Coronary Artery Remodeling Research Articles

Whys and Wherefores of Coronary Arterial Positive Remodeling.

Positive remodeling (PR) is an atherosclerotic plaque feature defined as an increase in arterial caliber at the level of an atheroma, in response to increasing plaque burden. The mechanisms that lead to its formation are incompletely understood, but its role in coronary atherosclerosis has major clinical implications. Indeed, plaques with PR have elevated risk of provoking acute cardiac events. Hence, PR figures among the high-risk plaque features that cardiac imaging studies should report. This review aims to provide an overview of the current literature on coronary PR. It outlines the pathophysiology of PR, the different techniques used to assess its presence, and the imaging findings associated to PR, on both noninvasive and invasive studies. This review also summarizes clinical observations, trials, and studies, focused on the impact of PR on clinical outcome.

Coronary Artery Aneurysm or Ectasia as a Form of Coronary Artery Remodeling: Etiology, Pathogenesis, Diagnostics, Complications, and Treatment.

Coronary artery aneurysm or ectasia (CAAE) is a term that includes both coronary artery ectasia (CAE) and coronary artery aneurysm (CAA), despite distinct phenotypes and definitions. This anomaly can be found in 0.15-5.3% of coronary angiography. CAE is a diffuse dilatation of the coronary artery at least 1.5 times wider than the diameter of the normal coronary artery in a patient with a length of over 20 mm or greater than one-third of the vessel. CAE can be further subdivided into diffuse and focal dilations by the number and the length of the dilated vessels. Histologically, it presents with extensive destruction of musculoelastic elements, marked degradation of collagen and elastic fibers, and disruption of the elastic lamina. Conversely, CAA is a focal lesion manifesting as focal dilatation, which can be fusiform (if the longitudinal diameter is greater than the transverse) or saccular (if the longitudinal diameter is smaller than the transverse). Giant CAA is defined as a 4-fold enlargement of the vessel diameter and is observed in only 0.02% of patients after coronary. An aneurysmal lesion can be either single or multiple. It can be either a congenital or acquired phenomenon. The pathophysiological mechanisms responsible for the formation of CAAE are not well understood. Atherosclerosis is the most common etiology of CAAE in adults, while Kawasaki disease is the most common in children. Other etiological factors include systemic connective tissue diseases, infectious diseases, vasculitis, congenital anomalies, genetic factors, and idiopathic CAA. Invasive assessment of CAAE is based on coronary angiography. Coronary computed tomography (CT) is a noninvasive method that enables accurate evaluation of aneurysm size and location. The most common complications are coronary spasm, local thrombosis, distal embolization, coronary artery rupture, and compression of adjacent structures by giant coronary aneurysms. The approach to each patient with CAAE should depend on the severity of symptoms, anatomical structure, size, and location of the aneurysm. Treatment methods should be carefully considered to avoid possible complications of CAAE. Simultaneously, we should not unnecessarily expose the patient to the risk of intervention or surgical treatment. Patients can be offered conservative or invasive treatment. However, there are still numerous controversies and ambiguities regarding the etiology, prognosis, and treatment of patients with coronary artery aneurysms. This study summarizes the current knowledge about this disease's etiology, pathogenesis, and management.

Transient formation of collaterals contributes to the restoration of the arterial tree during cardiac regeneration in neonatal mice

Revascularization of ischemic myocardium following cardiac damage is an important step in cardiac regeneration. However, the mechanism of arteriogenesis has not been well described during cardiac regeneration. Here we investigated coronary artery remodeling and collateral growth during cardiac regeneration. Neonatal MI was induced by ligature of the left descending artery (LAD) in postnatal day (P) 1 or P7 pups from the Cx40-GFP mouse line and the arterial tree was reconstructed in 3D from images of cleared hearts collected at 1, 2, 4, 7 and 14 days after infarction. We show a rapid remodeling of the left coronary arterial tree induced by neonatal MI and the formation of numerous collateral arteries, which are transient in regenerating hearts after MI at P1 and persistent in non-regenerating hearts after MI at P7. This difference is accompanied by restoration of a perfused or a non-perfused LAD following MI at P1 or P7 respectively. Interestingly, collaterals ameliorate cardiac perfusion and drive LAD repair, and lineage tracing analysis demonstrates that the restoration of the LAD occurs by remodeling of pre-existing arterial cells independently of whether they originate in large arteries or arterioles. These results demonstrate that the restoration of the LAD artery during cardiac regeneration occurs by pruning as the rapidly forming collaterals that support perfusion of the disconnected lower LAD subsequently disappear on restoration of a unique LAD. These results highlight a rapid phase of arterial remodeling that plays an important role in vascular repair during cardiac regeneration.

Donepezil attenuates progression of cardiovascular remodeling and improves prognosis in spontaneously hypertensive rats with chronic myocardial infarction.

The acetylcholinesterase inhibitor donepezil restores autonomic balance, reduces inflammation, and improves long-term survival in rats with chronic heart failure (CHF) following myocardial infarction (MI). As arterial hypertension is associated with a significant risk of cardiovascular death, we investigated the effectiveness of donepezil in treating CHF in spontaneously hypertensive rats (SHR). CHF was induced in SHR by inducing permanent MI. After 2 weeks, the surviving SHR were randomly assigned to sham-operated (SO), untreated (UT), or oral donepezil-treated (DT, 5 mg/kg/day) groups, and various vitals and parameters were monitored. After 7 weeks of treatment, heart rate and arterial hypertension reduced significantly in DT rats than in UT rats. Donepezil treatment improved 50-day survival (41% to 80%, P = 0.004); suppressed progression of cardiac hypertrophy, cardiac dysfunction (cardiac index: 133 ± 5 vs. 112 ± 5 ml/min/kg, P < 0.05; left ventricular end-diastolic pressure: 12 ± 3 vs. 22 ± 2 mmHg, P < 0.05; left ventricular +dp/dtmax: 5348 ± 338 vs. 4267 ± 114 mmHg/s, P < 0.05), systemic inflammation, and coronary artery remodeling (wall thickness: 26.3 ± 1.4 vs. 34.7 ± 0.7 μm, P < 0.01; media-to-lumen ratio: 3.70 ± 0.73 vs. 8.59 ± 0.84, P < 0.001); increased capillary density; and decreased plasma catecholamine, B-type natriuretic peptide, arginine vasopressin, and angiotensin II levels. Donepezil treatment attenuated cardiac and coronary artery remodeling, mitigated cardiac dysfunction, and significantly improved the prognosis of SHR with CHF.

Post-angioplasty remodeling of coronary arteries investigated via a chemo-mechano-biological in silico model

This work presents the application of a chemo-mechano-biological constitutive model of soft tissues for describing tissue inflammatory response to damage in collagen constituents. The material model is implemented into a nonlinear finite element formulation to follow up a coronary standard balloon angioplasty for one year. Numerical results, compared with available in vivo clinical data, show that the model reproduces the temporal dynamics of vessel remodeling associated with subintimal damage. Such dynamics are bimodular, being characterized by an early tissue resorption and lumen enlargement, followed by late tissue growth and vessel constriction. Applicability of the modeling framework in retrospective studies is demonstrated, and future extension towards prospective applications is discussed.

Pulmonary Hypertension Induces Serotonin Hyperreactivity and Metabolic Reprogramming in Coronary Arteries via NOX1/4-TRPM2 Signaling Pathway.

Clinical evidence revealed abnormal prevalence of coronary artery (CA) disease in patients with pulmonary hypertension (PH). The mechanistic connection between PH and CA disease is unclear. Serotonin (5-hydroxytryptamine), reactive oxygen species, and Ca2+ signaling have been implicated in both PH and CA disease. Our recent study indicates that NOXs (NADPH [nicotinamide adenine dinucleotide phosphate] oxidases) and TRPM2 (transient receptor potential cation channel subfamily M member 2) are key components of their interplay. We hypothesize that activation of the NOX-TRPM2 pathway facilitates the remodeling of CA in PH. Left and right CAs from chronic hypoxia and monocrotaline-induced PH rats were collected to study vascular reactivity, gene expression, metabolism, and mitochondrial function. Inhibitors or specific siRNA were used to examine the pathological functions of NOX1/4-TRPM2 in CA smooth muscle cells. Significant CA remodeling and 5-hydroxytryptamine hyperreactivity in the right CA were observed in PH rats. NOX1/4-mediated reactive oxygen species production coupled with TRPM2-mediated Ca2+ influx contributed to 5-hydroxytryptamine hyperresponsiveness. CA smooth muscle cells from chronic hypoxia-PH rats exhibited increased proliferation, migration, apoptosis, and metabolic reprogramming in an NOX1/4-TRPM2-dependent manner. Furthermore, the NOX1/4-TRPM2 pathway participated in mitochondrial dysfunction, involving mitochondrial DNA damage, reactive oxygen species production, elevated mitochondrial membrane potential, mitochondrial Ca2+ accumulation, and mitochondrial fission. In vivo knockdown of NOX1/4 alleviated PH and suppressed CA remodeling in chronic hypoxia rats. PH triggers an increase in 5-hydroxytryptamine reactivity in the right CA and provokes metabolic reprogramming and mitochondrial disruption in CA smooth muscle cells via NOX1/4-TRPM2 activation. This signaling pathway may play an important role in CA remodeling and CA disease in PH.

Cardiac allograft vasculopathy in heart transplanted recipients: The multivessel study

BackgroundCardiac Allograft Vasculopathy (CAV) is a prevailing complication following heart transplantation. We aimed to investigate if CAV causes equal vascular remodeling in the major coronary arteries using quantitative Optical Coherence Tomography (OCT) and to explore the prognostic potential of OCT derived measurements from each coronary artery. Methods64 heart transplanted patients had a combined total of 114 full three-vessel OCTs and coronary angiographies performed between 2013 and 2019. OCT pullbacks were categorized by angiographic CAV classification. Registration of disease progression was censored on July 1, 2022. ResultsOCT recordings were classified as follows: No significant CAV, n = 73; mild CAV, n = 18; moderate CAV, n = 13 and severe CAV, n = 10. From inter-coronary comparison of severe CAV, we found significant differences by both average lumen/intima ratio (p<0.0001) and average intima/media ratio (p<0.0001). The left descending artery (LAD) showed increasingly smaller luminal areas and larger intimal areas within CAV groups compared with the remaining coronary arteries. No differences were seen between major coronary arteries without significant CAV.LAD derived average intima/media ratio (HR: 3.39; 95% CI: 1.33 to 8.63; p = 0.01) and average lumen/intima ratio (HR: 2.77; 95% CI: 1.09 to 7.05; p = 0.03) were the strongest predictors of CAV progression. LAD predictions were superior to predictions based on all three coronary arteries. ConclusionsLAD derived OCT measurements were increasingly affected by CAV compared with the circumflex and right coronary artery. Average lumen/intima and intima/media ratios were the strongest predictors of CAV progression.

Negative coronary artery remodeling in young properly controlled diabetic patients is associated with diabetes duration

Abstract Introduction Coronary artery remodeling is a focal compensatory change in the vessel wall in response to atherosclerotic plaque. Computed tomography coronary angiography (CTCA) is very useful in assessing remodeling pattern of atherosclerotic lesions. Patients with type 2 diabetes mellitus (T2DM) has extensive atherosclerotic burden with inadequate compensatory remodeling. Diabetes duration is independently associated with macro-and microvascular events. The goal of this study was to characterize the pattern of coronary artery remodeling and its relation with diabetes duration in a group of properly controlled diabetic patients. Methods We prospectively studied 263 patients below age of 60 years (mean age 54 ± 6 years) who were scheduled for CTCA. CTCA was performed using 256-MDCT scanner with dedicated software for calcium measurement. Positive coronary remodeling (PR) was defined as remodeling index (RI) &amp;gt;1.05, and negative coronary remodeling (NR) as RI &amp;lt;0.95.Atherosclerotic burden was assessed using Gensini score and coronary calcium score (CCS). Results Patients with NR had longer diabetes duration (8.8 ± 5.7 vs. 5.5 ± 4.4 years, p&amp;lt;0.001) higher prevalence of insulin (31% vs. 20%, p= 0.041) and statin therapy (70.8% vs. 58.7%, p= 0.043) higher Gensini (24.9 ±26.9 vs.18.2 ± 21.9, p= 0.039) and calcium scores (295.8 ± 301.8 vs. 170.2 ± 201.2, p&amp;lt;0.001). NR was correlated with CACS (r= -0.138, p= 0.025) and diabetes duration (r= -0.313, p&amp;lt;0.001) Conclusion Longer diabetes mellitus duration was associated with higher prevalence of NR in young patients with controlled T2DM.

Parameters of complete blood count and coronary lesions in predicting inhospital mortality in patients with acute ST-segment elevation myocardial infarction after percutaneous coronary intervention

Aim. To evaluate the predictive potential of complete blood count (CBC) and coronary involvement parameters for predicting inhospital mortality in patients with ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI).Material and methods. This single-center cohort retrospective study was conducted using data from 4677 electronic medical records of patients with STEMI (3203 men and 1474 women). Two groups of people were identified: group 1 — 318 (6,8%) patients who died in hospital; group 2 — 4359 (93,2%) patients with a favorable outcome. The degree of influence of predictors on the end point was determined by the Shapley method.Results. The best quality metrics had a model with structure included, in addition to 7 CBC factors, indicators of three-vessel coronary involvement, left coronary artery remodeling and coronary perfusion after PCI with the TIMI score &lt;2 (AUC — 0,845, sensitivity — 0,78, specificity — 0,786) . The greatest contribution to the implementation of the end point was associated with the level of hemoglobin, white blood cells, immune-inflammatory index and neutrophils &gt;75,4%. Coronary artery parameters had a less noticeable effect on inhospital mortality, and the minimal effect was plateletcrit &gt;0,22%, lymphocytes &lt;13,3% and erythrocyte sedimentation rate.Conclusion. This multivariate logistic regression model based on a combination of CBC indicators and indicators characterizing the coronary system has high predictive accuracy, which determines the prospects for its further use as one of the available risk assessment tools in clinical practice.

Giant postinfarction posterolateral left ventricular aneurysm, complicated by mitral insufficiency

Ischemic heart disease holds the leading position in the structure of cardiovascular diseases. Early reperfusion therapy for acute myocardial infarction led to a decrease in mortality and severe complications of coronary artery disease. Despite advances in the treatment of coronary artery disease, dilatation and remodeling of the left ventricle develop in 20% of patients who have had a heart attack, leading to mitral insufficiency and systolic dysfunction of the left ventricle. Aneurysm of the left ventricle is a delayed severe complication of myocardial infarction, which significantly worsens the prognosis. Large aneurysms of the left ventricle cause progressive dilatation of the left ventricle, its volumetric overload with an increase in wall tension in the non-infarction zone, decreased functional characteristics of the left ventricle, thrombosis in the aneurysm cavity, life-threatening arrhythmias, and sudden death. Postinfarction left ventricular remodeling can lead to secondary mitral regurgitation, which is an independent predictor of mortality in the longterm period. Surgical treatment of coronary heart disease and its complications is one of the main problems of modern cardiovascular surgery.

Mechanistic Target of Rapamycin Inhibition Prevents Coronary Artery Remodeling in a Murine Model of Kawasaki Disease.

Remodeling of the coronary arteries is a common feature in severe cases of Kawasaki disease (KD). This pathology is driven by the dysregulated proliferation of vascular fibroblasts, which can lead to coronary artery aneurysms, stenosis, and myocardial ischemia. We undertook this study to investigate whether inhibiting fibroblast proliferation might be an effective therapeutic strategy to prevent coronary artery remodeling in KD. We used a murine model of KD (induced by the injection of the Candida albicans water-soluble complex [CAWS]) and analyzed patient samples to evaluate potential antifibrotic therapies for KD. We identified the mechanistic target of rapamycin (mTOR) pathway as a potential therapeutic target in KD. The mTOR inhibitor rapamycin potently inhibited cardiac fibroblast proliferation in vitro, and vascular fibroblasts up-regulated mTOR kinase signaling in vivo in the CAWS mouse model of KD. We evaluated the in vivo efficacy of mTOR inhibition and found that the therapeutic administration of rapamycin reduced vascular fibrosis and intimal hyperplasia of the coronary arteries in CAWS-injected mice. Furthermore, the analysis of cardiac tissue from KD fatalities revealed that vascular fibroblasts localizing with inflamed coronary arteries up-regulate mTOR signaling, confirming that the mTOR pathway is active in human KD. Our findings demonstrate that mTOR signaling contributes to coronary artery remodeling in KD, and that targeting this pathway offers a potential therapeutic strategy to prevent or restrict this pathology in high-risk KD patients.

Quercetin decreases cardiac hypertrophic mediators and maladaptive coronary arterial remodeling in renovascular hypertensive rats without improving cardiac function.

Oxidative stress and MMP activity are found in the hearts and arteries in hypertension and contribute to the resulting hypertrophy and dysfunction. Quercetin is a flavonoid that reduces MMP-2 activity and ameliorates hypertrophic vascular remodeling of hypertension. The hypothesis is that treatment of hypertensive rats with quercetin ameliorates coronary maladaptive remodeling and decreases hypertrophic cardiac dysfunction by decreasing oxidative stress and MMP activity. Male Sprague-Dawley two-kidney, one-clip (2K1C) and Sham rats were treated with quercetin (10mg/kg/day) or its vehicle for 8weeks by gavage. Rats were analyzed at 10weeks of hypertension. Systolic blood pressure (SBP) was examined by tail-cuff plethysmography. Cardiac left ventricles were used to determine MMP activity by in situ zymography and oxidative stress by dihydroethidium. Immunofluorescence was performed to detect transforming growth factor (TGF)-β and nuclear factor kappa B (NFkB). Morphological analyses of heart and coronary arteries were done by H&E and picrosirius red, and cardiac function was measured by Langendorff. SBP was increased in 2K1C rats, and quercetin did not reduce it. However, quercetin decreased both oxidative stress and TGF-β in the left ventricles of 2K1C rats. Quercetin also decreased the accentuated MMP activity in left ventricles and coronary arteries of 2K1C rats. Quercetin ameliorated hypertension-induced coronary arterial hypertrophic remodeling, although it did not reduce cardiac hypertrophic remodeling and dysfunction. Quercetin decreases cardiac oxidative stress and TGF-β and MMP activity in addition to improving coronary remodeling, yet does not ameliorate cardiac dysfunction in 2K1C rats.

Mean Coronary Cross-Sectional Area as a Measure of Arterial Remodeling Using Noncontrast CT Imaging in Persons With HIV.

Background Persons with HIV have a higher prevalence of coronary artery disease compared with their HIV-negative counterparts. Earlier identification of subclinical atherosclerosis may provide a greater opportunity for cardiovascular disease risk reduction. We investigated coronary cross-sectional area (CorCSA) by noncontrasted computed tomography imaging as a noninvasive measure of arterial remodeling among virally suppressed persons with HIV. Methods and Results We assessed 105 persons with HIV with a spectrum of cardiometabolic health. All participants underwent computed tomography imaging to assess the mean corCSA of the proximal left anterior descending artery and 28 participants underwent additional coronary computed tomography angiography. Partial Spearman rank correlations adjusted for cardiovascular disease risk factors were used to assess relationships of corCSA with anthropometric measurements, HIV-related factors, and plasma cytokines. Mean corCSA measured by noncontrast computed tomography and coronary computed tomography angiography were strongly correlated (ρ=0.91, P<0.0001). Higher mean corCSA was present in those with coronary artery calcium (P=0.005) and it correlated with participants' atherosclerotic cardiovascular disease risk score (ρ=0.35, P=0.01). After adjusting for established cardiovascular disease risk factors, we observed an inverse relationship between corCSA and CD4+ T-cell count (ρ=-0.2, P=0.047). Removal of age from the model strengthened the relationships between corCSA and antiretroviral therapy duration (from ρ=0.19, P=0.08 to ρ=0.3, P=0.01). CorCSA was also inversely correlated with plasma IL-10 (ρ=-0.25, P=0.03) but had no relationship with IL-6 (ρ=0.11, P=0.4) or IL-1β (ρ=0.08, P=0.5). Conclusions Positive coronary arterial remodeling, an imaging marker of subclinical atherosclerosis, is associated with a lower CD4 T-cell count, lower circulating IL-10, and possibly a longer antiretroviral therapy duration in persons with HIV. Registration Clinicaltrials.gov; Unique identifier: NCT04451980.

Positive remodelling of coronary arteries on computed tomography coronary angiogram: an observational study.

Coronary artery disease (CAD) due to atherosclerosis is projected to be the leading cause of morbidity and mortality worldwide until 2040. CAD affects approximately 2.6 million people in the United Kingdom (UK), and 1 in 4 of them do not experience any symptoms. The aim of this study was to assess the characteristics and outcomes of patients with plaque features of positive remodelling (PR) on their computed tomography coronary angiogram (CTCA) images. Patients who were referred for CTCA from June 2018 to January 2020 were retrospectively identified. Patients underwent prospective, gated 128-slice dual-source CTCA. Patients with PR were compared to those without PR for demographics and outcomes. A total of 861 patients were included in our study; 241 (28%) had PR, and 620 (72%) had no PR. Patients with PR were older (PR: 63.9±11.0 years vs no PR: 62.1±11.2 years; p=0.04), more likely to be male (PR: 65.6% vs no PR: 55.8%; p=0.01) and underwent coronary angiography more frequently (PR: 25.7% vs no PR: 14.4%; p<0.01). There were also significant increases in subsequent acute coronary syndrome (ACS) events (PR: 2.5% vs no PR: 0.0%; p<0.01) and the need for revascularisation therapy (PR: 15.4% vs no PR: 7.8%; p<0.01) in patients with PR despite being on statins (not a high dose). There was no difference in all-cause mortality. Detection of PR on CTCA is a reliable prognostic indicator of future cardiovascular events and presents a valuable opportunity for initiation of aggressive primary prevention therapy.

Coronary CT Value in Quantitative Assessment of Intermediate Stenosis.

Background and Objectives: Cardiac computed tomography angiography (CCTA) is an excellent non-invasive imaging tool to evaluate coronary arteries and exclude coronary artery disease (CAD). Managing intermediate coronary artery stenosis with negative or inconclusive functional tests is still a challenge. A regular stenosis evaluation together with high-risk plaque features, using semi-automated programs, are becoming promising tools. This case–control study was designed to evaluate the intermediate lesion features’ impact on CAD outcomes, using a semi-automated CCTA atherosclerotic plaque analysis program. Materials and Methods: We performed a single-center, prospective cohort study. A total of 133 patients with low to intermediate risk of CAD, older than 18 years with no previous history of CAD and good quality CCTA images were included in the study, and 194 intermediate stenosis (CAD-RADS 3) were analyzed. For more detailed morphological analysis, we used semi-automated CCTA-dedicated software. Enrolled patients were prospectively followed-up for 2 years. Results: Agatston score was significantly higher in the major adverse cardiovascular events (MACE) group (p = 0.025). Obstruction site analysis showed a significantly lower coronary artery remodeling index (RI) among patients with MACE (p = 0.037); nonetheless RI was negative in both groups. Plaque consistency analysis showed significantly bigger necrotic core area in the MACE group (p = 0.049). In addition, unadjusted multivariate analysis confirmed Agatston score and RI as significant MACE predictors. Conclusions: The Agatston score showes the total area of calcium deposits and higher values are linked to MACE. Higher plaque content of necrotic component is also associated with MACE. Additionally, negatively remodeled plaques are linked to MACE and could be a sign of advanced CAD. The Agatston score and RI are significant in risk stratification for the development of MACE.

Increased Remnant Lipoproteins in Apo E Deficient Mice Induce Coronary Atherosclerosis following Transverse Aortic Constriction and Aggravate the Development of Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure.

Murine coronary arteries are very resistant to the development of atherosclerosis, which may be related to their intramyocardial course. Blood pressure promotes atherosclerotic plaque formation by acting as a physical force that potentiates the migration of pro-atherogenic lipoproteins across the endothelium. C57BL/6N apolipoprotein (apo) E deficient mice have increased remnant lipoproteins that are a risk factor for coronary atherosclerosis. In this study, our aim was to quantify coronary atherosclerosis and artery remodeling following transverse aortic constriction (TAC) in C57BL/6N apo E−/− mice and to evaluate the impact of increased remnant lipoproteins on the development of pressure overload-induced cardiac hypertrophy and heart failure. Advanced atherosclerotic lesions were observed in the left coronary artery of C57BL/6N apo E−/− TAC mice but not in C57BL/6N TAC mice. Pressure overload resulted in markedly increased cardiac hypertrophy and more pronounced heart failure in C57BL/6N apo E−/− TAC mice in comparison to C57BL/6N TAC mice. Pathological hypertrophy, as evidenced by increased myocardial fibrosis and capillary rarefaction, was more prominent in C57BL/6N TAC apo E−/− than in C57BL/6N TAC mice and led to more marked cardiac dysfunction. In conclusion, TAC in apo E deficient mice induces coronary atherosclerosis and aggravates the development of pathological cardiac hypertrophy and heart failure.

Aronia melanocarpa Fruit Juice Modulates ACE2 Immunoexpression and Diminishes Age-Related Remodeling of Coronary Arteries in Rats.

The aim of the study is to evaluate the effect of Aronia melanocarpa fruit juice (AMJ) supplementation on age-related coronary arteries remodeled in aged rat hearts. Male Wistar rats (n = 24) were divided into three groups: (1) young controls (CY), aged 2 months, without AMJ supplementation; (2) old controls (CO), aged 27 months, without AMJ supplementation; and (3) the AMJ group (A), which used 27-month old animals, supplemented orally with AMJ for 105 days. AMJ supplementation did not influence the wall-to-diameter parameter (Kernohan index) of the coronary arteries of test animals. Aged rats supplemented with AMJ showed a significant decrease in the amount of collagen fibers in their coronary tunica media, as compared with the old controls. The intensity of the immunoreaction for alpha smooth muscle actin (αSMA) in the coronary tunica media was significantly lower in the supplemented group than in the old controls. The intensity of the angiotensin-converting enzyme 2 (ACE2) immunoreaction in the coronary tunica media of the supplemented group was significantly higher than the one observed in the old controls. These results indicate the positive effects of AMJ supplementation on the age-dependent remodeling of coronary arteries and support for the preventive potential of antioxidant-rich functional food supplementation in age-related diseases.

Coronary Microvascular Dysfunction

Coronary microvascular dysfunction (DMK) is a condition of patients who are accompanied by complaints of chest pain where the results of coronary angiography examination are normal and this is almost 49% with 60% of patients diagnosed with DMK. Another study said that about 40% of patients with DMK showed coronary flow reserve (CFR &lt;2) of about 40% and the WISE study (Women's Ischaemia Syndrome Evaluation) showed that about 47% of patients with chest pain had normal coronary arteries. DMK can be divided into 4 groups; DMK with no coronary arterial disease (CAD) obstruction and myocardial disease, DMK with myocardial disease where this occurs due to remodeling of intramural coronary arteries, DMK with CAD (coronary arterial disease) or acute myocardial infarction with or without ST segment, iatrogenic typhoid DMK occurs after coronary recanalization caused by vasoconstriction and distal embolization. The mechanism of action of DMK can be caused by several factors, namely endothelial dysfunction, smooth muscle dysfunction, decreased diastolic perfusion time, damage to blood vessels and damage to the vascular and microvascular remodeling. And to enforce this DMK, there are several tests carried out in diagnosing the disease, some of which are invasive and non-invasive so that by enforcing the diagnosis of this disease, treatment for DMK can be done immediately and optimally.

Abstract 10716: Etanercept as an Adjunct Therapy for Acute Kawasaki Disease: A Long Term Follow Up

Introduction: Etanercept, a soluble TNF receptor, is beneficial when given as an adjunct to IVIg to children with acute Kawasaki disease (KD) and coronary artery (CA) involvement. A multi-center phase III trial, Etanercept as Adjunctive Treatment for Acute Kawasaki Disease (EATAK), showed that this TNF antagonist prevented progression of CA dilation over 6 weeks after acute KD. Aims: This study is aimed to test the long-term benefit of Etanercept in improving CA outcome. Methods: Patients enrolled in the placebo controlled double blind EATAK trial from 3 institutions (Seattle, Montreal, Bronx) who had CA dilation (z≥2.5) on initial presentation were included in this study ( n =40). The percent reduction in the size of affected vessels from echocardiogram at presentation to mid-year (4-8 months), 1-year (9-23 months) and ≥2 years after diagnosis were analyzed, and two-tailed t test used to compare Etanercept (0.8 mg/kg x3 doses) and placebo ( n =18) groups. Results: Both groups showed mean reduction (20%) in coronary artery diameter over a 2 year period (Figure). However, patients treated with Etanercept had accelerated and significantly greater improvement in diameter of affected vessels in the first 6 months after diagnosis [22% ( n =25) vs. 6.8% ( n =13), p =0.015]. The trend continued at 1-year follow up ([24.1% ( n =35) vs. 17.5% ( n =27), p =0.24], and by 2 years both groups showed similar overall change [19.6% ( n =31) vs. 24.7% ( n =24), p =0. 43]. Conclusions: Etanercept as an adjunct treatment to IVIg in acute KD with CA involvement accelerates regression of CA dilation over at least a 6 month period after acute inflammation. Etanercept is a potent anti-inflammatory agent that has both early and long-term benefit in CA remodeling in KD. Acceleration of CA healing by Etanercept may provide long term coronary artery benefit.

Measurement of compensatory arterial remodelling over time with serial coronary computed tomography angiography and 3D metrics.

The magnitude of alterations in which coronary arteries remodel and narrow over time is not well understood. We aimed to examine changes in coronary arterial remodelling and luminal narrowing by three-dimensional (3D) metrics from serial coronary computed tomography angiography (CCTA). From a multicentre registry of patients with suspected coronary artery disease who underwent clinically indicated serial CCTA (median interscan interval = 3.3 years), we quantitatively measured coronary plaque, vessel, and lumen volumes on both scans. Primary outcome was the per-segment change in coronary vessel and lumen volume from a change in plaque volume, focusing on arterial remodelling. Multivariate generalized estimating equations including statins were calculated comparing associations between groups of baseline percent atheroma volume (PAV) and location within the coronary artery tree. From 1245 patients (mean age 61 ± 9 years, 39% women), a total of 5721 segments were analysed. For each 1.00 mm3 increase in plaque volume, the vessel volume increased by 0.71 mm3 [95% confidence interval (CI) 0.63 to 0.79 mm3, P < 0.001] with a corresponding reduction in lumen volume by 0.29 mm3 (95% CI -0.37 to -0.21 mm3, P < 0.001). Serial 3D arterial remodelling and luminal narrowing was similar in segments with low and high baseline PAV (P ≥ 0.496). No differences were observed between left main and non-left main segments, proximal and distal segments and side branch and non-side branch segments (P ≥ 0.281). Over time, atherosclerotic coronary plaque reveals prominent outward arterial remodelling that co-occurs with modest luminal narrowing. These findings provide additional insight into the compensatory mechanisms involved in the progression of coronary atherosclerosis.