Coronary Artery Remodeling Research Articles

Relationship Between Coronary Artery Remodeling and Plaque Composition in Culprit Lesions An Intravascular Ultrasound Radiofrequency Analysis

The relationship between coronary artery remodeling and culprit plaque composition in vivo has not been fully evaluated by spectral analysis of intravascular ultrasound (IVUS) radiofrequency (RF) data. IVUS RF analyses were performed for 56 consecutive de novo culprit lesions of 52 patients undergoing percutaneous coronary intervention. Remodeling of culprit lesions was determined using the remodeling index (RI), calculated as the external elastic membrane area of the minimum lumen area (MLA) site divided by that of the proximal reference site. Positive remodeling was defined as RI >1.05, intermediate remodeling as 0.95< or = RI < or =1.05 and negative remodeling as RI <0.95. Among the 56 lesions, positive remodeling was detected in 24, intermediate remodeling in 16, and negative remodeling in 16. At MLA sites, positive remodeling lesions had a larger percentage of the fibrofatty component than negative remodeling lesions (22.5+/-10.3% vs 10.4+/-6.6%, p=0.0001), whereas the latter contained a larger percentage of the dense calcium component than the former (2.8+/-2.9% vs 8.4+/-7.0%, p=0.016). Culprit plaques with positive remodeling have a large lipid burden, whereas those with negative remodeling contain a large amount of calcium.

Increased Oxidative Stress Modulates Coronary Artery Remodeling and Passive Stiffness in db/db Diabetic Mice

Alterations in coronary artery (CA) structure regulate arterial stiffness and may lead to decreased cardiac perfusion and coronary flow reserve. Although oxidative stress affects coronary pathology, its contribution to vascular remodeling in diabetes is undefined. This study established a link between oxidative stress and CA remodeling and stiffness. Coronary arteries (<100 μ) from heterozygous (Db/db) and diabetic (db/db) mice at ages 8–16 wks were isolated and mounted on a pressure myograph for measurement of structural and passive mechanical properties. Mean arterial pressure (MAP) was monitored by telemetry. DHE staining was used as a marker for oxidative stress. NAD(P)H oxidase subunits and MnSOD expression was assessed by real time RT-PCR and immunohistochemistry. No changes in MAP between groups were observed. Increased DHE staining was observed in 12 wk db/db mice vs. Db/db and was associated with increased mRNA expression and staining for the NAD(P)H oxidase Nox1 and gp91phox subunits and decreased MnSOD. Significant inward remodeling was not detected until 16 wks in the db/db vs. Db/db, defined by decreased lumen:media ratio (29±6 vs. 12±2%) and compliance and increased remodeling index (46±5%) and passive stiffness. In vivo treatment with TEMPOL (10 mM in the drinking water from 8–16 wks) reduced DHE staining and attenuated inward remodeling of db/db CA. These data suggest that increased oxidative stress is critical for altered structural and functional remodeling of CA in Type 2 diabetes. Supported by HL56046 and P20RR18766.

Calcium mediates collagen production in coronary artery adventitial fibroblasts stimulated by testosterone

Extracellular matrix (ECM) remodeling occurs as a compensatory response in hypertension and can result in increased fibrosis. Sex hormones affect vascular ECM in opposite ways: testosterone (T) increases collagen and estrogen (E) decreases it. The aim was to study the effect of T and E on collagen production in coronary adventitial fibroblasts and to determine if calcium modulated the hormone effect. Adventitial fibroblasts were cultured from the left anterior descending coronary artery (LAD) from adult male spontaneously hypertensive rats. Treatment included 24h exposure to 10−7 M T or E alone or combined with BAPTA/AM, a calcium chelator. Collagen type I was measured by ELISA. Comparison of control and T treat groups demonstrated a T effect; control cells produced 1.163 ±0.103 μg and treated cells produced 1.746±0.238 μg after T treatment (50% rise, p<0.05). However, with calcium chelated, T only increased collagen 5%. Estrogen had no significant effect on collagen production with only a 2% (1.188±0.036 μg) difference over control. Collagen in the E + BAPTA/AM group was equal to control. In conclusion, T influences the deposition of collagen in LAD fibroblasts and E does not; the T effect on collagen is calcium mediated where calcium may be part of a signaling pathway or acting as a modulator on key molecules in the pathway; and adventitial fibroblasts play a major role in the ECM remodeling of coronary arteries.

Characteristics of Transplant Coronary Artery Disease after Heart Transplantation in Koreans: A Serial Intravascular UltraSound Analysis

Background and Objectives:Coronary artery disease (CAD) in a transplanted heart has been a major cause of morbidity and mortality for the transplantation patients who survive more than 1 year. The incidence and characteristic pattern of coronary artery disease after heart transplantation in Koreans are not known. The aim of this study is to determine the incidence and characteristics of significant CAD and the coronary arterial remodeling pattern after heart transplantation by using intravascular ultrasound (IVUS). Subjects and Methods:We evaluated a total of 101 consecutive patients who had been examined via serial (over one year interval) IVUS and coronary angiogram. The patients were divided into two groups according to the period of the serial IVUS follow-up. The post-transplant early period (EP) group (n=58) was defined when IVUS was performed within the first month and at one year after heart transplantation, and the post-transplant late period (LP) group (n=43) was defined when IVUS was performed after one year and subsequently over another one year interval. Results:The CADfree survival rates, as assessed by coronary angiogram, were 99% at 5 years, 89% at 7 years and 71% at 9 years. In the EP group, 17 patients (29%) had donor lesions and 8 patients (14%) had de novo lesions. For the donor lesions, the diffuse and concentric lesions were 12%, respectively, and the remodeling index was 2.3±6.5, which represents a positive remodeling pattern. For the de novo lesion, the diffuse lesions were 25%, the concentric lesions were 13% and the remodeling index was -2.5±4.9, which represent a negative remodeling pattern. Conclusions: The incidence of significant CAD with diffuse and concentric lesions after heart transplantation was low in Koreans. The coronary arterial remodeling pattern was negative in the early period, and then it became positive during the late period. (Korean Circulation J 2007;37:9-15)

Human Coronary Artery Remodeling, Beginning and End of the Atherosclerotic Process

Background, Aims of the StudyThe objective of the study was to relate the progress of coronary artery remodeling to the earliest stages of the atherosclerotic process. For this purpose, a mathematical model for description of dimensional change of the coronary artery wall and its constituent components was developed and applied.Materials and MethodsThe study used coronary artery samples randomly taken from each of 83 consecutive, unselected postmortems. All samples were routinely fixed and processed to paraffin for the preparation of right-angled, 5-micron sections, routinely stained and mounted for subsequent analysis. Computer assisted image analysis, using 32 systematic random, radial sampling lines, was used for interactive measurements of distance from centre of lumen to points defining intima, media and adventitia thickness along the radial intercept, which were subsequently tabled for analysis of variance, calculations of (group –vessel) means, and related to stage of pathology.ResultsPre-atherosclerotic changes, before any localised changes in especially intima dimensions, are found, consisting of a process of gradual vascular widening, associated with temporally at least partly dissociated increases in width, which as a fraction of total vessel radius show a phased process. In these, the intima first increases, subsequently remains stable, and finally reduces in width proportionally to the increasing diameter. The media shows a similar initial increase, on average stabilising in the third phase after reaching a plateau value in the second. The adventitia, already increasing in phase 1, continues to increase in phase 2, accelerating in phase 3. The complex process, as found, occurs systematically in all vessels, is distributed circumferentially, and precedes the development of localised lesions of the intima.ConclusionsThe findings suggest the existence of a diffuse complex of changes, consisting of a gradual vascular widening followed by narrowing, with associated mural changes reflecting the atherosclerotic process.

Pravastatin Enhances Beneficial Effects of Olmesartan on Vascular Injury of Salt-Sensitive Hypertensive Rats, via Pleiotropic Effects

This work was undertaken to investigate comparative effect of AT1 receptor blocker (ARB), 3-hydroxy-3-methylglutaryl (HMG) coenzymeA (CoA) reductase inhibitor (statin), and their combination on vascular injury of salt-sensitive hypertension. Salt-loaded Dahl salt-sensitive hypertensive rats (DS rats) were treated with (1) vehicle, (2) hydralazine (5 mg/kg/d), (3) olmesartan (0.5 mg/kg/d), (4) pravastatin (100 mg/kg/d), and (5) combined olmesartan and pravastatin for 4 weeks. Olmesartan or pravastatin significantly and comparably improved vascular endothelium-dependent relaxation to acetylcholine, coronary arterial remodeling, and eNOS activity of DS rats. Olmesartan prevented vascular eNOS dimer disruption or the downregulation of dihydrofolate reductase (DHFR) more than pravastatin, whereas Akt phosphorylation was enhanced by pravastatin but not olmesartan, indicating differential pleiotropic effects between olmesartan and pravastatin. Add-on pravastatin significantly enhanced the improvement of vascular endothelial dysfunction and remodeling by olmesartan in DS rats. Moreover, pravastatin enhanced the increase in eNOS activity by olmesartan, being associated with additive effects of pravastatin on phosphorylation of Akt and eNOS. Olmesartan and pravastatin exerted beneficial vascular effects in salt-sensitive hypertension, via differential pleiotropic effects. Pravastatin enhanced vascular protective effects of olmesartan. Thus, the combination of ARB with statin may be the potential therapeutic strategy for vascular diseases of salt-sensitive hypertension.

A Possible Anti-Inflammatory Role of Angiotensin II Type 2 Receptor in Immune-Mediated Glomerulonephritis during Type 1 Receptor Blockade

We previously reported that angiotensin II type 1 receptor (AT1R) blockade attenuates renal inflammation/fibrogenesis in immune-mediated glomerulonephritis via angiotensin II type 2 receptor (AT2R). In the present study, further in vivo experiments revealed that AT2R was expressed in tubular epithelial cells of nephritic kidneys in mice, and feedback activation of the renin-angiotensin system during AT1R blockade significantly reduced p-ERK, but not intranuclear nuclear factor-kappaB, levels via AT2R. This led to reduction in mRNA levels of the proinflammatory mediator monocyte chemoattractant protein-1 and overall interstitial inflammation and subsequent fibrogenesis. Specific blockade of ERK expression in tubular epithelium by anti-sense oligodeoxynucleotides also attenuated interstitial inflammation, mimicking the anti-inflammatory action of AT2R in nephritic kidneys. Alternatively, we succeeded in confirming such an AT(2)R function by demonstrating that AT1R blockade did not confer renoprotection in nephritic, AT2R gene-deficient mice. Additional in vitro experiments revealed that AT2R activation did not affect nuclear factor-kappaB activation by tumor necrosis factor-alpha in cultured tubular epithelial cells, although it inhibited ERK phosphorylation, which reduced monocyte chemoattractant protein-1 mRNA levels. These results suggest that feedback activation of AT2Rs in tubular epithelium of nephritic kidneys plays an important role in attenuating interstitial inflammation.

Effect of Simvastatin on Coronary Lesion Site Remodeling: A Serial Intravascular Ultrasound Study

Background: Direct evidence of coronary artery remodeling can be derived only from serial changes in the external elastic membrane (EEM) and plaque area. The aim of the study was to assess the effect of simvastatin on coronary remodeling in serial intravascular ultrasound (IVUS) studies. Methods: In 39 male patients ECG-triggered transducer pullback IVUS was performed at baseline, after 3 months on a lipid-lowering diet (control period), and after another 12 months of simvastatin 40 mg/day. The lesion site was the image slice with maximum plaque burden at 3 months. Results: Absolute changes in the EEM area correlated significantly with changes in plaque area during the control period [B = 0.966, r = 0.792 (95% CI 0.71–1.22); p < 0.001] and during simvastatin treatment [B = 0.945, r = 0.822 (95% CI 0.73–1.16); p < 0.001], but there was no significant difference in the slope (ΔEEM/Δplaque) between the two time intervals. After 12 months of simvastatin, there was a significant reduction in the lesion EEM area of 4.6% (p = 0.006) and in the lesion plaque area of 5.9% (p < 0.001), but there was no change in reference measurements. As a result, the remodeling index was reduced by simvastatin from 1.01 ± 0.12 to 0.95 ± 0.09 (p < 0.001). Conclusion: Simvastatin decreases the remodeling index by reducing lesion, but not reference plaque and EEM area. However, simvastatin does not affect direct evidence of remodeling (ΔEEM/Δplaque) obtained using serial IVUS studies.

Cardiac S100A1 Protein Levels Determine Contractile Performance and Propensity Toward Heart Failure After Myocardial Infarction

Diminished cardiac S100A1 protein levels are characteristic of ischemic and dilated human cardiomyopathy. Because S100A1 has recently been identified as a Ca2+-dependent inotropic factor in the heart, this study sought to explore the pathophysiological relevance of S100A1 levels in development and progression of postischemic heart failure (HF). S100A1-transgenic (STG) and S100A1-knockout (SKO) mice were subjected to myocardial infarction (MI) by surgical left anterior descending coronary artery ligation, and survival, cardiac function, and remodeling were compared with nontransgenic littermate control (NLC) and wild-type (WT) animals up to 4 weeks. Although MI size was similar in all groups, infarcted S100A1-deficient hearts (SKO-MI) responded with acute contractile decompensation and accelerated transition to HF, rapid onset of cardiac remodeling with augmented apoptosis, and excessive mortality. NLC/WT-MI mice, displaying a progressive decrease in cardiac S100A1 expression, showed a later onset of cardiac remodeling and progression to HF. Infarcted S100A1-overexpressing hearts (STG-MI), however, showed preserved global contractile performance, abrogated apoptosis, and prevention from cardiac hypertrophy and HF with superior survival compared with NLC/WT-MI and SKO-MI. Both Gq-protein-dependent signaling and protein kinase C activation resulted in decreased cardiac S100A1 mRNA and protein levels, whereas Gs-protein-related signaling exerted opposite effects on cardiac S100A1 abundance. Mechanistically, sarcoplasmic reticulum Ca2+ cycling and beta-adrenergic signaling were severely impaired in SKO-MI myocardium but preserved in STG-MI. Our novel proof-of-concept study provides evidence that downregulation of S100A1 protein critically contributes to contractile dysfunction of the diseased heart, which is potentially responsible for driving the progressive downhill clinical course of patients with HF.

Static and serial assessments of coronary arterial remodeling are discordant: An intravascular ultrasound analysis from the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial

Arterial remodeling is a major determinant of the clinical manifestations of coronary artery disease. Assessment of arterial remodeling with intravascular ultrasound (IVUS) used to rely on comparing the external elastic membrane (EEM) areas of lesion and reference sites at a single time point (static assessment). Recently, performance of serial IVUS provided the opportunity for direct assessment of remodeling. Our aim was to study the concordance of the static and serial methods. We identified 210 focal coronary lesions on the baseline IVUS interrogations of the REVERSAL trial. A follow-up IVUS was performed at 18 months. Static assessment was performed by calculating the remodeling index (RI) (lesion EEM area / reference EEM area) and serial assessment by comparing the changes in atheroma and EEM areas at follow-up. Using the serial method, there was a 1.24 mm2 increase in EEM area for every 1 mm2 increase in atheroma area at the lesion site, which was indicative of expansive (overcompensatory) remodeling. By using the static method, the RI was paradoxically lower at follow-up (1.062 +/- 0.15 at baseline vs 1.027 +/- 0.14 at follow-up, P < .001), indicating a trend toward constrictive remodeling. The reason for decreased RI at follow-up was the relatively larger expansion of the EEM areas at the reference sites. Static and serial assessments of arterial remodeling are discordant. This is due to concomitant remodeling of the reference sites used in the static assessment. Intravascular ultrasound performed at a single point in time does not reflect the dynamic remodeling response.

Coronary artery remodelling in atherosclerosis: unfortunately unpredictable

Coronary heart disease is the main cause of mortality and morbidity worldwide, and occurs because of the growth and complications of coronary atherosclerosis. Therefore, efforts in the understanding of how atherosclerotic plaques grow and undergo complications, and in identifying predictors of such dramatic events are welcome and worthwhile. Atherosclerosis has long been considered a relentless process by which the accumulation of lipids and extracellular matrix leads to progressive lumen encroachment. Two notions in the past 20 years have dramatically altered this conception. One is that most cases of myocardial infarction likely derive from acute plaque complications (plaque fissuring in most instances), and not from progressive lumen stenosis1. The other is that the growth of atherosclerotic plaques is not necessarily towards the lumen, but may also occur towards the outer vessel layers, leading to an actual overall enlargement of the vessel, contrary to the previous tenet that atherosclerosis is similar to the encrustation of metal pipes in a building. This second aspect, although less appreciated in current literature than the burgeoning plethora of investigations on mechanisms of plaque rupture, is also fertile of important clinical consequences. In a series of human histopathological observations, Glagov et al .2 were the first to identify a significant direct correlation between the plaque area—calculated as the area defined externally by the internal elastic lamina (internal elastic membrane, IEM) and internally by the vessel lumen (intimal area) and the potential lumen area—i.e. the area circumscribed by the internal elastic lamina, taken as a measure of the area of the arterial lumen if no plaque had been present and the intima remained a virtual space. This finding indicated that, in general, the larger the plaque, the larger the vessel, and allowed the inference that plaques also grow towards the outside (‘positive remodelling’). These results have … *Corresponding author. Tel: +39 (0) 871 41512; fax: +39 (0) 871 402817. E-mail address : rdecater{at}unich.it

Morphogenesis and variants of remodeling of atherosclerotic heart

Morphogenesis of atherosclerotic heart is presented on the basis of complex pathomorphological analysis of 1000 autopsies. Special attention was paid to the dilatation and hypertrophic variants and to structural mechanisms of heart and coronary vessel remodeling under conditions of atherosclerotic process. Predominant remodeling of atherosclerotic heart and coronary arteries by the dilatation variant determines unfavorable prognosis of heart failure. Compensatory and adaptive processes (cardiomyocyte hypertrophy and collateral circulation) developing in the heart compensate for functional insufficiency of the organ for some time.

Relation between baseline plaque burden and subsequent remodelling of atherosclerotic left main coronary arteries: a serial intravascular ultrasound study with long-term (&gt;=12 months) follow-up

Glagov's histopathological observation and non-serial intravascular ultrasound studies (IVUS) concluded that compensatory coronary remodelling diminishes as 40% atherosclerotic plaque burden is reached. We tested this hypothesis with serial IVUS. Serial IVUS examinations of 46 atherosclerotic non-stenotic left main stems (18+/-8 months apart) were analysed to assess the relation between baseline plaque burden (=plaque+media area/vessel area) vs. serial remodelling (=vessel area at baseline - at follow-up). There were 25 plaques with baseline plaque burden <40% (30.1+/-6.6%, group A) and 21 plaques with baseline plaque burden > or =40% (46.1+/-5.8%, group B). There was no relation between baseline plaque burden vs. subsequent changes in vessel area overall (r=0.07, P=0.7), for group A (r=0.03, P=0.6), and group B (r=0.01, P=0.8). The frequency of positive serial remodelling (vessel area increase) vs. negative or intermediate serial remodelling (no change or decrease) were similar in group A [17 (68%) vs. 8 (32%)] and group B lesions [18 (86%) vs. 3 (14%)] (P=0.2). IVUS demonstrates that serial coronary remodelling is not related to baseline plaque burden. Lesions with baseline plaque burden <40% may subsequently show a lack of compensation or frank arterial shrinkage, whereas lesions with baseline plaque burden >40% may continue to develop compensatory enlargement.

Lipoprotein(a)

In this issue of Stroke , the Atherosclerosis Risk in Communities (ARIC) study provides evidence that lipoprotein(a) [Lp(a)] is a significant predictor of stroke.1 This is an important finding, because ARIC is both large and prospective. Over 14 000 patients were enrolled in 1987 to 1989, and during 13.5 years of follow-up, they experienced 496 ischemic strokes. Lp(a) remained a significant predictor of stroke after adjustment for age, race, systolic blood pressure, antihypertensive medication, smoking status, use of postmenopausal hormone therapy, diabetes, LDL cholesterol, HDL cholesterol, fibrinogen, and von Willebrand factor. It thus seems likely that Lp(a) is potentially an important treatable risk factor. But what is Lp(a), and how does it relate to atherosclerosis and cardiovascular events? A meta-analysis of prospective studies of coronary events2 seems to establish that Lp(a) is also a predictor of myocardial infarction, but numerous studies indicate that it does not seem to predict the burden of atherosclerosis as assessed by intima-media thickness,3,4 except perhaps in patients with renal …

Prevention of Positive Coronary Artery Remodeling with Statin Therapy in Patients with Coronary Artery Diseases

Since positive coronary artery remodeling with large plaque burden is associated with subsequent coronary events, the authors tested their hypothesis that secondary prevention of coronary events by a statin may be associated with inhibition of the process of positive coronary artery remodeling in underlying coronary atherosclerotic lesions in patients with coronary artery diseases. They evaluated the intravascular ultrasound imaging in angiographically normal coronary lesions at baseline and after 6 months of therapy in 64 patients with coronary artery diseases. External elastic membrane area was defined as the vessel area, and the difference between the vessel and lumen area was calculated as plaque area. The relative echogenicity of coronary plaque to adventitia was evaluated as acoustic characteristics of coronary plaque. Twenty-five patients were treated with a statin and 39 patients did not receive a statin. In patients treated with a statin, plaque area decreased by 12% (p = 0.013) compared to an increase in plaque area of 13% (p = 0.023) in those who did not receive a statin. The vessel area was not enlarged in patients treated with a statin but did show positive remodeling in patients who had plaque progression without a statin. The relative echogenicity of plaque was unchanged in patients treated with a statin but significantly decreased in patients not receiving a statin. A statin may prevent positive coronary artery remodeling via inhibition of plaque progression in underlying coronary atherosclerotic lesions in patients with coronary artery diseases.

The Impact of Coronary Artery Disease Risk Factors on Intravascular Ultrasound‐Derived Morphologic Indices of Human Coronaries

The relationship of intravascular ultrasound (IVUS)-derived measurements of atherosclerotic plaque to various coronary artery disease (CAD) risk factors is not well known. The purpose of this study was to examine the relationship of percent coronary luminal stenosis by IVUS to other IVUS measures of CAD, as well as the relationship of common IVUS measures of CAD to traditional CAD risk factors. We hypothesized that one or more IVUS measures of CAD might relate more strongly to CAD risk factors than does percent luminal coronary stenosis. The records of 897 consecutive patients (57% men, mean age 62 years) who underwent IVUS investigation of their coronary arteries from 1996 through 2001 were retrospectively reviewed. IVUS was performed using a 20-MHz probe (Jomed, Rancho Cordoba, CA) and a manual pull-back technique to image the coronary arteries. Coronary artery remodeling ratio-i.e., the ratio of coronary lesion external elastic membrane cross-sectional area (EEM CSA) to proximal reference artery EEM CSA; plaque burden-i.e., plaque plus media CSA divided by EEM CSA; calcium arc; and percent stenosis of luminal cross-sectional area were measured by a single reader. Percent area stenosis, the most commonly used IVUS parameter, did not correlate with the other three IVUS-derived parameters, nor was it related to any of the CAD risk factors considered. In contrast, remodeling ratio was directly correlated with plaque burden (r=0.22, P<0.001), but inversely related to calcium arc (r=-0.13, P=0.01). IVUS plaque burden was significantly correlated with male gender (P<0.0001) and diabetes mellitus (DM) (P=0.003). In multivariate analyses including age, gender, and CAD risk factors, plaque burden was significantly associated with age, male gender, and DM, but not with chronic renal failure, hypertension, or hypercholesterolemia. The multivariate model also revealed that the calcium arc was significantly associated with male gender and age. These IVUS findings provide anatomic documentation that the traditional CAD risk factors relate more strongly to plaque burden than to percent coronary arterial luminal narrowing.

Remodeling Index Compared to Actual Vascular Remodeling in Atherosclerotic Left Main Coronary Arteries as Assessed With Long-Term (≥12 Months) Serial Intravascular Ultrasound

We present the remodeling index (RI) versus serial intravascular ultrasound (IVUS) data. The RI, derived by comparing lesion external elastic membrane (EEM) cross-sectional area versus the reference at one time point, is used in various IVUS studies as a substitute of true remodeling (change in EEM over time), assuming that it represents true remodeling. We studied 46 non-stenotic left main arteries using serial IVUS (follow-up 18 +/- 8 months). Plaques were divided into subgroups according to the follow-up RI: follow-up RI >1 (n = 27) versus follow-up RI < or =1 (n = 19). Lesions with a follow-up RI >1 had an increase in lumen despite an increase in plaque because of an increase in EEM. Conversely, lesions with a follow-up RI < or =1 had a reduction in lumen as a result of both a plaque increase and EEM decrease. Overall, the follow-up RI correlated directly with changes in lesion site EEM (baseline-to-follow-up). Although there was no correlation between the follow-up RI and changes in reference EEM area, changes in reference EEM area did correlate directly with changes in lesion EEM area. In nearly 90% of lesions with a follow-up RI >1, there was a previously documented increase in EEM area. Using multivariate linear regression analysis, the follow-up RI was dependent on the baseline RI, the increase in lesion EEM area, and the decrease in reference EEM area. The follow-up RI was not dependent on changes in lesion plaque area. The vast majority of left main lesions with a remodeling index >1 had evidence of a previous increase in lesion-site EEM area.

Adaptive-Outward and Maladaptive-Inward Arterial Remodeling Measured by Intravascular Ultrasound in Hyperhomocysteinemia and Diabetes

Coronary artery remodeling implies structural changes in the vessel wall in response to various pathophysiologic conditions. However, the classification of remodeling is unclear. We hypothesized that the adaptive, positive-outward remodeling is a reactive and compensatory response to the stress. The maladaptive negative-inward constrictive remodeling is a passive atherosclerotic condition in which the vessel becomes stiffer. Patients with atherosclerotic lesions underwent intravascular ultrasound (IVUS) scans. The size of the vessels distal to and proximal to plaques were analyzed by IVUS. Diabetes was created in mice by an intraperitoneal injection of alloxan (65 mg/kg). To reduce remodeling, mice received ciglitazone, an agonist of peroxisome proliferators activated receptor-gamma (PPARgamma) in drinking water. After 8 weeks, atherosclerotic vessels were analyzed for collagen and elastin. IVUS data suggest an adaptive coronary arterial remodeling was a positive compensatory response to various pathologic stimuli; for example, with the deposition of atherosclerotic plaque, coronary arterial segments enlarged to maintain luminal area. This phenomenon was commonly observed during the initial phases of the development of atherosclerosis. However, negative coronary artery remodeling, or a decrease in vessel area with the formation of atherosclerotic plaque, was maladaptive and was associated with smoking, hypertension, hyperhomocysteinemia, diabetes mellitus, and also after percutaneous coronary interventions (restenosis). In diabetic mice, there was increased collagen and decreased elastin contents; however, treatment with ciglitazone ameliorated the decrease in elastin contents. Global enlargement of the coronary vascular tree occurs during pressure and volume overload associated with ventricular hypertrophic states such as athletic conditioning, hypertensive heart disease, and dilated cardiomyopathy. On the other hand, maladaptive coronary arterial remodeling occurs in patients with severe deconditioning, diabetes mellitus, after coronary artery bypass surgery, and in some instances, postintervention.

Compensatory enlargement of human coronary arteries during progression of atherosclerosis is unrelated to atheroma burden: serial intravascular ultrasound observations from the REVERSAL trial

On the basis of the evidence from autopsy studies, it is accepted that compensatory enlargement (remodelling) of coronary arteries during progression of atherosclerosis diminishes once atheroma burden (cross-sectional area stenosis) reaches approximately 40%. Our aim was to evaluate whether atheroma burden is a limiting factor for coronary arterial remodelling using in vivo serial intravascular ultrasound (IVUS). From the cohort of the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial, we identified 210 focal coronary lesions at baseline IVUS. Of these, 128 lesions that had an increase in atheroma area at the 18-month follow-up IVUS were included in the analysis. Lesions were matched at baseline and follow-up. The increase in external elastic membrane (EEM) area for each mm(2) increase in atheroma area was not significantly different in lesions with <40 and >or=40% atheroma burden at baseline (1.62 vs. 1.28 mm(2), P=0.30). There were no correlations between atheroma burden at baseline and change in EEM (r=0.02, P=0.86) or change in lumen (r=0.04, P=0.64) areas. Assessment of coronary arterial remodelling by serial IVUS revealed that compensatory remodelling is not limited by atheroma burden. Atheroma burden is not a determinant of arterial enlargement during the progression of atherosclerosis.

The eccentric lumenology

Coronary angiography has a poor predictive value for the detection of eccentric plaque morphology. Many reports have demonstrated discordance between the angiographic classification and the intravascular ultrasound (IVUS) classification. Although eccentricity is usually considered a dichotomous character, more than two-thirds of all coronary stenosis have some degree of eccentricity. The American College of Cardiology/American Heart Association (ACC/AHA) Task force included lesion eccentricity as a risk factor for moderate procedural success (60-85%) and moderate complications (type B). Although lesion eccentricity has been implicated as a risk factor for reduced short-term procedural results, current available data does not support the adverse impact of eccentricity on procedural success or restenosis. The present article reviews the incidence and the various clinical scenarios known to be associated with the eccentric lumenogram and the impact of coronary artery remodeling contributing to misinterpretation of disease eccentricity. Various therapeutic modalities with reference to eccentric lesions are also considered.