Parameters Of Left Ventricular Remodeling Research Articles

P912 Echocardiographic analysis of acute effects after treatment of functional mitral regurgitation by percutaneous mitral annuloplasty

Abstract Background Secondary or functional mitral regurgitation (FMR) is associated with increased morbidity and mortality, especially in heart failure patients, patients with many comorbidities and/or in the elderly. Previous studies about percutaneous mitral annuloplasty have shown evidence for long-term reduction of degree of FMR severity and left ventricular (LV) remodeling. In comparison to previous studies the present study did focus on the echocardiographic analysis of acute effects after percutaneous mitral annuloplasty (PMA). Methods Transthoracic echocardiography (TTE) has been performed in 30 patients with moderate or severe FMR before and after (± 3.5 days) percutaneous mitral annuloplasty (Carillon®). LV volumes and LV ejection fraction and semi-quantitative parameters, e.g. tenting Area, vena contracta and velocity-time-integral ratios of transmitral inflow and LV outflow (VTIMV/VTILVOT) were assessed. The assessment of the regurgitant volume (RV), regurgitant fraction (RF) and effective regurgitant orifice area (EROA) was quantitatively performed by the PISA method. RV and RF was also estimated by subtracting the effective forward stroke volume (SVLVOT, SVRVOT) from the total stroke volume (SVLV planimetry). Further, parameters of left ventricular contractility, e.g. global longitudinal strain (GLS), cardiac efficiency, peak power index etc., were assessed. Results a postinterventional reduction of degree of FMR severity was achieved in 25/30 patients (83%). In average, RF was reduced from 49 ± 11% to 34 ± 13% (p < 0.001), RV from 33 ± 13ml to 25 ± 12ml (p < 0.001) and EROA from 0.24 ± 0.1cm2 to 0.19 ± 0.1cm2 (p < 0.05). Significant decreases were also noted for vena contracta and VTIMV/LVOT. DiamMV (long axis) was reduced from 3.6 ± 0.6cm to 3.4± 0.6cm (p < 0.001), DiamMV (4-chamber view) from 3.9 ± 0.5cm to 3.6 ± 0.6cm (p < 0 .05). In patients with sinus rhythm (SR) or pacemacer stimulation a considerably higher reduction of RF was observed (ΔRF 20 ± 12%) in comparison to patients with atrial fibrillation (ΔRF 10 ± 12%). No significant changes were obtained for parameters of LV remodeling and LV contractility, e.g. GLS, cardiac efficiency, peak power index. Conclusion A reduction of degree of FMR severity can be achieved by percutaneous mitral annuloplasty (PMA) and acute effects can be quantitatively assessed by echocardiography. Further data are necessary to evaluate whether these acute effects will maintain in follow-up investigations. Abstract P912 Figure. Fig1-Reduction of RF and VC after PMA

P1501Can we measure the stiffening of hypertensive hearts non-invasively? A shear wave imaging study using ultra-high frame rate echocardiography

Abstract Background Cardiac shear wave (SW) elastography is a novel technique based on high-frame-rate (HFR) echocardiography which has been shown to be related to myocardial stiffness. In this study we explore the relation between myocardial SW velocity and myocardial remodelling in remodelled hearts of patients with arterial hypertension (AH). Methods We prospectively included 33 treated AH patients with hypertrophic left ventricular (LV) remodelling (59±14 years, 55% male) and 26 aged matched healthy controls (55±15 years, 77% male). AH patients were further divided according to their LV geometric pattern into a concentric remodelling (CR) group (13 patients) and a concentric hypertrophy (CH) group (20 patients). LV parasternal long axis views were acquired with an experimental HFR ultrasound scanner (HD-PULSE) at 1266±317 frames per seconds. Myocardial acceleration maps were created from the HFR-datasets and an anatomical M-mode line was drawn along the midline of the interventricular septum (IVS). The propagation velocity of natural SWs occurring at mitral valve closure (MVC) was measured on these M-modes (Figure A) in order to assess passive myocardial stiffness. Standard echocardiography using a commercial scanner was performed to evaluate LV remodelling. Results SW velocities at MVC differed significantly between AH patients and controls (5.83±1.20 m/s vs. 4.04±0.96 m/s; p<0.001). Within the patient group, patients with CH had highest SW velocities at MVC (p<0.001), whereas values between controls and patients with CR were comparable (p=0.075) (Figure B). In AH patients, significant positive correlations were found between SW velocity at MVC and parameters of LV remodelling (IVS thickness: r=0.728, p<0.001; LV mass index: r=0.780, p<0.001, LV end-diastolic volume: r=0.604, p=0.008) (Figure C) and also parameters of diastolic function (E/e': r=0.495, p=0.005, left atrium diameter: r=0.866, p<0.001, left atrium volume index: r=0.661, p<0.001). Figure A, B, C Conclusions SW velocity – and therefore myocardial stiffness – is higher in AH patients compared to healthy controls and increases with increasing severity of hypertensive heart disease. Patients with concentric remodelling have still close-to-normal passive myocardial properties while patients with concentric hypertrophy show significant stiffening. Echocardiographic shear wave elastography is a promising new technique for the non-invasive assessment of myocardial stiffness and might provide valuable new insights into myocardial function and the pathophysiology of myocardial disease.

Comparison of left ventricular remodeling and cardiac work evolution at 6 month between percutaneous mitral valve repair and optimal medical treatment in secondary mitral regurgitation

Left ventricular (LV) pressure-strain loops (PSLs) have been recently validated as a non-invasive index of myocardial performance. Aim of the present study is to compare LV function, myocardial work, and energy dispersion in patients with severe secondary mitral regurgitation (MR) and decreased left ventricular ejection fraction (LVEF) before percutaneous mitral valve repair (PMVR, by Mitraclip® system) and at 6-month follow-up (FU) compared to optimal medical treatment. We included in this study 56 patients (mean age: 72years) with secondary MR and decreased LVEF. Thirty-seven undergoing PMVR according to local heart team compared with 19 with optimal medical treatment. All patients underwent standard echocardiography and speckle tracking echocardiography (STE) at inclusion and at 6-month FU. Strain traces and valvular event times were used to calculate LV-PSLs and Global Work Index (GWI), Constructive Work (CW), and Wasted work (WW) were therefore obtained. The main results are shown in Table 1 . Despite a strongest decrease of NYHA class (2.6 ± 0.6 vs. 1.8 ± 0.7; P < 0.0001) in PMVR group, no significant difference in LV function and remodeling parameters was observed at FU between both groups. Interestingly, whereas GWI and WW remained unchanged, CW significantly improved in the same proportion at 6-month FU in both groups (1101 vs. 977; P = 0.003 and 1110 vs. 967 mmHg.%, P = 0,002). On the contrary than patients with severe MR and high surgical risk undergoing optimal medical treatment, patients undergoing PMVR experienced a significant improvement in symptoms. On the other hand, the evolution of classical parameters of LV function/remodeling as well as new indices of myocardial work was not different. These findings support the hypothesis that the symptoms improvement result in another mechanism than a left ventricular remodeling.

Expression and Implication of Clusterin in Left Ventricular Remodeling After Myocardial Infarction

Left ventricular remodeling (LVR) after myocardial infarction is associated with an increased risk of heart failure and death. In spite of a modern therapeutic approach, LVR remains relatively frequent and difficult to predict in clinical practice. Our aim was to identify new biomarkers of LVR and understand their involvement in its development. Proteomic analysis of plasma from the REVE-2 study (Remodelage Ventriculaire)-a study dedicated to the analysis of LVR which included 246 patients after a first anterior myocardial infarction-identified increased plasma levels of CLU (clusterin) in patients with high LVR. We used a rat model of myocardial infarction to analyze CLU expression in the LV and found a significant increase that was correlated with LVR parameters. We found increased CLU expression and secretion in primary cultures of rat neonate cardiomyocytes hypertrophied by isoproterenol. Silencing of CLU in hypertrophied neonate cardiomyocytes induced a significant decrease in cell size, ANP (atrial natriuretic peptide), and BNP (B-type natriuretic peptide) expression, associated with a decreased ERK (extracellular signal-regulated kinase) 1/2 activity, suggesting a prohypertrophic role of CLU. We then confirmed a significant increase of both intracellular p-CLU (precursor form of CLU) and m-CLU (mature form of CLU) in failing human hearts. Finally, the circulating levels of CLU (secreted form) were increased in patients with chronic heart failure who died from cardiovascular cause during a 3-year follow-up (n=99) compared with survivors (n=99). Our results show for the first time that plasma CLU levels are associated with LVR post-myocardial infarction, have in part a cardiac origin, and are a predictor of early death in heart failure patients.

The Effects of Dopamine Receptor D3 Deficiency in Age‐dependent Left Ventricular Remodeling

Aging is an independent risk factor for cardiovascular disease. Additionally, normal aging associates with a decrease on the levels of the neuromodulator dopamine (DA). While the role of DA in the pathophysiology of hypertension and in autonomic function is well‐established in young animals, much less is known on how DA levels and signaling affect cardiac aging. Decreased receptor expression/function of the D2‐like DA receptor family (DRD2 and DRD3) have been implicated in the development of renal and cardiac fibrosis. It is well established that myocardial aging is characterized by left ventricular (LV) fibrosis, which is a component of LV adverse remodeling. Accordingly, the goal of this study was to elucidate the effects of DRD3 deficiency in age‐dependent LV remodeling.MethodsWe used 3, 6, 12, and 18 month old (m.o.) wild type (WT) and DRD3 knockout (D3KO) male and female mice (n=6/sex/age/genotype). Cardiac function was assessed by serial echocardiography, and plasma and left ventricle were harvested to analyze molecular parameters of LV remodeling, particularly extracellular matrix composition.ResultsEchocardiography analysis demonstrated that D3KO mice have a continuous, age‐dependent, increase of the LV anterior wall (LVAW), compared to WT, in both genders, but more markedly in females. This suggests that female D3DKO may have age‐dependent hypertrophy. In addition, the interior diameter in diastole (LVIDd) of D3KO animals was consistently smaller than WT mice of the same age, particularly at 6 and 12 m.o. (Figure 1). Cardiac fibrosis increased in the older male animals (18 m.o.) compared to all other ages in both genotypes. Females, however, showed a distinct genotype‐dependent pattern, suggesting sex‐differences in collagen metabolism with age. Genes associated with cardiac remodeling, as Gsta1, Nrp2, Mmp12 and Vcam1 showed increased expression with aging in WT females, but not in D3KO. Male D3KO however, displayed increased Ccl2 and Ecm1 at 18 m.o. compared to all other ages and Casp1 (an inflammatory response initiator) was increased in D3KO with time.ConclusionOur data suggests that DRD3 function in the heart plays an important gender‐specific role in age‐dependent cardiac remodeling.Support or Funding InformationWe acknowledge support from American Heart Association (14SDG18860050) and the Research and Graduate School at East Carolina University.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Stem-cell therapy in ST-segment elevation myocardial infarction with reduced ejection fraction: A multicenter, double-blind randomized trial.

Left ventricular ejection fraction (LVEF) is a major determinant of long-term prognosis after ST-segment elevation myocardial infarction (STEMI). STEMI patients with reduced LVEF have a poor prognosis, despite successful reperfusion and the use of renin-angiotensin-aldosterone inhibitors. Intracoronary infusion of bone marrow-derived mononuclear cells (BMMC) may improve LVEF in STEMI patients successfully reperfused. The main inclusion criteria for this double-blind, randomized, multicenter study were patient age 30 to 80 years, LVEF ≤50%, successful angioplasty of infarct-related artery, and regional dysfunction in the infarct-related area analyzed before cell injection. Cardiac magnetic resonance imaging was used to assess LVEF, left ventricular volumes, and infarct size at 7 to 9 days and 6 months post-myocardial infarction. One hundred and twenty-one patients were included (66 patients in the BMMC group and 55 patients in the placebo group). The primary endpoint, mean LVEF, was similar between both groups at baseline (44.63% ± 10.74% vs 42.23% ± 10.33%; P = 0.21) and at 6 months (44.74% ± 12.95 % vs 43.50 ± 12.43%; P = 0.59). The groups were also similar regarding the difference between baseline and 6 months (0.11% ± 8.5% vs 1.27% ± 8.93%; P = 0.46). Other parameters of left ventricular remodeling, such as systolic and diastolic volumes, as well as infarct size, were also similar between groups. In this randomized, multicenter, double-blind trial, BMMC intracoronary infusion did not improve left ventricular remodeling or decrease infarct size.

Myocardium of patients with dilated cardiomyopathy presents altered expression of genes involved in thyroid hormone biosynthesis.

BackgroundThe association between dilated cardiomyopathy (DCM) and low thyroid hormone (TH) levels has been previously described. In these patients abnormal thyroid function is significantly related to impaired left ventricular (LV) function and increased risk of death. Although TH was originally thought to be produced exclusively by the thyroid gland, we recently reported TH biosynthesis in the human ischemic heart.ObjectivesBased on these findings, we evaluated whether the genes required for TH production are also altered in patients with DCM.MethodsTwenty-three LV tissue samples were obtained from patients with DCM (n = 13) undergoing heart transplantation and control donors (n = 10), and used for RNA sequencing analysis. The number of LV DCM samples was increased to 23 to determine total T4 and T3 tissue levels by ELISA.ResultsWe found that all components of TH biosynthesis are expressed in human dilated heart tissue. Expression of genes encoding thyroperoxidase (–2.57-fold, P < 0.05) and dual oxidase 2 (2.64-fold, P < 0.01), the main enzymatic system of TH production, was significantly altered in patients with DCM and significantly associated with LV remodeling parameters. Thyroxine (T4) cardiac tissue levels were significantly increased (P < 0.01), whilst triiodothyronine (T3) levels were significantly diminished (P < 0.05) in the patients.ConclusionsExpression of TH biosynthesis machinery in the heart and total tissue levels of T4 and T3, are altered in patients with DCM. Given the relevance of TH in cardiac pathology, our results provide a basis for new gene-based therapeutic strategies for treating DCM.

Percutaneous mitral valve repair in secondary mitral regurgitation improves cardiac work

Left ventricular (LV) pressure-strain loops (PSLs) have been recently validated as a non-invasive index of myocardial performance. Aim of the present study is to compare LV function, myocardial work, and energy dispersion in patients with severe mitral regurgitation (MR) and decreased left ventricular ejection fraction (LVEF) before percutaneous mitral valve repair (PMVR, by Mitraclip ® system) and at 6-month follow-up (FU). We included in this study 32 patients (mean age: 71 ± 10 years) with MR (18 with ischemic cardiomyopathy, 14 with dilated cardiomyopathy) and decreased LVEF undergoing PMVR according to local heart team. All patients underwent standard echocardiography and speckle tracking echocardiography (STE) before PMVR and at 6-month FU. Strain traces and valvular event times were used to calculate LV-PSLs and Global cardiac Work (GW), Positive Work (PW), and Negative work (NW) were therefore obtained. The main results are shown in Table 1 . Despite a strong decrease of NYHA class (2.6 ± 0.6 vs. 1.8 ± 0.7; P < 0.001), no significant difference in LV function and remodeling parameters was observed at FU. Interestingly, whereas GW and NW remained unchanged, PW significantly improved at 6-month FU (999 ± 399 vs. 1112 ± 444; P = 0.05). Patients with severe MR and high surgical risk undergoing PMVR experienced a significant improvement in symptoms, which was associated to an increase in PW. On the other hand, no classical parameters of LV function/remodeling resulted in, ameliorated at FU. These findings support the hypothesis that the estimation of PW by LV-PSLs might be more sensible that commonly used index of myocardial performance to detect early improvement in myocardial function.

4D flow MRI, cardiac function, and T1 -mapping: Association of valve-mediated changes in aortic hemodynamics with left ventricular remodeling.

Patients with bicuspid aortic valve (BAV) show altered hemodynamics in the ascending aorta that can be assessed by 4D flow MRI. Comprehensive cardiac MRI was applied to test the hypothesis that BAV-mediated changes in aortic hemodynamics (wall shear stress [WSS] and velocity) are associated with parameters of left ventricular (LV) remodeling. Retrospective data analysis. Forty-nine BAV patients (mean age = 50.2 ± 13.5, 62% male). Balanced steady-state free precession (bSSFP)-CINE, pre- and postcontrast T1 mapping with modified Look-Locker inversion recovery (MOLLI), time-resolved 3D phase-contrast (PC) MRI with three-directional velocity encoding (4D flow MRI) at 1.5 and 3T. Quantification of LV volumetric data and myocardial mass, extracellular volume fraction (ECV), aortic valve stenosis (AS), and regurgitation (AR). 3D aortic segmentation, quantification of peak systolic velocities, and 3D WSS in the ascending aorta (AAo), arch, and descending aorta (DAo). Two-sided nonpaired t-test to compare subgroups. Pearson correlation coefficient for correlations between aortic hemodynamics and LV parameters. Of the 49 BAV patients, 35 had aortic valve dysfunction (AS [n = 7], AR [n = 16], both AS and AR [n = 12]). Mean systolic WSS in the AAo, peak systolic velocities in the AAo and arch, and LV mass were significantly higher (P < 0.001) in the AS/AR group compared to the patients without AS/AR. In the complete group, we observed significant relationships between increased LV mass and elevated peak systolic velocity (r = 0.57, r = 0.58; P < 0.001) and WSS in the AAo and arch, respectively (r = 0.54, r = 0.46; P < 0.001). We detected an association between ECV and WSS in the AAo (r = 0.38, P = 0.02). These relations did not hold true for patients without AV dysfunction. AS and AR in BAV patients have a major impact on elevated aortic peak velocities and WSS that were associated with parameters of LV remodeling. 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017.

Serum apolipoprotein B is inversely associated with eccentric left ventricular hypertrophy in peritoneal dialysis patients

The study aimed to examine the relationship of serum apolipoprotein B level with left ventricular (LV) structural and functional characteristics, in particular, LV remodeling parameters in peritoneal dialysis (PD) patients. A total of 182 patients with end-stage renal disease (ESRD) receiving PD were identified. Conventional echocardiography was performed for each patient, and echocardiographic characteristics were analyzed according to apo B quartile groups. Multivariate linear regression models were used to determine the associations between serum apo B and LV remodeling indices. A high serum apo B level was significantly related to the reduction in left atrium dimension (r=-0.20, P=0.011), LV dimensions (end-diastolic: r=-0.27, P=0.001; end-systolic: r=-0.24, P=0.003), peak velocities of early filling divided by peak velocities of atrial filling (r=-0.38, P<0.001), and LV volumetric dimension (end-diastolic: r=-0.27, P<0.001; end-systolic: r=-0.28, P<0.001). After adjustment for clinical confounding factors, the effect of serum apo B on LV eccentric remodeling modestly weakened but remained statistically significant (P=0.038), while other associations were not significant. In multivariate linear regression analysis, conventional lipid profiles were not significantly associated with LV eccentric remodeling, whereas serum apo B was an independent determinant of LV dilatation (β: -42.10, 95% CI -74.82 to -9.38, P=0.012). Serum apo B was significantly and inversely associated with LV dilatation, independently of conventional lipids and other CV risk factors in our ESRD patients undergoing PD. It suggested that low serum apo B level could be a powerful risk marker for eccentric left ventricular geometry remodeling and could be potentially used to risk-stratify PD patients.

Reappraising myocardial fibrosis in severe aortic stenosis: an invasive and non-invasive study in 133 patients.

AimsTo investigate myocardial fibrosis (MF) in a large series of severe aortic stenosis (AS) patients using invasive biopsy and non-invasive imaging.Methods and resultsOne hundred thirty-three patients with severe, symptomatic AS accepted for surgical aortic valve replacement underwent cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) and extracellular volume fraction (ECV) quantification. Intra-operative left ventricular (LV) biopsies were performed by needle or scalpel, yielding tissue with (n = 53) and without endocardium (n = 80), and compared with 10 controls. Myocardial fibrosis occurred in three patterns: (i) thickened endocardium with a fibrotic layer; (ii) microscopic scars, with a subendomyocardial predominance; and (iii) diffuse interstitial fibrosis. Collagen volume fraction (CVF) was elevated (P < 0.001) compared with controls, and higher (P < 0.001) in endocardium-containing samples with a decreasing CVF gradient from the subendocardium (P = 0.001). Late gadolinium enhancement correlated with CVF (P < 0.001) but not ECV. Both LGE and ECV correlated independently (P < 0.001) with N-terminal pro-brain natriuretic peptide and high-sensitivity-troponin T. High ECV was also associated with worse LV remodelling, left ventricular ejection fraction and functional capacity. Combining high ECV and LGE better identified patients with more adverse LV remodelling, blood biomarkers and histological parameters, and worse functional capacity than each parameter alone.ConclusionMyocardial fibrosis in severe AS is complex, but three main patterns exist: endocardial fibrosis, microscars (mainly in the subendomyocardium), and diffuse interstitial fibrosis. Neither histological CVF nor the CMR parameters ECV and LGE capture fibrosis in its totality. A combined, multi-parametric approach with ECV and LGE allows best stratification of AS patients according to the response of the myocardial collagen matrix.

Thyroid hormone biosynthesis machinery is altered in the ischemic myocardium: An epigenomic study

BackgroundAbnormal thyroid hormone (TH) metabolism is significantly associated with impaired left ventricular (LV) function and death. Although TH was traditionally thought to be produced exclusively by the thyroid gland, an increasing number of studies report TH production in other tissues. Based on these findings, we evaluated whether the genes required for TH biosynthesis are expressed in the human heart, and whether their expression is altered in patients with ischemic cardiomyopathy (ICM) and is related to epigenetic variations. MethodsTwenty-three LV tissue samples were obtained from ICM patients (n=13) undergoing heart transplantation and control donors (n=10) for RNA sequencing analysis. We increased the LV samples to 27 for the ELISA determination of total T4 and T3 tissue levels. For epigenomic studies, 850K Infinium MethylationEPIC BeadChip platform was performed. ResultsUsing RNA-sequencing, we displayed the expression levels of all components required for TH biosynthesis in human heart tissue. We observed significantly altered expression of genes encoding thyroperoxidase (TPO; −2.48-fold, P<0.05) and dual oxidase 2 (2.83-fold, P<0.05), the main enzymatic system of TH production, and significant relationships between their altered expression and LV remodeling parameters. In addition, epigenetic analysis revealed a differential methylation pattern in TPO, and triiodothyronine tissue levels were significantly decreased (P<0.01). ConclusionsThese results showed that the human heart expresses the TH biosynthesis machinery, being altered its main enzymatic system in patients with ICM. Given the relevance of TH in cardiac pathology, our results provide a foundation for new therapeutic approaches based on TPO for treating ICM.

Predictors of left ventricular remodeling after ST-elevation myocardial infarction

Adverse left ventricular (LV) remodeling after acute ST-elevation myocardial infarction (STEMI) is associated with morbidity and mortality. We studied clinical, biochemical and angiographic determinants of LV end diastolic volume index (LVEDVi), end systolic volume index (LVESVi) and mass index (LVMi) as global LV remodeling parameters 4 months after STEMI, as well as end diastolic wall thickness (EDWT) and end systolic wall thickness (ESWT) of the non-infarcted myocardium, as compensatory remote LV remodeling parameters. Data was collected in 271 patients participating in the GIPS-III trial, presenting with a first STEMI. Laboratory measures were collected at baseline, 2 weeks, and 6–8 weeks. Cardiovascular magnetic resonance imaging (CMR) was performed 4 months after STEMI. Linear regression analyses were performed to determine predictors. At baseline, patients were 21% female, median age was 58 years. At 4 months, mean LV ejection fraction (LVEF) was 54 ± 9%, mean infarct size was 9.0 ± 7.9% of LVM. Strongest univariate predictors (all p < 0.001) were peak Troponin T for LVEDVi (R2 = 0.26), peak CK-MB for LVESVi (R2 = 0.41), NT-proBNP at 2 weeks for LVMi (R2 = 0.24), body surface area for EDWT (R2 = 0.32), and weight for ESWT (R2 = 0.29). After multivariable analysis, cardiac biomarkers remained the strongest predictors of LVMi, LVEDVi and LVESVi. NT-proBNP but none of the acute cardiac injury biomarkers were associated with remote LV wall thickness. Our analyses illustrate the value of cardiac specific biochemical biomarkers in predicting global LV remodeling after STEMI. We found no evidence for a hypertrophic response of the non-infarcted myocardium.

Post-infarct treatment with [Pyr1]apelin-13 exerts anti-remodelling and anti-apoptotic effects in rats' hearts.

Ischaemic heart disease is the main cause of mortality in the world. After myocardial infarction (MI) cardiomyocytes apoptosis and ventricular remodelling have occurred. Apelin is a peptide that has been shown to exert cardioprotective effects. The aim of this study was to investigate the anti-apoptotic and anti-remodelling effects of [Pyr¹]apelin-13 in the rat model of post-MI. Thirty-six male Wistar rats were randomly divided into three groups: (1) sham, (2) MI, and (3) MI treated with [Pyr¹] apelin-13 (MI+Apel). MI animals were subjected to 30-min ligation of the left anterior descending coronary artery (LAD) and 14 days of reperfusion. Twenty-four hours after LAD ligation, [Pyr¹]apelin-13 (10 nmol/kg/day, i.p.) was administered for five consecutive days. Hypertrophic parameters, left ventricular (LV) remodelling, and gene expression of Apel, apelin receptor (Apelr), Bax, caspase-3 (Casp-3), and Bcl-2 by real-time polymerase chain reaction and cardiomyocytes apoptosis by TUNEL immunostaining were assessed on day 14 post-MI. Post-infarct treatment with [Pyr¹]apelin-13 improved myocardial hypertrophic and LV remodelling parameters and led to a significant increase in the expression of Apel, Apelr, and Bcl-2, and a decrease in the expression of Bax and Casp-3. Furthermore, treatment with [Pyr¹]apelin-13 decreased cardiomyocyte apoptosis. [Pyr¹]apelin-13 has anti-hypertrophic, anti-remodelling, and anti-apoptotic effects via overexpression of Apel, Apelr, and Bcl-2 and reduces gene expression of Bax and Casp-3 in the infarcted myocardium, which can in turn lead to repair myocardium.

Serum Soluble ST2 and Diastolic Dysfunction in Hypertensive Patients.

Background Echocardiographic evaluation of left ventricular (LV) structural and functional alterations in hypertension has some limitations, potentially overcome by using biomarkers. ST2, a prognostic biomarker for heart failure and myocardial infarction patients, was less studied in hypertension. Aim To analyze the relationship between serum ST2 levels and diastolic dysfunction (DD) in hypertension. Method We enrolled 88 hypertensive outpatients (average age 65 years, 69.3% females) in a prospective study, stratified for presence of LV hypertrophy (LVH). For each patient clinical examination, lab workup (routine and serum ST2 levels) and echocardiography were performed. Results Hypertensive patients with LVH had higher age, pulse pressure, mean arterial pressure, and serum ST2, while having lower serum albumin than those without LVH. Serum ST2 levels correlate with parameters of LV remodeling and DD. We found that 5.3% of ST2 level variability was caused by a 1-unit variation of cardiovascular risk. We identified cut-off values for discriminating hypertension with LVH versus that without LVH and grade 2 DD versus normal diastolic performance. Conclusion ST2 could be used as diagnostic biomarker for cardiac remodeling and altered diastolic performance in hypertension, providing additional data to echocardiography. It could represent a milestone in early detection of cardiac performance alteration.

Cardiac mechanics and heart rate variability in patients with systemic sclerosis: the association that we should not miss.

We aimed to determine left ventricular (LV) and right ventricular (RV) structure, function and mechanics, as well as heart rate variability (HRV), and their relationship, in patients with systemic sclerosis (SSc). The study included 41 SSc patients and 30 age-matched healthy volunteers. All the patients underwent clinical examination, serological tests, pulmonary function testing, 24-h Holter monitoring and complete two-dimensional echocardiography including strain analysis. The parameters of LV structure (interventricular septum thickness and LV mass index) and RV structure (RV wall thickness) were significantly higher in SSc patients. LV and RV diastolic function (estimated by mitral and tricuspid E/e' ratio) was significantly impaired in SSc group comparing with the healthy controls. LV and RV longitudinal function was significantly deteriorated in SSc patients. LV circumferential strain was also significantly lower in SSc group, whereas LV radial strain was similar between the observed groups. All parameters of time and frequency domain of HRV were decreased in SSc patients. LV and RV cardiac remodeling parameters, particularly diastolic function and longitudinal strain, were associated with HRV indices without regard to the main demographic or the clinical and echocardiographic characteristics. Rodnan Skin Score was also independently associated with biventricular cardiac remodeling in SSc patients. LV and RV structure, function and mechanics, as well as autonomic nervous function, were significantly impaired in SSc patients. There is the significant association between biventricular cardiac remodeling and autonomic function in these patients, which could be useful for their everyday clinical assessment.

The relationship between heart rate variability and left ventricular layer-specific deformation in uncomplicated diabetic patients.

The aim of this study was to investigate heart rate variability (HRV) and left ventricular (LV) remodeling in uncomplicated diabetic patients. Furthermore, we sought to investigate the association between HRV indices and LV structural, functional and mechanical parameters. This cross-sectional study included 50 uncomplicated patients with type 2 diabetes and 40 healthy controls without cardiovascular risk factors. All study subjects underwent 24-h Holter monitoring, laboratory analyses and complete two-dimensional echocardiography examination (2DE). LV structure and diastolic function were significantly deteriorated in the diabetic patients comparing with the controls. LV global longitudinal, circumferential and radial strains were significantly reduced in the diabetic group. LV endocardial, mid-miocardial and epicardial longitudinal and circumferential strains were significantly decreased, whereas LV twist was significantly increased, in the diabetic patients; 24-h, daytime and nighttime heart rates were higher in the diabetic patients. All parameters of time and frequency domain of HRV were reduced in the diabetic subjects. LV mass index, mitral E/e' ratio and 2DE LV endocardial and mid-miocardial longitudinal and circumferential strains correlated with HRV parameters. A multivariate regression analysis showed that E/e' ratio and 2DE LV layer-specific strains were associated with HRV parameters independently of age, BMI, systolic blood pressure and LV mass index. HRV and LV mechanics are significantly deteriorated in uncomplicated diabetic individuals. Parameters of LV remodeling are independently associated with HRV indices, which could indicate the importance of HRV determination in diabetics.

42 Myocardial Lipid Accumulation and Cardiac Remodelling in Heart Failure with Reduced and Preserved Ejection Fraction

Introduction Heart failure (HF) is characterised by alterations in myocardial metabolism with a compensatory shift from fatty acid to glucose metabolism. This could potentially lead to myocardial lipid accumulation (steatosis). We aimed to determine if myocardial lipid is increased in HF with reduced (HFrEF) and preserved (HFpEF) ejection fraction (EF), and assess whether it is related to cardiac structure and function. Methods 71 subjects (25 HFrEF due to dilated cardiomyopathy-DCM, 18 HFpEF and 28 normal volunteers were prospectively recruited). HFpEF was defined by left ventricular (LV) ejection fraction (EF) >50%, abnormal diastolic function, maximum oxygen consumption 1 H-MR spectroscopy (MRS) to quantify myocardial lipid/water (%). Results All subjects were matched for gender, body mass index, blood glucose, free fatty acids and lipid profile. As expected HFrEF patients had significantly increased LV volumes and reduced EF, whilst HFpEF patients had significantly increased LV mass to end-diastolic volume ratio (LV mass/EDV). Importantly, cardiac lipid was increased in both HFrEF and HFpEF when compared to normal controls (cardiac lipid/water 0.67 ± 0.42% in HFrEF; 1.06 ± 0.83% in HFpEF vs. normal controls 0.44 ± 0.17, all p Conclusions Myocardial steatosis occurs in both HFrEF and HFpEF and is related to parameters of LV remodelling. This suggests that myocardial lipid may play a role in the pathophysiological processes of LV remodelling in both HFrEF and HFpEF. Cardiac lipid accumulation may be a potential therapeutic target in these conditions.

Early diastolic dyssynchrony in relation to left ventricular remodeling and function in hypertension

BackgroundCardiac synchronization is important in maintaining myocardial performance, but the mechanism of diastolic dyssynchrony leading to failing myocardium is unclear. We aim to study the relation of left ventricular (LV) diastolic dyssynchrony with diastolic dysfunction in patients with hypertension. MethodsTwo-D, three-D and Doppler echocardiography were performed using the GE Vivid E9 system on 230 subjects. Among them, 154 patients with hypertension were divided into group 1 (86 patients with mild to moderate hypertension, BP 152±8/91±11mmHg) and group 2 (68 patients with severe hypertension, BP 188±12/105±24mmHg), age 76, gender matched normotensive subjects (119±6/76±9mmHg) as control. The routine 2D and Doppler parameters were measured and LV systolic and diastolic dyssynchrony indices were determined as the standard deviation of the time interval from the peak R of the QRS complex to peak myocardial systolic strain rate (Ts-SD), and to early diastolic strain rate (Te-SD) of 12 LV segments. ResultsLV relative wall thickness, mass index, and Te-SD were significantly higher in patients with hypertension than in control group (p<0.0001), but Ts-SD showed no significant differences. Te-SD and diastolic dysfunction worsened progressively with increasing severity of hypertension (p<0.05). Te-SD was significantly and independently associated with parameters of LV remodeling and diastolic function. ConclusionOur study demonstrated that LV diastolic dyssynchrony was associated with LV remodeling, which seems to contribute to diastolic dysfunction in hypertension. This diastolic dyssynchrony index derived from speckle tracking echocardiography can be used as a marker for studying the LV function and effects of therapy in hypertensive heart disease.

Outcome of super-responders to cardiac resynchronization therapy defined by endpoint-derived parameters of left ventricular remodeling: a two-center retrospective study.

Various studies have attempted to identify super-responders to cardiac resynchronization therapy (CRT) by echocardiographic parameters of reverse remodeling. However, scientific evidence regarding those parameters is scarce. This study aimed at validating the definition of super-response to CRT based on the following frequently employed echocardiographic parameters: left ventricular ejection fraction (LVEF), end-diastolic volume index (EDVI), and end-systolic volume index (ESVI). We retrospectively investigated echocardiographic data and outcomes of 542 patients after CRT implantation. The primary endpoint comprised all-cause mortality, heart transplantation, ventricular assist device implantation (VAD), and hospitalization for heart failure. Secondary endpoints were hospitalization for heart failure, and the combination of all-cause mortality, heart transplantation and VAD. Two approaches were employed defining super-response based on improvement of echocardiographic parameters: one derived from the negative predictive value (NPV) for clinical endpoints, and second from best quartiles of improvement. Using the NPV method, an absolute 25 % increase in LVEF, a relative 38 % reduction in EDVI, and 46 % in ESVI were calculated as optimal cut-offs identifying 4.9, 18.5, and 21.3 % as super-responders. The best quartiles method resulted in lower cut-off values, i.e. 14 % increase in LVEF, 26 % reduction in EDVI, and 36 % in ESVI. All cut-offs except LVEF ≥ 25% were significantly associated with improved outcomes after 5 years (median follow-up 35.7 months). NPV- and best quartile-based cut-offs validate previously applied empirical echocardiographic cut-offs to define super-response to CRT. These data provide evidence for using these empirical cut-offs in daily practice and facilitate inter-study comparability.