Left Ventricular Remodeling Process Research Articles

Simulated Effects of Acute Left Ventricular Myocardial Infarction on Mitral Regurgitation in an Ovine Model.

Ischemic mitral regurgitation (IMR) occurs from incomplete coaptation of the mitral valve (MV) after myocardial infarction (MI), typically worsened by continued remodeling of the left ventricular (LV). The importance of LV remodeling is clear as IMR is induced by the post-MI dual mechanisms of mitral annular dilation and leaflet tethering from papillary muscle (PM) distension via the MV chordae tendineae (MVCT). However, the detailed etiology of IMR remains poorly understood, in large part due to the complex interactions of the MV and the post-MI LV remodeling processes. Given the patient-specific anatomical complexities of the IMR disease processes, simulation-based approaches represent an ideal approach to improve our understanding of this deadly disease. However, development of patient-specific models of left ventricle-mitral valve (LV-MV) interactions in IMR are complicated by the substantial variability and complexity of the MR etiology itself, making it difficult to extract underlying mechanisms from clinical data alone. To address these shortcomings, we developed a detailed ovine LV-MV finite element (FE) model based on extant comprehensive ovine experimental data. First, an extant ovine LV FE model (Sci. Rep. 2021 Jun 29;11(1):13466) was extended to incorporate the MV using a high fidelity ovine in vivo derived MV leaflet geometry. As it is not currently possible to image the MVCT in vivo, a functionally equivalent MVCT network was developed to create the final LV-MV model. Interestingly, in pilot studies, the MV leaflet strains did not agree well with known in vivo MV leaflet strain fields. We then incorporated previously reported MV leaflet prestrains (J. Biomech. Eng. 2023 Nov 1;145(11):111002) in the simulations. The resulting LV-MV model produced excellent agreement with the known in vivo ovine MV leaflet strains and deformed shapes in the normal state. We then simulated the effects of regional acute infarctions of varying sizes and anatomical locations by shutting down the local myocardial contractility. The remaining healthy (noninfarcted) myocardium mechanical behaviors were maintained, but allowed to adjust their active contractile patterns to maintain the prescribed pressure-volume loop behaviors in the acute post-MI state. For all cases studied, the LV-MV simulation demonstrated excellent agreement with known LV and MV in vivo strains and MV regurgitation orifice areas. Infarct location was shown to play a critical role in resultant MV leaflet strain fields. Specifically, extensional deformations of the posterior leaflets occurred in the posterobasal and laterobasal infarcts, while compressive deformations of the anterior leaflet were observed in the anterobasal infarct. Moreover, the simulated posterobasal infarct induced the largest MV regurgitation orifice area, consistent with experimental observations. The present study is the first detailed LV-MV simulation that reveals the important role of MV leaflet prestrain and functionally equivalent MVCT for accurate predictions of LV-MV interactions. Importantly, the current study further underscored simulation-based methods in understanding MV function as an integral part of the LV.

Abstract 12559: Functional Autoantibodies Against Angiotensin II Receptor Type 1 and Endothelin-1 Receptor Type A Predict Adverse Remodeling and Cardiovascular Events After Acute Myocardial Infarction

Introduction: Myocardial infarction is a leading cause of death worldwide. Although advances have been made in acute treatment, an incomplete understanding of left ventricular (LV) remodeling (LVR) processes has limited the effectiveness of therapies to reduce late-stage mortality. Hypothesis: We hypothesized that autoantibodies (AAs) activating angiotensin II receptor type 1 (AT1R-AAs) and endothelin-1 receptor type A (ETAR-AAs) are associated with LVR after ST-elevation myocardial infarction (STEMI) and with recurrent major adverse cardiac events (MACE). Methods: We studied 131 STEMI patients (age 61±11 years, 112 males) treated with primary percutaneous coronary intervention between February 2021 and January 2022 at Padua University Medical Center. Within 48 hours of admission standard 2D echocardiography was performed and blood samples were obtained for AAs level measurement. Echocardiography was performed at 6 months repeatedly in all patients. The endpoint was LVR, defined as an increase of 20% or more of LV end-diastolic volume index. Results: Overall, 41 (32%) patients experienced LVR. The titer for the autoantibodies was significantly higher in patients with LVR (p=0.009 for AT1R-AAs; p=0.01 for ETAR-AAs). The prevalence of AT1R-AAs and ETAR-AAs seropositivity was higher in patients with LVR (39% vs. 11%, p<0.001 and 37% vs. 12%, p=0.001, respectively). At multivariable analysis, AT1R-AAs seropositivity was the strongest predictor of LVR (OR=4.25, p=0.002). Similarly, AT1R-AAs seropositivity was a strong predictor of recurrent MACE, both before (OR, 4.09; p = 0.006) and after (OR 19.6; p=0.002) adjusting for the confounding factors. Conclusions: Our results support the hypothesis that AT1R-AAs and ETAR-AAs concentration are a risk factor for LVR in STEMI patients. AT1R-AAs is also a predictor of recurrent MACE. These initial observations may set the stage for a better pathophysiological understanding of the mechanisms contributing to LVR.

Reduced Left Ventricular Twist Early after Acute ST-Segment Elevation Myocardial Infarction as a Predictor of Left Ventricular Adverse Remodelling.

The left ventricular (LV) remodelling process represents the main cause of heart failure after a ST-segment elevation myocardial infarction (STEMI). Speckle-tracking echocardiography (STE) can detect early deformation impairment, while also predicting LV remodelling during follow-up. The aim of this study was to investigate the STE parameters in predicting cardiac remodelling following a percutaneous coronary intervention (PCI) in STEMI patients. The study population consisted of 60 patients with acute STEMI and no history of prior myocardial infarction treated with PCI. The patients were assessed both by conventional transthoracic and ST echocardiography in the first 12 h after admission and 6 months after the acute phase. Adverse remodelling was defined as an increase in LVEDV and/or LVESV by 15%. Adverse remodelling occurred in 26 patients (43.33%). By multivariate regression equation, the risk of adverse remodelling increases with age (by 1.1-fold), triglyceride level (by 1.009-fold), and midmyocardial radial strain (mid-RS) (1.06-fold). Increased initial twist decreases the chances of adverse remodelling (0.847-fold). The LV twist presented the largest area under the receiver operating characteristic (ROC) curve to predict adverse remodelling (AUROC = 0.648; 95% CI [0.506;0.789], p = 0.04). A twist value higher than 11° has a 76.9% specificity and a 72.7% positive predictive value for reverse remodelling at 6 months.

Late left ventricular myocardial remodeling after pulmonary artery banding for end-stage dilated cardiomyopathy in infants: an imaging study

BackgroundUnderstanding the macroscopic biventricular changes induced by pulmonary artery banding (PAB) in children with dilated cardiomyopathy (DCM) represents the first step to unraveling the regenerative potential of the myocardium. We herein investigated the phases of left ventricular (LV) rehabilitation in PAB responders, using a systematic echocardiographic and cardiac magnetic imaging (CMRI) surveillance protocol. MethodsWe prospectively enrolled all patients with DCM treated with PAB from September-2015 at our institution. Among 9 patients, 7 positively responded to PAB and were selected. Transthoracic 2D echocardiography was performed before PAB; and 30, 60, 90, and 120 days after PAB; and at the last available follow-up. CMRI was performed before PAB (whenever possible) and one year after PAB. ResultsIn PAB responders, LV ejection fraction showed a modest 10% increase 30–60 days after PAB, followed by its almost complete normalization after 120 days (median of 20[10–26]% vs 56[44.5–63.5]%, at baseline and 120 days after PAB, respectively). Parallelly, the LV end-diastolic volume decreased from a median of 146(87–204)ml/m2 to 48(40–50)ml/m2. At the last available follow-up (median of 1.5 years from PAB), both echocardiography and CMRI showed a sustained positive LV response, although myocardial fibrosis was detected in all patients. ConclusionsEchocardiography and CMRI show that PAB can promote a LV remodeling process, which starts slowly and can culminate in the normalization of LV contractility and dimensions 4 months later. These results are maintained up to 1.5 years. However, CMRI showed residual fibrosis as evidence of a past inflammatory injury whose prognostic significance is still uncertain.

Acute myocardial calcification in a patient with fulminant myocarditis.

Relationship with Industry: None A 38-year-old man was admitted with a 3-week history of rapid clinical deterioration. The patient presented with multisystem inflammatory syndrome associated with multi-organ failure (white blood and polynuclear cells counts at respectively 54.40 and 51.60 *109/L; C-reactive protein, Ferritin and Fibrinogen levels at respectively, 214 mg/L, 1624 μg/L, and 8.31 g/L; and creatinine and bilirubin levels at respectively 397 μmol/L (4,49 mg/dL) and 57 μMol/L (3,33 mg/dL)). Large screening and multiple testing for bacterial and viral infections remained negative in a patient with Covid-19 infection 3-months earlier without vaccination. The patient was transferred to the Intensive Care Unit necessitating mechanical ventilation, hemodialysis, and inotropic support. Rapidly, diffuse ST elevation on electrocardiogram and increased levels of high-sensitivity cardiac I troponin (hs-cTnI = 135000 ng/L) and natriuretic peptide (NT-ProBNP = 72114 ng/L) were found. Coronary angiogram showed no significant coronary disease and transthoracic echocardiography (TTE) showed reduced left ventricular ejection fraction (LVEF = 40%). Cardiac magnetic resonance imaging confirmed diffuse and extensive gadolinium uptake. Despite negative cardiac biopsies, the diagnosis of fulminant myocarditis was made and the patient underwent corticosteroids bolus and intravenous immunoglobulin therapies. Clinical evolution was deemed favourable with a progressive decrease in systemic inflammatory process associated with a decrease in cardiac biomarkers levels. However, 2 weeks later, chest X-ray (Panel A) and TTE (Panel B) showed acute and impressive left ventricular calcified remodelling process with diffuse epicardial calcification and septal patchy fibrosis (whites triangles). The positron emission tomography (PET-CT) confirmed the diffuse FDG uptakes suggesting persistent local inflammatory process (Panel C) associated with large epicardial calcified remodelling (Panel D). The patient was discharged 1 month after the index admission with optimized heart-failure therapy and planned follow-up at the Heart Failure Clinic.

Sex-related differences in left ventricular remodeling and outcome after alcohol septal ablation in hypertrophic obstructive cardiomyopathy: insights from cardiovascular magnetic resonance imaging

BackgroundAlcohol septal ablation (ASA) has been proven to reverse left ventricular (LV) remodeling in hypertrophic cardiomyopathy (HCM). However, there are no studies on the effect of sex on LV remodeling after ASA. We aimed to investigate whether sex differences affect the process of LV remodeling and outcome after ASA.MethodsA total of 107 patients with obstructive HCM (54 men and 53 women, mean age 51 ± 8 years) were recruited. Cardiovascular magnetic resonance (CMR) was performed at baseline and 16 months after ASA. The extent of late gadolinium enhancement (LGE) was measured.ResultsWomen had a higher indexed LV mass and smaller indexed LV end-systolic volumes than men at the time of ASA. After ASA, both men and women exhibited a regression of LV mass, and the percentage of mass regression was greater in men than women (15.3% ± 4.3% vs. 10.7% ± 1.8%, p < 0.001). In multivariable analysis, male sex, higher reduction of LV outflow tract (LVOT) gradient and lower baseline LV mass index were independently associated with greater LV mass regression after ASA. Kaplan–Meier analysis showed significantly higher cardiovascular events in women than in men (p = 0.015). Female sex [hazard ratio (HR) 3.913, p = 0.038] and LV mass preablation (HR, 1.019, p = 0.010) were independent predictors of cardiovascular outcomes.ConclusionsMales with HCM had favorable reverse remodeling with greater LV mass regression post-ASA than female patients. This favorable LV reverse remodeling might provide a mechanistic explanation for the survival advantage in men.

In Vivo Performance of a Cell and Factor Free Multifunctional Fiber Mesh Modulating Postinfarct Myocardial Remodeling

AbstractGuidance of postinfarct myocardial remodeling processes by an epicardial patch system may alleviate the consequences of ischemic heart disease. As macrophages are highly relevant in balancing immune response and regenerative processes their suitable instruction would ensure therapeutic success. A polymeric mesh capable of attracting and instructing monocytes by purely physical cues and accelerating implant degradation at the cell/implant interface is designed. In a murine model for myocardial infarction the meshes are compared to those either coated with extracellular matrix or loaded with induced cardiomyocyte progenitor cells. All implants promote macrophage infiltration and polarization in the epicardium, which is verified by in vitro experiments. 6 weeks post‐MI, especially the implantation of the mesh attenuates left ventricular adverse remodeling processes as shown by reduced infarct size (14.7% vs 28–32%) and increased wall thickness (854 µm vs 400–600 µm), enhanced angiogenesis/arteriogenesis (more than 50% increase compared to controls and other groups), and improved heart function (ejection fraction = 36.8% compared to 12.7–31.3%). Upscaling as well as process controls is comprehensively considered in the presented mesh fabrication scheme to warrant further progression from bench to bedside.

Effect of p-Tyrosol on the Process of Left-Ventricular Remodeling in the Long Period after Myocardial Infarction.

The effect of p-tyrosol on the main hemodynamic parameters and contractile function of the heart was studied and a morphometric assessment of left-ventricular remodeling was performed in Wistar rats 2 months after acute 1-h myocardial ischemia followed by reperfusion. p-Tyrosol in a dose of 20 mg/kg was injected intraperitoneally 5 times: 20 min before the start of reperfusion, 4 h after the start of reperfusion, and then once a day over the next 3 days. Administration of p-tyrosol to animals in the acute period of myocardial infarction slowed down the formation of systolic and diastolic myocardial dysfunction, improved the pumping function of the heart, maintained the hemodynamic parameters at a significantly higher level, and reduced left-ventricular remodeling in the late period of myocardial infarction. In 2 months after acute myocardial ischemia modeling, the dimensions of the left-ventricular cavity, the area of the postinfarction focus, and the area of connective tissue in rats treated with p-tyrosol were significantly lower than in the control group. In the group treated with p-tyrosol, no anterior left-ventricular wall aneurysms were found.

Оптимізація лікування стабільної ішемічної хвороби серця у разі супутнього цукрового діабету 2 типу з використанням кверцетину та емпагліфлозину

The risk of developing cardiovascular complications is the same in people with diabetes mellitus and in patients with coronary artery disease. Diabetes mellitus is usually referred to as cardiovascular pathology and is considered as a pathogenetic link of the most common disorders of the human organism. Comprehensive correction of glycemia, hyperlipidemia and hypertension is the main target of therapy aimed at reducing the risk of progression of stable coronary artery disease (SCAD) in patients with type 2 diabetes mellitus. It remains relevant to study the possibility and feasibility of using drugs with multimodal action, which could effectively affect the many pathogenetic components of combined pathology. Study aim – to evaluate the effectiveness of drug therapy of stable coronary artery disease and concomitant type 2 diabetes mellitus using bioflavonoid quercetin and empagliflozin, considering the impact on modified risk factors and left ventricular remodeling processes. Methods. 96 patients were examined, all of them had SCAD FC II-III and type 2 diabetes mellitus. Depending on the treatment received, patients were divided into four groups: group I (n = 22) – patients who received basic therapy, group II (n = 26) – received quercetin with basic therapy, group III (n = 25) – took empagliflozin, and group IV (n = 23) – patients who received quercetin on the with basic therapy and empagliflozin. Duration of therapy was 12 weeks. Results. The use of quercetin probably helped to reduce angina pain, palpitations, shortness of breath, and empagliflozin helped to eliminate the manifestations of diabetic polyneuropathy, polydipsia and polyuria, and contributed to weight loss. In patients receiving empagliflozin, HbA1c reduction results in optimized carbohydrate metabolism. In addition, empagliflozin is likely to contribute to the normalization of high-density lipoproteins, and quercetin to both low and high-density lipoproteins. The use of empagliflozin has been shown to have a positive effect on intracardiac hemodynamics, which is contributed by the regression of left ventricular hypertrophy and the improvement of diastolic function. Conclusions. 1. The use of quercetin and empagliflozin in patients with coronary artery disease and concomitant type 2 diabetes mellitus contributed to a significant improvement in the general well-being of patients, the elimination of leading symptoms. 2. Patients with SCAD and concomitant type 2 diabetes mellitus have more profound changes in the lipid spectrum of the plasma, which is characterized by dyslipidemia being more atherogenic in nature. Studied therapy enhanced the antiatherogenic effect of statins, helped to reduce the level of total cholesterol and normalized the ratio of its fractions. 3. Additional administration of empagliflozin allowed to improve the components of transmitral diastolic flow: decreased IVRT, increased the E/A ratio. The improvement in LV diastolic function was accompanied by a decrease of LV mass index, a decrease in LV end diastolic diameter, an improvement in LV systolic function.

Beta3-Adrenergic Receptor Activation Alleviates Cardiac Dysfunction in Cardiac Hypertrophy by Regulating Oxidative Stress.

Background Excessive myocardial oxidative stress could lead to the congestive heart failure. NADPH oxidase is involved in the pathological process of left ventricular (LV) remodeling and dysfunction. β3-Adrenergic receptor (AR) could regulate cardiac dysfunction proved by recent researches. The molecular mechanism of β3-AR regulating oxidative stress, especially NADPH oxidase, remains to be determined. Methods Cardiac hypertrophy was constructed by the transverse aortic constriction (TAC) model. ROS and NADPH oxidase subunits expression were assessed after β3-AR agonist (BRL) or inhibitor (SR) administration in cardiac hypertrophy. Moreover, the cardiac function, fibrosis, heart size, oxidative stress, and cardiomyocytes apoptosis were also detected. Results β3-AR activation significantly alleviated cardiac hypertrophy and remodeling in pressure-overloaded mice. β3-AR stimulation also improved heart function and reduced cardiomyocytes apoptosis, oxidative stress, and fibrosis. Meanwhile, β3-AR stimulation inhibited superoxide anion production and decreased NADPH oxidase activity. Furthermore, BRL treatment increased the neuronal NOS (nNOS) expression in cardiac hypertrophy. Conclusion β3-AR stimulation alleviated cardiac dysfunction and reduced cardiomyocytes apoptosis, oxidative stress, and fibrosis by inhibiting NADPH oxidases. In addition, the protective effect of β3-AR is largely attributed to nNOS activation in cardiac hypertrophy.

Serum Levels of Bone Morphogenetic Proteins 2 and 4 in Patients with Acute Myocardial Infarction.

Background: Bone morphogenetic proteins-2 and -4 (BMPs) have been implicated in left ventricular remodeling (LVR) processes such as an inflammation and fibrogenesis. We hypothesized that this knowledge could be translated into clinics. Methods: We studied the dynamics of serum levels of BMPs, its correlation with markers of LVR and with parameters of echocardiography in patients (n = 31) during the six-month follow-up period after myocardial infarction (MI). Results: Elevated serum levels of BMPs decreased by the six-month follow-up period. BMP-2 decreased from the first day after MI, and BMP-4 decreased from the Day 14. The elevated level of BMP-2 at Day 1 was associated with a lower level of troponin I, reperfusion time and better left ventricular ejection fraction (LV EF) at the six-month follow-up. Elevated serum level of BMP-4 at Day 1 was associated with a lower level of a soluble isoform of suppression of tumorigenicity 2 (sST2), age and reperfusion time. An elevated level of BMP-2 at the six-month follow-up was associated with higher levels of BMP-4, high-sensitivity C-reactive protein (hCRP) and sST2. High serum level of BMP-2 correlated with high levels of hCRP and matrix metalloproteinase (MMP)-9 on Day 7. High serum level of BMP-4 correlated with low levels of hCRP, MMP-9 at Day 3, sST2 at Day 1 and with decreased LV EF on Day 7. The findings of multivariate analysis support the involvement of BMP-2 in the development of post-infarction LVR. Conclusions: Our research translates experimental data about the BMPs in the development of adverse LVR into the clinic. Elevated serum levels of BMPs decreased by the end of the six-month period after MI. BMP-2 decreased from the first day and BMP-4 decreased from Day 14. BMP-2 and BMP-4 were associated with the development of LVR. Their correlations with markers of inflammation, degradation of the extracellular matrix, hemodynamic stress and markers of myocardial damage further support our hypothesis. Diagnostic and predictive values of these BMPs at the development of post-infarction LVR in vivo should be investigated further.

The study of border zone formation in ischemic heart using electro-chemical coupled computational model.

Myocardial infarction (MI) is the most common cause of a heart failure, which occurs due to myocardial ischemia leading to left ventricular (LV) remodeling. LV remodeling particularly occurs at the ischemic area and the region surrounds it, known as the border zone. The role of the border zone in initiating LV remodeling process urges the investigation on the correlation between early border zone changes and remodeling outcome. Thus, this study aims to simulate a preliminary conceptual work of the border zone formation and evolution during onset of MI and its effect towards early LV remodeling processes by incorporating the oxygen concentration effect on the electrophysiology of an idealized three-dimensional LV through electro-chemical coupled mathematical model. The simulation result shows that the region of border zone, represented by the distribution of electrical conductivities, keeps expanding over time. Based on this result, the border zone is also proposed to consist of three sub-regions, namely mildly, moderately, and seriously impaired conductivity regions, which each region categorized depending on its electrical conductivities. This division could be used as a biomarker for classification of reversible and irreversible myocardial injury and will help to identify the different risks for the survival of patient. Larger ischemic size and complete occlusion of the coronary artery can be associated with an increased risk of developing irreversible injury, in particular if the reperfusion treatment is delayed. Increased irreversible injury area can be related with cardiovascular events and will further deteriorate the LV function over time.

Phosphorylation of GATA4 at serine 105 is required for left ventricular remodelling process in angiotensin II-induced hypertension in rats.

In this study, we investigated whether local intramyocardial GATA4 overexpression affects the left ventricular (LV) remodelling process and the importance of phosphorylation at serine 105 (S105) for the actions of GATA4 in an angiotensin II (AngII)‐induced hypertension rat model. Adenoviral constructs overexpressing wild‐type GATA4 or GATA4 mutated at S105 were delivered into the anterior LV free wall. AngII (33.3 µg/kg/h) was administered via subcutaneously implanted minipumps. Cardiac function and structure were examined by echocardiography, followed by histological immunostainings of LV sections and gene expression measurements by RT‐qPCR. The effects of GATA4 on cultured neonatal rat ventricular fibroblasts were evaluated. In AngII‐induced hypertension, GATA4 overexpression repressed fibrotic gene expression, reversed the hypertrophic adult‐to‐foetal isoform switch of myofibrillar genes and prevented apoptosis, whereas histological fibrosis was not affected. Overexpression of GATA4 mutated at S105 resulted in LV chamber dilatation, cardiac dysfunction and had minor effects on expression of myocardial remodelling genes. Fibrotic gene expression in cardiac fibroblasts was differently affected by overexpression of wild‐type or mutated GATA4. Our results indicate that GATA4 reduces AngII‐induced responses by interfering with pro‐fibrotic and hypertrophic gene expressions. GATA4 actions on LV remodelling and fibroblasts are dependent on phosphorylation site S105.

Speckle-Tracking Echocardiography Enables Model-Based Identification of Regional Stiffness Indices in the Left Ventricular Myocardium.

Left ventricular (LV) remodeling is a critical process underlying heart failure (HF) development and progression. While LV global longitudinal strain determined by speckle-tracking echocardiography (STE) provides a promising basis to monitor LV remodeling, reported strain measures are limited by the masking of regional differences and a dependency on hemodynamic load. Our goal is to extend two-dimensional STE to enhance regional mechanical assessment of the LV myocardium-providing clinically accessible and load-independent response variables that directly reflect the LV remodeling process. An inverse finite element analysis was employed with a pattern search optimization algorithm to identify regional indices of LV myocardial stiffness based on STE-derived regional LV longitudinal strains and wall geometries. Our framework was applied in two distinct porcine models of early LV remodeling, specifically following myocardial infarction and onset of LV pressure overload. Regional and temporal changes in computed indices of LV myocardial stiffness over diastolic pressures correlate with conventional indices of LV remodeling and show enhanced early sensitivity as compared to LV global longitudinal strain. Our findings suggest that STE-integrated computational modeling can be used to track indices of LV myocardial stiffness and, thus, is a potential tool for HF diagnosis and prognosis.

PERFORMANCE OF THE VASCULAR STIFFNESS INDICATORS AND THE PROCESS OF LEFT VENTRICLE REMODELING IN HYPERTENSIVE PATIENTS UNDER RENAL REPLACEMENT THERAPY

Objective. The objective of our study was to compare the performance of vascular stiffness (VS) and the left ventricular (LV) remodeling process indicators in patients with arterial hypertension (AH) under renal replacement therapy (RRT), and patients with essential hypertension.Design and methods. 158 people were included in the study, divided into 4 comparable age groups: 32 patients receiving programmed hemodialysis (PH), 37 recipients of renal transplant (RT), 69 patients with essential AH and 20 healthy volunteers. All the patients underwent 24-hour blood pressure (BP) monitoring with an assessment of VS and central BP (SBPao) and echocardiography (EchoCG).Results. The patients under PH and after RT did not have any significant differences in the values of central and peripheral BP. Comparing the groups of patients under RRT with the group of essential AH, the office systolic (SBP) and diastolic (DBP) BP values did not differ significantly. Аlthough, at night, considerably higher DBP(n) and SBPao(n) values were detected in patients under RRT, and in the patients after RT SBP(n) and PP(n) values were also increased. An increase in the SBPao values of more than 10 m/sec was detected only in the groups of patients under RRT. In all the groups with hypertension all indicators of daily VS differed significantly from the group of healthy volunteers. PTIN (Pulse Time Index of Norm) in the studied groups had more evident differences: in the healthy volunteers it was in the range of 80-90%, in the patients with essential hypertension — 50-60%, and in the patients under PH and after RT — 20-40%. In all groups of patients with AH, the average the posterior wall thickness (PWT) of the LV and the interventricular septum thickness (IVST) were close to the upper limit of the norm. In the groups of patients with AH an increase in the relative wall thickness (RWT) of the LV was also detected. Furthermore, considerably higher the values of ILVmass, IVST were found in the group of patients on PH in comparison with the patients after RT. In addition, in all the groups of patients with AH, there was a tendency to LV spherification in comparison with the healthy volunteers, and in the group of essential AH the difference was more pronounced compared with the group under RRT.Conclusion. In the patients with arterial hypertension who undergo renal replacement therapy, higher average values of central BP, higher vascular stiffness (daily pulse wave velocity in the aorta and a longer period of pulse wave velocity increase in the aorta during the day (PTIN)) and less pronounced left ventricular spherification are recorded in comparison with the patients with essential hypertension while office BP values remained consistent.

KDM3A inhibition modulates macrophage polarization to aggravate post-MI injuries and accelerates adverse ventricular remodeling via an IRF4 signaling pathway

It has been reported that KDM3A participates in several cardiovascular diseases through epigenetic mechanisms. However, its biological role post myocardial infarction (MI) has not been explored. Excessive and prolonged inflammation period can aggravate post-MI injuries and accelerates left ventricular (LV) remodeling. Previous studies have shown that macrophages play a momentous role in post-MI injuries by regulating the balance between the inflammatory phase. In this study, we aimed to demonstrate whether KDM3A could regulate the polarization of macrophages to affect the inflammatory response after myocardial infarction and whether targeting KDM3A could influence the prognosis of myocardial infarction and adverse LV remodeling. To explore the biological function of KDM3A and the underlying mechanisms, the loss of function experiments were designed in vitro and vivo. we analyzed the function of macrophages by a phagocytosis and migration assay and explored the polarization of macrophages. The expression of macrophage inflammation-related genes in the acute inflammatory phase and surface markers was detected by western blot and immunofluorescence assays. Echocardiography, Masson's trichrome staining and hematoxylin and eosin (H&E) staining were used to detect cardiac ventricular function. Our data showed that KDM3A is essential for the biological function of rat bone marrow macrophages (BMDMs), and KDM3A deficiency decreases the capacity for phagocytosis and migration, promoting M1 but restraining M2 macrophage phenotype polarization in vitro. Furthermore, we constructed MI models of male rats to verify that KDM3A deficiency could regulate macrophage polarization to aggravate the inflammatory response and accelerate LV remodeling in vivo. Among them, we confirmed that IRF4 is a downstream effector of the KDM3A-dependent pathway which could epigenetically influence the transcription of IRF4 by enhancing histone H3 lysine 9 di-methylation(H3K9me2) accumulation on the IRF4 gene proximal promoter region to modulate macrophage polarization. These results demonstrated that KDM3A plays an essential role in the cardiac repair process of post-MI and LV remodeling by modulating the macrophage phenotype, thereby suggesting a promising therapy to treat post MI injuries.

Abstract P137: Immune Response Factors in Patients With Arterial Hypertension, Diabetes Mellitus and Acute Coronary Syndrome

Purpose: To study cardiac remodeling in patients with arterial hypertension (AH) and acute coronary syndrome (ACS) complicated with diabetes mellitus (DM) through analysis of laboratory parameters and echocardiogram. Methods: A total of 67 patients were prospectively enrolled (age range: from 36 to 79 years; average: 60,96 ± 9,22 years) with AH and ACS who were admitted to Emergency Hospital. The patients were divided into 2 groups depending on the presence of DM: 23 patients with DM (age average: 65,09 ± 7,73 years) and 44 without DM (age average: 58,79 ± 9,19 years). Serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), high sensitive C reactive protein (hs-CRP), antibodies to LPS General Enterobacteriaceae, antibodies to LPS Re-Glycolipid were tested for all patients. Echocardiograms were obtained on all the patients, interventricular septal thickness (IVSd) and others parameters were measured by taking the mean values of three continuous heartbeat cycles in the expiratory state. All indicators were calculated using the statistics program Statistica, a P-value of &lt; 0,05 was considered statistically significant. Results: There were no significant differences in the levels of serum hs-CRP, TC, HDL-C, LDL-C; but TG levels were significantly higher in patients with DM ( 3,16 ± 2,61 mmol/l) than in controls (1,75 ± 1,33 mmol/l, p&lt;0,05). Serum antibodies to LPS General Enterobacteriaceae levels (441,52 ± 303,70 A.U.O.D) were also significantly higher in the DM group than in controls (271,41 ± 200,13 A.U.O.D, p&lt;0,05). The levels of serum antibodies to LPS General Enterobacteriaceae were positively correlated with IVSd (r = 0,765, p&lt;0,05). Conclusion: The data demonstrated, that patients with DM and AH have a greater immune response which correlates with indicators of left ventricular remodeling. The mechanism of the cardiac function impairment, however, has not been clearly explained yet. The role of the immune response in the development of cardiac muscle remodeling is not fully understood. It Is currently considered that these changes may participate in the pathological process of left ventricular remodeling in patients with AH and DM.

Predictors of Left Ventricular Remodeling Post Acute Myocardial Infarction. Protocol for a Clinical Study

Abstract Heart failure is a clinical syndrome that appears as a consequence of a structural disease, and the most common cause of left ventricular systolic dysfunction results from myocardial ischemia. Cardiac remodeling and neuroendocrine activation are the major compensatory mechanisms in heart failure. The main objective of the study is to identify the association between serum biomarkers illustrating the extent of myocardial necrosis (highly sensitive troponin as-says), left ventricular dysfunction (NT-proBNP), and systemic inflammatory response (illustrated via serum levels of hsCRP and interleukins) during the acute phase of a myocardial infarction, and the left ventricular remodeling process at 6 months following the acute event, quantified via speckle tracking echocardiography. The study will include 400 patients diagnosed with acute myocardial infarction without signs and symptoms of heart failure at the time of enrollment that will undergo a complex clinical examination and speckle tracking echocardiography. Serum samples from the peripheral blood will be collected in order to determine the inflammatory serum biomarkers. After 6 months, patients will be divided into 2 groups according to the development of ventricular remodeling, quantified by speckle tracking echocardiography: group 1 will consist of patients with a remodeling index lower than 15%, and group 2 will consist of patients with a remodeling index higher than 15%. All clinical and imaging data obtained at the baseline will be compared between these two groups in order to determine the features associated with a higher risk of deleterious ventricular remodeling and heart failure.

Abstract 487: Immune Response Factors in Patients With Diabetes Mellitus and Acute Coronary Syndrome

Purpose: To study cardiac remodeling in patients with ACS complicated with DM through analysis of laboratory parameters and echocardiogram. Methods: A total of 67 patients were prospectively enrolled (age range: from 36 to 79 years; average: 60,96 ± 9,22 years) with ACS who were admitted to Emergency Hospital. The patients were divided into 2 groups depending on the presence of DM: 23 patients with DM (age average: 65,09 ± 7,73 years) and 44 without DM (age average: 58,79 ± 9,19 years). Serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), high sensitive C reactive protein (hs-CRP), antibodies to LPS General Enterobacteriaceae, antibodies to LPS Re-Glycolipid were tested for all patients. Echocardiograms were obtained on all the patients, interventricular septal thickness (IVSd) and others parameters were measured by taking the mean values of three continuous heartbeat cycles in the expiratory state. All indicators were calculated using the statistics program Statistica, a P-value of &lt; 0,05 was considered statistically significant. Results: There were no significant differences in the prevalence of smoking, family history of CVD, hypertension between groups. No differences were observed in the levels of serum hs-CRP, TC, HDL-C, LDL-C; but TG levels were significantly higher in patients with DM ( 3,16 ± 2,61 mmol/l) than in controls (1,75 ± 1,33 mmol/l, p&lt;0,05). Serum antibodies to LPS General Enterobacteriaceae levels (441,52 ± 303,70 A.U.O.D) were also significantly higher in the DM group than in controls (271,41 ± 200,13 A.U.O.D, p&lt;0,05). The levels of serum antibodies to LPS General Enterobacteriaceae were positively correlated with IVSd (r = 0,765, p&lt;0,05). Conclusion: The data demonstrated, that patients with DM have a greater immune response which correlates with indicators of left ventricular remodeling. The mechanism of the cardiac function impairment, however, has not been clearly explained yet. The role of the immune response in the development of cardiac muscle remodeling is not fully understood. It Is currently considered that these changes may participate in the pathological process of left ventricular remodeling in patients with DM.

Novel Myocardial PET/CT Receptor Imaging and Potential Therapeutic Targets.

Activation of myocardial cannabinoid type 1 receptors (CB1-R) and/or angiotensin II type 1 receptors (AT1-R) likely plays an important mechanistic role in determining the left-ventricular remodeling process in systolic heart failure. We provide an overview on novel radiotracer probes and positron emission tomography (PET)/computed tomography (CT) imaging to noninvasively probe the expression of myocardial CB1-R and/or AT1-R. Recent translational investigations have demonstrated the feasibility of 11C-OMAR or 11C-KR31173 and PET/CT to image and quantify myocardial CB1-R and/or AT1-R expression, respectively. There is an increasing understanding of the mechanisms of activated myocardial CB1-R and/or AT1-R to influence the left-ventricular remodeling process in systolic heart failure in different disease entities. The review summarizes contributions of PET to image myocardial CB1-R and AT1-R expression that may have the potential to serve as a target to tailor preventive medical care in the individual patient.