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Biomedical subjects

S E Nissen

Publications and source records attributed to S E Nissen.

At least 19 recordsLinked to original sources
PubMed2003

[Imaging of coronary atherosclerotic plaque].

Selective coronary angiography allows the precise definition of highly stenotic coronary lesions and therefore remains the basis for catheter-based or surgical myocardial revascularization. However, the accumulation of atherosclerotic plaque in the coronary arterial wall begins much earlier than the development of luminal stenosis. In fact, most acute coronary syndromes are initiated by sudden disruption of atherosclerotic plaques that caused neither significant stenosis nor angina pectoris prior to the event. These early, but potentially vulnerable, lesions are therefore the topic of intensive research but their description with angiography alone is incomplete. Invasive, tomographic imaging modalities, in particular intravascular ultrasound, allow direct visualization of the atherosclerotic plaque and therefore supplement angiography. These techniques have advanced our understanding of coronary artery disease (CAD) progression and stability but are limited because of their invasive character. Current developments in particular of computed tomography already allow the non-invasive imaging of coronary arteries and may have an important role in the early identification of CAD and the prevention of its complications.

Coronary Angiography↗
PubMed2001

Coronary intravascular ultrasound: implications for understanding the development and potential regression of atherosclerosis.

The incremental value of intravascular ultrasound (IVUS), compared with angiographic analysis of coronary atherosclerosis, originates principally from 2 key features-its tomographic perspective and the ability to image coronary atheroma directly. Whereas angiography depicts the cross-sectional coronary anatomy as a planar silhouette of the lumen, ultrasound directly images the atheroma within the vessel wall, allowing measurement of atheroma size, distribution, and to some extent, composition. Although angiography remains the principal method to assess the extent of coronary atherosclerosis and to guide percutaneous coronary interventions, IVUS is rapidly altering conventional paradigms in the diagnosis and therapy of coronary artery disease. Thus, IVUS has become a vital adjunctive imaging modality for the aggressive coronary interventional cardiologist. As such, ultrasound has earned a role as a viable complementary technique relative to angiography, rather than an alternative to conventional angiographic methods. This article reviews the rationale, technical advantages and limitations, and interpretation of intravascular ultrasonography from the perspective of the general and invasive cardiologist. We emphasize the impact that IVUS studies have had on our understanding of the atherosclerotic coronary artery disease process, because these findings have important implications for all cardiologists. We then review several trials that are currently using intravascular ultrasonography for the study of coronary artery disease regression.

Coronary Artery Disease↗
PubMed2001

Effectiveness of statins in acute coronary syndromes.

Over the past several years, results of clinical trials of lipid lowering have increased our understanding of the pathophysiology of coronary atherosclerosis and ischemia. Evidence is accumulating that cholesterol lowering has potential anti-ischemic effects and may have immediate consequences that have a favorable impact on coronary events, possibly even acute coronary syndromes. Yet, less than one half of all patients hospitalized for acute coronary syndromes have their cardiovascular risks appropriately modified. The results of recent statin trials provide impetus for the implementation of aggressive risk-reduction strategies in patients with coronary atherosclerosis, including those with recent acute coronary syndromes. Prevention is now a viable therapeutic goal.

Acute Disease↗
PubMed2001

Lumen loss in transplant coronary artery disease is a biphasic process involving early intimal thickening and late constrictive remodeling: results from a 5-year serial intravascular ultrasound study.

BACKGROUND: Coronary artery disease is the major cause of late cardiac allograft failure. However, few data exist regarding the natural history of changes in intimal and external elastic membrane (EEM) areas after heart transplantation. METHODS AND RESULTS: In 38 transplant recipients, serial intravascular ultrasound examinations were performed 3.7+/-2.2 weeks after transplantation and annually thereafter for 5 years. In 59 coronary arteries, we compared 135 matched segments among serial studies. In each segment, intravascular ultrasound images were digitized at 1-mm intervals, and mean values of EEM and lumen and intimal areas were analyzed. In the first year after transplantation, the intimal area increased significantly from 1.8+/-1.6 to 3.0+/-2.1 mm(2) (P<0.001). Subsequently, the annual increase in intimal area decreased. EEM area did not change during the first year; however, between years 1 and 3, significant expansion of EEM area occurred (15.4+/-4.6 to 17.2+/-5.4 mm(2), P<0.001). Thereafter, EEM area decreased significantly from 17.2+/-5.4 mm(2) (year 3) to 15.1+/-4.9 mm(2) (year 5, P=0.01). Different mechanisms of lumen loss were observed during 2 phases after transplantation: early lumen loss primarily caused by intimal thickening and late lumen loss caused by EEM area constriction. CONCLUSIONS: This serial ultrasound study revealed that most of the intimal thickening occurred during the first year after heart transplantation. Changes in the EEM area showed a biphasic response, consisting of early expansion and late constriction. Thus, different mechanisms of lumen loss were observed during the early and late phases after transplantation.

Adult↗
PubMed2001

High prevalence of coronary atherosclerosis in asymptomatic teenagers and young adults: evidence from intravascular ultrasound.

BACKGROUND: Most of our knowledge about atherosclerosis at young ages is derived from necropsy studies, which have inherent limitations. Detailed, in vivo data on atherosclerosis in young individuals are limited. Intravascular ultrasonography provides a unique opportunity for in vivo characterization of early atherosclerosis in a clinically relevant context. METHODS AND RESULTS: Intravascular ultrasound was performed in 262 heart transplant recipients 30.9+/-13.2 days after transplantation to investigate coronary arteries in young asymptomatic subjects. The donor population consisted of 146 men and 116 women (mean age of 33.4+/-13.2 years). Extensive imaging of all possible (including distal) coronary segments was performed. Sites with the greatest and least intimal thickness in each CASS segment were measured in multiple coronary arteries. Sites with intimal thickness >/=0.5 mm were defined as atherosclerotic. A total of 2014 sites within 1477 segments in 574 coronary arteries (2.2 arteries per person) were analyzed. An atherosclerotic lesion was present in 136 patients, or 51.9%. The prevalence of atherosclerosis varied from 17% in individuals <20 years old to 85% in subjects >/=50 years old. In subjects with atherosclerosis, intimal thickness and area stenosis averaged 1.08+/-0.48 mm and 32.7+/-15.9%, respectively. For all age groups, the average intimal thickness was greater in men than women, although the prevalence of atherosclerosis was similar (52% in men and 51.7% in women). CONCLUSIONS: This study demonstrates that coronary atherosclerosis begins at a young age and that lesions are present in 1 of 6 teenagers. These findings suggest the need for intensive efforts at coronary disease prevention in young adults.

Adolescent↗
PubMed2001

Intravascular ultrasound: novel pathophysiological insights and current clinical applications.

Intravascular ultrasound (IVUS) is a valuable adjunct to angiography, providing new insights in the diagnosis of and therapy for coronary disease. Angiography depicts only a 2D silhouette of the lumen, whereas IVUS allows tomographic assessment of lumen area, plaque size, distribution, and composition. The safety of IVUS is well documented, and the assessment of luminal dimensions represents an important application of this modality. Comparative studies show the greatest disparities between angiography and ultrasound after mechanical interventions. In young subjects, normal intimal thickness is typically approximately 0.15 mm. With IVUS, lipid-laden lesions appear hypoechoic, fibromuscular lesions generate low-intensity echoes, and fibrous or calcified tissues are echogenic. Calcium obscures the underlying wall (acoustic shadowing). The extent and severity of disease by angiography and ultrasound are frequently discrepant. Arterial remodeling refers to changes in vascular dimensions during the development of atherosclerosis. At diseased sites, the external elastic membrane may actually shrink in size, contributing to luminal stenosis. The interpretation of IVUS relies on simple visual inspection of acoustic reflections to determine plaque composition. However, different tissue components may look quite similar, and artifacts may adversely affect ultrasound images. IVUS commonly detects occult disease in angiographically "normal" sites. In ambiguous lesions, ultrasound permits lesion quantification, particularly for left main coronary disease. IVUS has emerged as the optimal method for the detection of transplant vasculopathy. An important potential application of ultrasound is the identification of atheromas at risk of rupture. The mechanisms of action of interventional devices have been elucidated using IVUS, and ultrasound is used by some operators to select the most suitable interventional device. IVUS-derived residual plaque burden is the most useful predictor of clinical outcome. In restenosis after balloon angioplasty, negative remodeling is a major mechanism of late lumen loss. IVUS is not routinely used for stent optimization, and there is no consensus regarding optimal procedural end points. Ultrasound has proven useful in evaluating brachytherapy. New and emerging applications for IVUS are continuing to evolve, particularly in atherosclerosis regression-progression trials.

Blood Vessels↗
PubMed2001

Impact of lipid abnormalities in development and progression of transplant coronary disease: a serial intravascular ultrasound study.

OBJECTIVES: We sought to determine the role of conventional atherosclerosis risk factors in the development and progression of transplant coronary artery disease (CAD) using serial intravascular ultrasound imaging. BACKGROUND: Transplant artery disease is a combination of allograft vasculopathy and donor atherosclerosis. The clinical determinants for each of these disease processes are not well characterized. Intravascular ultrasound imaging is the most sensitive tool to serially study these processes. METHODS: Baseline intravascular ultrasound imaging was performed 0.9 +/- 0.5 months after transplantation to identify donor atherosclerosis. Follow-up imaging was performed at 1.0 +/- 0.07 year to evaluate progression of donor atherosclerosis and development of transplant vasculopathy. Conventional risk factors for CAD included recipient age, gender, smoking history, diabetes mellitus, hypertension and hypercholesterolemia. RESULTS: Donor-transmitted atherosclerosis was present in 36 patients (39%). At follow-up, progression of donor lesions was seen in 15 patients (42%) and 42 patients (45%) developed transplant vasculopathy, leaving 35 patients (38%) without any disease. There was no difference in any conventional risk factors in patients with and without allograft vasculopathy. However, the severity of allograft vasculopathy was associated with a larger increase in low density lipoprotein (LDL) cholesterol from baseline (p = 0.02). High one-year posttransplant serum triglyceride level and pretransplant body mass index were the only significant predictors (p = 0.03) for progression of donor atherosclerosis. CONCLUSIONS: Conventional atherosclerosis risk factors do not predict development of allograft vasculopathy, but greater change in serum LDL cholesterol level during the first year after transplant is associated with more severe vasculopathy. Therefore, maintenance of LDL cholesterol as close to pretransplant values as possible may help to limit the rate of progression of acquired allograft vasculopathy.

Cholesterol, LDL↗
PubMed2001

Arterial remodeling and coronary artery disease: the concept of "dilated" versus "obstructive" coronary atherosclerosis.

Traditionally, the development of coronary artery disease (CAD) was described as a gradual growth of plaques within the intima of the vessel. The outer boundaries of the intima, the media and the external elastic membrane (EEM), were thought to be fixed in size. In this model plaque growth would always lead to luminal narrowing and the number and severity of angiographic stenoses would reflect the extent of coronary disease. However, histologic studies demonstrated that certain plaques do not reduce luminal size, presumably because of expansion of the media and EEM during atheroma development. This phenomenon of "arterial remodeling" was confirmed in necropsy specimens of human coronary arteries. More recently, the development of contemporary imaging technology, particularly intravascular ultrasound, has allowed the study of arterial remodeling in vivo. These new imaging modalities have confirmed that plaque progression and regression are not closely related to luminal size. In this review, we will analyze the role of remodeling in the progression and regression of native CAD, as well as its impact on restenosis after coronary intervention.

Angioplasty, Balloon, Coronary↗
PubMed2001

Normal CK, elevated MB predicts complications in acute coronary syndromes.

The implications of an elevated Creatine kinase (CK)-MB isoenzyme (MB) in suspected acute coronary syndromes, with a normal total CK, is not well established. Despite many guidelines on managing patients with acute coronary ischemia, none indicates strategies for patients with elevated MB and with a normal CK. The outcome consequence of this result is not firmly established. Our objective was to prospectively evaluate outcomes in patients with suspected acute coronary syndromes, normal initial total CK, and increased MB. All Emergency Department patients with suspected acute coronary syndromes and creatinine < 2.0 mg/dL were eligible for study entry. Serial CK and MB fractions were measured on arrival in the Emergency Department, then 8 and 16 h postpresentation. A composite outcome of death, Q-wave myocardial infarction, or revascularization was defined at the index visit and 6 months later. Outcomes were determined by blinded record review and by telephone contact. In the 698 patients entered, the acute composite outcome rate was 25% (175) and 6.3% (44) at 6 months. Acute and 6 month adverse outcome rates were statistically the same for all patients with an elevated MB fraction, regardless of the total CK level. An elevated MB conferred a higher event rate than did a normal MB. We conclude that the adverse event rate for patients with suspected acute coronary syndromes and an elevated MB is the same whether or not the total CK is elevated. These patients should be considered as having had an acute coronary syndrome.

Angioplasty, Balloon, Coronary↗
PubMed2001

Cellular rejection and rate of progression of transplant vasculopathy: a 3-year serial intravascular ultrasound study.

Intravascular ultrasound (IVUS) is established as the optimal method for early detection of transplant vasculopathy. The association between cellular rejection and development of transplant vasculopathy remains controversial. This study attempts to determine the rate of progression of transplant vasculopathy lesions and its relationship with cellular rejection in a long-term (> 1 year) IVUS serial follow-up.A study cohort of 47 patients undergoing heart transplantation from 1993 to 1995 was evaluated. Intravascular ultrasound was performed at baseline (within 8 weeks) and annually for a period of 3 years to determine maximum intimal thickness and maximum plaque area in each coronary segment. Significant allograft vasculopathy was defined as a site with intimal thickness > 0.5 mm not present at baseline. Biopsy results were scored by assigning a numerical weight to each ISHLT grade during the first year. Donor lesions ranged from 0.86 to 1.1 mm, showing no evidence of progression at serial follow-up. De novo lesions were identified in 30 patients. These lesions appeared yearly but progressed slowly. The average biopsy score in the entire cohort was 1.1 +/- 0.8. Average biopsy score was > 1.0 in 35 patients with significant linear correlation between the rate of intimal progression and biopsy score (r = 0.42, p = 0.01). Multivariate analysis demonstrated that only the biopsy score correlated with the rate of progression. Lesions of donor atherosclerosis do not change significantly after transplantation. However, de novo lesions continue to develop every year. In patients with evidence of rejection, the rate of progression of transplant vasculopathy correlates with the severity of rejection.

Adult↗
PubMed2001

Prognostic value of absolute versus relative measures of the procedural result after successful coronary stenting: importance of vessel size in predicting long-term freedom from target vessel revascularization.

BACKGROUND: The procedural result is a major determinant of the incidence of 6-month target vessel revascularization (TVR) after successful coronary stenting. However, the prognostic implications of the different measures of the procedural result or procedural end points have not been directly compared. In this study, we sought to assess and compare the impact of achieving different procedural end points on the long-term (2-year) incidence of TVR. METHODS AND RESULTS: We studied 234 patients in whom 1 or 2 stents were successfully deployed and ultrasound imaging performed after angiographic optimization. End points included a visually estimated angiographic residual stenosis <10% and ultrasound stent-to-mean reference lumen area > or = 80%. After 2 years, TVR was required in 48 (20.5%) patients. Qualitative predictors of TVR were vein graft lesions, 3-vessel disease, and baseline TIMI flow grade < 3. Quantitatively, reference diameter by quantitative coronary angiography (QCA), final minimum lumen diameter (MLD) by QCA, and in-stent minimum lumen area (MLA) by ultrasound were predictive of TVR. Stent-to-reference ratios were not significantly predictive of TVR. By multivariable analysis, vein graft location and MLA by ultrasound were the only significant predictors of TVR (relative risk, 2.9 [1.5, 5.4] and 0.72 [0.6, 0.9], respectively). Receiver operator curves for MLD by QCA and MLA by ultrasound were similar in predicting TVR. Neither was significantly superior to reference vessel diameter. CONCLUSIONS: Commonly used angiographic and ultrasound stent-to-reference ratios do not predict the incidence of TVR. Absolute measures of the lumen size (MLA by ultrasound and MLD by QCA) were the most important quantitative predictors of TVR within 2 years. This emphasizes the role of the vessel size as the limiting factor in determining the long-term outcome of coronary stenting.

Blood Vessel Prosthesis Implantation↗
PubMed2000

Rationale for a postintervention continuum of care: insights from intravascular ultrasound.

In 1987, Glagov published a provocative hypothesis that the principal initial response to plaque accumulation was enlargement of the vessel as a whole (remodeling), which preserved luminal diameter until the lesion occupied a substantial proportion of the area within the elastic external membrane (EEM). This model has been confirmed and extended by intravascular ultrasound (IVUS) studies. Remodeling renders most atheromas invisible to angiography. In patients with single-vessel disease, the mean percent of EEM area occupied by atheroma at a segment with an angiographically normal appearance is 39%. IVUS studies further show that the disease progresses in a diffuse manner and that stenotic lesions represent only a small proportion of the total disease burden. We further know that disease can begin as early as the teenage years. Data suggest that up to 25% of individuals < 25 years old may be affected. Atherosclerotic lesions can be effectively targeted with lipid-lowering therapy. Preliminary data suggest that as plaques stabilize and become smaller, a reverse modeling occurs: the EEM area decreases but the lumen size remains unchanged. This may explain why significant reductions in cardiovascular events in clinical trials were accompanied by only modest angiographic evidence of regression. This hypothesis will be tested prospectively in the Reversal of Atherosclerosis with Lipitor (REVERSAL) study.

Coronary Angiography↗