaged at 'baseline' with P947-enhanced MRI. Atherosclerotic rabbits were divided into three groups: five rabbits were sacrificed ('baseline' group); five rabbits continued to be fed a lipid-supplemented diet ('high-fat' group); and five rabbits were switched from atherogenic to a purified chow diet ('low-fat' group). Four months later, a second P947-enhanced MRI was acquired in the 10 remaining rabbits. A significantly lower signal was detected in the aortic wall of rabbits from the 'low-fat' group as compared with rabbits from the 'high-fat' group (21 ± 6 vs. 46 ± 3%, respectively; P = 0.04). Such differences were not detected with the contrast agent P1135, which lacks the MMP-specific peptide sequence. In addition, the intensity of aortic wall enhancement detected with MRI after injection of P947 strongly correlated with actual MMP-2 gelatinolytic activity measured in corresponding aortic segments using zymography (r = 0.87). CONCLUSION: P947-enhanced MRI can distinguish dietary-induced variations in MMP-related enzymatic activity within plaques in an experimental atherosclerotic model, supporting its utility as a clinical imaging tool for in vivo detection of arterial wall remodelling.
Subject(s)
Aortic Diseases/pathology , Atherosclerosis/pathology , Matrix Metalloproteinases/metabolism , Animals , Aorta, Abdominal , Atherosclerosis/metabolism , Cholesterol/metabolism , Contrast Media , Diet, Fat-Restricted , Diet, High-Fat , Heterocyclic Compounds/metabolism , Magnetic Resonance Angiography , Organometallic Compounds/metabolism , Plaque, Atherosclerotic/metabolism , Plaque, Atherosclerotic/pathology , RabbitsABSTRACT
OBJECTIVE: Diffuse coronary artery disease makes cardiac surgeons hesitant regarding whether coronary artery bypass grafting (CABG) surgery is feasible or not. Coronary artery reconstruction using the internal thoracic artery (ITA) allows bypassing of coronary arteries with diffuse atheromatous plaques without systematically resorting to endarterectomy. The aim of the present study was to evaluate the medium-term results of coronary artery reconstruction. METHODS: All patients undergoing coronary artery reconstruction using the ITA between 1999 and 2002 (233 patients) were included in the study. The mean age was 61.9 ± 9.8 years. Two hundred and eighty-one coronary artery reconstructions using the ITA were performed (mean length 3.6 ± 2 cm) for 514 CABGs. Coronary artery reconstruction using the ITA was associated with endarterectomy in 48 cases (17%). RESULTS: In-hospital mortality was 2.6%. Follow-up data were compiled in December 2008. Mean follow-up was 73.4 ± 16.7 months. The actuarial survival rate at 7 years was 89.3 ± 2.1%, and 88% of patients were free of major cardiac events at 7 years. CONCLUSIONS: Coronary artery reconstruction gives comparable medium-term results to conventional coronary surgery, even though it is indicated for patients with more severe lesions.
Subject(s)
Coronary Artery Disease/surgery , Mammary Arteries/transplantation , Aged , Coronary Artery Bypass/methods , Coronary Artery Bypass/mortality , Coronary Artery Disease/mortality , Exercise Tolerance/physiology , Female , Hospital Mortality , Humans , Male , Middle Aged , Postoperative Complications/mortality , Risk Factors , Survival Analysis , Treatment OutcomeABSTRACT
BACKGROUND: Conventional coronary angiography (CA) is still recommended before valvular surgery. Preliminary studies suggest that multislice spiral computed tomography coronary angiography (MSCT-CA) can be used to rule out coronary artery disease (CAD). AIM: To assess prospectively the safety of ruling out CAD before surgery solely on the basis of normal MSCT-CA in patients with severe aortic valve disease. METHODS: We included all consecutive patients scheduled for aortic valve surgery. We first estimated the calcium score (Agatston score equivalent [ASE]). Patients underwent injected MSCT if the ASE was<1000. CA was cancelled when MSCT-CA quality was sufficient and showed no significant CAD. Our primary endpoint was the occurrence of perioperative myocardial infarction in patients who underwent surgery with no prior CA. RESULTS: Between 1st July 2005 and 30th June 2008, we included 199 patients with severe aortic valve disease: 118 men (59%); mean age 69+/-12 years; 63 patients (32%) underwent CA directly because the ASE was > or =1000. Of 136 patients who underwent MSCT-CA, 106 (78%) had a normal MSCT-CA and underwent aortic valve surgery without prior CA; CA was performed in 30 patients because of abnormal (n=18) or bad quality (n=12) MSCT-CA. One patient of the 106 (0.94%, 95% confidence interval 0.17-5.15) had a perioperative myocardial infarction. CONCLUSIONS: When the ASE is <1000, MSCT is safe and may be recommended instead of CA as a first-line means of ruling out CAD in patients with severe aortic valve disease.
Subject(s)
Aortic Valve Insufficiency/epidemiology , Aortic Valve Stenosis/epidemiology , Coronary Angiography , Coronary Artery Disease/diagnosis , Coronary Artery Disease/epidemiology , Adolescent , Adult , Aged , Aortic Valve Insufficiency/surgery , Aortic Valve Stenosis/surgery , Child , Female , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Preoperative Care , Prospective Studies , Tomography, Spiral Computed , Young AdultABSTRACT
UNLABELLED: Macrophages play a key role in atherosclerotic plaque rupture. The iodine-based contrast agent N1177 accumulates in macrophages, allowing for their detection with CT. In this study, we tested whether the intensity of enhancement detected with CT in the aortic wall of rabbits injected with N1177 correlated with inflammatory activity evaluated with (18)F-FDG PET/CT and macrophage density on histology. METHODS: Atherosclerotic plaques were induced in the aorta of New Zealand White rabbits (n = 7) by a repeated balloon injury (4 wk apart) and 4 mo of hyperlipemic diet. Noninjured rabbits, fed a chow diet, were used as controls (n = 3). A CT scan of the aorta (n = 10) was acquired in each rabbit before, during, and at 2 h after intravenous injection of N1177 (250 mg of iodine/kg). One week later, the same rabbits underwent PET/CT 3 h after injection of (18)F-FDG (37 MBq/kg [1 mCi/kg]). CT enhancement was calculated as the difference in aortic wall densities between images obtained before and images obtained at 2 h after injection of N1177. Mean standardized uptake values were measured on PET axial slices of the aorta in regions of interest encompassing the vessel wall. Macrophage density was measured by immunohistology (anti-RAM-11 antibody) on corresponding aortic cross-sections. RESULTS: N1177-enhanced CT measured stronger enhancement in the aortic wall of atherosclerotic rabbits than in control rabbits (10.0 +/- 5.2 vs. 2.0 +/- 2.1 Hounsfield units, respectively; P < 0.05). After the injection of (18)F-FDG, PET detected higher standardized uptake values in the aortic wall of atherosclerotic rabbits than in control rabbits (0.61 +/- 0.12 vs. 0.21 +/- 0.02; P < 0.05). The intensity of enhancement in the aortic wall measured with CT after injection of N1177 correlated with (18)F-FDG uptake on PET/CT (r = 0.61, P < 0.001) and macrophage density on immunohistology (r = 0.63, P < 0.001). CONCLUSION: The intensity of enhancement detected with CT in the aortic wall of rabbits injected with N1177 correlates with intense uptake of (18)F-FDG measured with PET and with macrophage density on histology, suggesting a role for N1177 in noninvasive identification of high-risk atherosclerotic plaques with CT.
Subject(s)
Atherosclerosis/diagnostic imaging , Contrast Media , Inflammation/diagnostic imaging , Macrophages/diagnostic imaging , Positron-Emission Tomography/methods , Radiopharmaceuticals , Tomography, X-Ray Computed/methods , Animals , Atherosclerosis/pathology , Fluorodeoxyglucose F18 , Inflammation/pathology , Male , Rabbits , Radiographic Image EnhancementABSTRACT
PURPOSE: To test whether B-22956/1, a novel intravascular contrast agent with a high affinity to serum albumin (Bracco Imaging SpA.), allowed quantifying neovessel and macrophage density in atherosclerotic plaques of rabbits using MRI. MATERIALS AND METHODS: A T1-weighted MRI of the aorta was acquired in 10 rabbits (7 atherosclerotic and 3 control rabbits) before and up to 2 h after intravenous injection of 100 mumol/kg of Gd-DTPA or 75 mumol/kg of B-22956/1. Plaque enhancement was measured at different time points. Immunohistochemistry was performed using anti-CD 31 antibodies and anti-RAM 11 antibodies to correlate to neovessel and macrophage density, respectively. RESULTS: MRI showed a significant plaque enhancement 2 h after B-22956/1 versus Gd-DTPA in the atherosclerotic group (39.75% versus 9.5%; P < 0.0001. Early atherosclerotic plaques (n = 146) enhancement positively correlates with neovessel density on corresponding histological sections (r = 0.42; P < 0.01). Enhancement of atherosclerotic plaques 2 h after injection of B-22956/1 correlated with macrophage density (r = 0.71; P < 0.01). CONCLUSION: Enhancement of atherosclerotic plaques with MRI correlated with neovessel density at early time points after the injection of B-22956/1 and with macrophage density, at later time points. Hence, B-22956/1-enhanced MRI represents a promising imaging technique for the identification of "high-risk" plaques.
Subject(s)
Albumins/metabolism , Atherosclerosis/diagnosis , Contrast Media/administration & dosage , Magnetic Resonance Imaging/methods , Neovascularization, Pathologic/diagnosis , Organometallic Compounds , Animals , Aorta, Abdominal/pathology , Aorta, Abdominal/ultrastructure , Atherosclerosis/pathology , Disease Models, Animal , Gadolinium DTPA , Image Enhancement/methods , Image Processing, Computer-Assisted/methods , Male , Neovascularization, Pathologic/pathology , Rabbits , Time FactorsABSTRACT
OBJECTIVE: The association of inflammatory cells and neovessels in atherosclerosis is considered a histological hallmark of high-risk active lesions. Therefore, the development and validation of noninvasive imaging techniques that allow for the detection of inflammation and neoangiogenesis in atherosclerosis would be of major clinical interest. Our aim was to test 2 techniques, black blood dynamic contrast enhanced MRI (DCE-MRI) and 18-fluorine-fluorodeoxyglucose (18F-FDG) PET, to quantify inflammation expressed as plaque neovessels content in a rabbit model of atherosclerosis. METHODS AND RESULTS: Atherosclerotic plaques were induced in the aorta of 10 rabbits by a combination of 2 endothelial abrasions and 4 months hyperlipidemic diet. Six rabbits underwent MRI during the injection of Gd-DTPA, whereas 4 rabbits were imaged after injection of 18F-FDG with PET. We found a positive correlation between neovessels count in atherosclerotic plaques and (1) Gd-DTPA uptake parameters evaluated by DCE-MRI (r=0.89, P=0.016) and (2) 18F-FDG uptake evaluated by PET (r=0.5, P=0.103 after clustered robust, Huber-White, standard errors analysis). CONCLUSIONS: DCE-MRI and 18F-FDG PET may allow for the evaluation of inflammation in atherosclerotic plaques of rabbits. These noninvasive imaging modalities could be proposed as clinical tools in the evaluation of lesion prognosis and monitoring of anti-angiogenic therapies.
Subject(s)
Aortic Diseases , Atherosclerosis , Fluorodeoxyglucose F18 , Magnetic Resonance Angiography , Neovascularization, Pathologic , Positron-Emission Tomography , Radiopharmaceuticals , Animals , Aortic Diseases/diagnostic imaging , Aortic Diseases/etiology , Aortic Diseases/pathology , Area Under Curve , Atherosclerosis/diagnostic imaging , Atherosclerosis/etiology , Atherosclerosis/pathology , Catheterization/adverse effects , Cholesterol, Dietary/administration & dosage , Contrast Media , Disease Models, Animal , Gadolinium DTPA , Male , Neovascularization, Pathologic/diagnostic imaging , Neovascularization, Pathologic/etiology , Neovascularization, Pathologic/pathology , Predictive Value of Tests , Rabbits , Research DesignABSTRACT
OBJECTIVES: Cardiac tamponade represents a life-threatening condition that may complicate almost any cause of pericarditis. We conducted a 10-year prospective survey on patients with cardiac tamponade requiring an emergency drainage. METHODS: From 1996 to 2005, 114 consecutive patients were admitted to the University Hospital of Brest for medical cardiac tamponade. Data on medical history, and volume, characteristics and histology of the pericardial fluid as well as short- and long-term follow-up data were collected. RESULTS: Malignant disease was the primary cause of medical tamponade (74 patients; 65%), followed by viral history (11; 10%) and intra-pericardial bleeding due to anti-coagulation treatment (4; 3%). In 12 cases, aetiology remained unknown (10%). Pericardiocentesis was immediately performed in 80 cases and surgical pericardiotomy in 34. The mean volume drained was 593 +/- 313 ml. In-hospital mortality was 10% without any difference between malignant and non-malignant diseases (p = 0.8). One-year mortality was 76.5% in patients with malignant disease and 13.3% in those without malignant disease (p < 0.0001). Median survival in case of malignant disease was 150 days. CONCLUSION: Compared to previously published data, our survey shows a decrease in some historical causes of tamponade such as tuberculosis, myxoedema or uraemia. The leading cause is currently malignant disease, which carries a very poor prognosis.
Subject(s)
Cardiac Tamponade/epidemiology , Cardiac Tamponade/etiology , Pericardial Effusion/epidemiology , Pericardial Effusion/etiology , Aged , Cardiac Tamponade/surgery , Comorbidity , Female , Follow-Up Studies , France/epidemiology , Hospitals, University , Humans , Male , Middle Aged , Neoplasms/complications , Pericardial Effusion/surgery , Pericardiectomy , Pericardiocentesis , Prospective Studies , Survival Analysis , Treatment OutcomeABSTRACT
Macrophages have been identified as a critical factor in the pathogenesis of atherosclerosis. Ultrasmall iron oxide particles (USPIOs) have been used to passively target intraplaque macrophages. For dextran-based USPIOs, uptake into macrophages may be modulated by particle size. The aim of the current study was to test the efficacy of fractionated Feridex with respect to macrophage uptake in atherosclerotic rabbits. Fractionation of Feridex resulted in a 15-nm USPIO that exhibited a blood half-life of 15.9 h and liver retention of 6.4%. Blood clearance and liver retention of Feridex was 0.46 h and 60%, following administration of 4.8 mg Fe/kg Feridex. Atherosclerotic rabbits were administered 0.5 or 4.8 mg Fe/kg dosages of either fractionated Feridex or Feridex. MRI was performed at 1.5T over a 24-h time period postinjection. Perls and RAM-11 staining was performed to identify iron deposition. MRI showed a dose-dependent signal loss using conventional gradient echo (GRE) sequences following administration of fractionated Feridex. Even at low dose, significant signal loss was observed that correlated with histology. No signal attenuation or iron deposition was observed in the vessel wall of rabbits administered Feridex. Results of this study suggest that it may be possible to optimize USPIOs for intraplaque macrophage detection.
Subject(s)
Coronary Artery Disease/metabolism , Coronary Artery Disease/pathology , Image Enhancement/methods , Iron/pharmacokinetics , Magnetic Resonance Imaging/methods , Oxides/pharmacokinetics , Animals , Chemical Fractionation/methods , Contrast Media/pharmacokinetics , Dextrans , Ferrosoferric Oxide , Magnetite Nanoparticles , Metabolic Clearance Rate , Rabbits , Tissue DistributionABSTRACT
OBJECTIVES: This trial sought to assess the influence of omeprazole on clopidogrel efficacy. BACKGROUND: Clopidogrel has proved its benefit in the treatment of atherothrombotic diseases. In a previous observational study, we found clopidogrel activity on platelets, tested by vasodilator-stimulated phosphoprotein (VASP) phosphorylation, to be diminished in patients receiving proton pump inhibitor (PPI) treatment. METHODS: In this double-blind placebo-controlled trial, all consecutive patients undergoing coronary artery stent implantation received aspirin (75 mg/day) and clopidogrel (loading dose, followed by 75 mg/day) and were randomized to receive either associated omeprazole (20 mg/day) or placebo for 7 days. Clopidogrel effect was tested on days 1 and 7 in both groups by measuring platelet phosphorylated-VASP expressed as a platelet reactivity index (PRI). Our main end point compared PRI value at the 7-day treatment period in the 2 groups. RESULTS: Data for 124 patients were analyzed. On day 1, mean PRI was 83.2% (standard deviation [SD] 5.6) and 83.9% (SD 4.6), respectively, in the placebo and omeprazole groups (p = NS), and on day 7, 39.8% (SD 15.4) and 51.4% (SD 16.4), respectively (p < 0.0001). RESULTS: Omeprazole significantly decreased clopidogrel inhibitory effect on platelet P2Y12 as assessed by VASP phosphorylation test. Aspirin-clopidogrel antiplatelet dual therapy is widely prescribed worldwide, with PPIs frequently associated to prevent gastrointestinal bleeding. The clinical impact of these results remains uncertain but merits further investigation.
Subject(s)
Omeprazole/pharmacology , Platelet Aggregation Inhibitors/therapeutic use , Proton Pump Inhibitors/pharmacology , Ticlopidine/analogs & derivatives , Aged , Angioplasty, Balloon, Coronary , Cell Adhesion Molecules/metabolism , Clopidogrel , Double-Blind Method , Drug Antagonism , Drug Therapy, Combination , Female , Humans , Male , Microfilament Proteins/metabolism , Middle Aged , Myocardial Infarction/therapy , Omeprazole/therapeutic use , Phosphoproteins/metabolism , Phosphorylation , Platelet Aggregation/drug effects , Prospective Studies , Proton Pump Inhibitors/therapeutic use , Stents , Ticlopidine/antagonists & inhibitors , Ticlopidine/therapeutic useABSTRACT
Spondyloarthropathies are associated with a greater cardiovascular risk than expected based on the cardiac lesions known to occur in these diseases. The prevalence of several conventional risk factors is high in spondyloarthropathy patients, and chronic inflammation also contributes to premature plaque formation. In addition, susceptibility genes for spondyloarthropathies may be associated with an increased risk of cardiovascular disease. Finally, several drugs used to treat spondyloarthropathies may contribute to the occurrence of cardiovascular events. A careful evaluation of the cardiovascular risk profile is a key component of the management of patients with spondyloarthropathies.
Subject(s)
Cardiovascular Diseases/epidemiology , Spondylarthropathies/epidemiology , Antirheumatic Agents/pharmacology , Antirheumatic Agents/therapeutic use , Atherosclerosis/physiopathology , Atrioventricular Block/epidemiology , Atrioventricular Block/genetics , Comorbidity , Cyclooxygenase 2 Inhibitors/pharmacology , Cyclooxygenase 2 Inhibitors/therapeutic use , Genetic Predisposition to Disease , HLA-B27 Antigen/genetics , Heart Conduction System/physiopathology , Heart Valve Diseases/epidemiology , Humans , Lactones/pharmacology , Lactones/therapeutic use , Risk Factors , Smoking/epidemiology , Spondylarthropathies/drug therapy , Spondylarthropathies/genetics , Sulfones/pharmacology , Sulfones/therapeutic use , Tumor Necrosis Factor-alpha/antagonists & inhibitorsABSTRACT
BACKGROUND: The gold standard test for the diagnosis of coronary artery disease (CAD) is conventional coronary angiography (C-CAG). Lately, multislice computed tomographic coronary angiography (MSCT-CAG) demonstrated a high sensitivity and a negative predictive value for a CAD primary diagnosis when compared with C-CAG. The aim of our study is to prospectively assess the safety of ruling out CAD based solely on a normal MSCT-CAG result. METHODS: From June 15, 2004, to January 20, 2006, consecutive patients initially scheduled for C-CAG for a primary diagnosis of CAD underwent MSCT-CAG instead. Patients with a highly calcified coronary network or with an abnormal or a noninterpretable MSCT-CAG result underwent secondary C-CAG and were excluded from the study. We included patients whose diagnosis of CAD was ruled out by a normal MSCT-CAG result; in those patients, C-CAG was not performed. All patients underwent further follow-up with clinical end points (death, subsequent C-CAG, and myocardial infarction). RESULTS: In 141 patients, MSCT-CAG results were considered normal. During the follow-up period (mean, 14.7 months), those patients experienced 0% mortality, a 3.5% rate of subsequent C-CAG, and a 0.7% rate of myocardial infarction. The risks of subsequent death, new referral for C-CAG, or coronary events compare favorably with those following normal C-CAG, which were 0.4%, 4.3%, and 0.6%, respectively. CONCLUSIONS: Multislice computed tomographic CAG safely rules out CAD in patients with suspected disease and allows patients to be managed less invasively, by reducing the number in whom C-CAG has to be performed.
Subject(s)
Coronary Artery Disease/diagnostic imaging , Tomography, X-Ray Computed , Coronary Artery Disease/therapy , Female , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Reference Values , Time FactorsABSTRACT
Sudden fibrous cap disruption of 'high-risk' atherosclerotic plaques can trigger the formation of an occlusive thrombus in coronary arteries, causing acute coronary syndromes. High-risk atherosclerotic plaques are characterized by their specific cellular and biological content (in particular, a high density of macrophages), rather than by their impact on the vessel lumen. Early identification of high-risk plaques may be useful for preventing ischemic events. One major hurdle in detecting high-risk atherosclerotic plaques in coronary arteries is the lack of an imaging modality that allows for the identification of atherosclerotic plaque composition with high spatial and temporal resolutions. Here we show that macrophages in atherosclerotic plaques of rabbits can be detected with a clinical X-ray computed tomography (CT) scanner after the intravenous injection of a contrast agent formed of iodinated nanoparticles dispersed with surfactant. This contrast agent may become an important adjunct to the clinical evaluation of coronary arteries with CT.