Intramyocardial Fibrosis Research Articles

Chitosan Versus Dapagliflozin in a Diabetic Cardiomyopathy Mouse Model.

Diabetes mellitus is a metabolic disorder with global economic implications that can lead to complications such as diabetic cardiomyopathy. The aim of this study was to compare the effects of chitosan versus dapagliflozin in mouse diabetic cardiomyopathy. We used 32 C57Bl/6 male mice aged between 8 and 10 weeks, which were randomly divided into Control-without diabetes mellitus (DM), type 1 DM (T1DM), T1DM + Chitosan, and T1DM + Dapapgliflozin groups. We induced diabetes with streptozotocin and treated the animals for 12 weeks. The analysis showed a reduction in intramyocardial fibrosis in the T1DM + Dapapgliflozin compared to T1DM animals. In T1DM + CHIT, a reduction in intramyocardial fibrosis was observed although, accordingly, there was also no significant decrease in blood glucose. The level of oxidative stress was reduced in the groups of treated animals compared to T1DM. All these observed changes in the structure and function of hearts were highlighted in the echocardiographic examination. In the treated groups, there was delayed appearance of left ventricular (LV) hypertrophy, a slight decrease in the ejection fraction of the LV, and an improved diastolic profile. The results demonstrate that chitosan has promising effects on diabetic cardiomyopathy that are comparable to the beneficial effects of dapagliflozin.

Potential for intramyocardial fibrosis detection based on estimation of extracellular volume using dual-energy computed tomography

An increase in left ventricular (LV) extracellular volume (ECV) is an important parameter of LV morphology and is considered synonymous with myocardial fibrosis, as well as a reliable marker of myocardial injury and impaired cardiac function. Accurate methods for detecting and assessing myocardial fibrosis are very important for clinical practice. The current standard for myocardial fibrosis imaging is delayed gadolinium enhanced cardiac magnetic resonance imaging (MRI) or T1 mapping, but these techniques have limitations. They can be avoided by using dual-energy computed tomography (DECT), which makes it possible to identify myocardial fibrosis, including small-focal fibrosis, in two different ways (subtraction technique and iodine density measurement technique). The literature analysis carried out by the authors showed good comparability of MRI and DECT results in determining ECV in patients with various heart diseases of both ischemic and non-ischemic nature, including cardiomyopathies, aortic stenosis, pulmonary hypertension, sarcoidosis, and amyloidosis. In addition, the use of DECT to identify myocardial fibrosis is also possible if cardiac inflammation is suspected. In addition to evaluating the effectiveness of DECT compared with MRI, different scanning protocols were analyzed, since there is currently no consensus on the optimal contrast administration regimen. The issue of radiation exposure in modern DECT scanners is also separately considered. The authors showed that DECT is an important tool for determining ECV, which is of interest for clinical practice.

Endomyocardial substrate of ventricular arrhythmias in patients with autoimmune rheumatic diseases.

Delayed enhancement-magnetic resonance imaging (DE-MRI) has demonstrated that nonischemic cardiomyopathy is mainly characterized by intramural or epicardial fibrosis whereas global endomyocardial fibrosis suggests cardiac involvement in autoimmune rheumatic diseases or amyloidosis. Conduction disorders and sudden cardiac death are important manifestations of autoimmune rheumatic diseases with cardiac involvement but the substrates of ventricular arrhythmias in autoimmune rheumatic diseases have not been fully elucidated. 20 patients with autoimmune rheumatic diseases presenting with ventricular tachycardia (VT) (n = 11) or frequent ventricular extrasystoles (n = 9) underwent DE-MRI and/or endocardial electroanatomical mapping of the left ventricle (LV). Ten patients with autoimmune rheumatic diseases underwent VT ablation. Global endomyocardial fibrosis without myocardial thickening and unrelated to coronary territories was detected by DE-MRI or electroanatomical voltage mapping in 9 of 20 patients with autoimmune rheumatic diseases. In the other patients with autoimmune rheumatic diseases, limited regions of predominantly epicardial (n = 4) and intramyocardial (n = 5) fibrosis or only minimal fibrosis (n = 2) were found using DE-MRI. Endocardial low-amplitude diastolic potentials and pre-systolic Purkinje or fascicular potentials, mostly within fibrotic areas, were identified as the targets of successful VT ablation in 7 of 10 patients with autoimmune rheumatic diseases. Global endomyocardial fibrosis can be a tool to diagnose severe cardiac involvement in autoimmune rheumatic diseases and may serve as the substrate of ventricular arrhythmias in a substantial part of patients.

P350 LOOKING FOR RED FLAGS

Abstract Case report: a 81 years old man with systemic hypertension, dyslipidemia, past smoking habit, was admitted to the ER of our hospital with acute decompensated heart failure. Since July he complained of worsening of dyspnea and paroxysmal nocturnal dyspnea. His blood pressure was of 155/80 mmHg, the HR was of 78 bpm in atrial fibrillation. He reported past myocardial infarction at the age of 32, thenceforth he underwent periodic cardiac check–up. From 2013 he had developed atrial fibrillation. He had suspended Amiodarone because of dysthyroidism, rate control was obtained with Bisoprolol. In 2015, he underwent coronary angiography for a positive scintigraphy showed absence of lesions. During the same hospitalization there was evidence of nocturnal bradycardia (35 bpm). In 2016, a cardiac MR showed subendocardial and intramyocardial fibrosis at mid–basal wall resembling post ischemic events. He underwent past carpal tunnel syndrome surgery. During the actual hospitalization, the EKG showed atrial fibrillation (78 bpm), complete left bundle branch block (both already known). Serum and urinary light–chain assessment and determination of immunoglobulin light chains levels were negative for AL amyloidosis. The echocardiogram documented: hypertrophy of the interventricular septum, mildly reduced LV systolic function (EF=43%). Invasive coronary angiography showed absence of lesions. CMR showed: left ventricular size at the upper limit of normal with hypertrophy of the interventricular septum and the anterior wall, diffused left transmural LGE, focal fibroadipose infiltration of lower basal SIV. During the hospitalization multiple episodes of non sustained ventricular tachycardia occurred, so that a CRT–D device was implanted in secondary prevention. There was a strong suspicion of cardiac amyloidosis so that definitive diagnosis was obtained by the use of 99m Tc scintigraphy coupled with haematologic tests (already done, resulted negative). Scintigraphy showed myocardial uptake of the radiotracer greater than the bone (Grade 3 Perugini score). Conclusion cardiac amyloidosis is a restrictive cardiomyopathy. Early diagnosis is really important, firstly, because new treatments, such as a TTR stabilizer, have transformed this once incurable disease to a treatable condition. Secondly, diagnostic tools now allow earlier and more accurate non–invasive diagnosis. It is crucial to put the attention on red flags which have to be found to rise the clinical suspicion.

Cardiovascular Disease Among Persons Living With HIV: New Insights Into Pathogenesis and Clinical Manifestations in a Global Context

Widespread use of contemporary antiretroviral therapy globally has transformed HIV disease into a chronic illness associated with excess risk for disorders of the heart and circulatory system. Current clinical care and research has focused on improving HIV-related cardiovascular disease outcomes, survival, and quality of life. In high-income countries, emphasis on prevention of atherosclerotic coronary artery disease over the past decade, including aggressive management of traditional risk factors and earlier initiation of antiretroviral therapy, has reduced risk for myocardial infarction among persons living with human immunodeficiency virus-1 infection. Still, across the globe, persons living with human immunodeficiency virus-1 infection on effective antiretroviral therapy treatment remain at increased risk for ischemic outcomes such as myocardial infarction and stroke relative to the persons without HIV. Unique features of HIV-related cardiovascular disease, in part, include the pathogenesis of coronary disease characterized by remodeling ectasia and unusual plaque morphology, the relative high proportion of type 2 myocardial infarction events, abnormalities of the aorta such as aneurysms and diffuse aortic inflammation, and HIV cerebrovasculopathy as a contributor to stroke risk. Literature over the past decade has also reflected a shift in the profile and prevalence of HIV-associated heart failure, with a reduced but persistent risk of heart failure with reduced ejection fraction and a growing risk of heart failure with preserved ejection fraction. Cardiac magnetic resonance imaging and autopsy data have emphasized the central importance of intramyocardial fibrosis for the pathogenesis of both heart failure with preserved ejection fraction and the increase in risk of sudden cardiac death. Still, more research is needed to better characterize the underlying mechanisms and clinical phenotype of HIV-associated myocardial disease in the current era. Across the different cardiovascular disease manifestations, a common pathogenic feature is that HIV-associated inflammation working through different mechanisms may amplify underlying pathology because of traditional risk and other host factors. The prevalence and phenotype of individual cardiovascular disease manifestations is ultimately influenced by the degree of injury from HIV disease combined with the profile of underlying cardiometabolic factors, both of which may differ substantially by region globally.

Опыт применения 3-суточного мониторирования электрокардиограммы по Холтеру с телеметрией (3G) на примере обследования детей с гипертрофической кардиомиопатией

Objective. To evaluate the results of 72-hour monitoring of Holter electrocardiograms with telemetry in children with hypertrophic cardiomyopathy (HCM). Patients and methods. A randomized retrospective study of 55 children with the confirmed diagnosis of HCM was conducted on the basis of the Federal State Autonomous Institution of the Ministry of Health of Russian Federation "National Children Medical Research Center"; all patients were hospitalized in the cardiology department for the examination and treatment in the period 2021–2023. The study included 33 boys and 22 girls aged 6 to 17.8 years; age and documented functional limitations in both groups were comparable. All patients underwent electrocardiography (ECG) on the 12-channel electrocardiograph; 3-channel 3-day monitoring of Holter electrocardiograms with telemetry using the Astrocard-Telemetry 3G complex (Meditek, Russia); magnetic resonance imaging (MRI) of the heart with intravenous contrast. Parents of 43 patients filled out questionnaires identifying direct and indirect signs of sleep disorders. The obtained data were presented in fractions, as well as as M ± m; minimum, Q1, Q3, maximum; and the Kendall rank correlation coefficient and the Friedman criterion were calculated daily. The differences were considered significant at p < 0.05. The work has been approved by an independent local ethics committee. All parents (or legal representatives) of the children signed the voluntary informed Results. 12-channel ECG revealed various and non-specific disorders (arrhythmias, signs of overload of the heart chambers) in 50 (90.9%) patients. Long-term (3-day) Holter monitoring revealed practically no significant differences in the mean values of the studied indicators between days; by the 3rd day of the study, two trends were revealed: an increase in the average number of episodes of ventricular tachycardia (p = 0.058) and an elongation of the QTc interval in boys (p = 0.053). The significant decrease in heart rate was recorded in girls on the 3rd day of the study (p = 0.011). According to the results of MRI, intramyocardial fibrosis was detected in 37 (67.3%) cases: in 23 (69.7%) boys and 14 (63.6%) girls. In 16 (29.1%) patients, the volume of myocardial lesion was ≥10%. Direct and/or indirect signs of respiratory disorders during sleep were recorded in 28 (65.1%) children. In children with signs of sleep disorders, significant positive correlations were found with the number of supraventricular and ventricular extrasystoles and episodes of ventricular tachycardia. Signs of an increased risk of sudden vascular death were recorded in 8 (14.5%) children. Conclusion. Long-term (3-day) Holter monitoring of electrocardiograms is well adapted to children; all major rhythm disturbances were detected during the first 24 hours. Prolongation of the study may be recommended to solve certain clinical problems (diagnosis of syncopal conditions, paroxysms of unclear etiology, sleep apnea). In children with HCM, it is necessary to identify direct and indirect signs of sleep disorders that have significant correlations with cardiac arrhythmias, including those that are an integrative indicator of the risk of sudden cardiac death. Key words: sudden cardiac death, hypertrophic cardiomyopathy, children, multi-day monitoring of electrocardiogram with telemetry, rhythm disturbances, sleep disorders

Berardinelli-Seip Congenital Lipodystrophy Discovered Following a STEMI Event.

Berardinelli-Seip congenital lipodystrophy (BSCL) is a rare congenital lipodystrophy, with an incidence of 1-9 per million population, which is usually diagnosed at birth and is associated with pathogenic variants of the BSCL2 and AGPAT2 genes.Due to the absence of functional adipocytes, lipid storage occurs in other tissues, including skeletal muscle and liver.Diagnosis is based on the presence of three major or two major and two minor characteristics.

Correlation of Serum Fibroblast Growth Factor 23 With Left Ventricular Diastolic Function in Chronic Kidney Patients

Chronic Kidney Disease (CKD) is one of most common world’s health problems with constantly increasing prevalence and many complications, and cardiovascular is one of them. The earliest cardiovascular damage that can be seen is left ventricular diastolic dysfunction. In patients with CKD, there will be mineral metabolism disorders, including phosphate. Persistently increased phosphate in CKD will cause rising in Fibroblast Growth Factor 23 (FGF23) that regulates phosphate in the circulation. High level of FGF23 will directly damage the heart and stimulates cardiac remodeling that will result in cardiomyocyte damage, atherosclerosis and intramyocardial cells fibrosis. This will cause myocardial stiffness and diastolic dysfunction. The purpose of the study is to discover correlation between Fibroblast Growth Factor 23 (FGF23) serum and left ventricle diastolic function in patients with chronic kidney disease. This is an observational study with cross-sectional methods. The sample is 30 patients diagnosed with chronic kidney disease (CKD). Patients are evaluated for Fibroblast Growth Factor 23 (FGF23) level in their serum, assessed the left ventricle diastolic function by measuring early diastolic velocity of the left ventricle (lateral e’) using echocardiography.There is significantly increased of FGF23 serum levels and decreased of lateral e’ value in chronic kidney disease case. There’s also a strong correlation between FGF23 serum and filtration glomerulus rate (LFG) (p<0.05), and a strong correlation between FGF23 serum level with lateral e’ as a component of left ventricle diastolic function. There’s a strong correlation between FGF23 with left ventricle diastolic function in patients with CKD.

MO440: Intramyocardial Artery Fibrosis and Media Hypertrophy are Associated With Beta-Catenin and Calcineurin Expression in the Model of Arterial Hypertension and CKD

Abstract BACKGROUND AND AIMS Intramyocardial arteries (IA) are one of the components of pathological cardiac remodeling. We have previously shown that cardiomyocytes hypertrophy and interstitial fibrosis are accompanied by calcineurin (CaN) and β-catenin (βCat) up-regulation in the model of arterial hypertension (AH) and chronic kidney disease (AH-CKD). In this pilot study, we investigated whether IA remodeling is associated with CaN and βCat expressions in medial (MC) and adventitial (AC) cells in AH-CKD. METHOD AH-CKD was induced by 5/6 nephrectomy (5/6NE) in spontaneously hypertensive rats (SHR-NE, n = 8). Sham-operated (SO) SHR (SHR-SO, n = 8) and Wistar Kyoto rats (WKY-SO, n = 8) were controls. Systolic blood pressure (SBP), myocardial mass index (MMI), serum creatinine (Cr), FGF23, renal Klotho (rKl), IA wall thickness (WT), perivascular fibrosis (PF), number of AC, βCat-positive AC (βCat + AC) to all AC ratio, CaN and βCat expression in MC were analyzed for 2 months after 5/6NE or SO. RESULTS The cardiac remodeling indexes—SBP, MMI, WT, AC, PF, as well as FGF23, were higher and rKl was lower in SHRs vs WKY-SO and in SHR-NE versus SHR-SO (Table). The increase in WT was accompanied by MC hypertrophy (Figure 1) with cytoplasmic CaN expression (data not shown) and PF with the increase in the number of AC in SHR-SO vs WKY-SO (Table). PF, medial hypertrophy and fibrosis of IA were accompanied by the apparent expression of CaN and βCat in the MC (Figure 1), an increase in the total number of AC and the βCat + AC accumulation in AH-CKD (Table, Figure 2). CONCLUSION IA remodeling in the setting of AH and CKD seems to be associated with СаN and βCat up-regulation in medial and adventitial cells subpopulations. Further study is needed to identify the origin of CaN/βCat expressing cells and the mechanisms of their involvement in the pathology of vascular wall alterations.

Rare Case of an Adult With Double-Chambered Left Ventricle.

The rare case of an adult with a double-chambered left ventricle was revealed using multimodality imaging using echocardiography and cardiac magnetic resonance imaging in a 38-year-old asymptomatic male patient. The congenital malformation was dominated by a second, coarsely trabeculated muscular shelf dividing the left ventricle into 2 chambers without signs for left ventricular inflow or outflow tract obstruction. The partition wall did not show any signs for intramyocardial fibrosis in late gadolinium enhancement cardiovascular magnetic resonance imaging. Flow measurements excluded a relevant intracardial shunt across the additive perimembranous ventricular septal defect. There were no signs for global right and left ventricular dysfunction with left and right ventricular volumes and ejection fraction within normal limits. A conservative approach was recommended. In summary, we are able to present the case of an adult with a double-chambered left ventricle with a second muscular "septum" partially dividing the left ventricular cavity without causing a relevant impact on cardiac function or clinical signs for heart failure.

Congenitally Corrected Transposition of the Great Arteries: Conduction Anomalies: A Case Report

Introduction: Congenitally corrected transposition of the great arteries (CCTGA) is a rare heart disease that encompasses an atrioventricular and ventriculoarterial discordance and accounts for less than 1 percent of congenital heart diseases. Objective: To present an atypical case of a man with complex congenital heart disease and conduction anomalies. Case Presentation: This is a case of a 34-year-old patient who came to the hospital with 1 week of dyspnea on exertion and episodes of lipothymia. The patient was referred to our hospital after an electrocardiogram from his primary care with evidence of blocked atrial fibrillation. During the initial evaluation blocked atrial fibrillation was confirmed with a rescue ventricular rate of 38 bpm. A magnetic resonance confirmed the presence of the atrioventricular and ventriculoarterial discordance, the aorta had a left anterior position, perimembranous ventricular septal defect with a right to left shunt, biventricular systolic dysfunction, moderate tricuspid, and mitral regurgitation, interventricular septal intramyocardial and biatrial fibrosis, left atrial dilation, and dilation of the pulmonary artery. After pacemaker placement, the patient has an improvement in his clinical symptoms and quality of life. Conclusions: Cardiac arrhythmias are CCTGA’s leading cause of death, mostly ventricular tachycardia, and atrial fibrillation. Right bundle branch block is a previously unreported and potentially very rare presentation of this disease. This, added to the fact that our patient was diagnosed at an advanced age, but without symptoms of heart failure, makes him an atypical case of CCTGA, with new potential treatment options.

Reverse electromechanical modelling of diastolic dysfunction in spontaneous hypertensive rat after sacubitril/valsartan therapy.

AimsHypertension is a significant risk for the development of left ventricular hypertrophy, diastolic dysfunction, followed by heart failure and sudden cardiac death. While therapy with sacubitril/valsartan (SV) reduces the risk of sudden cardiac death in patients with heart failure and systolic dysfunction, the effect on those with diastolic dysfunction remains unclear. We hypothesized that, in the animal model of hypertensive heart disease, treatment with SV reduces the susceptibility to ventricular arrhythmia.Methods and resultsYoung adult female spontaneous hypertensive rats (SHRs) were randomly separated into three groups, which were SHRs, SHRs treated with valsartan, and SHRs treated with SV. In addition, the age‐matched and weight‐matched Wistar Kyoto rats were considered as controls, and there were 12 rats in each group. In vivo ventricular tachyarrhythmia induction and in vitro optical mapping were used to measure the inducibility of ventricular arrhythmias and to characterize the dynamic properties of electrical propagation. The level of small‐conductance Ca2+‐activated potassium channel type 2 (KCNN2) was analysed in cardiac tissue. Compared with SHR with left ventricular hypertrophy, treatment with SV significantly improved cardiac geometry (relative wall thickness, 0.68 ± 0.11 vs. 0.76 ± 0.13, P < 0.05) and diastolic dysfunction (isovolumetric relaxation time, 59.4 ± 3.2 vs. 70.5 ± 4.2 ms, P < 0.05; deceleration time of mitral E wave, 46 ± 4.8 vs. 42 ± 3.8, P < 0.05). The incidence of induced ventricular arrhythmia was significantly reduced in SHR treated with SV compared with SHR (ventricular tachycardia, 1.14 ± 0.32 vs. 2.91 ± 0.5 episodes per 10 stimuli, P < 0.001; ventricular fibrillation, 1.72 ± 0.31 vs. 5.81 ± 0.42 episodes per 10 stimuli, P < 0.001). The prolonged action potential duration (APD) and increase of the maximum slope of APD restitution were observed in SHR, while the treatment of SV improved the arrhythmogeneity (APD, 37.12 ± 6.18 vs. 92.41 ± 10.71 ms at 250 ms pacing cycle length, P < 0.001; max slope 0.29 ± 0.01 vs. 1.48 ± 0.04, P < 0.001). These effects were strongly associated with down‐regulation of KCNN2 (0.38 ± 0.07 vs. 0.74 ± 0.12 ng/ml, P < 0.001). The treatment of SV also decreased the level of N‐terminal pro‐B‐type natriuretic peptide, cardiac bridging integrator‐1, and intramyocardial fibrosis of SHR.ConclusionsIn conclusion, synergistic blockade of the neprilysin and the renin–angiotensin system by SV in SHRs results in KCNN2‐associated electrical remodelling in ventricle, which stabilizes electrical dynamics and attenuates arrhythmogenesis.

Arrhythmias and Sudden Death Risk in Hypertrophic Cardiomyopathy

The risk of sudden death in hypertrophic cardiomyopathy is related to the presence of ventricular arrhythmias in most cases. Finding the best schemes to assess the probability of arrhythmic complications will remain a challenge for modern Cardiology. Meanwhile, the multifactorial approach is the best strategy to avoid the unnecessary implantation of devices such as the implantable cardioverter defibrillator. Although the electrocardiogram remains an excellent diagnostic tool, even before echocardiographic expression, it does not have a clear role as a risk factor. However, the identification of associated arrhythmias such as preexcitation or long QT and variants of presentation as apical hypertrophic cardiomyopathy, allows identifying patients with high probability of sudden death. During the last few years, cardiac resonance and quantification of intramyocardial fibrosis (the basic mechanism of ventricular arrhythmias) have gained an important role in the evaluation of these patients.In particular, pediatric patients must have an individualized approach due to the poor prognosis at early ages and the uncertain role of different tools for risk assessment and treatment.

Brief Report: Adiponectin Levels Linked to Subclinical Myocardial Fibrosis in HIV.

Persons living with HIV (PLWH) are at an increased risk of myocardial dysfunction and metabolic disturbances represent one of several potential contributing factors. Adiponectin is an adipokine that enhances insulin sensitivity with potential cardioprotective effects. We therefore investigated the relationship between myocardial fibrosis, adiponectin, and related metabolic parameters to better understand the pathophysiologic mechanisms of myocardial injury in PLWH. This is a prospective, cross-sectional study of PLWH without known cardiovascular disease (n = 87) and 28 healthy matched controls. Diffuse myocardial fibrosis and epicardial adipose tissue (EAT) were evaluated using cardiac magnetic resonance imaging and cardiac computed tomography. Myocardial fibrosis was increased in PLWH and was correlated with adiponectin (r = 0.26, P = 0.004) and EAT (r = -0.42, P < 0.0001). Myocardial fibrosis was not associated with smoking pack years or CD4/CD8 ratio. In multivariate analysis that included body mass index, HIV status (P = 0.04), female sex (P < 0.0001), higher adiponectin (P = 0.046) and lower EAT (P = 0.01) were independently associated with myocardial fibrosis. We describe a novel association between serum adiponectin and subclinical intramyocardial fibrosis, as well as a significant inverse relationship between intramyocardial fibrosis and EAT. Adiponectin may represent a target for preventing myocardial injury in the future; however, our findings reflect the complexity of the metabolic interactions of adiponectin and epicardial adipose as factors associated with the myocardial architecture.

New Variant of &lt;i&gt;MYH7&lt;/i&gt; Gene Nucleotide Sequence in Familial Non-Compaction Cardiomyopathy with Benign Course

Left ventricular non-compaction (LVNC) is a genetically determined cardiomyopathy characterized by different variants of the clinical course. LVNC family cases allow to study in more details the role of genetic factors in cardiomyopathy pathogenesis and prognosis, as well as to determine clinical course features. Aim . To demonstrate a case of LVNC familial form with a stable benign course and to assess the possible relationship of the detected mutation with the disease prognosis. Material and methods . A family with LVNC was included in the study. The patient with LVNC and his 1st and 2nd degree of kinship relatives underwent clinical and instrumental examination and exome sequencing. LVNC was diagnosed in proband and proband's father. LVNC diagnosis was established basing on echo and magnetic resonance imaging (MRI) criteria. Results . This article presents the results of a comprehensive clinical and instrumental examination of a family with LVNC with a new variant in the MYH7 gene, the absence of intramyocardial fibrosis according to MRI of the heart and a favorable disease course, both in proband's father and proband himself. A comparative analysis of the data obtained with the results of recent large-scale studies and meta-analyses devoted to the study of prognostic factors in patients with LVNC, with identified variants in the MYH7 gene. Conclusions . The variant of p.His1338Pro identified in the MYH7 gene may be associated with the development of LVNC with a benign course.

Isolated Endomyocardial Fibrosis of the Right Ventricle

We describe a case of tropical right ventricular (RV) endomyocardial fibrosis. By CMR, a typical pattern of RV dilatation with apical obliteration was found, and late gadolinium enhancement of the obliterated part was present, confirming fibrosis. By T1-mapping, myocardial extracellular volume was elevated suggesting associated intramyocardial interstitial fibrosis and highlighting the importance of tissue characterisation to diagnose this condition.

Altered Ca2+ and Na+ Homeostasis in Human Hypertrophic Cardiomyopathy: Implications for Arrhythmogenesis.

Hypertrophic cardiomyopathy (HCM) is the most common mendelian heart disease, with a prevalence of 1/500. HCM is a primary cause of sudden death, due to an heightened risk of ventricular tachyarrhythmias that often occur in young asymptomatic patients. HCM can slowly progress toward heart failure, either with preserved or reduced ejection fraction, due to worsening of diastolic function. Accumulation of intra-myocardial fibrosis and replacement scars underlies heart failure progression and represents a substrate for sustained arrhythmias in end-stage patients. However, arrhythmias and mechanical abnormalities may occur in hearts with little or no fibrosis, prompting toward functional pathomechanisms. By studying viable cardiomyocytes and trabeculae isolated from inter-ventricular septum samples of non-failing HCM patients with symptomatic obstruction who underwent myectomy operations, we identified that specific abnormalities of intracellular Ca2+ handling are associated with increased cellular arrhytmogenesis and diastolic dysfunction. In HCM cardiomyocytes, diastolic Ca2+ concentration is increased both in the cytosol and in the sarcoplasmic reticulum and the rate of Ca2+ transient decay is slower, while the amplitude of Ca2+-release is preserved. Ca2+ overload is the consequence of an increased Ca2+ entry via L-type Ca2+-current [due to prolongation the action potential (AP) plateau], combined with a reduced rate of Ca2+-extrusion through the Na+/Ca2+ exchanger [due to increased cytosolic (Na+)] and a lower expression of SERCA. Increased late Na+ current (INaL) plays a major role, as it causes both AP prolongation and Na+ overload. Intracellular Ca2+ overload determines an higher frequency of Ca2+ waves leading to delayed-afterdepolarizations (DADs) and premature contractions, but is also linked with the increased diastolic tension and slower relaxation of HCM myocardium. Sustained increase of intracellular [Ca2+] goes hand-in-hand with the increased activation of Ca2+/calmodulin-dependent protein-kinase-II (CaMKII) and augmented phosphorylation of its targets, including Ca2+ handling proteins. In transgenic HCM mouse models, we found that Ca2+ overload, CaMKII and increased INaL drive myocardial remodeling since the earliest stages of disease and underlie the development of hypertrophy, diastolic dysfunction and the arrhythmogenic substrate. In conclusion, diastolic dysfunction and arrhythmogenesis in human HCM myocardium are driven by functional alterations at cellular and molecular level that may be targets of innovative therapies.

PARP-1 inhibition attenuates cardiac fibrosis induced by myocardial infarction through regulating autophagy

Post-MI heart failure is characterized by structural remodeling, in which intramyocardial fibrosis takes a important part. Poly(ADP-ribose) polymerase 1 (PARP-1) is a extensive nuclear enzyme and plays a critical role in various diseases. It was shown that PARP-1 inhibition could alleviate heart failure and dowregulate autophagy, but whether PARP-1 regulates autophagy and thus impacts the activities of CFs remain unknown. We transfected cultured cardiac fibroblasts (CFs) with small interfere RNA-PARP-1 (siPARP-1) to downregulate PARP-1 and analyzed the ability of proliferation, migration, differentiation, and autophagy levels of CFs under different treatments using CCK8 assays, transwell migration assays, immunofluorescence assays detecting expression of α-SMA, western blot assays detecting autophagy-related proteins respectively. Furthermore, rat models of myocardial infarction (MI) were induced by ligation of left anterior descending coronary artery and PARP-1 inhibitor, 4-aminobenzamide (4-AB), was injected intraperitoneally after MI, followed by echocardiography detection, masson assays, immunohistochemistry assays detecting expression of α-SMA and western blot assays detecting autophagy-related proteins to investigate whether PARP-1 inhibition could regulate autophagy, alleviate cardiac fibrosis and improve cardiac function in vivo. In cultured CFs, siPARP-1 repressed TGF-β1-induced proliferation, migration, and differentiation through regulating autophagic levels. The in vitro results was verified by the in vivo study, indicating that PARP-1 inhibition partially decreased autophagy, abrogated cardiac fibrosis and significantly improved cardiac function post-MI. In conclusion, this work demonstrated the vital connection of PARP-1 and autophagy in the activation of CFs, and provided solid evidence supporting PARP-1 inhibition as a feasible strategy for the treatment of post-MI heart failure.

Cardiac magnetic resonance imaging in myocardial inflammation in autoimmune rheumatic diseases: An appraisal of the diagnostic strengths and limitations of the Lake Louise criteria

Myocardial inflammation in autoimmune rheumatic diseases (ARDs) is the endpoint of various pathophysiologic processes. The Lake Louise-criteria is the most popular approach for the diagnosis of myocarditis. However, due to the diversity of myocardial inflammation in ARDs, some issues should be acknowledged.Of the three Lake Louise indices, early and late gadolinium enhancement (EGE and LGE respectively) measurements may be affected by co-existing disease processes or be present due to a fibrotic ARD like systemic sclerosis, leaving T2-ratio as the only uniformly robust measurement across ARDs. It thus becomes apparent that the Lake Louise criteria suffer from a number of limitations when ARD patients are assessed based on them. The introduction of T1/T2 mapping allowed the quantification of intramyocardial fibrosis missed by LGE and the detection of myocardial oedema respectively, both commonly found in ARDs.The Lake Louise criteria play an important role in the evaluation of AIMI in ARDs. However, the pathophysiologic background of cardiac involvement in ARDs should always be acknowledged in their evaluation. Even though the inclusion of T1/T2 mapping and ECV may better describe diffuse oedema and fibrosis, further investigation pertaining to their implementation in ARD assessment algorithms through multicenter studies is needed.

Abstract 8: Effectiveness of Combination Allogeneic Stem Cells in a Novel Large Animal Model of Chronic Kidney Disease-induced Heart Failure With Preserved Ejection Fraction (HFpEF)

Background: Chronic Kidney Disease (CKD) is an independent risk factor for cardiovascular morbidity and mortality. Left ventricular (LV) hypertrophy and heart failure with preserved ejection fraction (HFpEF) are the primary manifestations of the cardiorenal syndrome in 60 to 80% of CKD patients. Therapies that improve morbidity and mortality in HFpEF are lacking. Stem cell therapy reduces fibrosis, increases neovascularization, and promotes cardiac repair in ischemic and non-ischemic cardiomyopathies. We hypothesized that stem cell treatment ameliorates HFpEF in a CKD model. Methods: Yorkshires pigs (n=27) underwent 5/6 nephrectomy via renal artery embolization and 4-weeks later received either: allogeneic (allo-) MSC (10х10 6 ), allo-kidney c-kit + cells (c-kit; 10х10 6 ), combination (MSC+c-kit; 1:1 ratio [5х10 6 each]), or placebo (each n=5). Cell therapy was delivered via the patent renal artery. Kidney function, renal and cardiac MRI, and PV loops were measured at baseline, and at 4- and 12-weeks (euthanasia) post-embolization. Results: The CKD model was confirmed by increased creatinine and BUN and decreased GFR. Mean arterial pressure (MAP) was not different between groups from baseline to 4 weeks (p=0.7). HFpEF was demonstrated at 4 weeks by increased LV mass (20.3%; p= 0.0001), wall thickening (p&lt;0.008), EDP (p=0.01), EDPVR (p=0.005), and arterial elastance (p=0.03), with no change in EF. Diffuse intramyocardial fibrosis was evident in histological analysis and delayed enhancement MRI imaging. After 12 weeks, there was a significant difference in MAP between groups (p=0.04), with an increase in the placebo group (19.97± 8.65 mmHg, p=0.08). GFR significantly improved in the combination group (p=0.033). EDV increased in the placebo (p=0.009) and c-kit (p=0.004) groups. ESV increased most in the placebo group (7.14±1.62ml; p=0.022). EF, wall thickness, and LV mass did not differ between groups at 12 weeks. Conclusion: A CKD large animal model manifests the characteristics of HFpEF. Intra-renal artery allogeneic cell therapy was safe. A beneficial effect of cell therapy was observed in the combination and MSC groups. These findings have important implications on the use of cell therapy for HFpEF and cardiorenal syndrome.