Multidetector CT coronary angiography: where we are, and where we are going...
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Coronary Angiography↗
Biomedical subjects
Robert S Schwartz
Publications and source records attributed to Robert S Schwartz.
Patent foramen ovale: standards for a preclinical model of prevalence, structure, and histopathologic comparability to human hearts.
BACKGROUND: This study evaluated and standardized a Patent Foramen Ovale (PFO) preclinical model in gross anatomic and histopathologic features. METHODS: We examined 150 necropsy-derived domestic porcine hearts, age 4-6 months for PFO prevalence, appearance, and size. Histopathologic preparations were standardized and processed identically to 24 post-mortem human hearts aged 16-62 years. A measurement scheme was developed for PFO atrial openings, tunnel length, and histopathologic features to compare porcine and patient hearts. RESULTS: PFO was found in 32 of the 150 porcine hearts (prevalence 21.3%). Twenty-five porcine PFO underwent standard characterization by tunnel length, and right, and left atrial orifice diameters. Logarithmic regression analysis between porcine PFO tunnel length and left atrial orifice area demonstrated a significant positive relationship (P = 0.0162, R(2) = 0.227). The porcine PFO tunnel length was significantly longer than in humans (12.0 +/- 4.0 mm vs. 7.1 +/- 3.1 mm respectively, P < 0.0001). Histopathologic comparison was made using serial sections perpendicular to the atrial septum and the tunnel long axis. Human and porcine PFO lesions demonstrated strong similarities in tissue cells, connective tissue, and matrix composition. CONCLUSIONS: PFO assessment was standardized in both macroscopically and histopathologically, with quantitative and qualitative comparisons feasible using a porcine preclinical model. PFO prevalence in domestic swine is identical to humans, and microscopic structures very similar to humans. The domestic swine PFO model appears useful to evaluate new interventional closure technologies due to comparability in microscopic features. Tunnel length should be carefully evaluated due to differences across pigs and patients.
Adolescent↗
Clinical utility of coronary CT angiography: coronary stenosis detection and prognosis in ambulatory patients.
INTRODUCTION: Multislice CT coronary angiography (MSCTA) accurately detects stenosis in patients undergoing coronary arteriography, but its accuracy in clinical outpatients is less certain. This study retrospectively analyzed MSCTA performance in a large outpatient cohort and examined 6-month clinical follow-up in those without invasive CA. METHODS: Patients underwent MSCTA for clinical indications including symptoms or noninvasive results being either equivocal or suspected as incorrect by referring clinicians. Standard 16-slice CT scanner techniques were used, and results were analyzed on the basis of both patient and vessel. Patients were treated medically or sent to invasive angiography on the basis of MSCTA results and judgment of referring clinicians. All invasive angiograms were analyzed using quantitative coronary angiography. Six-month clinical follow-up was determined in patients without CA. RESULTS: One thousand fifty-three consecutive patients were referred for MSCTA, resulting in 994 interpretable scans. Mean age was 58+/-13 years, 55% were male, 50% had prior noninvasive testing, and 90% had symptoms. Invasive angiography was performed in 160 patients, with significant stenoses present in 69%. MSCTA demonstrated 87% and 89% accuracy by patient- and vessel-based analysis, respectively, and was most accurate in the left main and right coronary arteries. Only two patients not referred for angiography had significant stenosis in those undergoing 6-month follow-up. CONCLUSIONS: MSCTA accurately detects obstructive coronary stenosis in clinical patients with possible cardiac symptoms, and effectively triages them for invasive angiography. Negative results are highly accurate in ruling out obstructive disease. Six-month prognosis is excellent in patients without significant disease determined by MSCT.
Aged↗
The effects of granulocyte-colony stimulating factor in bare stent and sirolimus-eluting stent in pigs following myocardial infarction.
OBJECTIVES: The purpose of this study was to compare the effects of granulocyte-colony stimulating factor (G-CSF) on in-stent restenosis (ISR) in bare and sirolimus-eluting stents (SES) in a porcine myocardial infarction model. BACKGROUND: Using G-CSF to mobilize stem cells has shown promise in infarcted heart. However, G-CSF may aggravate ISR and an aggressive strategy to prevent ISR is needed. METHODS: Bare stents and SES were implanted in coronary arteries (Group I, bare stents; Group II, bare stents with G-CSF; Group III, SES; Group IV, SES with G-CSF, n=10 in each group) 72 h after experimental myocardial infarction (MI). G-CSF (10 microg/kg/day) was injected for 7 days from 24 h after stent implantation. RESULTS: In coronary angiographic and histomorphometric analysis, percent area stenosis was significantly increased in Group II compared with that in Group I at 28 days (P<0.05). The ratio of inflammatory cells in the neointima was higher in Group II (P<0.05). No significant differences were observed between Group III and IV. In Group II, phosphorylated signal transducers and activators of transcription (STAT)-3, STAT-3, and vascular endothelial growth factor (VEGF) showed increased neointimal expression. In porcine aortic smooth muscle cells (PASMC), G-CSF increased the growth rate, migration, STAT-3 phosphorylation, and VEGF, which were suppressed by rapamycin and AG490, a STAT-3 inhibitor. CONCLUSIONS: STAT-3 and VEGF are important in the development of enhanced ISR by G-CSF in bare stents. SES could be a good strategy to prevent the G-CSF-stimulated proliferation and migration of smooth muscle cells, which could be responsible for neointimal hyperplasia.
Analysis of Variance↗
The politics and promise of stem-cell research.
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Adult↗
Pregnancy associated plasma protein-A and risk stratification of patients presenting with chest pain in the emergency department.
BACKGROUND: The aim of this study was to evaluate the clinical utility of serum pregnancy associated plasma protein-A (PAPP-A) levels in assisting triage of an intermediate to high-risk patient presenting with chest pain in the Emergency Department and no definite evidence of an acute coronary syndrome. METHODS: Serum levels of PAPP-A were measured in 59 patients presenting with chest pain to the Emergency Department. The patients were independently grouped according to the presence of acute coronary syndromes or the absence thereof. RESULTS: In a multivariate model that corrected for age, sex, type of chest pain, number of risk factors, history of coronary artery disease, troponin levels, and non-specific ECG changes, PAPP-A levels were still predictive of a final diagnosis of acute coronary syndrome in patients presenting with chest pain to the Emergency Department (Odds Ratio, 2.093; 95th confidence intervals, 1.037-4.224; p=0.039). CONCLUSIONS: Elevated serum PAPP-A levels were predictive of a diagnosis of acute coronary syndrome in intermediate- to high-risk patients presenting to the Emergency Department with chest pain and no definite evidence of an acute coronary syndrome. Thus, serum PAPP-A may be valuable as an adjunct, minimally invasive marker to improve risk stratification in chest pain patients.
Acute Disease↗
From vulnerable plaque to vulnerable patient--Part III: Executive summary of the Screening for Heart Attack Prevention and Education (SHAPE) Task Force report.
Screening for early-stage asymptomatic cancers (eg, cancers of breast and colon) to prevent late-stage malignancies has been widely accepted. However, although atherosclerotic cardiovascular disease (eg, heart attack and stroke) accounts for more death and disability than all cancers combined, there are no national screening guidelines for asymptomatic (subclinical) atherosclerosis, and there is no government- or healthcare-sponsored reimbursement for atherosclerosis screening. Part I and Part II of this consensus statement elaborated on new discoveries in the field of atherosclerosis that led to the concept of the "vulnerable patient." These landmark discoveries, along with new diagnostic and therapeutic options, have set the stage for the next step: translation of this knowledge into a new practice of preventive cardiology. The identification and treatment of the vulnerable patient are the focuses of this consensus statement. In this report, the Screening for Heart Attack Prevention and Education (SHAPE) Task Force presents a new practice guideline for cardiovascular screening in the asymptomatic at-risk population. In summary, the SHAPE Guideline calls for noninvasive screening of all asymptomatic men 45-75 years of age and asymptomatic women 55-75 years of age (except those defined as very low risk) to detect and treat those with subclinical atherosclerosis. A variety of screening tests are available, and the cost-effectiveness of their use in a comprehensive strategy must be validated. Some of these screening tests, such as measurement of coronary artery calcification by computed tomography scanning and carotid artery intima-media thickness and plaque by ultrasonography, have been available longer than others and are capable of providing direct evidence for the presence and extent of atherosclerosis. Both of these imaging methods provide prognostic information of proven value regarding the future risk of heart attack and stroke. Careful and responsible implementation of these tests as part of a comprehensive risk assessment and reduction approach is warranted and outlined by this report. Other tests for the detection of atherosclerosis and abnormal arterial structure and function, such as magnetic resonance imaging of the great arteries, studies of small and large artery stiffness, and assessment of systemic endothelial dysfunction, are emerging and must be further validated. The screening results (severity of subclinical arterial disease) combined with risk factor assessment are used for risk stratification to identify the vulnerable patient and initiate appropriate therapy. The higher the risk, the more vulnerable an individual is to a near-term adverse event. Because <10% of the population who test positive for atherosclerosis will experience a near-term event, additional risk stratification based on reliable markers of disease activity is needed and is expected to further focus the search for the vulnerable patient in the future. All individuals with asymptomatic atherosclerosis should be counseled and treated to prevent progression to overt clinical disease. The aggressiveness of the treatment should be proportional to the level of risk. Individuals with no evidence of subclinical disease may be reassured of the low risk of a future near-term event, yet encouraged to adhere to a healthy lifestyle and maintain appropriate risk factor levels. Early heart attack care education is urged for all individuals with a positive test for atherosclerosis. The SHAPE Task Force reinforces existing guidelines for the screening and treatment of risk factors in younger populations. Cardiovascular healthcare professionals and policymakers are urged to adopt the SHAPE proposal and its attendant cost-effectiveness as a new strategy to contain the epidemic of atherosclerotic cardiovascular disease and the rising cost of therapies associated with this epidemic.
Coronary Artery Disease↗
Effects of dehydroepiandrosterone replacement therapy on bone mineral density in older adults: a randomized, controlled trial.
CONTEXT: Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) decrease with aging and are important androgen and estrogen precursors in older adults. Declines in DHEAS with aging may contribute to physiological changes that are sex hormone dependent. OBJECTIVE: The aim was to determine whether DHEA replacement increases bone mineral density (BMD) and fat-free mass. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blinded, controlled trial was conducted at an academic research institution. Participants were 70 women and 70 men, aged 60-88 yr, with low serum DHEAS levels. INTERVENTION: The intervention was oral DHEA 50 mg/d or placebo for 12 months. MEASUREMENTS: BMD, fat mass, and fat-free mass were measured before and after intervention. RESULTS: Intent-to-treat analyses revealed trends for DHEA to increase BMD more than placebo at the total hip (1.0%, P = 0.05), trochanter (1.2%, P = 0.06), and shaft (1.2%, P = 0.05). In women only, DHEA increased lumbar spine BMD (2.2%, P = 0.04; sex-by-treatment interaction, P = 0.05). In secondary compliance analyses, BMD increases in hip regions were significant (1.2-1.6%; all P < 0.02) in the DHEA group. There were no significant effects of DHEA on fat or fat-free mass in intent-to-treat or compliance analyses. CONCLUSIONS: DHEA replacement therapy for 1 yr improved hip BMD in older adults and spine BMD in older women. Because there have been few randomized, controlled trials of the effects of DHEA therapy, these findings support the need for further investigations of the benefits and risks of DHEA replacement and the mechanisms for its actions.
Aged↗
Pregnancy-associated plasma protein-a is markedly expressed by monocyte-macrophage cells in vulnerable and ruptured carotid atherosclerotic plaques: a link between inflammation and cerebrovascular events.
OBJECTIVES: The study aim was to evaluate serologic expression of pregnancy-associated protein-A (PAPP-A) in patients affected by cerebrovascular accidents and to correlate it with histopathologic carotid plaque complexity. BACKGROUND: Little is known about PAPP-A expression in carotid atherosclerotic disease and whether this protein represents a marker of plaque vulnerability also in carotid district. METHODS: Seventy-two carotid plaques from patients submitted to surgical endarterectomy (19 who suffered a major stroke, 24 transient ischemic attack, and 29 asymptomatic) were evaluated. Serologic PAPP-A levels were determined by enzyme-linked immunoadsorbent assay. Plaques were divided in three groups based on histology: 1) stable (n = 38); 2) vulnerable (n = 13); 3) ruptured with thrombus (n = 14). Immunohistochemical staining for PAPP-A, smooth muscle cells, macrophages, and T-lymphocytes was performed in all cases. Real-time polymerase chain reaction assessed local PAPP-A production, and double immunofluorescence confocal microscopy (ICM) characterized cell type expressing PAPP-A. RESULTS: Pregnancy-associated protein-A (serologic values were 4.02 +/- 0.18 mIU/l in Group 1, 7.43 +/- 0.97 mIU/l in Group 2, and 6.97 +/- 0.75 mIU/l in Group 3 [1 vs. 3, p = 0.01; 1 vs. 2, p = 0.004; 2 vs. 3, p = 0.71, respectively]). Pregnancy-associated protein-A (expression showed a mean score value of 0.62 +/- 0.06 for stable plaques, 2.54 +/- 0.14 for vulnerable plaques, and 2.71 +/- 0.12 for ruptured plaques [1 vs. 2, p = 0.001; 1 vs. 3, p = 0.001; 2 vs. 3, p = 0.37, respectively]). Real-time polymerase chain reaction demonstrated local messenger ribonucleic acid PAPP-A production, and double ICM confirmed monocyte/macrophage expression of PAPP-A in Groups 2 and 3 but not Group 1. CONCLUSIONS: This study suggests that PAPP-A is a marker of carotid plaque destabilization and rupture. Further studies are necessary to determine if PAPP-A can represents a new target for stratifying the risk of cerebrovascular events.
Aged↗
Role of stent design and coatings on restenosis and thrombosis.
More than 15 years have passed since stent technology was introduced by Sigwart et al. [U. Sigwart, J. Puel, V. Mirkovitch, F. Joffe, et al. Intravascular stents to prevent occlusion and restenosis after transluminal angioplasty. N. Engl. J. Med. 316 (1987) 701-706.] among interventional cardiologists. Recently drug eluting stents have assumed dominance in the interventional world as positive trial results revealed their efficacy for preventing restenosis. Stent design, delivery-vehicle materials, and drug properties affect the function of these stents. Stainless steel stents with tubular and multicellular design have proven superior to coil or hybrid stent models. This chapter describes stents which have subtle influences of modular design, metal coverage, strut thickness, strut shape, surface smoothness, and coating materials like an alloy composition.
Biomedical Engineering↗
Zotarolimus-eluting stents reduce experimental coronary artery neointimal hyperplasia after 4 weeks.
AIMS: The addition of drug elution to coronary stents plays an integral role in coronary restenosis prevention. The present study was undertaken to determine the mechanism of action and the in vitro and in vivo efficacy of zotarolimus, a new chemical entity designed specifically for elution from phosphorylcholine (PC)-coated stents, for the reduction of neointimal hyperplasia in porcine coronary arteries. METHODS AND RESULTS: In vitro studies of Zotarolimus bound to FKBP-12 potently inhibited smooth muscle cells (SMCs) and endothelial cell (EC) proliferation. Twenty PC-only and 20 stents eluting zotarolimus 10 microg/mm were implanted in the coronary arteries of 20 domestic juvenile swine. After 28 days, zotarolimus stents exhibited less area stenosis (22.4+/-8.6 vs. 35.7+/-13%, P = 0.01), less neointimal area (1.69+/-0.55 vs. 2.78+/-1.07 mm(2), P = 0.01), less neointimal thickness (0.25+/-0.07 vs. 0.38+/-0.13 mm, P = 0.01), and greater lumen area (6.07+/-1.39 vs. 5.02+/-1.3 mm2, P = 0.01). All arteries in both the polymer-only and polymer/drug stent showed near-complete healing and minimal toxicity. Zotarolimus did not affect the extrastent segments nor alter the overall artery size (external elastic lamina cross-sectional area 9.18+/-1.19 vs. 9.06+/-1.28 mm2, P = 0.7). CONCLUSION: Zotarolimus binds to FKBP-12 and in vitro inhibits SMC and EC proliferation. Zotarolimus applied to PC-coated stents reduces neointima in the swine coronary model after 28 days. These results suggest potentially promising human clinical application for coronary stenting with this polymer/drug combination.
Animals↗
Radiation following percutaneous balloon aortic valvuloplasty to prevent restenosis (RADAR pilot trial).
OBJECTIVES: We wished to determine the feasibility and early safety of external beam radiation therapy (EBRT) used following balloon aortic valvuloplasty (BAV) to prevent restenosis. BACKGROUND: BAV for calcific aortic stenosis (AS) has been largely abandoned because of high restenosis rates, i.e., > 80% at 1 year. Radiation therapy is useful in preventing restenosis following vascular interventions and treating other benign noncardiovascular disorders. METHODS: We conducted a 20-patient, pilot study evaluating EBRT to prevent restenosis following BAV in elderly patients with calcific AS. Total doses ranging from 12-18 Gy were delivered in fractions over a 3-5 day post-op period to the aortic valve. Echocardiography was performed pre and 2 days post-op, 1, 6, and 12 months following BAV. RESULTS: One-year follow-up is completed (age 89 +/- 4). There were no complications related to EBRT. Eight patients died prior to 1 year; 5 of 10 (50%) in the low-dose (12 Gy) group and 3 of 10 (30%) in the high-dose (15-18 Gy) group. None of these 8 patients had restenosis, i.e., > 50% loss of the initial AVA gain, and only three deaths were cardiac in origin. One patient underwent aortic valve replacement and none repeated BAV. By 1 year, 3 of the initial 10 (30%) in the low-dose group and 1 of 9 (11%) in the high-dose group demonstrated restenosis (21% overall). CONCLUSIONS: EBRT following BAV in elderly patients with AS is feasible, free of early complications, and holds promise in reducing the 1 year restenosis rate in a dose-dependent fashion.
Aged, 80 and over↗
Acute modulation of adipose tissue lipolysis by intravenous estrogens.
OBJECTIVE: The aim of this study was to determine whether intravenous (IV) conjugated estrogens (EST) acutely enhance the suppression of whole-body or regional subcutaneous adipose tissue (SAT) lipolysis by insulin in postmenopausal women. RESEARCH METHODS AND PROCEDURES: We assessed whole-body lipolysis by [(2)H(5)]glycerol rate of appearance (Glyc(RA)) and abdominal and femoral SAT lipolysis (interstitial glycerol; Glyc(IS)) by subcutaneous microdialysis. Postmenopausal women (n = 12) were studied on two occasions, with IV EST or saline control (CON), under basal conditions and during a 3-stage (4, 8, and 40 mU/m(2)/min) hyperinsulinemic, euglycemic clamp. Ethanol outflow/inflow ratio and recovery of [(13)C]glycerol during microdialysis were used to assess blood flow changes and interstitial glycerol concentrations, respectively. RESULTS: Compared with CON, EST did not affect systemic basal or insulin-mediated suppression of lipolysis (Glyc(RA)) or SAT nutritive blood flow. Basal Glyc(IS) in SAT was reduced on the EST day. However, insulin-mediated suppression of lipolysis in SAT was not significantly influenced by EST. DISCUSSION: These findings suggest that estrogens acutely reduce basal lipolysis in SAT through an unknown mechanism but do not alter whole-body or SAT suppression of lipolysis by insulin.
Body Composition↗
Preclinical restenosis models: challenges and successes.
Coronary artery disease remains a major problem for Western societies. The advent of percutaneous interventions, including stents has brought clinical care to a new level of efficacy, yet problems remain. Restenosis following stenting in human coronary arteries appears at last to be yielding to therapeutic strategies, especially drug eluting stents. Because therapeutic percutaneous coronary intervention is widely dominated by the intracoronary stent, restenosis therapies must include the stented coronary artery. Animal models and in particular the porcine coronary model seem to represent the human coronary artery reaction to stenting. It mimics several clinical conditions including thrombosis and neointimal formation. A key question in the era of intravascular technologies is how well this and other models can predict clinical events. This paper discusses the models and their application.
Animals↗
Percutaneous recanalization of chronically occluded coronary arteries: a consensus document: part II.
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Angioplasty, Balloon, Coronary↗
Percutaneous recanalization of chronically occluded coronary arteries: a consensus document: part I.
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Animals↗
Faith healers and physicians--teaching pseudoscience by mandate.
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Biological Evolution↗
Patent foramen ovale: current pathology, pathophysiology, and clinical status.
Patent foramen ovale (PFO) is experiencing increased clinical interest as a congenital cardiac lesion persisting into adulthood. It is implicated in several serious clinical syndromes, including stroke, myocardial infarction, and systemic embolism. The PFO is now amenable to percutaneous interventional therapies, and multiple novel technologies are either available or under development for lesion closure. The PFO should be better understood to take advantage of emerging percutaneous treatment options. This paper reviews PFO anatomy, pathology, pathophysiology, and clinical impact and discusses current therapeutic options.
Heart Septal Defects, Atrial↗