N-terminal pro-brain natriuretic peptide (NT-proBNP) as the benchmark and tried to establish a multi-biomarker approach to heart failure (HF) in hypertensive patients. In 120 hypertensive patients with or without overt heart failure, the incremental predictive value of the following biomarkers was investigated: Collagen III N-terminal propeptide (PIIINP), cystatin C (CysC), lipocalin-2/NGAL, syndecan-4, tumor necrosis factor-α (TNF-α), interleukin 1 receptor type I (IL1R1), galectin-3, cardiotrophin-1 (CT-1), transforming growth factor β (TGF-β) and N-terminal pro-brain natriuretic peptide (NT-proBNP). The highest discriminative value for HF was observed for NT-proBNP (area under the receiver operating characteristic curve (AUC) = 0.873) and TGF-β (AUC = 0.878). On the basis of ROC curve analysis we found that CT-1 > 152 pg/mL, TGF-β < 7.7 ng/mL, syndecan > 2.3 ng/mL, NT-proBNP > 332.5 pg/mL, CysC > 1 mg/L and NGAL > 39.9 ng/mL were significant predictors of overt HF. There was only a small improvement in predictive ability of the multi-biomarker panel including the four biomarkers with the best performance in the detection of HF—NT-proBNP, TGF-β, CT-1, CysC—compared to the panel with NT-proBNP, TGF-β and CT-1 only. Biomarkers with different pathophysiological backgrounds  give additive prognostic value for incident HF in hypertensive patients compared to NT-proBNP alone.We assessed the predictive ability of selected biomarkers using  Hypertension is a major contributor to the development of heart failure (HF). Our understanding of the epidemiology and pathophysiology of HF in relation to hypertension has increased considerably in recent years. Currently, we are aware of the fact that the pathophysiologic relationship between hypertension and heart failure is more complex than simply the development of left ventricular hypertrophy. A growing array of biological pathways support the syndrome we recognize as heart failure. These include deleterious pathways promoting heart failure development and progression, as well as compensatory cardioprotective pathways. Components of these pathways can be utilized as biomarkers of this condition in order to facilitate the diagnosis and prognostication and potentially direct the management .N-terminal pro-brain natriuretic peptide (NT-proBNP) are widely studied factors, having a potentially important but still evolving role in prognosis determination and as a surrogate endpoint in clinical trials [i.e., the elevation of the left ventricular (LV) filling pressure [Brain natriuretic peptide (BNP) and l trials . BNP andl trials . They arpressure . Measuripressure . Such mepressure ,7. As a pressure .N-terminal propeptide (PIIINP), syndecan, tumor necrosis factor α (TNF-α), cardiotrophin 1 (CT-1), interleukin 1 receptor, type I (IL1R1) and NT-proBNP. We stated the hypothesis that biomarkers which reflects different biological pathways may give additional predictive information in patients with hypertension. Therefore the purpose of the current study was to evaluate which heart failure biomarkers may be of value when combined in a multi-marker panel with the biochemical gold standard NT-proBNP.After the analysis of available literature concerning biomarkers in the databases including PubMed and MEDLINE and based on our preliminary results ,10, we cPatients’ characteristics are presented in p < 0.0001; p = 0.007; p < 0.0001; p < 0.0001; p < 0.0001 and p < 0.0001 respectively). The detailed data on biomarkers in study groups is presented in Compared to non-HF patients, HF hypertensive patients had significantly lower values of TGF-β, and higher levels of NGAL, CT-1, syndecan, NT-proBNP and CysC (p < 0.0001) and LV volumes (p < 0.0001), lower left ventricular ejection fraction (LVEF) (p < 0.0001), significantly increased left atrial (LA) diameter (p < 0.0001), greater wall thickness of the left ventricle , lower late mitral diastolic inflow velocity (A) (p = 0.01), lower ratio of early to late mitral inflow velocities (E/A ratio) (p < 0.008), longer deceleration time of peak early mitral filling velocity (DT) (p = 0.04) and lower tricuspid annular plane systolic excursion (TAPSE) (p = 0.005)  dimensions (= 0.005) .p = 0.0001; 95% CI (0.803–0.943)) and TGF-β )—All biomarkers analyzed in this study were used in the assessment of heart failure discriminative value. Biomarkers with significant AUC , which may facilitate the diagnosis of heart failure, are presented in On the basis of receiver-operating characteristic (ROC) curve analysis we found that CT-1 > 152 pg/mL, TGF-β < 7.7 ng/mL, syndecan > 2.3 ng/mL, NT-proBNP > 332.5 pg/mL, CysC > 1 mg/L and NGAL > 39.9 ng/mL were significant predictors of overt heart failure in patients with hypertension. The optimal cut-off points of biomarkers for the occurrence of overt heart failure in patients with hypertension are presented in To evaluate the predictive value of selected biomarkers, multivariate models were used.p < 0.0001). The highest discriminative value was found for NT-proBNP and TGF-β . Higher values of NT-proBNP, CT-1, syndecan and CysC and a lower level of TGF-β increased the risk of heart failure. The results are summarized in In univariate analysis, biomarkers which statistically significantly increased the risk of overt heart failure were as follows: CT-1, TGF-β, syndecan, NT-proBNP and CysC  and left ventricular dysfunction. Clinical guidelines advocate their use in the diagnostic work-up in case of HF suspicion to limit the number of potential cases requiring echocardiography by ruling out the condition where the natriuretic peptide level is low, although recommended rule-out cut-off points vary between studies and guidelines ,13. AccoHowever, in order to diagnose heart failure, knowledge of the non-cardiac factors that influence NT-proBNP is crucial. Anemia, which is common in heart and renal failure, is one of the independent factors affecting natriuretic peptides. In chronic kidney disease, anemia is mainly caused by the reduced erythropoietin production ,15.For these reasons, NT-proBNP was concluded to be of diagnostic value in patients with heart failure and proper renal functions. Previous studies have identified a variety of non-cardiac factors influencing natriuretic peptide levels, including age, sex, BMI, renal function, hepatic damage and diastolic pressure ,17,18.Not unexpectedly, BNP/NT-proBNP fails to fulfill all the criteria for an ideal biomarker. The selection of additional biomarkers and the development of the multi-biomarker approach will be an important step towards improving the diagnosis and the treatment of patients with chronic and acute decompensated heart failure. This study is the first investigating serum levels of PIIINP, CysC, lipocalin-2/NGAL, syndecan-4, tumor necrosis factor-α (TNF-α), interleukin 1 receptor type I (IL1R1), galectin-3, CT-1 and TGF-β in patients with hypertension and heart failure. Furthermore, these biomarkers were compared with NT-proBNP—the gold standard biomarker in chronic heart failure.p < 0.0001; p = 0.007; p < 0.0001; p < 0.0001; p = 0.0001;and p < 0.0001, respectively).In this study we investigated in patients with hypertension the diagnostic and prognostic multi-marker approach towards heart failure using selected biomarkers  and using NT-proBNP as the benchmark. Compared to non-HF patients, HF hypertensive patients had significantly lower values of TGF-β, and higher levels of CT-1, NAGAL, syndecan, NT-proBNP and CysC . In the multi-biomarker approach, four biomarkers with the best performance in the detection of heart failure  had superior value in the recognition of heart failure compared to NT-proBNP alone. There was only a small improvement in the predictive value of the multi-biomarker score with NT-proBNP, TGF-β, CT-1 and CysC compared to the panel comprising NT-proBNP, TGF-β and CT-1.On the basis of receiver operating characteristic (ROC) curve analysis, we found that CT-1 > 152 pg/mL, TGF-β < 7.7 ng/mL, syndecan > 2.3 ng/mL, NT-proBNP > 332.5 pg/mL, CysC > 1 mg/L and NGAL > 39.9 ng/mL were significant predictors of overt heart failure in patients with hypertension. The highest discriminative values in univariate analysis were found for NT-proBNP and TGF-β . Similarly, in our study, patients with hypertension and heart failure had lower TGF-β levels than those with hypertension alone. This decrease may result from a higher consumption of TGF-β1 within the impaired myocardium or anti-fibrotic functions of natriuretic peptides. However, in our analysis, low TGF-β1 serum levels were significantly increased in patients suffering from arterial hypertension and heart failure.A higher release from the inactive latent complex and a higher consumption of the active measureable serum TGF-β1 molecule in the context of cardiac fibrosis may explain the decrease of measurable serum TGF-β1 levels in peripheral blood in patients with heart failure. This supports experimental data from the literature, in which natriuretic peptides have been shown to suppress adverse structural remodeling in the atria and ventricles. Atrial natriuretic peptide (ANP) and BNP inhibit collagen synthesis previously induced before by angiotensin II, endothelin and specific fibroblast growth factors, via influencing its mRNA level . In a moet al.  investiget al. [p = 0.001, r = 0.349).Cardiotrophin-1 (CT-1) is a newly identified member of the interleukin-6 (IL-6) family of cytokines and one of the endogenous ligands for gp130 signaling pathways in the heart. CT-1 induces hypertrophic growth and contractile dysfunction in cardiomyocytes. CT-1 is increased in various cardiovascular diseases, including hypertension and chronic heart failure. In the study of Celik et al.  plasma let al. [p < 0.001) in hypertensive patients with heart failure in comparison to controls. In vitro, CT-1 stimulated the differentiation of human cardiac fibroblast to myofibroblasts (p < 0.05) and the expression of procollagen type I (p < 0.05) and III (p < 0.01) mRNAs [The study of Lopez et al. , which i1) mRNAs .et al. [In the study of Ravassa et al. , serum Cet al. .et al. [n = 8), cardiac hypertrophy (n = 9) and heart failure (HF) (n = 10). The serum levels of CT-1 were significantly higher in patients with LVH or heart failure compared with controls. Subgroup analysis revealed that CT-1 levels were highest in patients with hypertension-induced hypertrophy and heart failure and slightly lower in patients with hypertension-induced LVH without heart failure [The meta-analysis of Song et al.  includin failure . Increas failure . CT-1 maCystatin C (CysC) is a small, low-molecular weight protein from the group of cysteine proteinase inhibitors . It is pImpaired renal function is an independent marker for LVH and a good predictor of morbidity and mortality in cardiovascular disease . In patiet al. [LVH is an important form of target organ damage in essential hypertension . Furtheret al. , there wElevated CysC levels are an independent risk factor for increased mortality in elderly heart failure patients .et al. [p = 0.004) [p for trend = 0.015) [In the study of Manzano-Fernandez et al. , the autet al. . In cont= 0.004) . A multi= 0.015) .et al. [Moran et al.  examinedet al. .Serum CysC is a novel and stable biomarker not influenced by sex, age, exertion, diet, body mass index, muscle mass or serum creatinine . The incThe study involved a relatively small number of patients, and the findings need to be confirmed in a larger population. The present study was conducted as a prospective, consecutive recruitment of patients with hypertension.There were 120 hypertensive patients consecutively included in the study between October 2012 and April 2014. The exclusion criteria were as follows: Unstable hypertension, New York Heart Association (NYHA) class IV heart failure, evidence of pulmonary hypertension on echocardiography, obstructive or restrictive pulmonary disease, hyperthyroidism and hypothyroidism, pregnancy and lactating, hemodynamically significant acquired heart defects with the exception of mitral incompetence secondary to left ventricular dilatation, cancer, significant anemia, abuse of alcohol or drugs, chronic inflammatory and other diseases, operation or severe injury during a month prior to blood collection or lack of informed consent to participate in the study.All patients were divided into two groups: 60 patients without heart failure (non-HF group) and 60 patients with overt systolic heart failure (left ventricular ejection fraction (LVEF) <50% and clinical symptoms) (HF group). Dyspnea was graded on the basis of the NYHA functional classification .Angina pectoris was graded on the basis of the Canadian Cardiovascular Society (CCS) scale . FastingApproval from the Bioethics Commission of the Medical University of Lodz (No. RNN/80/12/KB) was obtained. Written informed consent was obtained from all the patients.N-terminal propeptide (PIIINP), syndecan-4, interleukin-1 receptor-like protein 1 (IL1RL1), transforming growth factor β 1 (TGF-β1) and lipocalin-2/NGAL were determined using the EMax Endpoint ELISA Microplate Reader analyzer . TNF-α was analyzed with the enzyme-linked immunosorbent assay , with two polyclonal antibodies directed against TNF-α. Determination of NT-proBNP and CT-1 was performed with reagents of USCN Life Science Inc. /Cloud-Clone Corp , using a sandwich ELISA assay according to the manufacturer’s protocol. Measurement of CysC was performed using a sandwich enzyme immunoassay  developed for the quantitative measurement of this marker in human serum. Analysis of the concentration of PIIINP, syndecan-4 and IL1RL1 was performed with a USCN Life Science Inc./Cloud-Clone Corp kit, using a sandwich ELISA assay according to the manufacturer’s protocol. Measurement of TGF-β1 was performed using a sandwich enzyme immunoassay  designed for the quantitative detection of TGF-β1 levels in cell culture supernatants, human serum, plasma or other body fluids. Determination of lipocalin-2/NGAL was conducted using the BioVendor Human Lipocalin-2/NGAL ELISA sandwich enzyme immunoassay. Analysis of the concentration of galectin-3 (GAL3) was performed with a USCN Life Science Inc./Cloud-Clone Corp kit, using a sandwich ELISA assay.The concentrations of NT-proBNP, cardiotrophin-1 (CT-1), cystatin C (CysC), tumor necrosis factor α (TNF-α), collagen III All patients were examined following a standardized protocol using an ALOKA Α 10 Premier  with a 3–11 MHz probe.Quantitative echocardiography was used following current guidelines . Left vet test for continuous and discrete variables with normal distribution and non-parametric Mann-Whitney U test if the distribution was not normal were applied.The STATISTICA 10 software package  was used for analysis. All values presented are the mean ± standard deviation (SD) for continuous variables and the number of patients and the percentage of total patients for categorical variables. The Shapiro-Wilk test was used to assess the normality of distribution. To study the relationship between qualitative variables, the chi-square test for independence or chi-square test with Yates’s correction and the chi-square test for maximum likelihood were used. To compare two groups, Student’s p < 0.10) were used for the construction of a stepwise logistic regression model. The quality of the models and the usefulness of the markers were evaluated using receiver operating characteristic (ROC) curves, tables of reclassification [p < 0.05.For quantitative variables (continuous and discrete) to evaluate correlations between variables, Spearman’s rank correlation coefficient was used. Variables significant in univariate analysis  enhanced the additive diagnostic value for incident heart failure in hypertensive patients compared to NT-proBNP alone.Hypertensive patients could be monitored for these indexes once a year or earlier when HF symptoms occur to detect potential risk of developing heart failure, renal complications of hypertension and the risk of myocardial hypertrophy in order to determine the indications for accurate staging complications of hypertension and modification and intensification of pharmacotherapy.Additional predictive information from different biological pathways reflects the multi-systemic character of heart failure.


Histopathologic changes of the SM may include fibrosis and fatty degeneration2. The aim of this study is to evaluate myocardial structure in preserved ejection fraction (EF).Myotonic dystrophy type II (MD2) is a genetic multisystemic disorder characterized by skeletal muscle (SM) symptoms, metabolic changes as well as arrhythmias3  was performed to identify myocardial fat deposits. Furthermore, we used 1H magnetic resonance spectroscopy (MRS)  to quantify myocardial Triglycerides (MTG). Data were analyzed using cvi42 and standard line-fitting procedure.We prospectively enrolled 32 subjects with a genetically confirmed diagnosis of MD2. Exclusion criteria were known cardiac diseases and contraindication for CMR. We assessed left-ventricular (LV) volumes, mass and function applying state of the art cine imaging using a 1.5 T Scanner. Late enhancement imaging  7 mm) was performed to detect myocardial fibrosis 10 minutes after injection of gadoteridol (0.2 mmol/kgbw). We applied T1 Mapping based on MOLLI  before and 15 minutes after contrast application and assessed resultant extracellular volume fraction (ECV). Fat-water-separated imaging26 data sets were totally completed . None of the patients had wall motion abnormalities. LGE was detectable in 6 of 28 subjects ; the location was mostly subepicardial inferolateral basal (Figure Despite preserved LVEF we could detect myocardial injury in patients with myotonic dystrophy type II. Already native T1-values were increased in case of subepicardial fibrosis compared to remote myocardium. To conclude, this is the first study constituted that CMR is feasible to detect subclinical myocardial manifestations in MD2.N/A.


Postsystolic shortening (PSS) has been proposed as a marker of myocardial dysfunction. Percutaneous transluminal septal myocardial ablation (PTSMA) is an alternative therapy for patients with hypertrophic obstructive cardiomyopathy (HOCM) that results in sustained improvements in atrial structure and function. We investigated the effects of PTSMA on PSS in HOCM patients using speckle tracking imaging.Conventional echocardiographic and PSS parameters were obtained in 18 healthy controls and 30 HOCM patients before and half a year after PTSMA.Compared with the healthy controls, the number of segments having PSS and the average value of PSS were significantly increased in the HOCM patients. At 6 months after PTSMA, both the number of segments having PSS  and the average value of PSS  were significantly reduced. Moreover, the reductions in the average value of PSS correlated well with the reductions in the E-to-Ea ratio .Both the number of segments having PSS and the average value of PSS were significantly increased in the HOCM patients. PTSMA has a favourable effect on PSS, which may partly account for the persistent improvement in LV diastolic function in HOCM patients after PTSMA. Postsystolic shortening (PSS) is considered myocardial shortening after the point of aortic valve closure, which has been known for years. PSS is found in one-third of normal myocardium This study was reviewed and proved by the Ethics Committee of Beijing Fuwai Hospital. Written informed consents were obtained from all patients and control subjects.The study population consisted of 38 patients with symptomatic obstructive HCM (HOCM) who were referred for PTSMA to our centre between May 2012 and December 2012. However, 5 patients underwent surgical myectomy and mitral-valve replacement, and 3 patients failed to return for the follow-up examination. The final cohort included 30 patients. The diagnoses of HCM were obtained by means of 2-dimensional echocardiography in patients with interventricular septal thicknesses ≥1.5 cm who had no other causes attributed to their left ventricular (LV) hypertrophy. The selection criteria for PTSMA were as follows: the persistence of symptoms despite being administered the maximum tolerated dosage of medication; a left ventricular outflow tract (LVOT) gradient >50 mmHg at rest or >100 mmHg after provocation; accessible septal branches, particularly of the left anterior descending coronary artery; the absence of a significant intrinsic abnormality of the mitral valve; and other conditions for which cardiac surgery was indicated. PTSMA were performed as previously described Each subject underwent an echocardiographic evaluation using a commercially available echocardiographic scanner  that was equipped with an S5-1 transducer  before and half a year after the PTSMA procedure. One lead electrocardiogram was recorded continuously. A 2-dimensionally guided M-mode echocardiography was performed to measure the thicknesses of the interventricular septum and left ventricular posterior wall (LVPW). The wall thickness was measured at the level of the mitral valve and papillary muscles in each of the four myocardial segments and at the apical level in the anterior and posterior segments using parasternal short-axis views. The maximum LV wall thickness was defined as the greatest thickness in any single segment. The left ventricular ejection fraction (LVEF) and the left atrial end-systolic volume (LAV) were calculated using a modified Simpson's biplane method in the apical 4- and 2-chamber views. The maximal early and late diastolic inflow velocities (E and A waves), E-to-A ratio, and deceleration time (DT) of the E wave were obtained using a pulsed-wave Doppler. The sample volume was placed immediately below the level of the mitral leaflet tips in the apical 4-chamber view. The LV outflow tract (LVOT) gradient was measured using a continuous-wave Doppler in the apical 5-chamber view. The TDI of the mitral annulus movement was performed using the apical 4-chamber view. A 1.5-mm sample volume was placed at the lateral side of mitral annular. The velocity of mitral annular was measured in early diastole (Ea) and with atrial contraction (Aa). Analyses of the isovolumic relaxation time (IVRT) were performed.−1. The off-line longitudinal strain data analysis was performed with QLAB 6.0 software . Eighteen segments from 6 LV walls were assessed, namely, the basal, mid, and apical segments for the inferior and anterior septum, and the anterior, anterolateral, inferolateral and inferior wall. The peak negative systolic strain was recorded to assess segmental myocardial systolic function. PSS was defined as the segmental shortening in the diastole beyond the minimum systolic segment length (the peak negative strain in the diastole minus the peak negative strain in the systole). If the minimum segment length was within the systole, PSS was set to zero .The data are presented as the mean±SD for the continuous variables or as percentages for the categorical variables. The clinical characteristics were compared using the The basic clinical characteristics of the HOCM patients and healthy controls are summarised in The conventional echocardiographic parameters in HOCM patients before PTSMA and the control group are shown in During the ablation procedure, the mean amount of alcohol that was injected was 2.37±0.90 ml. Right-bundle branch blocks occurred at a rate of 36.7% (11 patients). Transitory trifascicular blocks occurred at a rate of 23.3% (7 patients). No patient underwent a permanent pacemaker implantation following the procedure. There was no peri-interventional mortality during the observational period.Changes in the conventional echocardiographic parameters in the patients with HOCM at half a year following the PTSMA procedure are shown in As shown in Our study provides unprecedented data regarding the PSS parameters in HOCM patients before and half a year after a PTSMA procedure. We found that compared with healthy controls, both the number of myocardial segments having PSS and the average value of PSS were significantly increased in the HOCM patients. At half a year following PTSMA, both parameters of PSS were significantly improved. Moreover, the reduction of the average value of PSS in the patients was significantly correlated with the reduction of the E-to-Ea ratio.In 1986, Bertha and colleagues observed myocardial segments shorting after the point of the aortic valve closure into the early diastole using the sonomicrometry technique; they named the phenomenon “postsystolic shortening” Hypertrophic cardiomyopathy (HCM) is a genetically transmitted myocardial disease characterised by varying degrees of myocardial hypertrophy. Microvascular dysfunction, characterised by a blunted vasodilator reserve in the absence of an epicardial coronary stenosis, is very common in patients with HCM 15O-water PET study to obtain the resting myocardial blood flow and the coronary vasodilator reserve in 15 HOCM patients before and half a year after the PTSMA. In the study, Timmer observed similar results as Soliman, and he further proved that with the improvement of microvascular dysfunction, myocardial energy was restored in the HOCM patients after PTSMA. Furthermore, some studies have suggested that PTSMA can also partly reverse myocardial fibrosis in HOCM patients Currently, PTSMA is considered to be an alternative therapy to surgical myomectomy for patients with HOCM that results in the immediate relief of a LVOT obstruction, the regression of LV hypertrophy and the sustained improvement in LV diastolic function Impaired LV diastolic function is the most common pathophysiological feature of HCM, which has been implicated as the primary determinant of symptoms related to heart failure in HCM patients This study had several limitations. In addition to the relatively small sample size and the retrospective study design, the invasive measurements of the LV diastolic function were not performed during the course of this study. Instead, we used the E-to-Ea ratio to reflect the LV filling pressure. However, Geske reported that there was only a modest correlation between the estimated LV filling pressure with the use of the E-to-Ea ratio and the directly measured pressure in HCM patients In conclusion, compared with the healthy controls, the number of segments having PSS and the average value of PSS were significantly increased in the HOCM patients prior to the septal ablation. PTSMA was found to have a favourable effect on PSS, which may partly account for the persistent improvement in the LV diastolic function in HOCM patients after PTSMA. A larger, prospective study with invasive catheters to evaluate the LV filling pressure is necessary to confirm our results.


The sequence was compared against two previously introduced T2-mapping techniques in a phantom and in vivo study, 12 healthy volunteers were examined on a clinical 1.5 T scanner. The three T2-mapping sequences were performed at three short-axis slices. Global myocardial T2 relaxation times were calculated and statistical analysis was performed. For assessment of pixel-by-pixel homogeneity, the number of segments showing an inhomogeneous T2 value distribution, as defined by a pixel SD exceeding 20 % of the corresponding observed T2 time, was counted.Phantom experiments were performed at 1.5 T using a commercially available cylindrical gel phantom. Three different T2-mapping techniques were compared: a Multi Echo Spin Echo , a T2-prepared balanced Steady State Free Precession (T2prep) and a Gradient Spin Echo sequence. For the subsequent In vivo, significant differences between mean T2 times were observed. In general, T2prep resulted in lowest (52.4 ± 2.8 ms) and GraSE in highest T2 estimates (59.3 ± 4.0 ms). Analysis of pixel-by-pixel homogeneity revealed the least number of segments with inhomogeneous T2 distribution for GraSE-derived T2 maps.Phantom experiments showed a greater difference of measured T2 values between T2prep and MESE than between GraSE and MESE, especially for species with low T1 values. Both, GraSE and T2prep resulted in an overestimation of T2 times compared to MESE. The GraSE sequence is a fast and robust sequence, combining advantages of both MESE and T2prep techniques, which promises to enable improved clinical applicability of T2-mapping in the future. Our study revealed significant differences of derived mean T2 values when applying different sequence designs. Therefore, a systematic comparison of different cardiac T2-mapping sequences and the establishment of dedicated reference values should be the goal of future studies. Alterations of myocardial T2 relaxation times can be induced by a variety of diseases, including edema –3 and irT2 maps are obtained by collecting multiple images with different T2-weighting, providing multiple points along the T2 decay curve for fitting of an exponential signal decay model , 11. SevThe Multi Echo Spin Echo (MESE) technique is widely accepted as the reference method for T2-mapping, but it involves long scan durations and may yield artifacts - e.g. induced by motion and flow, or incomplete blood suppression. In contrast, the T2prep technique in concert with a balanced SSFP image readout is inherently flow-insensitive and sufficiently fast to be acquired in a single breathhold. Thus, it allows coverage of the entire myocardium at a reasonable expenditure of scan time and is therefore more suitable for routine clinical use. However, compared to the MESE technique, the number of echoes acquired by the T2prep sequence is considerable lower providing only a limited number of data points along the T2 decay curve, which may compromise accuracy and limit its use to a narrow range of T2 species.In the current study we evaluate a T2-mapping sequence using a Gradient Echo Spin Echo (GraSE) technique , which pin vivo study were used (see below). For measuring T1, a Modified Look Locker Inversion Recovery sequence (MOLLI) was used. Typical imaging parameters were: TR/TE = 2.3/1.15 ms, FA 35 °, parallel imaging (SENSE = 2.0), eight single shot balanced SSFP readout trains .Phantom experiments were performed at 1.5 T  using a commercially available cylindrical gel phantom  comprising 12 samples with T1 ranging from 185 ms to 1183 ms and T2 ranging from 50 ms to 160 ms, respectively. Identical imaging parameters as in the subsequent 12 healthy volunteers were enrolled into the study  using a 5-channel cardiac phased array receiver coil and a 4-lead vectorcardiogram.2, matrix 256 × 256, slice thickness 8 mm, 50 cardiac phases.SSFP cine images were obtained during repeated breath-holds in two long axes and in a stack of short axes (SAX) covering the left ventricle (LV) to rule out wall motion abnormalities and allow for cardiac chamber quantification. Imaging parameters were: repetition time (TR) 2.8 ms, echo time (TE) 1.4 ms, flip angle (FA) 60 °, field of view (FOV) 343 × 380 mm3). The three sequences were ECG triggered and had the following parameters: T2prep: TR/TE = 2.3/1.15 ms, FA 35 °, parallel imaging (SENSE = 1.6), TE’s of the T2prep pulse: 0, 25, 50, 75 ms and breath hold (scan duration about 12 s); GraSE: TR = 1 heartbeat, 9 echoes , FA 90 °, parallel imaging (SENSE = 2), EPI factor = 7, black blood prepulse and breath hold (scan duration about 14 s); MESE: TR = 1 heartbeat, 9 echoes , FA 90 °, parallel imaging (SENSE = 2), black blood prepulse and navigator gating (mean scan duration about 5 min). A pixel-wise myocardial T2-map was generated using a monoexponential fit [For T2-mapping, data were acquired in a basal, midventricular, and apical SAX plane using three different T2-mapping sequences: i) a T2-prepared single-shot balanced SSFP technique . SSFP cine images were visually evaluated in order to exclude wall motion abnormalities. LV enddiastolic and endsystolic volume and LV mass were measured by manually contouring the endocardial and epicardial borders of the SAX in systole and diastole using Simpson’s method and indexed according to the body surface area.T2 map reconstruction and image analysis was done with OsiriX viewer for Mac OS X . T2 maps were calculated with a dedicated plug-in written for the OsiriX software. Selected T2-maps for each sequence in one healthy volunteer are shown in Fig. For assessment of pixel-by-pixel homogeneity in T2-maps the number of segments, in which the pixel SD exceeded 20 % of the mean T2 time of the corresponding segment, was counted. All statistical analyses were performed twice: i) without exclusion of any segment and ii) with exclusion of all segments demonstrating pixel-by-pixel inhomogeneity as defined above.Statistical analysis was performed in R 3.1.0 , using tT-Test.In the phantom experiments, the paired differences of the observed T2 times of the T2prep and GraSE sequence vs. that of the MESE sequence were tested for significance using paired Linear mixed effects models (with random effect for subject and for scans within subjects) were used to account for repeated measurements within each subject, allowing for different residual variances in different sequences . Tukey-tFor analysis of pixel-by-pixel homogeneity, observed proportions of segments in which the pixel-SD exceeded 20 % of the mean T2 time of the corresponding segment were analyzed in a generalized linear mixed model  with a fixed effect for the sequences and random effects for subjects and repeated scans within subjects. The overall effect of sequences was assessed using a likelihood ratio test. Tukey-type comparisons between the three sequences (adjusted for multiple comparisons) were performed based on the model estimates .The results of the phantom experiments are shown in Table In vivo global myocardial T2 relaxation times for each sequence are summarized in Table , T2 values differed slightly, but differences proved to be not significant at the 5 % level .Analysis of pixel-by-pixel homogeneity per segment revealed a variability of T2 values by a standard deviation of more than 20 % of the mean T2 time of the corresponding segment in 8 % of all analyzed myocardial segments. The highest number of segments meeting the definition of inhomogeneity was found for T2prep 14 %), followed by MESE (10 %)  and compared it against a T2prep and a MESE sequence in a phantom and 2 values , 13. AccIn our phantom study, both the T2prep and the GraSE sequence yielded higher T2 values for the sample probes compared to the MESE sequence, which served as our reference. This overestimation was most pronounced for the T2prep sequence and is in good agreement with previous reports by Giri et al., where a similar overestimation of T2 values by the T2prep sequence was found in phantoms . In addiIn vivo, a minor trend towards an underestimation of T2 was observed using the T2prep sequence in healthy myocardium with T2 < < T1, although the myocardial T2 values obtained with T2prep were in good agreement with previously reported values in the literature [terature , 25, 26.Conversely, a slight overestimation of T2 values was observed for the GraSE when compared with the MESE sequence. This small deviation was somewhat more pronounced in our in-vivo than in our phantom measurements (10 % vs. 6 %), which is most likely due to the longer echo-spaces of GraSe (7.7. ms vs. 5.8 ms) necessary to fit the Echo Planar Imaging (EPI) readouts, thereby making it more susceptible to motional blurring and through plane motion.Using a black blood prepulse, GraSE might be more prone to bright-blood artifacts due to incomplete blood nulling compared to T2prep, which does not use a black blood prepulse. In our cohort of healthy volunteers, however, we rarely observed bright blood artifacts. Nevertheless, we used a post-processing method with manual ROI-definition that allowed us to exclude any partial volume or bright blood artifact from quantitative analysis. Therefore, we assume that bright blood artifacts – if present - did not influence the obtained T2 values in the present study. It should be kept in mind, however, that bright blood artifacts might be more prevalent in critically ill patients with a reduced ejection fraction. Therefore, in a future study, the comparison of GraSe and T2prep should be performed in a patient cohort in a future study to investigate image quality and the potential influence of artifacts like those caused by incomplete blood nulling on the derived T2 times.When comparing interindividual variability of T2 values derived from the three sequences, standard deviation was marginally higher for the GraSE sequence. Conversely, homogeneity of pixel-by-pixel T2 values within a myocardial segment was highest for the T2 maps generated by the GraSE sequence. Compared to the T2prep sequence, nearly only a third the number of segments that showed pixel T2 values to vary by more than 20 % of the mean T2 time of the corresponding segment were found when using the GraSE sequence. As we do not expect the T2 values to vary significantly within a myocardial segment in a healthy volunteer, this higher homogeneity speaks in favor of a higher robustness of the T2 maps derived by the GraSE sequence when compared to the other mapping sequences.The combination of a higher number of echoes acquired along the T2 decay curve (9 echoes for GraSE and MESE compared to 4 echoes for T2prep) , a lowerA higher intra-individual consistency of T2 values is of particular importance when it comes to the definition of objective cut-off values for the differentiation of focal edema from remote unaffected myocardium in pathologies with focal disease manifestation, like in myocarditis. As T2 times may vary between segments, we set the SD of pixel intensities in relation to the respective segmental T2 mean. In case of focal disease manifestation, we assume that disease will result in an increased inhomogeneity of T2 times. While overall T2 times are known to vary considerably between individuals , thus coin vivo experiences for this newly introduced T2-mapping GraSE sequence at 1.5 T and we examined only a small number of healthy volunteers. Study limitations include the usual limitations for cardiac T2 imaging, i.e. the sensitivity to B1 inhomogeneity, the presence of stimulated echo pathways that cause the signal to decay with a mixture of T1 and T2 contributions, and the sensitivity to cardiac motion. As 3 T scanners are increasingly used for cardiac imaging, further studies are needed to investigate whether the identified advantages can equally be transferred to higher field strengths. Moreover, larger study cohorts are needed to establish reference values for the GraSE sequences and evaluate its potential clinical value in the detection of disease. Furthermore, the fast T2 mapping sequences  were optimized for patient comfort, i.e. short breathholds, rather than best possible T2 accuracy, and the same settings were used in vivo and in phantoms. The value of a potential individual edema detection by using the here employed pixel-by-pixel inhomogeneity should be the aim of further studies in an appropriate patient population. Moreover, the idea of intraindividual consistency of T2 times should be transferred to a larger context, e.g. by comparing mean T2 times on a segment- or slice-based approach. This should be done in a larger proband cohort to reach statistical significance.The results presented in our study are the first The GraSE sequence introduced in our study is a fast and robust sequence for myocardial T2-mapping, combining advantages of both MESE and T2prep techniques. By these means, this fast technique may facilitate the applicability of T2-mapping in clinical routine. Its improved intra-individual consistency of T2 values may be of particular value in the detection of acute focal myocardial disease, overcoming the known limitations of qualitative image assessment. Our study revealed significant differences of derived mean T2 values when applying different sequence designs underlining the necessity for dedicated reference values for each sequence.


We aimed to study whether pulmonary arterial distensibility (PAD) correlates with hemodynamic parameters in chronic thromboembolic pulmonary hypertension (CTEPH) using electrocardiogram (ECG)-gated 320-slice multidetector computed tomography (MDCT).ECG-gated 320-slice MDCT and right heart catheterization (RHC) was performed in 53 subjects  with CTEPH. We retrospectively measured the minimum and maximum values of the cross sectional area (CSA) of the main pulmonary artery (mainPA), right pulmonary artery (rtPA), and left pulmonary artery (ltPA) during one heartbeat. PAD was calculated using the following formula: PAD = [(CSAmaximum−CSAminimum)/CSAmaximum]×100(%). The correlation between hemodynamic parameters and PAD was assessed. Mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) were 40.8±8.7 mmHg and 8.3±3.0 wood units, respectively. PAD values were as follows: mainPA (14.0±5.0%), rtPA (12.8±5.6%), and ltPA (9.7±4.6%). Good correlations existed between mainPAD, with mPAP  and PVR . The correlation coefficients between rtPAD and ltPAD with pulmonary hemodynamics were all lower or equal than for mainPAD.PAD measured using ECG-gated 320-slice MDCT correlates with pulmonary hemodynamics in subjects with CTEPH. The mainPA is suitable for PAD measurement. Chronic thromboembolic pulmonary hypertension (CTEPH) can result from either single or recurrent pulmonary embolism arising from deep vein thrombosis State-of-the-art multidetector CT (MDCT) scanners are now widely available and permit rapid acquisition of a thin-slice dataset, even in breathless patients We hypothesized that ECG-gated 320-slice MDCT could be used for less invasive and simultaneous evaluation of the pulmonary artery and hemodynamic data in the diagnostic assessment of patients with CTEPH. This study therefore aimed to evaluate the relationship between PAD of mainPA, rtPA, and the left pulmonary artery (ltPA) on ECG-gated 320-slice MDCT and hemodynamic data measured by right heart catheterization (RHC).The study group consisted of consecutive patients with a high clinical suspicion of CTEPH who underwent ECG-gated 320-slice MDCT and RHC from September 2009 to December 2013. The study was approved by the ethics committee of Chiba University . Written informed consent to use their examination results in the future study was obtained from each patient before CT and RHC. Patients with complications including left heart disease, connective tissue disease, severe chronic obstructive pulmonary disease (GOLD Stage III–IV), and severe interstitial pneumonia were excluded.All CT scan results were obtained retrospectively from enhanced ECG-gated volume scanning using 320-slice MDCT  with a slice thickness of 0.5 mm and 0.35 sec/rotation. To acquire simultaneous images of the pulmonary arteries and the entire heart, an axial series of two gantry rotations in a craniocaudal direction was performed (double volume scan). The resulting dual volume data sets were automatically stitched. Because the most cranial and caudal parts of each volume data set (both 1.6 cm) were not used to create images, the effective scan length was 25.6 cm. The tube voltage and current were set at 120 kV and 580 mA, respectively, with tube current dose modulation. Using a mechanical injector , 100 mL of contrast media  was injected at 3.5 mL/s. Then a saline–contrast mixture was injected: 40 mL of contrast media at 2.0 mL/s, and 30 mL saline at 1.5 mL/s. Time-resolved (per second) single-section CT scans were acquired at the level of the bifurcation of the pulmonary artery without a breath hold. Ascending aortic time-resolved attenuation was then measured using the time-attenuation evaluation program accessible on the scanner. When the CT values in the ascending aorta had increased to 200 Hounsfield units (HU), we began the scan, and the subject was asked to hold the breath.The CT images were reconstructed at 5% intervals from 0% to 95% of the R–R interval. They were sent to a workstation  that created cine images of the pulmonary arteries. The cross-sectional area (CSA) of the mainPA (mainPA-CSA) was measured at the one-third position of the pulmonary valve side between the pulmonary valve and the bifurcation of pulmonary artery . The CSAPAD of the mainPA, rtPA, and ltPA  were calculated using the following equation, and expressed as percentage variation: PAD = [(CSAmaximum−CSAminimum)/CSAmaximum]×100  [14].A 7.5-French gauge Swan–Ganz thermodilution catheter  was used via a jugular approach. Pressure measurements were taken from the superior vena cava, right atrium, right ventricle, and mainPA at end-expiration. The zero point was defined as mid-thoracic. Cardiac output (CO) was determined using the thermodilution method by averaging a minimum of three measurements. Left-to-right shunting was ruled out by oximetry. Pulmonary vascular resistance (PVR) in Wood units (WU) was calculated using the equation: PVR = [mean pulmonary artery pressure (mPAP)−pulmonary artery wedge pressure (PAWP)]/CO. Cp was calculated by the ratio between stroke volume (SV) and pulmonary arterial pulse pressure (PAPP).The PAD measured by enhanced ECG-gated 320-slice MDCT were assessed against the following values obtained by RHC: mPAP, systolic pulmonary arterial pressure (sPAP), diastolic pulmonary arterial pressure (dPAP), PAPP, PVR, CO, cardiac output index (CI), SV, and Cp.The 13 patients who were administered sildenafil were followed for a mean of 24.8±11.1 months . Time to clinical worsening, indicated by death or hospitalization due to right heart failure, between two groups stratified by median value of main PAD (14%) was compared.The Bland–Altman analysis was used to determine the inter- and intra-observer variation in PAD measurements. Pearson’s correlation was used to assess the correlation between hemodynamic data from RHC with PAD obtained using ECG-gated 320-slice MDCT. Correlation analysis of parameters showing a non-normal distribution was carried out using the Kendall tau rank correlation. All results are expressed as the mean ± standard deviation, unless otherwise indicated. A P value<0.05 was considered statistically significant. All statistical analyses were performed using JMP 9.0 software .Survival curves were estimated using the Kaplan-Meier method, and the log-rank test was used to compare survival curves according to clinical characteristics.The study group comprised 53 consecutive patients  with CTEPH diagnosed by RHC and CT and/or pulmonary angiography. Among them, 24 patients underwent these examinations at the time of the diagnosis, and 29 patients underwent the examinations during follow-up after the diagnosis. PAD of the mainPA, rtPA, and ltPA showed a trend toward gradual reduction ; thus, PTime to clinical worsening was slightly longer in the higher main PAD group (≥14%) than in lower mainPAD group (<14%)  . When thAbsolute intra-observer agreement for mainPAD, rtPAD, and ltPAD was a mean difference of −0.25±0.30%, −0.06±0.20%, and −0.45±0.25%, respectively; the agreement range was 0.36 to −0.84%, 0.34 to −0.46%, and 0.05 to −0.95%, respectively. Absolute inter-observer agreement for mainPAD, rtPAD, and ltPAD was a mean difference of −0.09±0.47%, −0.37±0.48%, and 0.48±0.51%, respectively; the agreement range was 0.86 to −1.05%, 0.60 to −1.32%, and 1.52 to −0.55%, respectively.To the best of our knowledge, this is the first study to assess the ability of 320-slice MDCT to evaluate PAD of each pulmonary artery in subjects with CTEPH. There are two main findings. First, PAD assessed via ECG-gated 320-slice MDCT correlated significantly with mPAP, sPAP, dPAP, PAPP, PVR, CO, CI, SV, and Cp in subjects with CTEPH. Second, the mainPA is suitable for PAD measurements.The pathophysiological process of CTEPH includes both pulmonary arterial obstruction and the incomplete resolution and organization of pulmonary thromboemboli. However, it also includes vessel remodeling, the release of vasoconstrictive substances, and reflex vasoconstriction over time. This process results in vasculopathy of precapillary vessels similar to that seen in patients with idiopathic pulmonary arterial hypertension Toshner et al. reported that a relative area change (RAC) in the rtPA which is calculated using the following equation, and expressed as percentage variation: RAC = [(CSAmaximum−CSAminimum)/CSAminimum]×100, correlates with the functional response to sildenafil, the 6-minites walk test (6MWT), N-terminal pro-brain natriuretic peptide (NT pro-BNP), and WHO functional class MDCT has advantages over MRI for PAD evaluation. Using ECG-gated 320-slice MDCT, all cross-sections in the pulmonary artery cine images can be observed, even after imaging. Using MRI, it is necessary to select a cross-section to view before imaging; this requirement presents a limitation, as the pulmonary artery deforms easily and moves during the cardiac cycle. In addition, the breath-hold time was no more than 10 s with MDCT, which would be beneficial in patients with CTEPH who may be unable to perform the extended breath hold required for MRI This study had some limitations. First, this single-center retrospective study included a small number of subjects. However, because the disease is rare, the present report could be noteworthy within this field. Second, the correlation between enhanced ECG-gated 320-slice MDCT parameters and RHC pulmonary hemodynamic data should ideally be studied by performing the two examinations on the same day; in our study, most patients underwent the two examinations within 16 days of each other.PAD measured by enhanced ECG-gated 320-slice MDCT correlated with mPAP, sPAP, dPAP, PVR, CO, CI, SV and Cp in subjects with CTEPH. The mainPA is suitable for measuring of PAD.


In patients with hypertrophic cardiomyopathy (HCM), atrial fibrillation (AF) or flutter remains the most common disease complication and arrhythmia in patients with hypertrophic cardiomyopathy (HCM), occurring in up to 25% of the patients, which is 4-fold more common than the general population. Occurrence of AF in HCM, not only will lead to its notorious complications of ischemic stroke and systemic embolization, can cause symptomatic deterioration due to a significant reduction in preload. In addition to transthoracic echocardiography, cardiac MR (CMR) has played an important role in making the diagnosis as well as risk-stratifying the patients. The purpose of this study is to determine CMR predictors in patients with HCM for predicting occurrence of incident AF.All 58 consecutive patients with HCM, in sinus rhythm with no prior evidence of atrial arrhythmia who had CMR performed from 2008 to 2012, were identified. Patients' background demographics and various CMR parameters including maximum left atrial (LA) volume (LAmax), minimum LA volume (LAmin), LA ejection fraction, left ventricular (LV) ejection fraction, LV end diastolic and systolic volumes, LV mass, maximal septal thickness, and percentage of LV scar were prospectively recorded in our database. Patients were followed up for development of new onset atrial fibrillation as confirmed by ECG and/or Holter. Univariate analyses followed by multivariate logistic regression were used to assess the clinical impact of individual clinical and CMR parameters for predicting the development of AF.2, LA max of 28ml/m2 and LAEF <33%.58 patients  with diagnosis of 1) asymmetrical HCM 77%, 2) apical HCM 22.6%, 3) other forms of HCM 6.5%, were recruited. During a mean follow up of 4.1+/-0.8 years, 18 (31.0%) developed AF. When adjusted for covariates in our model, age, hypertension, minimum and maximum LA volumes  and LA ejection fraction (LAEF) were independent predictors for development of AF. Receiver operator curve were generated for minimum and maximum LA volume, and LA ejection fraction, with no significant differences between the areas under curve . Cut off points for greatest likelihood for AF occurrence would be LA min of 16ml/mLA ejection fraction, LA minmum and maximum volume on MRI are independent predictors of new onset of AF in patients with underlying hypertrophic cardiomyopathy.


Left ventricular (LV) trabeculation has been studied in certain forms of cardiomyopathy. However, the changes of LV endocardial trabeculation during the remodeling process leading to heart failure (HF) are unclear. Seventy-four patients with systolic heart failure (SHF), 65 with heart failure with preserved ejection fraction (HFpEF) and 61 without HF were prospectively enrolled. All subjects received magnetic resonance imaging (MRI) study including cine, T1 and late gadolinium enhancement (LGE) images. Trabecular-papillary muscle (TPM) mass, fractal dimension (FD) and extracellular volume (ECV) were derived. The results showed that TPM mass index was higher in patients with SHF than that in patients with HFpEF and non-HF. The TPM mass-LV mass ratio (TPMm/LVM) was higher in SHF group than that in HFpEF and non-HF. FD was not different among groups. The presence of LGE was inversely associated with TPM mass index and TPMm/LVM while the ECV were positively associated with TPMm/LVM. The FD was positively associated with LV chamber size. In conclusion, TPM increases in patients with SHF and are probably related to myocardial cell hypertrophy and fibrotic repair during remodeling. The FD increases with the dilatation of LV chamber but remain unchanged with the deterioration of LV function. Patients with heart failure (HF) carry an excess risk of morbidity and mortality, making it a major public health concernIn some forms of cardiomyopathy, hypertrabeculation has been associated with adverse cardiovascular outcomes35Myocardium remodeling starts with injury. When the pathological processes take effect, the activation of myofibroblasts and the increase in collagen synthesis result in two major types of fibrosis, reactive interstitial fibrosis and replacement fibrosis, commonly affect diastole first and subsequently involve systolic performanceIn this study, we plan to investigate the trabeculation of LV in a group of HF patients including systolic HF (SHF) and HF with preserved ejection fraction (HFpEF) by using non-HF patients as controls. Our goal is to study the changes of LV trabeculation in the remodeling process leading to HF and delineate its mechanisms related to myocardial fibrosis.~71.3 vs. 71.0; IQR: 60.0~77.5, P = 0.003) and there were more male patients in the SHF group compared to HFpEF  and non-HF  groups. Patients with SHF had higher body mass index (BMI) than that in non-HF group . Patients with SHF and HFpEF had higher rates of prior MI than patients without HF . More patients in SHF group received beta-blocker treatment as compared with that in HFpEF  and non-HF  groups. The other demographics were not statistically different.Sequential 74 patients with SHF, 65 patients with HFpEF, and 61 patients without HF were enrolled in the study. The demographics of the study population were summarized in ~43.1% vs. 30.7%; IQR: 28.6~32.5%, P = 0.003) and without HF . The mean ECV was also significantly higher in patients with HFpEF than that in patients without HF . For TPM, the TPM mass index was higher in patients with SHF than that in patients with HFpEF  and without HF . After normalization of TPM by LVM, the TPMm/LVM was higher in SHF group than that in HFpEF  and non-HF  groups. The trabecular complexity indicator, FD, was not different among three groups.The MRI parameters of the three groups were shown in ~6.300, P = 0.030) and the highest tertile of LVMi  were associated with higher TPM mass index while the presence of LGE  was inversely associated with TPM mass index. For TPMm/LVM, the presence of LGE was inversely associated with TPMm/LVM  while the highest tertile of ECV was positively associated with TPMm/LVM . For FD, higher LVEDVi  was associated with higher FD.The correlation coefficients (C.C) as well as their confidence interval (CI) of the multiple linear regression analyses were shown in In this study, we demonstrated that both TPM mass index and TPMm/LVM increase in patients with SHF. From the regression analyses, the TPM mass index increases with greater LVMi while the TPMm/LVM increases with greater ECV or interstitial fibrosis. We also showed that both TPM mass index and TPMm/LVM decrease with the presence of LGE. These findings are compatible with two forms of fibrotic repair during LV remodeling. The myocardium is composed for about the 70% of its volume by parallel cardiac muscle cells, embedding in an extracellular matrix network which forming the remaining 30% of the volume12Cardiac trabeculation occurs during the embryonic development of the heart presumably to increase the surface area to allow the myocardial mass to grow in the absence of a developed coronary circulation. The presence of trabeculae might contribute to a better mechanical efficiency of LV. Mathematical model has demonstrated that ventricular model with trabeculation is characterized by a higher compliance with respect to the smooth model~0.29) which is lower than the reference value in patients with non-compaction cardiomyopathy (1.392 ± 0.010) in literatureIn accord with the finding that LV trabeculation mass increases during remodeling process, another marker of trabeculaton complexity, FD is also demonstrated to increase with enlarged chamber but not with global LV systolic function in this study. FD is a highly reproducible index of trabecular complexity capable of detecting subtle subclinical trabecular phenotypesOur study also showed that LV trabeculation is associated with subjects’ demographics. For example, we found that the TPM mass index is positively correlated with male gender. The TPMm/LVM also has similar associations but the significance diminishes after the adjustment of other confounders. This result is similar to a large cohort with relative healthy participantsThere are several limitations of the study. First, the study population is small. Second, this study design was cross-sectional, we could not clarify the causal relationship between LV trabeculation and fibrotic repair during LV remodeling.LV TPM increases in patients with SHF probably related to myocardial cell hypertrophy and fibrotic repair during LV remodeling. The FD increases with dilatation of LV chamber but remains unchanged with the deterioration of LV function.The research was approved by the institutional review board of the National Taiwan University Hospital Ethics Committee. The study was conducted in accordance with the approved guidelines. All study participants provided written informed consent.2.The study enrolled patients with chronic HF from November 1, 2012 to July 31, 2015. Patients who met the following criteria were enrolled as the HF group: 1. they had HF symptoms of New York Heart Association (NYHA) classification functional Class II to III or a history of HF symptoms/signs by Framingham criteriaMRI was performed on a 3 T MRI system  with an 8-channel cardiovascular phased array torso coil. Myocardial T1 mapping was performed with an ECG-triggered Modified Look Locker Inversion recovery (MOLLI) sequence before and 10 minutes after a 0.15 mmole/kg intravenous administration of the gadolinium-based contrast agent . The MOLLI protocol used two Look-Locker cycles to acquire 7 images over 11 heart beats, the scanning parameters were TR/TE, 1.9 ms/1.0 ms; flip angle, 35°; minimum inversion time, 110 ms; inversion time increment, 80 ms; matrix size, 256 × 192; slice thickness, 6 mm; spatial resolution, 1.28 mm; GRAPPA acceleration factor, 2; number of inversions, 2; images acquired after first inversion, 5; pause 4 heart beats and images acquired after second inversion, 2. Five evenly-spaced short-axis slices were acquired sequentially from the LV base to apex. After post-contrast T1 acquisition, LGE images were acquired using an ECG-triggered phase-sensitive inversion recovery (PSIR) prepared segmented fast gradient echo pulse sequenceCine MRI was performed using a segmented balanced steady-state gradient echo pulse sequence with a retrospective ECG R-wave trigger. The scanning parameters were TR/TE, 3.0 ms/1.5 ms; flip angle, 46°; matrix size, 256 × 208 and spatial resolution, 1.21 mm. Multiple short-axis slices were prescribed from the mitral orifice to LV apex with slice thickness of 8 mm and gap of 2 mm. The true temporal resolution was 63 ms and thirty cardiac phases were reconstructed retrospectively for each slice level.Myocardial ECV is an indicator of myocardial interstitial diffuse fibrosisFor LV function and mass analysis, endocardial and epicardial contours of the LV were determined at each slice level on cine MRI and the area enclosed by each contour was computedThe analyses were performed by our in-house tool coding in Matlab environment . For TPM mass quantification, epicardial and endocardial left ventricle contours were first segmented by an automated contour detection algorithm which was presented in our previous workIn this study, fractal analysis was executed on the end-diastolic frames of each short-axis slice section. For each slice, the analysis procedure includes three steps: First, defining ROI; Second, extracting endocardial border via performing an image segmentation algorithm; Third, calculating the FD using box-counting approach. The ROI, in the first step, was selected by the user via interaction with the interface of the in-house tool. The endocardial borders were results of the segmentation step which was conducted by a region-based level set approach55Since Shapiro-Wilk test showed that some of the variables were not normally distributed, all the statistical analyses were performed by non-parametric methods. Continuous variables were expressed as medians and interquartile ranges (IQR) and categorical variables were expressed as percentages. Categorical variables were compared among different groups of patients by using Chi-square tests. Continuous variables were tested by the nonparametric Kruskal-Wallis test and the Mann-Whitney U test was used for post-hoc analysis for comparison of the medians between different groups. To investigate the determinants of LV trabeculation, a multiple linear regression model was constructed to analyze the relationship between TPM mass index, TPMm/LVM, FD and other MRI parameters since the distributions of these three parameters are similar to a normal distribution. The model was adjusted for age, gender, history of hypertension (HTN) and DM, etiology of HF , presence of LGE on MRI LGE images, LVMi, LVEDVi, ECV and LVEF. LVMi, LVEDVi, ECV were categorized into tertiles. To avoid model-dependent association, an association was considered significant only if both the univariate and multivariate model showed significant correlation. A Bonferroni test was performed for variables categorized into more than three groups to avoid multiple comparison bias. A value of P < 0.05 was considered significant. Statistical analyses were performed using the SPSS software package, version 19 .How to cite this article: Lin, L.-Y. et al. Endocardial Remodeling in Heart Failure Patients with Impaired and Preserved Left Ventricular Systolic Function-A Magnetic Resonance Image Study. Sci. Rep.6, 20868; doi: 10.1038/srep20868 (2016).


Systolic left ventricular function during therapeutic hypothermia is found both to improve and to decline. We hypothesized that this discrepancy would depend on the heart rate and the variables used to assess systolic function.In 16 pigs, cardiac performance was assessed by measurements of invasive pressures and thermodilution cardiac output and with 2D strain echocardiography. Left ventricle (LV) volumes, ejection fraction (EF), transmitral flow, and circumferential and longitudinal systolic strain were measured. Miniaturized ultrasonic transducers were attached to the epicardium of the LV to obtain M-mode images, systolic thickening, and diastolic thinning velocities and to determine LV pressure-wall dimension relationships. Preload recruitable stroke work (PRSW) was calculated. Measurements were performed at 38 and 33°C at spontaneous and paced heart rates, successively increased in steps of 20 up to the toleration limit. Effects of temperature and heart rate were compared in a mixed model analysis.Hypothermia reduced heart rate from 87 ± 10 (SD) to 76 ± 11 beats/min without any changes in LV stroke volume, end-diastolic volume, EF, strain values, or PRSW. Systolic wall thickening velocity (S′) and early diastolic wall thinning velocity decreased by approximately 30%, making systolic duration longer through a prolonged and slow contraction and changing the diastolic filling pattern from predominantly early towards late. Pacing reduced diastolic duration much more during hypo- than during normothermia, and combined with slow myocardial relaxation, incomplete relaxation occurred with all pacing rates. Pacing did not affect S′ or PRSW at physiological heart rates, but stroke volume, end-diastolic volume, and strain were reduced as a consequence of reduced diastolic filling and much more accentuated during hypothermia. At the ultimate tolerable heart rate during hypothermia, S′ decreased, probably as a consequence of myocardial hypoperfusion due to sustained ventricular contraction throughout a very short diastole.Systolic function was maintained at physiological heart rates during therapeutic hypothermia. Reduced tolerance to increases in heart rate was caused by lack of ventricular filling due to diastolic dysfunction and shorter diastolic duration. Mild (therapeutic) hypothermia 32 to 34°C) for a limited time interval 12–72 h) seems to improve neurological outcome in several clinical conditions, including patients resuscitated after out-of-hospital cardiac arrest (OHCA) [2–72 h se to 34°C Hypothermia is an integral part of cardiac surgery, and postoperative patients frequently are mildly hypothermic despite rewarming on cardiopulmonary bypass (CPB). Clinical  and expeConflicting results also exist regarding the physiological effect of therapeutic hypothermia on the normal heart and circulation ,15. In iAmong clinicians, however, there seem to be a widespread opinion that therapeutic hypothermia has a positive inotropic effect and improves cardiac systolic performance as long as heart rate is not increased ,18. In t2 = 0.4) with a tidal volume of 10 to 15 ml/kg, adjusted during hypothermia to maintain a stable PCO2.A total of 16 Norwegian land race swine with mean weight of 52.2 ± 6.3 kg were included in the study. The animals were sedated by intramuscular injection of ketamine (20 mg/kg), atropine (0.02 mg/kg), and azaperone (3 mg/kg). Anesthesia was induced by intravenous (iv) injection of pentobarbital 3 mg/kg and morphine 1.0 mg/kg and maintained by iv morphine-infusion (1 to 2 mg/kg/h) and isoflurane-inhalation (1.0 to 1.5%), keeping the end-tidal concentration at the same level during normo and hypothermia within individual animals. Muscle relaxants were not used. Plasma catecholamines were measured in two animals and showed no difference between normo and hypothermia. The animals underwent a tracheotomy and were ventilated by air/oxygen  into the LV cavity for measurements of LV pressure. For cooling and rewarming of the animals, a water-circulated catheter  was placed in the inferior vena cava from the left femoral vein and connected to a designated thermal regulation system . A pulmonary artery catheter  was put in place from the left jugular vein to measure cardiac output (CO) and central temperature. After sternotomy, epicardial ultrasonic transducers  were sutured to the anterior LV wall for continuous monitoring of wall thickness through the cardiac cycle. Two pacemaker leads were attached to the right atrial appendage. A snare was placed around the inferior caval vein for acute volume unloading. The preparation lasted for approximately 190 min followed by a minimum of 30 min of stabilization before measurements. All animals were handled according to international regulations. The study was approved by the Oslo University Hospital Institutional Animal Care and Use Commitee and was carried out in accordance with the Norwegian National Legislation on animal experimentation and the European Union Directive 2010/63/EU on the protection of animals used for scientific purposes.Measurements were made at normothermia (38°C) and during mild hypothermia (33°C) at spontaneous and paced heart rates. The water-circulated catheter was used to keep stable temperatures both during normo and hypothermia. Atrial pacing was performed at 100 beats/min, and then successively increased in steps of 20 beats/min up to the toleration limit. Measurements were performed after 5 min of stable hemodynamics. At each intervention, transient constriction of the inferior caval vein was performed for acute volume unloading. The first 11 animals were tested for maximal toleration to increases in heart rate. The limit of toleration was set to the maximal frequency at which the animal had stable hemodynamics for 5 min and through the following recording period. Pacing was stopped immediately if hemodynamic deterioration occurred. In the other five animals, pacing was stopped at 140 beats/min during normothermia and 120 beats/min during hypothermia because reliable recordings during caval vein constriction were not obtainable at higher heart rates. Except for the testing of heart rate toleration limits, results are therefore presented and compared within and between temperature levels up to frequencies of 140 and 120 beats/min for normo and hypothermia, respectively. In four animals, cooling was instituted during instrumentation, and hypothermic recordings were made first, followed by rewarming and normothermic recordings. In the other animals, normothermic recordings were performed first.max, dP/dtmin). Duration of systole was calculated from the onset of steep upstroke of dP/dt to dP/dtmin. Diastolic duration was calculated from dP/dtmin to onset of systole  was calculated as CO divided by heart rate. Peak systolic LVP, end-systolic LVP (ESP), and end-diastolic LVP (EDP) were recorded. LV afterload was estimated by arterial elastance (Ea) = ESP/SV. Peak positive and negative amplitude of the time derivative of LVP were recorded  was used directly on the heart with a gel stand off for 2D echocardiography/Doppler recordings. End-diastolic volumes (EDV) were calculated by Simpson biplane method. Ejection fraction (EF) was calculated as SV/EDV. Longitudinal and circumferential strain in septum and lateral wall mid-segments were calculated by speckle tracking in 2D grey scale images (frame rate 63 ± 11). Transmitral flow was measured from Doppler recordings with assessments of early (E) and late (A)  diastolic filling velocities.Wall thickness was measured through the cardiac cycle by M-mode recordings from the epicardial ultrasonic transducers Figure . This alWall thickness through the cardiac cycle was plotted towards LVP resulting in pressure-wall thickness (P-WTh) loops for calculation of regional work. Regional preload recruitable stroke work (PRSW) was calculated as the relationship between P-Wth loop area and end-diastolic WTh (EDWTh) during caval constrictions.t-test. To study the effect from the interventions, the data were analyzed using a linear mixed model to handle the dependencies introduced by repeated measurements within in each subject. The data were analyzed using temperature level and heart rate (HR)  as determinants in a model where variable = β + β1 (temp) + β2 (HR) + β3 (temp × HR). Time of recording was included as a covariate to account for the order of measurements and assess the effect of time. Model selection was made choosing the covariance structure with the lowest Akaike information criteria. Predicted values and residuals were inspected for goodness of model fit. Differences were considered significant if p ≤ 0.05.Data are reported as mean ± SD. The data from 38 and 33°C at spontaneous and paced heart rates were compared using paired Recordings of good quality were obtained from all experiments except from caval constriction recordings in four animals. The cooling period lasted about 100 min, while warming in the 'cold first' animals lasted 220 min on average. The average duration of each experiment was 560 min. The effects of temperature and heart rate changes were not dependent on the order of the temperature level.max decreased, demonstrating slower myocardial contraction. Systolic duration increased, and there was a small increase in end-systolic wall thickness (ESWth). ESP and Ea decreased, reflecting a reduction in left ventricular afterload during hypothermia, which also was reflected by a reduction in P-Wth loop area. The peak LVP, MAP, and CO decreased while EDP increased, and systemic vascular resistance (SVR) did not change.The results are summarized in Tables min and e′ decreased, whereas τ increased, reflecting slow and prolonged myocardial relaxation. The relative reduction in e′ was not significantly different from the relative reduction in S′, 35 ± 21 and 28 ± 15% (p = 0.24), respectively. There was a shift from predominately early to predominantly late ventricular filling with reversion of the E/A relationship (data not shown), and there was an increase in left ventricular stiffness [The diastolic changes have been reported in detail previously . In summtiffness , reflectmax, and S′ did not change with increasing heart rates, whereas EF decreased at higher heart rates. During normothermia, CO increased slightly with increasing heart rates up to 120 beats/min and started to decline at heart rates above 140 beats/min. Peak LVP and MAP did not change, whereas SVR slightly decreased with increasing heart rates up to 140 beats/min . At normothermia, all 11 pigs tolerated a paced frequency of 140, seven pigs tolerated 160, and four tolerated 180 beats/min. During hypothermia, all pigs tolerated 120 beats/min, eight pigs tolerated 140, and three tolerated 160 beats/min. Because of variations in heart rate tolerability between individual animals, we made comparisons with penultimate and ultimate tolerable heart rates to detect physiological changes occurring close to the toleration limit both during normo and hypothermia. These data are shown in Figure p = 0.20). ESWTh was unchanged during normothermia (p = 0.54), and the decrease during hypothermia was not statistically significant (p = 0.11). There was a further, but not statistically significant (p = 0.15), increase in τ at the ultimate heart rate during hypothermia, reflecting further reduction in relaxation velocity parallel to the reduction in contraction velocity. Taken together with a further increase in EDPVR, this indicates maintained ventricular contraction throughout diastole.The tolerance to increases in heart rate was significantly reduced during hypothermia ) and PRSW was well preserved, but not increased at any heart rate. Therapeutic hypothermia impaired the tolerance to increasing heart rates induced by atrial pacing, by impeding diastolic filling due to slow relaxation and successive shortening of diastolic duration. Pacing itself had no effect on myocardial velocities, except during hypothermia at heart rates close to the toleration limit, where contraction and relaxation velocities further decreased. The latter is probably related to impaired myocardial perfusion due to shortness of diastolic duration and incomplete diastolic relaxation with persisting myocardial contraction at end diastole.The kinetics of cardiac contraction and relaxation are tightly linked during different physiological conditions , and theDuring hypothermia, the slower myocardial contraction measured by systolic wall thickening velocity was compensated for by prolonged systolic duration, allowing enough time to maintain SV, EF, and strain. Reduced afterload may have facilitated ventricular ejection as indicated by a small increase in ESWth and thus masked a systolic dysfunction, but no change in the load independent variable PRSW indicated preserved pump function. This is in contrast to improved systolic function found by Post and co-workers . Going iThis may, at least partly, explain the difference between the in situ heart and isolated cardiac trabeculae which have little supportive tissue and where only isometric contractile force is measured .Although slow relaxation was not compensated for by a corresponding increase in diastolic duration, there was enough time for complete relaxation and filling demonstrated by 3.5τ/DD < 1 and maintained EDV. EDWth, however, increased slightly, indicating a small reduction in diastolic filling that could not be detected by the biplane Simpson method. Increased wall stiffness is probably the cause of this small decrease in diastolic filling and is supported by the increase in EDPVR.PRSW was not significantly reduced during pacing, and the tolerance to increases in heart rate seemed mainly to be limited by diastolic filling. Atrial pacing not only reduced diastolic duration but also successively reduced the diastolic fraction of the cardiac cycle, and both absolute and relative diastolic shortening were accentuated by hypothermia Table . Time foWith the possible exception for the ultimate tolerable heart rate, the slower S′ during hypothermia did not significantly affect systolic emptying, demonstrating that systolic duration was long enough to adequately empty the heart from the actual EDV. This prolongation of systole at the expense of diastole during hypothermia seems to be an inappropriate response to pacing induced increases in heart rate. Successive shortening of diastolic duration with incomplete relaxation and persisting myocardial contraction throughout diastole as demonstrated by successive increases in EDPVR Figure  could jer2 = 0.88 ± 0.11), making the P-Wth loops good estimates of myocardial work.The regional measurements from the epicardial transducers were used to estimate global myocardial changes. There is no data to indicate that therapeutic hypothermia should have different effects in various regions of the healthy myocardium and there was accordance between the epicardial and global 2D echocardiographic recordings as also demonstrated previously . The parCardiac performance was well maintained during hypothermia at spontaneous heart rate, but at a less afterload and, hence, stroke work. Reduced workload may be important for the injured or failing heart, and therapeutic hypothermia may thus have favorable effects on both cardiac and systemic oxygen supply-demand balance and contribute to the good outcome observed in patients with cardiogenic shock after OHCA . SimilarThe Doppler recordings demonstrated diastolic dysfunction at spontaneous heart rate, and 2D echocardiography showed reduced EF at increased heart rates during hypothermia. These findings indicate that interpretation of echocardiographic assessments of cardiac function is more complicated in hypothermic patients. The echocardiographic findings may at least partly be due to the hypothermia itself and will be reversed during rewarming.We did not obtain pre-hypothermia and post-hypothermia recordings at 38°C in each animal, but we did perform the intervention in reverse order in four of the animals. The effects of hypothermia returned to normal after warming to 38°C, and the order of the intervention did not prove significant in the mixed model analysis. Deep hypothermia reduces both systolic and diastolic function, and in a similar pig model, systolic function was only partially reversed after rewarming from 25°C. Diastolic function, however, reversed completely . In our Deep anesthesia reduces the sympathetic response to hypothermia, and no changes in plasma catecholamines were observed, similar to the findings of Filseth and co-workers . HoweverTherapeutic hypothermia during anesthesia reduces velocities of contraction and relaxation. Slow contraction is compensated for by prolongation of systole at all heart rates maintaining adequate emptying of the LV, and the ability to generate work is not reduced. Slow relaxation leads to diastolic dysfunction with reduced tolerance to pacing induced increases in heart rate because of reduced diastolic filling and sustained diastolic contraction at higher heart rates. Echocardiographic measurements of cardiac function in hypothermic patients should be interpreted cautiously because apparent systolic and diastolic dysfunction may at least partly, be due to effects caused by transient hypothermia.Abbreviation/variable/measurement/meaningEa/arterial elastance/calculated: Ea = ESP / SV/estimation of LV afterloadEF/ejection fraction/calculated: EF = SV / EDV/the fraction of EDV ejected during systoleEDV/end-diastolic volume/2D echocardiography (Simpson's biplane method)/marker of cardiac filling at end of diastole.EDWth/end-diastolic wall thickness/ultrasonography (miniaturized transducer)/LV wall thickness at end of diastole as a marker of cardiac fillingESWth/end-systolic wall thickness/ultrasonography (miniaturized transducer)/LV wall thickness at end of systole as a marker of systolic emptying of LVP-Wth loop/pressure-wall thickness loop/micromanometer and ultrasonography/the relationship between LV pressure and wall thickness through one cardiac cycle. The loop area is an estimate of regional myocardial stroke workPRSW/preload recruitable stroke work/micromanometer and ultrasonography/the relationship between EDWth and P-Wth loop area during diastolic unloading  as a marker of myocardial force (inotropy).e′/early LV wall thinning velocity/ultrasonography (miniaturized transducer)/LV wall thinning velocity during early diastolic filling as a marker of diastolic functiona′/late LV wall thinning velocity/ultrasonography (miniaturized transducer)/LV wall thinning velocity during atrial contractionS′/peak systolic LV wall thickening velocity/ultrasonography (miniaturized transducer)/a marker of contractile functionτ/tau: left ventricular relaxation time constant/micromanometer/a measure of LV myocardial relaxation during diastoleFor the following variables, a more detailed explanation is given as follows:


With advancing age the left ventricle (LV) undergoes structural and functional changes, thereby creating the substrate for the development of diseases. One possible mechanism of the ageing heart is a cellular senescence. Leukocyte telomere length (LTL) is a marker of replicative ageing. The purpose of this study was to evaluate the structure and function of the LV in people of different ages free of cardiovascular diseases (CVD) and regular drug medication and to assess their relationship with LTL. We hypothesized that age-related changes in LV myocardium are associated with telomere length.The study population consisted of 150 healthy, non-obese volunteers aged 28 to 78 years without history of CVD, significant deviations by 12-lead electrocardiogram and negative exercise test (treadmill stress test). All the participants underwent standardized transthoracic echocardiography using an available system . The LTL was measured by real-time quantitative polymerase chain reaction. We determined the relative ratio of telomere repeat copy number (T) to single-copy gene copy number (S).In the older people there was a higher wall thickness than in the younger , whereas LV mass index was comparable between them . There was a decrease in LV dimensions with advancing age (p<0.001). Older subjects had impairment in LV relaxation. LTL was associated with decreased E/A, Em/Am ratio  after adjusting for age, sex and risk factors. There is no relation between the LTL and the structure of LV.Our data suggest that the ageing process leads to changes in LV structure and diastolic function and is linked with a phenotype of concentric LV remodeling. Telomere attrition is associated with age-related LV diastolic dysfunction. Telomere length appears to be a biomarker of myocardial ageing. There are a number of structural and functional changes in the heart with ageing in people without diseases and each of these can have significant implications for cardiovascular disease (CVD). Conflicting data have been accumulated regarding the structural changes of LV. However, age-related impairments of the LV functions are well described. Despite maintenance of systolic function at rest, there are changes in the diastolic phase of the cardiac cycle that occur with ageing .TTAGGG) located at the ends of chromosomes which protect DNA from damage. Telomeres progressively shorten in somatic cells with increasing number of cell divisions. When the telomeres become critically short, the cell is no longer able to replicate and enters cellular senescence [In addition, the interest of scientists aims to identify genetic markers that allow evaluation of age-related changes of the cardiovascular system. Although the relation of advancing age with diastolic dysfunction is widely recognized, their association with cellular senescence is less clear. Telomere length has been regarded as a marker of biologic ageing. Telomeres are repetitive DNA sequences  or took any regular medications for CVD; diabetes, thyroid disease, hepatic or kidney failure, cancer, pregnancy and lactation were excluded. As a result, 240 participants aged 23–91 years were selected.2), a blood sampling for laboratory analyses, electrocardiogram recording and a treadmill stress test. A treadmill stress test was performed on a protocol BRUCE using available system . Patients with important abnormalities  were excluded. Subsequently, the study population consisted of 150 participants. Each subject underwent full echocardiographic examination and measurement of LTL. The study protocol was approved by the institutional Ethics Committee, and all participants gave written informed consent.Consenting subjects had a physical assessment including blood pressure (BP) determination, mmHg , heart rate, anthropometric measurements (body mass index (BMI); kg/mTransthoracic 2D echocardiography was performed with the available system . All echocardiographic measurements were averaged from 3 cardiac cycles. The following data were acquired: LV end-diastolic septal (SWT) and posterior wall thickness (PWT), LV diameter at the end of diastole (LVDD) and LV diameter at the end of systole (LVDS); LV volumes; LV mass index (LVMI) and LV diastolic function parameters. LV linear dimensions were measured from a parasternal long-axis view. LV mass was calculated by the area-length method and indexed to body surface area to obtain LVMI. Quantitative 2D methods (biplane Simpson’s) were performed to obtain an ejection fraction (EF).Doppler-echocardiographic mitral valve inflow velocities were recorded from an apical 4-chamber view with a cursor at the tips of the mitral valve leaflets. Peak velocity of early filling (E) and peak velocity of atrial filling (A) were measured and the E/A ratio was calculated. To measure isovolumic relaxation time (IVRT), the sample volume was placed between the anterior leaflet of the mitral valve and LV outflow tract and the E wave deceleration time (DTE) was calculated as the time between the peak of early filling and the upper deceleration slope extrapolated to the baseline .Pulsed Doppler of pulmonary venous flow was performed in the apical 4-chamber view with location of the sample volume in the right upper pulmonary vein. Peak systolic (S) velocity, peak anterograde diastolic (D) velocity, the S/D ratio, peak retrograde (PV Ar) velocity in late diastole and its duration (tApv) were evaluated .LV myocardial velocities were evaluated by tissue Doppler imaging (TDI). Pulsed TDI sample volume was placed at the level of the lateral mitral valve annulus in the apical 4-chamber view. Early diastolic (Em) and late diastolic (Am) velocities were measured, and Em/Am, E/Em ratios were calculated .S1 File).LTL was determined according to the method described by Cawthon . Genomic2. The level of statistical significance was set at p<0.05.The statistical analysis was performed by SAS 9.1 . The intergroup comparisons were performed using Student’s t-test or ANOVA when appropriate. Data are presented as means ± SD for continuous variables and as proportions for categorical variables. The association LTL with LV structure and function parameters were evaluated using correlation analysis (Spearman’s and Pearson coefficients), linear and multivariate regression analysis. We also used logistic regression models to estimate odds ratios and χ2) and 28 were smokers. The duration of hypertension was less than 0.6±0.3 years. None of the participant regularly received any other medication, including antihypertensive drugs. One hundred and fifty individual  was accepted. The subjects ranged between 28 and 78 years of age, with a mean age of 51.3±12.3 years. Of the study group, 31 subjects had mild arterial hypertension, 27 subjects was overweight  and of 60 to 78 years . The mean age was 39±7.9 year and 65±5.3 year, respectively (p<0.001). There were no significant differences in the sex, BMI and the levels of BP between the groups. SWT and PWT were larger in older individuals (p<0.01), but there was no difference between groups in LVMI (p = 0.2). Older subjects had lower values of LVDD, LV end-diastolic volume (LVDV) and end-systolic volume (LVSV).Analysis of the Doppler indices revealed significant differences between groups: E/A velocity ratio (0.96±0.31 vs 1.27±0.28) were lower in older subjects with a significant increase in IVRT (81±13.22 ms vs 70±10.90 ms) and DTE (198±33.80 ms vs 175±24.90 ms). The assessment of pulmonary venous flow showed significantly greater values of the S/D ratio (1.3±0.21 vs 1.0±0.04), PV Ar (30.6±0.51 cm/s vs 28.9±5.45 cm/s) and its duration (119±23.05 ms vs 102±23.80 ms) in a group of older people. 2 = 1.77, p = 0.18, OR = 1.44; 95% CI 0.84–2.47), LVMI .Median of leukocyte telomere length was 9.75. Telomeres were termed “short” if the LTL was <9.75, and “long” if the LTL was ≥9.75. Age was significantly related to telomere length . There is no relation between the LTL and the structure of LV. We evaluated associations between LTL and LVMI , SWT , LVDV  and LVSV . Correlation LTL with LVMI and SWT was weak. According to the logistic regression model, we have not received significant relation LTL with these parameters: SWT , Em/Am ratio , E′ , IVRT . Linear regression analysis showed comparable changes of Doppler measurements (E/A and Em/Am ratio) with increase LTL .2 = 52.07, p = 0.001; OR = 24.95; 95% CI 10.41–59.77) and Em/Am ratio . The lowest value of telomere length within the first quintile increase the risk of LV diastolic dysfunction  in 55 times . In older people with length of telomeres <9.75 diastolic dysfunction was diagnosed in 92% of cases. While in older adults with telomere length ≥ 9.75 was at 42% only. According to our expectations «short» LTL is a predictor of age-related changes in LV diastolic dysfunction and is associated with an early decrease in E/A and Em/Am ratio. Older individuals with “long” telomeres had higher values of these parameters than older subjects with “short” telomeres.In multivariate regression analysis LTL was associated with decreased E/A, Em/Am ratio  after adjusting for age, sex and risk factors. Shorter telomere was associated with an increased risk of reducing the E/A Click here for additional data file.