Eccentric Left Ventricular Hypertrophy Research Articles

Left atrial strain: a sensitive whistleblower lost in translation

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This work was supported by the Netherlands Organisation for Scientific Research (NWO- ZonMw, VIDI grant 016.176.340 to J.L.) and the Dutch Heart Foundation (ERA-CVD JTC2018 grant 2018T094; Dr. Dekker Program grant 2015T082 to J.L.) Background Left atrial (LA) function measured by peak/reservoir strain (PLAS) has been shown to be of prognostic value in various cardiac pathologies, including heart failure (HF). However, the underlying mechanisms leading to reduced PLAS remain poorly understood. Purpose To investigate how various combinations of left ventricular (LV) systolic-, diastolic, and LA failure affect PLAS. Method The CircAdapt computational model of the human heart and circulation is used to simulate the abovementioned LV and LA substrates, starting from a healthy reference simulation. LV systolic failure was simulated by a 25% decrease of LV contractility and LV eccentric hypertrophy (simultaneous increase of LV wall mass and area by 30%). LV diastolic failure was simulated by increasing LV myocardial stiffness by 100%, impairing LV relaxation function (increasing relaxation time constant from 35ms to 60ms, and LV concentric remodeling (increasing LV wall mass by 30%). LA failure was simulated by a fully non-contractile LA myocardium. Results LV systolic failure was characterized by reduced LV GLS (21 to 12%) and LVEF (54 to 34%), with marginal increase in PLAS (42 to 46%; Figure top row, first vs second column). LV diastolic failure was characterized by reduced PLAS (42 to 23%; Figure first vs third and fourth columns) with LA dilation (i.e. peak LA volume: 50 to 80 ml). Furthermore, LV concentric remodeling increased LVEF (54 to 64%). LA failure led to LA dilation and reduction of PLAS, regardless of LV substrate. Lastly, LV diastolic dysfunction and LA failure did not affect LV GLS (Figure bottom row). Conclusion Simulations showed that acute LV systolic failure hardly affected PLAS, but predominantly decreased LV GLS and LVEF. On the contrary, both LV diastolic dysfunction and LA failure reduced PLAS, rather than LV GLS and LVEF. Hence, LA strain can be considered as a whistleblower sensitive to various LV and/or LA abnormalities, which may explain why it is a rather nonspecific diagnostic marker. Abstract Figure. LA and LV strain in various substrates

Left ventricle structure and function relations with the levels of plasma markers of fibrosis in hypertensive patients with NonSTEMI

Abstract Funding Acknowledgements Type of funding sources: None. Introduction. The myocardial fibrosis lies in the basis of left ventricle remodelling in patients with hypertension. Cardiomyocites hypertrophy, fibroblasts proliferation, enlargement of interstitial collagen volume and their ratio disorders may increase severity of stroke and myocardial infarction. Purpose. The purpose of the study is to evaluate relations between the plasma levels of myocardium fibrosis markers and left ventricle remodelling, systolic and diastolic function in hypertensive patients with NonSTEMI. Methods. Were examined 138 hypertensive patients (both men and women) with NonSTEMI. The mean age of patients was 51.2 (11.2) years. Patients with arrhythmias and conduction abnormalities, diabetes mellitus and autoimmune diseases were excluded form the study. In all patients was performed ECG in 12 standard leads; EchoCG (according to ASE/EACVI 2015 recommendations); evaluation plasma levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) and insulin-like growth factor 1 (IGF-1). HF NYHA functional class was determined by performing 6MWT. Statistical significance was defined at the level of methods for p < 0,05. Results. The averaged levels for plasma markers of myocardium fibrosis were: TIMP-1 - 322.0 (250.0; 483.5) ng/mL; IGF-1 - 160.0 (141.0; 175.0) ng/mL. Results of correlative analysis revealed relations between IGF-1 and ILV mass (R=-0.59; p < 0.001), and weak correlation between IGF-1 and E/e" averaged (R=-0.19; p = 0.027) (Picture 1). These negative correlations may be explained by the growth in both fibroblasts and collagen production in myocardium. Also there were positive correlations between TIMP-1 and ILV mass (R = 0.63; p < 0.001) and TIMP-1 and E/e" average (R = 0.37; p < 0.001) (Picture 1) which may be due to an increase of myocardial stiffness as the result of fibrosis activity. The results of the comparison of TIMP-1 and ICF-1 plasma levels, structural and functional parameters of the LV in groups of patients with different types of LV geometry can be seen in Table 1. Conclusion. Thus, the results of the study show that plasma markers of fibrosis was significantly higher in patients with concentric and eccentric LV hypertrophy which may reflects the higher levels of myocardium stiffness. Abstract Table 1. Abstract Figure. Picture 1.

Pathophysiological alterations of left ventricular myocardial systolic function during normal pregnancy assessed by speckle tracking echocardiography: a prospective cohort echocardiography study

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Pregnancy induces a variety of haemodynamic and morphological changes, leading to the amplification of cardiac pumping function. These changes do not cause any significant left ventricular (LV) dysfunction by using conventional echocardiographic indices, but it is not fully elucidated whether subclinical or/and reversible myocardial dysfunction is provoked during pregnancy. Two-dimensional speckle tracking echocardiography (2D-STE) can detect subclinical myocardial dysfunction even when conventional echocardiography reveal LV normal ejection fraction (LVEF).Purpose: The aim of this study was to evaluate whether LV systolic performance is impaired during normal low risk pregnancy by using both conventional 2D and 3D echo indices and 2D-STE. Materials and methods: One hundred and twelve consecutive pregnant women without any history of heart disease were prospectively recruited. They underwent serial echocardiographic evaluation in each pregnancy trimester (1st: 8th-12th week, 2nd: 22th-26th week, 3rd: 32-36th week) and 6 months after delivery (time indicated as 4). LV dimensions, relative wall thickness (RWT), 2D-LVEF, 3D-LVEF, systolic S wave from Tissue Doppler Imaging, LV global longitudinal strain (LVGLS), LV global circumferential strain (LVGCS) and LV-twist were measured and compared to 31 nulliparous women of similar age, who served as a control group (c).Results: Progressive eccentric LV hypertrophy was observed during pregnancy, which was subsided postpartum (p1-2 = 0.08, p2-3= 0.002, p3-4 = 0.001, p1-3 < 0.001, p1-4= 0.789), while no significant change in LV dimensions was found. 2D-LVEF, 3D-LVEF and S wave values were not significantly different among the three trimesters, postpartum and controls. LVGLS progressively decreased during pregnancy (1st:-21.71 ± 2.13%, 2nd: -21.20 ± 2.30%, 3rd: -19.82 ± 2.10%,4th: -21.81 ± 2.05%, c: -21.71 ± 2.2[E1]%,overall p < 0,001 ) and returned to normal during puerperium. No significant difference was noted in LVGCS (1st: -18.08 ± 5.54%, 2nd: -18.57 ± 3.41%, 3rd: -18.20 ± 3.33%,4th: -17.95 ± 3.39%,c: -18.8 ± 2.2% , p > 0.3). LV-Twist was significantly higher in the 1st trimester compared to controls (p= 0.04) and remained constantly high during the rest of the pregnancy and puerperium (1st:13.80 ± 5.09°, 2nd :13.46 ± 5.35°, 3rd:13.58 ± 4.32°, 4th:13.37 ± 4.26°, c: 11.5 ± 4.3°, ).Conclusion: Left ventricular subclinical dysfunction seems to occur in the longitudinal axis even in low risk individuals with normal pregnancy. Increased torsional movement of the heart seems to counterbalance the temporal impairment of longitudinal systolic function.

Cardiac adaptations to frequent premature ventricular contractions

Frequent premature ventricular contractions (PVCs) are prevalent in adult patients and commonly associated with left ventricular (LV) systolic dysfunction. Animal translational models of PVC- induced cardiomyopathy (PVC-CM) are reproducible and allow for study of specific adaptations resulting from frequent PVCs. Our PVC-CM canine model has shown LV eccentric hypertrophy and downregulation of key Ca2+ handling proteins. We performed subsequent studies to understand cellular and chemical mediators involved in LV remodeling observed in PVC-CM.

Association of arterial stiffness, N-terminal pro-brain natriuretic peptide, insulin resistance, and left ventricular diastolic dysfunction with diabetic cardiac autonomic neuropathy

Aim: To investigate the changes of insulin resistance (IR), parameters of arterial stiffness, concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), and echocardiographic parameters in patients with cardiac autonomic neuropathy (CAN) and type 2 diabetes mellitus (T2D). Methods: This study recruited 44 patients with T2D (19 patients without CAN and 25 patients with CAN) and 15 healthy volunteers. Arterial stiffness, immunoreactive insulin, homeostasis model assessment IR, NT-proBNP parameters, and echocardiographic examination were assessed. Results: Development of CAN is associated with increase in NT-proBNP levels, IR parameters, and arterial stiffening. Among patients with CAN, arterial stiffness parameters were considered as high. We found out that among patients of this group, the value of brachial augmentation index was normal in 52%, elevated in 40%, and pathological in 8%; pulse wave velocity was normal in 16%, elevated in 52%, and pathological in 32% of cases. Obtained results showed that development of CAN is accompanied by more pronounced left ventricular diastolic dysfunction and by formation of left ventricular hypertrophy (LVH), mostly by concentric type. Among patients of this group concentric LVH was diagnosed among 76 % and eccentric LVH among 16% of persons. Multiple regression analysis, after controlling for age, sex, diabetes duration, blood pressure, HbA1c, and left ventricular mass index, showed an independent association of heart rate response to deep breathing with pulse wave velocity (P < 0.001). Conclusion: Development of CAN is associated with increased IR parameters, increased levels of NT-proBNP, arterial stiffening, left ventricular diastolic dysfunction, and formation of LVH, mostly by concentric type.

BIOMARKER AND ECHOCARDIOGRAPHIC CHARACTERISTICS OF HEART FAILURE IN PATIENTS HAVING ACUTE MYOCARDIAL INFARCTION COMBINED WITH DIABETES MELLITUS OF TYPE 2.

The aim: To investigate the level of B-type natriuretic peptide (BNP) and to establish its relationship with structural and functional indicators of the myocardium in patients having acute myocardial infarction (AMI), which is complicated by heart failure (HF) with concomitant type 2 diabetes mellitus (DM2). Materials and methods: The study included 120 patients who were grouped by clinical diagnosis. Every patient underwent transthoracic echocardiography of the heart: left ventricular (LV) ejection fraction (EF), left ventricular myocardial mass index (LVMI), LV relative wall thickness (LVWT), BNP, HbA1c. Results: LV EF was statistically significantly lower in group 2 compared with group 1. A significant difference was found. Significant difference between LVWT within indicators of groups 1 and 2 was found. There was a statistically significant increase of the LVMI in group 2 compared to group 1. Against the background of AMI, the formation of eccentric LVH prevailed in 61% cases. There was a statistically significant increase in BNP within the group of patients suffering of AMI with HF and concomitant DM2. Conclusions: There was found a statistically significant increase in BNP in patients suffering of AMI with HF and concomitant DM2, which indicates a significant degree of damage to cardiomyocytes and causes an aggravating course of HF. The relationship between BNP and LV EF was revealed , which can be used to prognostic the severity of HF in this category of patients. A strong correlation between BNP and HbA1 was discovered, which indicates a burdensome unity of metabolic disorders that accelerate the development and progression of HF.

GENDER FEATURES OF STRUCTURAL-GEOMETRIC REMODELING OF THE LEFT VENTRICLE IN PATIENTS WITH MYOCARDIAL INFARCTION WITHOUT ELEVATION OF ST SEGMENT

Recently, there has been a tendency to increase the incidence of myocardial infarction without elevation of the ST segment, which, according to some data, accounts for about half of all registered MI. The main problem with this type of infarction is that the long-term prognosis in these patients remains unsatisfactory, and mortality one year after the catastrophe is equal to or even higher than mortality from ST-segment elevation myocardial infarction, which encourages continued predictors of unfavorable prognosis.
 Objective: to determine the gender characteristics of the structural and geometric remodeling of the left ventricle in patients with myocardial infarction without ST segment elevation.
 Materials and methods. We conducted a comprehensive study of 200 patients with acute myocardial infarction without ST-segment elevation (NSTEMI) aged 38 to 80 (mean 62.0 ± 0.71, median 62 and interquartile range 55 and 70). The structural and functional state of the myocardium and types of left ventricular remodeling according to transthoracic echocardiography were studied.
 Results. Analysis of the obtained data shows that echocardiographic parameters in patients with NSTEMI depending on gender did not reveal significant differences between different groups. The exception was the size of the right atrium, which was significantly higher in the group of men compared to women with comparable values of the size of the right ventricle and the ratio of the size of the left to the right atrium. Analysis of the nature of structural and geometric remodeling of the left ventricle in general by groups showed that almost half of the subjects registered concentric hypertrophy of the left ventricle. Concentric left ventricle remodeling was observed in one third of patients and in other patients - normal geometry and eccentric left ventricle hypertrophy. Thus, it was found that concentric models of left ventricle – concentric hypertrophy and concentric remodeling – were registered in the vast majority of patients with NSTEMI. The latter can be explained by a significant proportion of hypertension which was identified by us in most patients and, of course, contributed to the development of concentric models of left ventricle.
 Analysis of the nature of structural and geometric remodeling of the left ventricle depending on gender showed that in the group of men, compared with women, there was a significant increase in the incidence of concentric remodeling. At the same time, in women, compared with men, there was a significant increase in cases of more severe types of structural remodeling - concentric and eccentric hypertrophy.
 Thus, we found that gender differences in echocardiographic parameters in patients with NSTEMI relate exclusively to indicators of structural and geometric remodeling of the left ventricle. Signs of concentric and eccentric left ventricular hypertrophy predominate in women, and indicators of normal geometry and concentric left ventricular remodeling in men. This distribution of types of remodeling indicates a more severe course and unfavorable prognosis of NSTEMI in women.

Presumptive vagally-mediated atrial flutter in a dog

An asymptomatic nine-year-old Dobermann Pinscher underwent a screening for dilated cardiomyopathy. Echocardiography revealed left ventricular eccentric hypertrophy and systolic dysfunction; the rest of the echocardiographic parameters were within normal limits. Holter monitoring demonstrated sinus rhythm as the dominant cardiac rhythm during the first hours of the recording. Then, during a period of physiologically enhanced vagal tone (sleep), spontaneous development of atrial flutter (AFL) associated with variable ventricular response was documented. Alternation between AFL and paroxysmal atrial fibrillation was also observed. Subsequently, during a period of physiological increase of sympathetic tone (physical activity/excitement), spontaneous conversion of AFL to sinus rhythm occurred. In light of these findings, a presumptive diagnosis of vagal AFL was made. The images here described allow us to study the onset, behavior and termination of this intriguing electrocardiographic entity.

751 Quantitative changes in intracardiac vortices between patients with different ventricular geometry

Abstract Aims Over the past decades growing evidence have demonstrated the promising role of intracardiac fluid-dynamics in evaluating cardiac performance. To investigate quantitative changes in vortices parameters in patients with different ventricular geometry. Methods and results We enrolled 50 consecutive patients with one of the following: LV concentric hypertrophy (CH), eccentric hypertrophy (EH), concentric remodelling, and normal LV geometry (CTRL). They underwent a complete echocardiographic examination with intracardiac fluid-dynamic analysis by Color Vector Flow Mapping (Hyperdoppler). The following parameters were obtained: vortex area (VA); vortex length (VL); and vortex depth (VD). Bland Altman Plot has been used to assess intra and inter-observer variability. Mean VD was higher in CR, CH, and EH compared to CTRL (P = 0.013, P = 0.001, and P = 0.022, respectively). Moreover, CH showed higher VL (P = 0.006) and larger VA (P = 0.012) compared to CTRL. A similar trend was noticed in EH patients, despite did not reach statistical significance (P = 0.21 and P = 0.07 for VA and VL, respectively). No significative differences in vortices parameters have been observed between CH and EH. Conclusions This is the first study providing quantitative echocardiographic parameters of vortex location and morphology in different LV geometries. Quantitative fluid-dynamic assessment was feasible and reliable in the whole population.

701 ECMO assistance during TAVI in high-risk patient with recent COVID-19 pneumonia

Methods and resultsA 87 years old woman, with history of dyslipidemia and permanent Atrial Fibrillation, already undergone full SARS-CoV2 vaccination few months before, referred to our E.R. with complain of dyspnoea and chest pain. COVID-19 molecular test resulted positive and CT Scan of the chest confirmed the presence of several areas of ground-glass opacity and consolidation together with bilateral pleural effusion (right 6 cm with pulmonary atelectasis; left 2 cm), not requiring drainage. Moreover, it showed severe calcification of both the aortic valve and root. Transthoracic echocardiogram showed eccentric LV hypertrophy with diffuse hypokinesia (EF 20–25%), ectatic ascending aorta (45 mm) with severe LF-LG aortic stenosis (AVAi 0.19 cm2) and moderate regurgitation, moderate-severe mitral regurgitation. During hospitalization in the COVID-19 Unit, despite O2 therapy she experienced worsening of the respiratory status with concomitant pulmonary oedema, hypotension and acute kidney injury, requiring administration of i.v. dobutamine and high dose diuretics. After gradual stabilization and COVID-19 negativization on 10th molecular test, she was transferred to our Coronary Care Unit. Coronary angiography showed absence of significant stenoses in the main vessels. In the following days the patient underwent a new clinical deterioration with dyspnoea, hypotension (BP 85/50 mmHg), oliguria and ankle swelling, requiring Ventimask O2 therapy and Dobutamine infusion. Transtoracic echocardiogram confirmed EF of 25% with PASP 30 mmHg. We decided to perform a ‘Rescue’ TAVI procedure, facilitated by extra-corporeal cardiac and respiratory support. CT Angiography of the chest, performed with low-dose contrast injection under amines infusion, showed severly calcific aortic valve with large sizes of the ring (Virtual Basal Ring area 620 mm2, perimeter 91 mm), measures compatible with the largest sizes of TAVI prostheses. After Veno-Arterial Extracorporeal Membrane Oxygenation (ECMO) cannulation, we performed the implantation of a 34 mm Evolut R (Medtronic) TAVI prosthesis, post-dilated with 24 mm balloon for under-expansion due to massive calcification. During both self-expandable TAVI delivery and balloon inflation the patient underwent two phases of cardiac arrest, during which the ECMO flow provided a proper circulatory support.ConclusionsSince percutaneous valve replacement the patient’s recovery was fast with rapid ECMO removal and discontinuation of inotropic therapy. Few weeks after discharge, at first follow-up examination, the patient appeared asymptomatic, in excellent clinical conditions. 701 Figure

Features of the structural state of the myocardium in patients with myocardial infarction without ST segment elevation depending on the nature of the anatomical lesion of the coronary arteries

Annotation. In Ukraine, one of the most pressing medical and social problems is coronary heart disease, in particular, such a form as myocardial infarction. Also, as in most countries, coronary heart disease plays a leading role in morbidity and mortality. In Ukraine, coronary heart disease accounts for 65% of the mortality from diseases of the circulatory system of the working population and is the main cause of disability. The aim of the work is to determine the features of the structural and functional state of the myocardium in patients with myocardial infarction without ST segment elevation depending on the nature of the anatomical lesion of the coronary arteries. We conducted a comprehensive study of 200 patients with acute myocardial infarction without ST-segment elevation (NSTEMI) aged 38 to 80 years. According to coronary angiography, the degree of damage to the coronary arteries was determined, and according to echocardiography – the structural and functional state of the myocardium. Comparison of percentages between groups was performed by the criterion χ2, absolute values – by Mann-Whitney U test. The structural condition of the left ventricular myocardium in NSTEMI patients deteriorated significantly. The total severity of coronary artery disease, calculated from coronary angiography, was> 3, indicating a more severe anatomical lesion of the coronary arteries in these patients. This pathology was associated primarily with an increase in the incidence of eccentric left ventricular hypertrophy. A similar association has been established with regard to the development of left ventricular diastolic dysfunction.

C74. Post covid-19 cardiomyopathy in an adolescent patient: a case report

Abstract Background Myocardial injury caused by viral myocarditis may occur during COVID-19 infections. This condition may lead to cardiomyopathy as the chronic sequela. We report a case of an adolescent COVID-19 survivor without underlying heart disease presented with dilated cardiomyopathy. Case Summary A 16-year-old male patient was referred to Cardiology Outpatient Clinic, Indonesian Army Central Hospital Gatot Soebroto. The patient presented with a chief complaint of fatigue and just recovered from mild to moderate COVID-19 one month before the visit. There was no prior history of heart disease. Physical examination was within normal limit, but laboratory findings showed highly elevated NT-proBNP (7705 pg/mL) and D-dimer (1850 ng/mL). ECG revealed normal sinus rhythm with poor R wave progression. Echocardiography detected all chamber dilatation, eccentric left ventricular hypertrophy, global hypokinetic, moderate mitral regurgitation, and reduced ejection fraction (22%). The patient was diagnosed with new-onset dilated cardiomyopathy as a COVID-19 sequela and we initiated treatment with ARB (candesartan), beta-blocker (bisoprolol), diuretics (furosemide and spironolactone), rivaroxaban, and trimetazidine. During a follow-up visit three months later, the patient’s recovery was stable. Discussion The occurrence of new-onset cardiomyopathy in our previously healthy young patient highlights the possible mechanism of COVID-19 as a single cause of myocardial injury without underlying heart disease. Comprehensive evaluation and optimal treatment should be taken during hospitalization and post-discharge period to prevent further complications. Additional examinations such as cardiac magnetic resonance and endomyocardial biopsy should be done to provide definitive confirmation.

C74. Post covid-19 cardiomyopathy in an adolescent patient: a case report

BackgroundMyocardial injury caused by viral myocarditis may occur during COVID-19 infections. This condition may lead to cardiomyopathy as the chronic sequela. We report a case of an adolescent COVID-19 survivor without underlying heart disease presented with dilated cardiomyopathy. Case SummaryA 16-year-old male patient was referred to Cardiology Outpatient Clinic, Indonesian Army Central Hospital Gatot Soebroto. The patient presented with a chief complaint of fatigue and just recovered from mild to moderate COVID-19 one month before the visit. There was no prior history of heart disease. Physical examination was within normal limit, but laboratory findings showed highly elevated NT-proBNP (7705 pg/mL) and D-dimer (1850 ng/mL). ECG revealed normal sinus rhythm with poor R wave progression. Echocardiography detected all chamber dilatation, eccentric left ventricular hypertrophy, global hypokinetic, moderate mitral regurgitation, and reduced ejection fraction (22%). The patient was diagnosed with new-onset dilated cardiomyopathy as a COVID-19 sequela and we initiated treatment with ARB (candesartan), beta-blocker (bisoprolol), diuretics (furosemide and spironolactone), rivaroxaban, and trimetazidine. During a follow-up visit three months later, the patient’s recovery was stable.Discussion The occurrence of new-onset cardiomyopathy in our previously healthy young patient highlights the possible mechanism of COVID-19 as a single cause of myocardial injury without underlying heart disease. Comprehensive evaluation and optimal treatment should be taken during hospitalization and post-discharge period to prevent further complications. Additional examinations such as cardiac magnetic resonance and endomyocardial biopsy should be done to provide definitive confirmation.

Abstract 13931: Upregulation of the AKT/mTOR Pathway in Premature Ventricular Contractions (PVC)-Induced Cardiomyopathy

Introduction: Premature ventricular contractions (PVCs) are early ventricular depolarizations that, if frequent, can be associated with PVC-induced cardiomyopathy (PVC-CM). PVC-CM in our translational model is characterized by LV systolic dysfunction and eccentric hypertrophy. However, the mechanisms involved in this LV remodeling remain unknown. Objectives: Evaluate changes in cardiomyocyte size and sarcomere shortening, along with classical molecular pathways involved in pathological or physiological hypertrophy in the PVC-CM model. Methods: Pacemakers were implanted in healthy canines to reproduce 3 months of bigeminal PVCs (50% burden at 200-220 ms coupling interval). Isolated ventricular cardiomyocytes were electrically paced to measure sarcomere length. Formaldehyde-fixed LV sections were stained with WGA-AF633. Expression of β-MHC, ACTA1, ANP, calcineurin, AKT, mTOR, S6, 4EBP1, NFAT and their phosphorylated forms were measured by Western blot. Calcineurin activity was determined by colorimetry. Results: Cardiomyocyte area was larger in PVC group vs. sham (357.4 ± 12.9 μm 2 n= 121 vs. 271.8 + 7 μm 2 n = 161, p<0.001). Time to peak sarcomere contraction was longer in the PVC group (124.9 + 25.2 ms, n=101 vs 116.2 + 27.4 ms, n=61, p<0.05), whereas maximal cell shortening was similar between groups. Western blot analyses (n=6) showed significant increases in AKT expression (1 + 0.18 vs 1.6 + 0.43, p<0.001), and in its downstream effectors, S6 (1 + 0.26 vs 1.46 + 0.4, p<0.05) and 4EBP1 (1 + 0.3 vs 1.57 + 0.38, p<0.001) in the PVC group, without changes in mTOR. On the contrary, PVC group displayed a reduction in phosphorylated AKT (Ser473, 1 + 0.14 vs 0.77 + 0.26, p<0.05) and 4EBP1 (Thr37/46, 1 + 0.15 vs 0.75 + 0.1, p<0.001) without changes in S6 (Ser235/236) or mTOR (Ser2448) phosphorylation. The activity and expression of calcineurin, total and phospho- NFAT, and the expression of β-MHC, ACTA1, and ANP were not different. Conclusion: The pathological calcineurin/NFAT/fetal genes pathway was unchanged in the PVC-induced eccentric hypertrophy. Thus, this hypertrophy is “atypical” characterized by an upregulation of the AKT/mTOR pathway and cellular hypertrophy, together with a paradoxical decrease in contractility and LV systolic dysfunction.

Cardiovascular remodeling as a result of fibroblast growth factor-23 (FGF-23)/Klotho imbalance in patients with CKD.

In chronic kidney disease (CKD) cardiovascular remodeling (CVR) is very frequent compared with general population and, as suppose, may be associated with «new» renal risk factors. The aim of study was to estimate association of new serum biomarkers (FGF-23, Klotho) and traditional biomarker of cardiac damage-serum Troponin I (sTr-I) with signs of CVR. One hundred thirty CKD G1-5D patients without cardiovascular disease (CVD) clinical manifestation were included. We measured serum FGF-23, Klotho and sTr-I. The instrumental methods were: echocardiography, SphygmoCor test [Pulse Wave Velocity (PWV), Central (aortic) Blood Pressure (CBP), Subendocardial Blood Supply (SBS)]. FGF-23 level correlated with: sTr-I (r = 0.512; p < 0.01), eccentric left ventricular hypertrophy, LVH (r = 0.543; p < 0.01), SBS (r = - 0.499; p < 0.05). There were no differences of FGF-23 level in patients with normal and high CBP. Klotho correlated with concentric LVH (r = - 0.451; p < 0.01), PWV (r = - 0.667; p < 0.001), Cardiac Calcification Score, CCS (r = - 0.581; p < 0.01). Multivariate analysis revealed positive independent association of FGF-23 with eccentric LVH (OR = 1.036, 95% CI (1.004-1.068); p = 0.038). Klotho was a negative determinant for concentric LVH (OR = 0.990, 95% CI 0.987-0.994; p < 0.001), increased PWV (OR = 0.984, 95% CI (0.977-0.991); p < 0.001) and CCS (OR = 0.991, 95% CI (0.988-0.995); p < 0.001). In addition, multivariate analysis revealed a relationship between serum Klotho (OR = 0.980, 95% CI (0.964-0.996); p = 0.016), FGF-23 (OR = 3.145, 95% CI (1.020-9.695); p = 0.046) and troponin I level. In CKD patients without CVD clinical manifestation increased serum FGF-23 level and decreased Klotho are associated with CVR: FGF-23 with eccentric LVH (independently of CBP), Klotho determinate concentric LVH, PWV and CCS. Moderately elevated sTr-I levels may be a manifestation of FGF-23/Klotho imbalance in CKD.

Aortic diameter, pulse wave velocity, central aortic pulse pressure, left ventricular parameters, and diastolic dysfunction in patients with aortic aneurysm

Abstract Background The enlargement of aortic aneurysm can alters pulse wave propagation and reflection, which may influence to left ventricular (LV) afterload changes. The relevance of pulse wave velocity (PWV) and central blood pressure depending on the locus of the aneurysm for LV structure and diastolic function (DF) are not clearly unknown. Purpose Assess the relationship between central pulse pressure (CPP), PWV and LV structure and DF in patients with ascending aortic aneurysm (AA) and abdominal aortic aneurysm (AAA). Methods 121 patients (95 male, 63±12 years) with aortic aneurysms and preserved LV systolic function were enrolled before aortic repair. 51 patients (37 male, 54±13 years) had AA and 70 patients (58 male, 69±7 years) had AAA. CPP and PWV were measured using applanation tonometry. A echocardiographic exam was performed with a Vivid 7 GE (USA). LV mass index (LVMI) and relative wall thickness (RWT) were calculated according to standard formulas. LV filling pressure (E/Em) was estimated by Doppler-derived ratio of mitral inflow velocity (E) to septal (Em) by tissue Doppler. Transmitral flow patterns (E/A ratio of E to late (A) ventricular filling velocities) were measured with the pulsed doppler method. Results Concentric LV hypertrophy (LVH) was observed in 51 (42%), eccentric LVH – in 35 (29%) patients. CPP was positively related with LVMI (r=0.362, P=0.001), but PWV was inversely associated with LVMI (r=−0.244, P=0.029). CPP was not associated with RWT (P≥0.5), whereas PWV was positively related (r=0.223, P=0.004). PWV decreased with increasing aortic diameter in AA and AAA (r=−0.360, P=0.029 and r=−0.315, P=0.019, respectively). 12 (23%) patients with AA and 36 (56%) patients with AAA had grade I diastolic dysfunction, 20 (40%) patients with AA and 12 (18%) patients with AAA had grade II diastolic dysfunction (P&amp;lt;0.001). Consequently, the E/A ratio was higher in patients with AA than in patients with AAA (1.21±0.39 vs 0.83±0.33; P=0.007). CPP and PWV was inversely associated with LV DF (E/A: r=−0.352 and −0.238; E/Em: r=−0.292 and −0.279, respectively; both P&amp;lt;0.05). E/A and E/Em increased with the expansion of the maximum aortic diameter at the level of the AA and AAA (E/A: r=0.612 and 0.416; E/Em: r=0.719 and 0.339, respectively; both P&amp;lt;0.005). RWT and LVMI were correlated with the aortic diameter at the level of the AA (r=−0.439, P=0.008 and r=0.286, P=0.05, respectively), but bore no relation with the aortic diameter at the level of the AAA. Conclusions In patients with aortic aneurysm CPP and PWV were conjointly but differently related to LV structure. Eccentric LV hypertrophy was accompanied by a significant decrease of PWV. Reduced PWV and decreased CPP exhibited association with more severe LV diastolic dysfunction, possibly due to the apparent effect of increased aortic aneurysm diameter. LV DF was severely reduced in the patients with AA compared by patients with AAA. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Almazov National Medical Research Centre

Different myocardial microRNA expression patterns are observed in pressure overload- and volume overload-induced chronic heart failure

Abstract Introduction MicroRNAs (miRNA) are short, single-stranded non-coding RNA molecules that regulate gene expression on the post-transcriptional level. Dysregulation of distinct miRNAs has been found to contribute to the development of chronic heart failure (CHF). However, whether distinct types of CHF are associated with different miRNA expression patterns is debated. Aim To characterize left ventricular (LV) miRNA expression in rat models of pressure overload (PO) versus volume overload (VO)-induced CHF. Methods Transverse aortic constriction (TAC) was performed to evoke PO-induced CHF. Aortocaval fistula (ACF) was created to establish VO-induced CHF. Age-matched sham-operated rats served as controls for TAC (ShamT) and ACF (ShamA), respectively. Pressure-volume analysis, echocardiography, histology and quantitative real-time PCR were carried out to assess alterations of the LV. Global miRNA expression profiling was performed using Nanostring technology. Bioinformatics analysis of differentially expressed miRNAs was also carried out to predict relevant miRNA-target interactions. Results Reduced LV systolic function (ejection fraction: 38±5 vs. 65±2% TAC vs. ShamT, 55±3 vs. 67±3%, ACF vs. ShamA, P&amp;lt;0.01) as well as elevated myocardial B-type natriuretic peptide and increased β-to-α myosin heavy chain gene expression confirmed the development of pathological remodeling and CHF in both models. Nevertheless, characteristic differences could be observed in LV morphology and ultrastructure. Accordingly, the TAC model was associated with robustly increased wall thickness, concentric LV hypertrophy and marked fibrotic remodeling. On the contrary, LV dilatation, eccentric LV hypertrophy and moderate fibrosis were the main morphometric findings in the ACF model. A group of miRNA (rno-miR-130a, 132, 199a-5p, 21, 210, 27b, 326) showed similar alterations in both phenotypes of CHF. However, other miRNAs demonstrated unique (specific to TAC: rno-miR-148b-3p, 150, 199a-3p, 203, 23b, 27b, let-7e; specific to ACF: rno-miR-140, 142-3p, 17-5p, 195, 20a, 204, 214, 27a, 29b, 322, 365, 425, 450a, let-7i) LV expressional changes in distinct phenotypes of CHF. In silico bioinformatics analysis revealed that the altered miRNA expression pattern predominantly controls the cardiac neural crest cell development, the inositol-phosphate pathway and the expression of microtubules-binding proteins. In contrast, alterations in the expression of genes responsible for redox state and epithelial-mesenchymal transition were modified only in the ACF group. Despite of the different signaling cascades, expression of Arhgap12 (Rho GTPase activating protein 12) was predicted to be strongly inhibited in both CHF models. Conclusions PO and VO-induced CHF are associated with unique miRNA expression patterns, which drive different signaling pathways. miRNA-controlled downregulation of Arhgap12 might represent a common feature in both phenotypes of CHF. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): ÚNKP-20-4-II-SE-20/New National Excellence Program of the Ministry of Human CapacitiesNVKP_16-1–2016-0017 (“National Heart Program”) National Research, Development and Innovation Fund of Hungary

Abnormal left ventricular geometry in female collegiate swimmers

Abstract Background There is a paucity of data describing left ventricular geometry changes in female athletes. While some studies suggest that female athletes participating in dynamic sports exhibit higher prevalence of eccentric left ventricular hypertrophy (LVH) when compared to men, a recent study suggested more concentric geometry changes in female basketball athletes. We were unable to identify studies describing the left ventricular geometry of female collegiate swimmers. Objectives To describe LV geometry changes in a cohort of female collegiate swimmers. Methods We analyzed a cohort of female collegiate swimmers who had a pre-participation cardiac evaluation by 12-lead ECG and 2-dimensional echocardiography. Left ventricular (LV) geometry was assessed based on relative wall thickness (RWT) (defined as: 2 x posterior wall thickness (PWT) divided by LV end-diastolic diameter (LVEDD)) and LV mass (LVM) (Devereux's formula: LVM = [0.8 x 1.04 [(LVEDD + interventricular septum + posterior wall thickness)3 − (LVEDD)3]] + 0.6g) and was indexed to body surface area (BSA).LVH was defined as LV mass index &amp;gt;95 g and was defined as concentric when associated with a relative wall thickness (RWT) &amp;gt;0.42 and as eccentric when RWT was ≤0.42. Concentric remodeling was defined as normal LVM index and increased RWT. Results A total of 83 female collegiate swimmers were included. Their age was 18.5±0.5 years (mean ± standard deviation, SD), 74 (89.2%) were White, BSA was 1.78±0.11 m2, height 173±6.3 cm, weight 66.2±7.2 K. Their interventricular septum diameter was 0.89±0.14 cm, PWT 0.92±0.15 cm, LVEDD 4.9±0.5 cm and LV end-systolic diameter (LVESD) 3.2±0.4 cm. Left atrium diameter ranged from 2.6 to 4.3 cm (mean 3.4 cm ± 0.4 cm). Aortic root diameter ranged from 1.9 to 3.5 cm (mean 2.7±0.3 cm) (Figure 1). LVH was present in 27 swimmers (32.5%). Eccentric LVH was present in 17 athletes (20.5%), concentric hypertrophy in 10 athletes (12%), and concentric remodeling in 12 (14.5%) (Figure 2). No athletes with LVH or concentric remodeling had borderline or abnormal ECG findings based on international criteria. Only two women with normal LV geometry had abnormal ECG findings: prolonged QT interval and abnormal T wave inversion. There was a linear correlation between BSA with LVEDD, LVESD and LV mass (r=0.40, 0.35, and 0.48 with P&amp;lt;0.001,0.002 and &amp;lt;0.001, respectively). However, there was no statistically significant difference between LV geometry groups based on BSA or blood pressure. Conclusion Our data document a high incidence of eccentric hypertrophy among female collegiate swimmers. Concentric remodeling and hypertrophy were also relatively high. Differentiating physiologic from pathologic cardiac remodeling in these athletes is critical to prevent potential complications such as sudden cardiac death, arrhythmias, and other adverse outcomes. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This work was supported in part by the American Medical Society for Sports Medicine (AMSSM) Foundation Research Grant 2016 awarded to KE, and the University of Florida REDCap uses the NIH National Center for Advancing Translational Sciences (NCATS) grant UL1 TR001427. Figure 1Figure 2. LV geometry in female swimmers

Impact of percutaneous ventricular septal defect closure on left ventricular remodeling and function

BackgroundVentricular septal defect (VSD) is the most common congenital heart disease. In patients with large VSD, left side chambers are subjected to volume overload with subsequent chambers dilatation and eccentric left ventricular hypertrophy. Percutaneous closure of VSD has been shown to be an effective method with equal safety and efficacy when compared to surgery. The effect of VSD closure on LV remodeling has been mainly assessed in patients treated with surgery and to date published data remain scarce. Therefore, we aim to evaluate the effect of percutaneous VSD closure on different LV parameters.ResultsSeventeen patients (median age 6 years (IQR 4.75–8 years), 70.6% females) who underwent percutaneous VSD closure were enrolled in the study. Sixteen patients (94%) had perimembranous VSD, and one patient had muscular VSD. The procedure was successful in all patients with no major complications. Nit Occlud® Lê coil device was implanted in 16 patients (94%), and one patient received Amplatzer PDA duct occlude device. At 6-months follow-up, there was a significant reduction in indexed LV dimensions [LVEDD/BSA (median 46.5 mm/m2 vs. 42.9 mm/m2, p = 0.03), LVESD/BSA (median 31.7 mm/m2 vs. 26.7 mm/m2, p = 0.02)], indexed LV volumes [LVEDV/BSA (median 52.6 ml/m2 vs. 37.3 ml/m2, p = 0.02), LVESV/BSA (median 31.7 ml/m2 vs. 23.3 ml/m2, p = 0.02)] and indexed LV mass (median 62.4 gm/m2 vs. 57.9 ml/m2, p = 0.01). There was a significant reduction in LVEDD Z-score (p = 0.01) and LVESD Z-score (p = 0.04). There was no significant change in LV EF.ConclusionsPercutaneous VSD closure is associated with improvement of various LV parameters with consequential favorable LV remodeling and function.

Assessment of intracardiac flow dynamics for the evaluation of patients with different ventricular geometry

Abstract Background Over the last decades growing evidence have demonstrated the promising role of intracardiac flow dynamic analysis in evaluating cardiac performance. Diastolic forces contribute to the formation of vortices, complex structures capable of kinetic energy storage and responsible of a smoother transition of blood from left ventricular (LV) inlet to outlet. Change in shape and location of these structures has been related with cardiovascular disease and prognosis. Purpose To investigate quantitative changes in vortices parameters in patients with different ventricular geometry. Methods We enrolled 72 consecutive patients (age 66±11 years, 49 male, 68%) with LV concentric hypertrophy (CH, n=15), eccentric hypertrophy (EH, n=13), concentric remodeling (CR, n=15) and normal LV geometry (CTRL, n=29). Each patient underwent a complete echocardiographic examination and a non-invasive intracardiac fluid dynamic analysis by Color Vector Flow Mapping. A 3-chamber apical view with a frame rate between 22 and 25 Hz has been acquired and subsequently analyzed offline by a semi-automatic software obtaining the following parameters: vortex area (VA) (the ratio between the total vortex area and the left ventricular (LV) area); vortex length (VL) (the longitudinal length of the vortex relative to the total LV length; vortex depth (VD) (the distance of the vortex center from the LV base relative to the total LV long axis). Bland Altman Plot has been used to assess intra and inter-observer variability. Results Mean VD was higher in CR, CH and EH compared to CTRL (p=0.013, p=0.001 and p=0.022, respectively). Moreover, CH showed higher VL (p=0.006) and larger VA (p=0.012) compared to CTRL. A similar trend was noticed in EH patients, despite did not reach statistical significance (p=0.21 and p=0.07 for VA and VL respectively). No significative differences in vortices parameters have been observed between CH and EH. Conclusion(s) This is the first study providing quantitative echocardiographic parameters of vortex location and morphology in different LV geometries. Higher values of VD were found in CR, CH and EG. Quantitative intra dynamic fluid assessment was feasible and reliable in the whole population and could provide additional information to the standard echocardiographic examination. Funding Acknowledgement Type of funding sources: None.