Fibroblast growth factor 23 (FGF23), with its co-receptor Klotho, plays a crucial role in phosphate metabolism. Several recent studies suggested that circulating FGF23 and α-Klotho concentrations might be related to cardiovascular abnormalities in patients with advanced renal failure.Using data from 100 cardiology inpatients who were not undergoing chronic hemodialysis, the association of circulating levels of FGF23, α-Klotho, and other calcium-phosphate metabolism-related parameters with the left ventricular ejection fraction (LVEF) and left ventricular mass (LVM) was analyzed.LVEF was measured using the modified Simpson method for apical 4-chamber LV images and the LVM index (LVMI) was calculated by dividing the LVM by body surface area. Univariate analysis showed that log transformed FGF23, but not that of α-Klotho, was significantly associated with LVEF and LVMI with a standardized beta of −0.35 (P<0.001) and 0.26 (P<0.05), respectively. After adjusting for age, sex, estimated glomerular filtration rate, and serum concentrations of intact parathyroid hormone, and 25-hydroxyvitamin D as covariates into the statistical model, log-transformed FGF23 was found to be a statistically positive predictor for decreased left ventricular function and left ventricular hypertrophy.In cardiology department inpatients, circulating FGF23 concentrations were found to be associated with the left ventricular mass and LVEF independent of renal function and other calcium-phosphate metabolism-related parameters. Whether modulation of circulating FGF23 levels would improve cardiac outcome in such a high risk population awaits further investigation. The study was approved by Local Ethics Committee at the Osaka Medical College and conducted in accordance to the Declaration of Helsinki.The current retrospective study has been approved by the Ethics Committee of Osaka Medical College. Between 2012 January and 2012 December, 102 patients gave informed consent were included in this study in whom sufficient clinical and echocardiographic information, in addition to serum FGF23 and α-Klotho concentrations and other calcium-phosphate metabolism-related parameters were available. Two of these patients were found to be undergoing chronic hemodialysis. Because chronic hemodialysis may substantially affect the serum levels of α-Klotho and FGF23 Blood samples were collected in the morning after an overnight fast. Aliquots of serum and plasma were immediately obtained and stored at -80 degrees until use. Serum level of soluble α-Klotho was measured using a solid-phase sandwich enzyme-linked immunosorbent assay (ELISA)  2D] were measured by the immunochemical detection method using electrochemiluminescence, competitive protein binding assay, and radioimmunoassay, respectively . The eGFR was calculated by the following Modification of Diet in Renal Disease equation modified for Japanese subjects: eGFR  = 194× (serum creatinine)–1.094× (age)–0.287  Ca, IP, C-reactive protein (CRP), and B-type natriuretic peptide (BNP) were measured by routine laboratory methods. When serum albumin was 4 mg/dL or lower, serum Ca levels were corrected using the formula [Ca + ], and designated as corrected Ca (cCa). Serum levels of intact PTH (iPTH), 25(OH)D, and 1,25-dihydroxyvitamin D  + 0.6 0.425× (height)0.725× 0.007184, and then the LVM index (LVMI) was calculated as the ratio of LVM to the BSA. When the LVMI was greater than 118 (men)/108 (women) g/m2, LV hypertrophy was defined to be present Echocardiographic examinations were performed with a Vivid 7 Dimension equipped with a multi-frequency transducer . Left ventricular (LV) end-diastolic dimension (LVDd), interventricular septal thickness (IVST) and posterior wall thickness (PWT) were measured at end diastole. LV volumes were calculated using the modified Simpson method using the apical 4-chamber view. Low LVEF was defined to be present when LVEF was <50%. For calculation of the LV mass (LVM), we used the formula proposed by Devereux et al. 2D) were not found to be normally distributed by the Kolmogorov-Smirnov test; therefore these values, and IP, were log-transformed for multivariate regression analysis although α-Klotho and cCa were not found to be completely normalized by log transformation. Multivariable logistic regression analysis was performed to examine the association between log(FGF23) concentrations and low LVEF or LV hypertrophy after adjusting for possible confounding variables including eGFR. Data analysis was performed by IBM SPSS statistics version 21.0 .Baseline characteristics were assessed with standard descriptive statistics. Data were expressed either as mean ± standard deviation, or median and interquartile range (IQR). Spearman rank correlation test was used to assess the correlation between two variables. Univariate or stepwise multivariate linear regression analysis was used to examine the association between LVMI or LVEF and demographic clinical, and laboratory variables. The calcium-phosphate metabolism-related parameters, except IP, D, 1,25(OH)2 and 70 patients (70%) had eGFR of <60 mL/min/1.73 m2. Only 7 patients (7%) had eGFR of less than 30 mL/min/m2. LVDd and LVEF in more than one-fourth of the patients were less than 55 mm and greater than 50%, respectively, in the current study population (2 and those with eGFR of <60 mL/min/1.73 m2.Demographic and laboratory data and echocardiographic results of the study subjects are shown in pulation . FGF23 a2D).Correlation between FGF23, α-Klotho, and clinical and laboratory parameters were analyzed , 4. FGF22, and they were −0.31 (P = 0.095) and 0.29 (P = 0.114), respectively, in 30 patients whose eGFRs were ≥60 mL/min/1.73m2 , log(iPTH), and log(25(OH)D) had significant associations with LVEF and that age, eGFR, log(FGF23), and log(iPTH) were significant associated with LVMI . Standarn/1.73m2 , 2. Ente3, log, but not log(α-Klotho), was associated with LVEF and LVMI. It was also found that several other calcium-phosphate metabolism-related parameters; however, after adjusting for such possible confounders, FGF23 remained to be significantly associated negatively with LVEF and positively with LV mass. To the best of our knowledge, this is the first study that targeted cardiology inpatients, namely, a high- risk population for cardiac abnormalities, for the assessment of relationships among FGF23, α-Klotho, left ventricular mass, and left ventricular function.Several previous studies have analyzed the relationship between circulating FGF23/α-Klotho levels in the general population and in subjects with chronic kidney disease (CKD) and more advanced renal failure 2, which may, at least in part, explain why FGF23 level did not significantly differ between low eGFR (<60 mL/min/m2) and preserved eGFR (≥60 mL/min/m2) groups. We found that correlation between log(FGF23) and LVEF was (borderline) significant in patients with eGFRs of ≥60 mL/min/1.73 m2. It may suggest the possibility that FGF23 plays a role in the cardiac remodeling even in non-CKD subjects or that FGF23 is regulated by certain factors that are modulated in response to cardiac performance. Considering that FGF23 has now been considered to mediate ‘off-target,’ direct, end-organ toxicity in the heart It has been reported that serum FGF23 levels were significantly elevated in CKD. In the current study, however, FGF23 levels did not significantly differ according to the two eGFR groups. Westerberg et al. reported that, by analyzing the data of adult out patients, FGF23 level was significantly elevated in those with CKD stage 4 or 5, but not in those with CKD stage 3, compared with subjects with CKD stage 1–2 The relationship between circulating α-Klotho in the general population and in patients with cardiovascular risk seems to have been less extensively assessed.Kim et al. analyzed the α-Klotho level in patients with various renal functions among the CKD cohort In the current study, multivariate analysis showed that 25(OH)D and iPTH were positively associated with LVEF and LVMI, respectively, findings that were in accordance with previous observations There are several limitations in the current study. First, the current study included patients with various cardiovascular diseases. The relationship between FGF23 and cardiac remodeling might differ according the etiology of the background disorders. Second, although exposure of primary cardiomyocytes to FGF23 was reported to result in elevated intracellular calcium and increased ventricular muscle strip contractility in the experimental model In summary, by analyzing data from cardiology inpatients, we found that circulating levels of FGF23 were positively associated with LV mass, LV hypertrophy, reduced LV systolic function, and plasma BNP concentration. This relationship was statistically significant after adjustment for other calcium-phosphate metabolism-related parameters including α-Klotho. Whether modulation of FGF23 activity would improve cardiac outcome in such a high-risk population awaits further investigation.


Whether 123I-mIBG will also play an important role for identifying and/or predicting sustained ventricular tachyarrhythmias in patients with cardiomyopathy and determining those who may benefit from ICD implantation is currently under investigation. Novel imaging approaches that pinpoint the site of ventricular arrhythmias and guide ventricular tachycardia ablation are presented.Implantable cardioverter-defibrillators (ICDs) significantly reduce mortality in patients with depressed left ventricular ejection fraction (LVEF) and heart failure (HF). However, shortcomings of LVEF to accurately identify those at greatest risk of ventricular tachyarrhythmias have led to the pursuit of alternative means to refine qualification criteria for ICD implantation. It is well established that imaging the cardiac nervous system with Sudden cardiac death is a significant public health issue, affecting 150,000-450,000 patients in the United States each year . Clinica123I meta-iodobenzylguanidine (123I-mIBG) SPECT and its potential role in predicting the risk of VTA and describe novel imaging approaches to identify the site of VTA to guide ventricular tachycardia (VT) ablation.Signal-averaged electrocardiogram (ECG), microvolt T-wave alternans, electrophysiologic testing, serum markers (including brain natriuretic peptide), and autonomic function evaluation (including heart rate variability (HRV), baroreflex sensitivity, heart rate turbulence, and deceleration capacity of heart rate) have all been studied, and have produced variable results . More re123I-mIBG has been the most common radiotracer studied for imaging cardiac innervation. It was first introduced in 1979 for imaging the adrenal medulla, and for the heart shortly thereafter [123I-mIBG is chemically modified from guanethidine, which is an analogue of the endogenous neurotransmitter norepinephrine, and uses the same uptake and storage mechanisms as norepinephrine. Two mechanisms of 123I-mIBG uptake from the synaptic cleft have been identified, one being neuronal and the other being non-neuronal, of which the former predominates in the human heart. This is evidenced by the fact that uptake is absent in enervated transplanted hearts [123I-mIBG is not metabolized by monoamine oxidase or catechol-O-methyltransferase, and does not interact with postsynaptic receptors. Thus, cardiac 123I-mIBG reflects uptake in only presynaptic sympathetic fibers in the myocardium [d hearts . Unlike ocardium .123I-mIBG cardiac images are usually acquired in the anterior planar view 5–40 minutes (early) and again 3–4 hours (delayed) after the injection of the radiotracer. From these planar images, the heart-to-mediastinal ratio (H/M) is calculated by dividing the mean counts per pixel from a cardiac region of interest by the mean counts per pixel from an area in the upper mediastinum. Delayed H/M ratio derived from the anterior planar view has been widely used to predict patient outcome and monitor response to medical treatment. In addition, 123I-mIBG washout rate (WR) is calculated by comparing early and delayed 123I-mIBG activities in the heart, reflecting the retention or turnover of 123I-mIBG in neurons. After each planar acquisition, a SPECT acquisition is performed, and images are analyzed in conventional orthogonal planes .123I-mIBG in HF patients at single centers has been found to be acceptable and highly reproducible [123I-mIBG labeling methods, disease status, and 123I-mIBG isotopes[123I-mIBG may decrease with age, especially in men [The reproducibility and inter-observer variability of  isotopes. Also, sy in men . Given ty in men .The autonomic nervous system is known to play a key role in the pathophysiology of HF. Neurohormonal feedback provides a means for compensation in the early stages of HF; however, as the disease progresses, chronic sympathetic output leads to detrimental effects, including interstitial fibrosis and left ventricular remodeling. Chronically elevated norepinephrine levels have been linked to an increased risk of mortality in HF . Additio123I-mIBGin HF patients. Patients with HF exhibit decreased cardiac uptake of 123I-mIBG (decreased H/M), and earlier release of 123I-mIBG from early to delayed imaging due to compromised neuronal integrity (increased WR). An inverse relationship has been shown between severity of HF classification and H/M 123I-mIBG ratio. Retrospective and single center studies over the past two decades have demonstrated that 123I-mIBGuptake predicts the risk of cardiac death cardiomyopathy  approval for cardiac application [A meta-analysis of 18 small trials including 1755 patients was published in 2008, and demonstrated that decreased H/M and elevated WR portends a worse prognosis, with increased risk of cardiac death and cardiac events . Based olication .123I-mIBGand myocardial perfusion imaging and were followed for two years. The subgroup of patients with 123I-mIBGH/M < 1.6 had a 2-year cardiac event rate  of 37 %, while those with H/M ≥ 1.6 had a 2-year event rate of 15 %. Each of the three components of the primary outcome were also significantly reduced in patients with H/M ≥ 1.6 . LVEF, BNP, NYHA class, and H/M were significantly predictive of event occurrence in multivariate analysis. Although WR was predictive in univariate analysis, it did not remain so in multivariate analysis.AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) prospective, multinational, multicenter, open-label study which enrolled 961 patients with LVEF ≤ 35 % and New York Heart Association (NYHA) functional class II-III was recently completed ••. PatieActivation of sympathetic nervous system is an important factor in the pathophysiology of ventricular tachyarrhythmias. All three known mechanisms of ventricular tachyarrhythmias, including enhanced automaticity, triggered automaticity, and reentrance, can be potentiated by the sympathetic nervous system. Sympathetic neuronal innervation has been shown to be denser in those with ventricular arrhythmias than in those without . It is t123I-mIBGuptake was present after myocardial infarction (MI) and correlated with ventricular ectopy [123I-mIBGfor ventricular tachyarrhythmias, to refine the utilization of ICDs, and to determine a possible clinical role for cardiac 123I-mIBGtesting. Multiple studies have evaluated the value of 123I-mIBGimaging in diverse groups of patients to predict the risk of ventricular tachyarrhythmias, sudden cardiac death, and ICD discharges  who underwent 123I-mIBGcardiac imaging prior to ICD implantation, 52 % of patients with large 123I-mIBG defects (summed score > 26) received appropriate ICD therapy (primary endpoint) during a mean follow up period of 23 months versus only 5 % of patients with a smaller 123I-mIBG defect (p < 0.01). Moreover, 57 % of those with a large 123I-mIBG defect experienced the secondary endpoint of appropriate ICD discharge or cardiac death versus only 10 % of those with smaller defects (p < 0.01) [The largest prospective, multicenter study to date designed to examine the predictive value of  < 0.01) ••.123I-mIBG abnormalities. In patients with Brugada syndrome, 47 % were found to have regional 123I-mIBG defects, most commonly in the inferior and septal regions [123I-mIBG defects, most commonly in the anteroseptal region. No difference in 123I-mIBG uptake pattern was noted between different long QT syndrome subtypes, between those with corrected QT (QTc) > 500 ms vs. those with QTc < 500 ms, or between those suffering from cardiac arrest or syncope [123I-mIBG imaging abnormalities may predict the risk for ventricular tachyarrhythmias are those with idiopathic ventricular fibrillation [Populations known to be at risk for ventricular tachyarrhythmias but without a history of HF have also been evaluated for cardiac  regions . Among p syncope . Other gillation , 44, arrillation ,hypertroillation , and aftillation .123I-mIBG uptake pattern in the heart has raised the possibility that regional inhomogeneities of innervation may be related to ventricular arrhythmias and could provide guidance for VT ablations. Magnetic resonance imaging (MR), positron emission tomography (PET) and computed tomography (CT) have all been well validated to provide detailed information about the cardiac anatomy or the myocardial scar, which is usually the target for substrate-guided ventricular tachycardia ablations [The localized information of abnormal blations , 60, 61.blations . These cOnly recently has PET imaging been used to guide and facilitate VT ablation •. InvestAn alternate attractive approach is the combination of PET with either CT or MR. While PET provides the metabolic differentiation between normal, hibernating, and scarred myocardium detailed anatomic information can be obtained from CT or MR with a spatial resolution of ≤1 mm or 2–3 mm, respectively. Fusing both datasets can enable a synergistic metabolic and morphological evaluation, which extends beyond what each imaging technique can offer as a stand-alone technology. New elastic algorithms are able to register PET with CT or MR images from separate scanners fast and with an accuracy that is similar to manual elastic registration performed by human experts using up to 32 anatomic landmarks .123I-mIBG abnormalities to guide ablation in patients with preexisting cardiomyopathy and ventricular arrhythmias. 3D reconstructions of the regional left ventricular 123I-mIBG innervation have been compared to high density voltage maps. Using the conventional 17-segment analysis [123I-mIBG denervation defect was found to be 75 %. Among the 25 % discordant segments, 20 % of the mismatch segments exhibited a larger123I-mIBG defect size when compared to the voltage scar. While 90 % of subsequent successful VT ablation sites were found in the area of voltage-defined scar, 10 % were located in an area of abnormal 123I-mIBG uptake that exhibited preserved voltage [123I-mIBG imaging within 6 months of VT ablation, there was a trend toward increased late H/M among patients with recurrent VT and decreased late H/M in those without recurrent VT. While this difference did not reach statistical significance, it was hypothesized that regeneration of sympathetic nerves within areas of scar may predispose these patients to VT, and may be reflected by increased 123I-mIBG . 11C-HED is taken up by cardiac presynaptic neurons but not metabolized by synaptic degradation enzymes. Similar to the 123I-mIBG planar and SPECT data, decreased 11C-HED PET retention in patients with HF has been associated with increased cardiac mortality and need for cardiac transplantation [11C-HED is limited due to its relatively short 20 minute half-life and complex production requiring an onsite cyclotron, which makes the entire production costly [Position emitting radiotracers have also been used to image the cardiac sympathetic nervous system using PET , 68. Theantation , 70. PET13 N-ammonia and innervation by 11C-epinephrine 4 to 12 weeks after myocardial infarction induced by balloon occlusion of the left anterior descending artery. Inducible VT was present in seven of the 11 animals studied, and in those with inducible VT, a significantly larger area of perfusion/innervation mismatch was present [Reduced cardiac neural regeneration after myocardial infarction has been theorized to be associated with arrhythmia risk. This was tested in a swine model, in which perfusion was assessed by  present . These f present .123I-mIBG is well established. While the radiotracer has not yet received FDA approval for cardiac application in the US, its potential role may also expand to the arena of electrophysiology, identifying and/or predicting sustained ventricular tachyarrhythmias in patients with cardiomyopathy, determining those who may benefit from ICD implantation, and pinpointing the site of ventricular arrhythmias to guide ventricular tachycardia ablation procedures.The clinical and prognostic value of imaging the cardiac nervous system in HF with


Thalassemia intermedia is a variety of beta thalassemia which shows clinical symptoms somewhere between asymptomatic carriers and thalassemia major. Cardiac dysfunctions due to chronic anemia and hemosiderosis are the major causes of death in these patients. The purpose of this study is to evaluate cardiac function in these patients by echocardiography. This case-control study was conducted on 22 thalassemic patients (mean: 16.5±5.8 years) and 66 healthy individuals (mean:16.07± 2.9years) as a control group from January 2007 to July 2008. There was no sign of cardiac involvement by physical examination, chest x-ray and ECG in patients. Echocardiographic parameters were measured in groups, and finally data was analyzed by SPSS software. The mean of left ventricular myocardial performance index (MPI)  and left ventricular mass index (LVMI)  have statistically significant difference. Mean of interventricular septal dimension in diastole (IVSD), left ventricular posterior wall thickness in diastole (LVPWD), interventricular septal dimension in systole (IVSS) and left ventricular posterior wall dimension in systole (LVPWS) were also statistically significant with a P-value of, 0.002, 0.001, 0.01, 0.003, respectively. Aortic Pre-ejection period/Ejection time (PEP/ET) , ejection fraction (EF) , fractional shortening (SF) , left ventricular isovolumetric contraction time (ICT)  and left ventricular isovolumetric relaxation time (IRT)  were statistically significant. Mean of right ventricular MPI  and IRT  were also significantly different between two groups. Others echocardiographic parameters were not statistically significant .Heart failures are earlier affected thalassemia intermedia patients compared with control group. Thalassemia is one of the most common hematologic disorders in human beings. This disease is prevalent in Mediterranean region, India, Burma, north of China, up to regions in Pacific Islands. Thalassemia is of two major types namely Alpha and Beta in which the alpha and beta globin chains are involved. The main feature of this anemia syndrome concerns the deficiency or the lack of one or more globin chains , 2. BetaThe main reasons of early death in such patients concern the cardiac complications such as systolic and diastolic disorders caused by hemosiderosis , 5. The Two factors have a major role in the heart failure in thalassemia major patients, the increase in cardiac output and vascular complications .In the absence of regular treatment of thalassemia intermedia patients the diastolic performance of the left ventricle is maintained stable, while the pressure of pulmonary arteries continues to rise which is the main cause of death in these patients . It seemThis case-control study conducted on 22 patients with thalassemia intermedia in the range of 8to25 years old that underwent treatment in pediatric ward of Ali Ebn-e Abitaleb (AS) hospital of Zahedan city, from January 2007 until July 2008. The patients were initially interviewed, clinically examined, and then underwent chest radiography and electrocardiography. Those participants who did not have any obvious cardiac disorder and patients who suffered from high blood pressure, metabolic, endocrine or kidney disorders or used to take heart drugs, or Hb<8g/dl were excluded from the study.Sixty-six healthy children with the same age and gender that referred to our hospital for routine checkup were selected as control group B. Written consent was obtained from each participant and the study was approved by the medical ethics committee of Zahedan University of Medical Science. Both groups underwent echocardiography test by 2D, M-mode, and Doppler methods and parameters such as Aorta/Left atrium diameter (AO/LA), Shortening fraction (SF), Ejection fraction (EF), Left ventricular end-systolic dimension (LVESD), Left ventricular end-diastolic dimension (LVEDD), Left ventricular posterior wall dimension in systole (LVPWS), Interventricular septal dimension in systole (IVSS), Left ventricular posterior wall dimension in diastole (LVPWD), Interventricular septal dimension in diastole (IVSD), Pre-ejection period/Ejection time (PEP/ET), Ejection time (ET), Pre-ejection period (PEP), Left ventricular mass index (LVMI), Myocardial performance index (MPI), E/A velocity ratio (E/A), Peak A velocity (Peak A), Peak E velocity (Peak E), Deceleration time (DT), Deceleration slope (DS), Acceleration time (AT), Isovolumic relaxation time (IRT), and Isovolumic contraction time (ICT) were measured in both groups.Statistical analysis2 (Chi-square) test and also Fisher Exact test were used as needed. Moreover, for comparison between two groups, we used t-test after determining the normality of data distribution by nonparametric Kolmogorov-Smirnov test. Pearson correlation coefficients also were used to determine the correlation between quantitative variables. A P-value of P-value<0.05 were considered as statistically significant.Data analysis was performed by SPSS software (version 18), χThe mean of the age in the group A was 16.5±5.8, while in the group B it was 16.07± 2.9 . Comparison of age and gender revealed no significantly difference between two groups of case and control .The average of hemoglobin and hematocrit in group A and B were 7.5 g/dl (24%) and 13 g/dl (42%), respectively. The mean of interventricular septal dimension in diastole (IVSD) of the group A and group B , the mean of left ventricular posterior wall dimension in diastole (LVPWD) , the mean of interventricular septal dimension in systole (IVSS) , and the mean of left ventricular posterior wall dimension in systole (LVPWD) , all indicated significant difference. The mean of left ventricular end-diastolic dimension, left ventricular end-systolic dimension in group A  and group B , did not show any significant difference. The mean of ejection fraction  and the mean of fraction shortening  in both groups was statistically significant. The mean of aorta (AO) diameter and left atrium (LA) diameter in diastole  and , respectively, and the LA/AO  in the group A and group B did not show statistically significant difference. The mean of ICT and IRT of the left ventricle in the group A and group B showed no statistically significant difference . The mean of acceleration time (AT) of mitral valve , deceleration slope (DS) , deceleration time (DT) , peak E velocity , peak A velocity  and E/A velocity  in both groups did not show statistically significant difference. The mean of pulmonary ET, PEP, and PEP/ET in the group A and group B was not statistically significant. The mean of AT, DS, DT, peak E velocity and E/A of tricuspid valve in both groups was not statistically significant, while the mean of peak A velocity in group A and B was statistically different . Beta-thalassemia intermedia is a subcategory of beta thalassemia that its clinical manifestations vary from thalassemia major to asymptomatic carriers. The patients with hemoglobin over 10gr/dl require no blood transfusion, and since they show no clinical traits, they may grow up to adulthood. Another group of patients have hemoglobin level of 6gr/dl and therefore, require blood transfusion, and they may display clinical feature such as bone deformity, arthritis, bone pain, progressive splenomegaly, growth failure, ankle ulcers and cardiovascular disorders. Cardiomyopathy is regarded as the main cause of mortality among these patients , 7. ThusOur study revealed that, MPI of the right and left ventricles of patients with thalassemia intermedia was higher than healthy individuals similar to the findings of Bosie et al .The increase of LVMI in the patients of our study was similar to the patients of Vaccari which is regarded as the main factor in the cardiac compliance of these patients that could be a reason for the high frequency of occurrence of diastolic dysfunction in such patients . The incWe also found that PEP in the left side shows a significant increase. The increase of PEP/ET indicates early changes of diastole performance in ventricles. The mean of IVSD of patients group was higher than control group which is in agreement with the findings of Bosie et al . The left ventricular end diastolic dimension in our study was similar to Aessopos and Bosie studies but the left ventricular end systolic dimension did not show this increase, which again agrees with Aessopos study . The meaIRT increase of the right ventricle is due to the disorder in the filling of right ventricle in thalassemia patients. IRT increase of the left ventricle which is a diastolic performance index has been reported in various studies on thalassemia patients that are due to disorder during rest time of the ventricle caused by iron deposits , 14. It It can be concluded that systolic and diastolic performance of thalassemia intermedia patients is affected in comparison with control group due to parameters including MPI, LVMI, IRT, EF, FS, IVSD and LVPWD. For more evaluation, more quantitative and comprehensive research suggested by evaluation of specific effective factors to psycho-social health of these patients.


In recent years, cardiac magnetic resonance (CMR) imaging has emerged as the reference standard for cardiac imaging in patients with many forms of congenital heart disease, in particular for lesions that affect the right ventricle. Few studies have been published in assessment of Ebstein anomaly by CMR imaging.CMR studies of patients with EA conducted from June 2007 to June 2011 were analized. Cine spin echo images in multiple views, and angiography were evaluated to assess chambers morphology and diameters, wall thickness and left ventricular function, also were measured the atrialized right ventricular portion and the functional tricuspid valve position. And Inversion Recovery sequence for determination of fibrosis.Ninety four patients were studied. Table CMR findings in EA were demonstrated. There was a clear positive relationship between the presence of LV fibrosis and the right ventricle dimensions.National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico.


Heart failure remains a major cause of mortality in thalassaemia major. The possible role of cardiac fibrosis in thalassemia major in the genesis of heart failure is not clear. It is also unclear whether cardiac fibrosis might arise as a result of heart failure.We studied 45 patients with thalassaemia major who had a wide range of current cardiac iron loading and included patients with prior and current heart failure. Myocardial iron was measured using T2* cardiovascular magnetic resonance (CMR), and following this, late gadolinium enhancement (LGE) was used to determine the presence of macroscopic myocardial fibrosis.The median myocardial T2* in all patients was 22.6 ms (range 5.3-58.8 ms). Fibrosis was detected in only one patient, whose myocardial T2* was 20.1 ms and left ventricular ejection fraction 57%. No fibrosis was identified in 5 patients with a history of heart failure with full recovery, in 3 patients with current left ventricular dysfunction undergoing treatment, or in 18 patients with myocardial iron loading with cardiacT2* < 20 ms at the time of scan.This study shows that macroscopic myocardial fibrosis is uncommon in thalassemia major across a broad spectrum of myocardial iron loading. Importantly, there was no macroscopic fibrosis in patients with current or prior heart failure, or in patients with myocardial iron loading without heart failure. Therefore if myocardial fibrosis indeed contributes to myocardial dysfunction in thalassemia, our data combined with the knowledge that the myocardial dysfunction of iron overload can be reversed, indicates that any such fibrosis would need to be both microscopic and reversible. Thalassaemia is the commonest single gene disorder worldwide, with approximately 94 million heterozygotes for beta thalassaemia and 60,000 homozygotes born each year . Life-loCardiac fibrosis can be studied using late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR). This technique uses an injection of a gadolinium chelate which is an MR contrast agent that concentrates in areas of expanded extracellular space, such as myocardial fibrosis, from 10 minutes after injection. LGE has been widely used to examine the role of replacement macroscopic fibrosis in a range of cardiomyopathies -14, and A total of 45 patients with beta-thalassaemia major were included in this study. Patients were referred for clinical evaluation according to local practice at external referring centers. There were 19 male and 26 female patients with a mean (±SD) age of 27.1 ± 9.6 years. This research had full ethical approval through Trent NHS Ethics Committee, and all patients gave written consent.Patients were scanned at 1.5 T  using previously reported techniques . In briet test. All normal variables are presented as mean ± SD and ranges or n (%) as appropriate. Statistical significance was set at P < 0.05.T2* values do not conform to a Gaussian distribution and are therefore presented as medians  unless otherwise stated. Comparison of T2* readings were made using the Mann-Whitney U test and comparisons of left ventricular indices were performed using Student's The baseline characteristics of the whole study group are shown in table In these 27 patients, the myocardial T2* was 32.0 ms , liver T2* was 6.8 ms 4.4, 21.0) and the LV EF was 68.3 ± 8.3%. No patient had a prior history of heart failure. There was fibrosis in one patient,  and there was no past history of heart failure or arrhythmia. The fibrosis was a small, discrete area in the subendocardium of the mid-inferolateral wall of the LV, with normal myocardial thickness throughout and no associated regional wall motion abnormalities , liver T2* was 2.9 ms  and the LV EF was 64.1 ± 6.2%. No patient had cardiac fibrosis despite 2 patients (4%) having a previous episode of heart failure. When compared with the normal group (T2* > 20), there was no significant difference in LVEF (p = 0.34).In these 3 patients, the myocardial T2* was 7.7 ms, liver T2* 2.2 ms and LV ejection fraction was 54.7 ± 3.5%. All 3 patients (100%) had a previous history of heart failure, but no patient has cardiac fibrosis. When compared with the normal group (T2* > 20) the LVEF was significant reduced (p < 0.01).Macroscopic cardiac fibrosis is detectable using LGE CMR and occurs commonly in non-ischemic heart disease such as dilated cardiomyopathy (DCM) ,15, and Another significant discrepancy related to the possibility of cardiac fibrosis causing ventricular dysfunction in thalassemia major is that the dysfunction can be reversed with successful iron chelation therapy with intravenous deferoxamine , or combThere is one previous study using CMR LGE in thalassemia from Pepe et al , which fLGE shows in-vivo macroscopic fibrosis, but interstitial fibrosis is too fine to be detected. However new techniques with T1 mapping , or steaDr Pennell is a consultant to ApoPharma, Novartis and Siemens, and is a director and stockholder in Cardiovascular Imaging Solutions. The other authors declare that they have no competing interests.PK and DP designed the study, collected the data and analyzed the results. JPC and MAT designed the study, and assisted in collecting the data. All authors have read and approved the final manuscript.


The objective of this study is to test the hypothesis that quantitative measures of myocardial fibrosis such as the myocardial extravascular extracellular volume fraction (Ve) are associated with markers of adverse cardiac remodeling such as the left atrial volume index (LAVi) and left ventricular sphericity index (Si).LAVi and Si are intermediate phenotypes that precede adverse outcomes. Myocardial fibrosis is quantifiable with contemporary CMR techniques, is treatable, and may represent a therapeutic target when these intermediate phenotypes are present.We measured myocardial Ve in 267 individuals referred for CMR without confounders such as myocardial infarction, where Ve= [λ ρ (1-Hct) - Vp]; the specific density of myocardial tissue, ρ=1.05; the myocardial plasma volume fraction, Vp=0.045, and λ=ΔR1myocardium/ ΔR1blood. T1 was measured with an ECG-gated MOLLI sequence acquired before and 20 minutes after a gadolinium contrast bolus (0.2 mmol/kg). LAVi and Si were measured from standard SSFP cine images: LAVi =[8/3π [(A1)(A2)/L] where A1 and A2 are LA areas from end-systolic 2-chamber and 4-chamber views, L represents the shortest anteroposterior LA dimension from either view, and Si =EDV/[LAX^3 π /6), where EDV is the end-diastolic volume measured from short axis stacks and LAX^3 is the cube of the long axis diastolic dimension from a 4 chamber view. Multivariable linear regression models quantified the association of Ve with LAVi and Si, adjusting for key characteristics identified by stepwise selection.Ve was associated with LAVi , and this association remained after adjusting for age, ejection fraction, EDV index, and left ventricular mass index . Ve was also associated with Si , and this association remained after adjusting for age, gender, EDV index, body mass index, and left ventricular mass index .Ve is associated with key intermediate phenotypes that indicate adverse cardiac remodeling such as LAVi and Si.Dr Erik Schelbert is supported by a University of Pittsburgh Foundation Grant, and by an American Heart Association Scientist Development Grant (09SDG2180083).


Diffuse myocardial fibrosis in hypertensive left ventricular hypertrophy (LVH) is not readily detected by conventional late gadolinium enhanced CMR. Our study was aimed to detect diffuse myocardial fibrosis in these patients as compared to age matched normal controls, using a T1 mapping technique. Fibrosis was quantified by calculating the partition coefficient (λ) and volume of distribution (Vd) of gadolinium (Gd) following a bolus injection of Gd. We observed that the values for λ and Vd were higher in LVH than controls. A positive association was also noted between LV mass and λ.Diffuse myocardial fibrosis can occur in hypertensive left ventricular hypertrophy (LVH) and is not readily detected by conventional late gadolinium enhanced CMR. We previously described a shortened Modified Look-Locker Inversion Recovery (3-5 MOLLI) T1-mapping technique which can quantify fibrosis by calculating the partition coefficient (λ) and volume of distribution (Vd) of gadolinium (Gd) following a bolus injection of Gd.[T1 mapping was performed in 11 subjects with hypertensive LVH (53±16 years) and normal ejection fraction, and 7 age-matched healthy volunteers (50±10 years) on a Siemens 1.5T Avanto using 3-5 MOLLI . Patients with known coronary disease, significant valvular disease, and other causes of LVH were excluded. LV mass and function was assessed by SSFP cine imaging. MOLLI sequence parameters included: TE/TR/FA 1.1 ms/2.5ms/35°, FOV= 340 x 260, resolution 1.8mm x 1.8mm, thickness 8mm. T1 was determined pre-contrast and 10,15 and 20 minutes following injection of 0.15 mmol/kg Gd-DTPA. Hematocrit (Hct) was measured in all subjects. T1 maps were calculated and manually segmented using an in-house MATLAB program. λ was determined from the slope of a plot of 1/T1 of the myocardium versus 1/T1 of the blood. Vd was calculated as (1-Hct)*λ. Values were compared between groups using 2-tailed unpaired t-tests.The LVH group had significantly higher blood pressure and LV mass than age-matched controls (Table). Heart rate, Hct and creatinine were similar between groups. Values for λ and Vd were higher in LVH (0.49±0.04 and 0.31±0.02) than controls (0.44±0.01 and 0.27±0.01) (p=0.003 and 0.004) respectively . There was a positive association between LV mass and λ .Determination of λ and Vd by T1 mapping after Gd bolus with a reduced breath-hold 3-5 MOLLI pulse sequence is a robust method capable of quantifying diffuse myocardial fibrosis in hypertensive patients with LVH and normal ejection fraction. λ correlates with LV mass. These findings support the application of T1 mapping to monitor therapies that regress hypertrophy and reduce fibrosis in hypertensive heart disease.Internal departmental funding


T2 values are related to the tissue water content, providing useful diagnostic information in cardiac diseases, especially in acute states such as myocardial infarction (MI). Visualization of edema, its regional distribution, and extent in acute and chronic heart disease may be useful as a diagnostic tool and help in guiding treatment in the patients with heart disease. Recently, edema detection (T2 elevation) using quantitative T2 maps has been shown more robust than qualitative clinical T2W imaging.Hypothesis: Whole heart coverage T2 mapping makes the global edema distribution available for quantitative myocardial edema assessment in the context of subacute MI.Under IACUC-approved protocol, MI was induced in swine (N = 4) by 120 min occlusion of the mid LAD. Imaging was carried out 2 to 9 days post MI using an Achieva 3T TX system . Normal animals (N=4) were imaged for reference T2 values. T2-mapping of the ventricles was carried using previously presented free-breathing 3D sequence. Post-contrast 3D Late Gadolinium enhancement with phase sensitive inversion recovery (PSIR) images were acquired ~30min post infusion of 0.2 mmol/kg of Magnevist. Both sequences were acquired in high-resolution  during free-breathing using independent respiratory navigator gating.3D T2 maps were calculated per voxel using linear regression of the log of the signal. Pixels with poor fits (corr. coeff. R2<0.9) were rejected. The left ventricle (LV) was manually segmented, excluding papillary muscle and epicardial/endocardial boundaries.MI with edema was observed in all animals; 3 animals displayed evidence of hemorrhage/clotting injuries as evidenced by microvascular obstruction and concomitantly reduced T2. Figs. The high resolution quantitative T2 maps enables monitoring of physiological changes over time, providing an objective assessment on the evolution of edema post MI.This work was funded in part by AHA-11SDG5280025.


Pro-arrhythmic concerns with most anti-arrhythmic agents in patients with significant left ventricular hypertrophy (LVH) limits options when anti-arrhythmic therapy is indicated. Ranolazine, an anti-anginal agent which inhibits late Na+ currents, indirectly causes a decrease in diastolic cardiomyocyte Ca++ levels producing an energy sparing effect. Ranolazine also inhibits triggered activity in animal studies and has anti-arrhythmic properties in patients with ischemic heart disease. Here we report the dramatic anti-arrhythmic effects of ranolazine in a patient with frequent ventricular and supraventricular ectopy in the setting of hypertrophic heart disease without significant coronary artery disease.A 72 year old hypertensive patient with palpitations and significant exercise intolerance due to dyspnea was evaluated with echocardiography, thallium stress testing and cardiac catheterization. Holter monitor data prior to, and after institution of ranolazine 1000 mg twice daily was compared. Patient tolerance and sense of well being after ranolazine was assessed.Significant LVH was noted and obstructive coronary artery disease was ruled out by cardiac catheterization. Within two hours of the initial dose of ranolazine a marked decrease in ventricular ectopy was observed. Ventricular ectopy on Holter monitor decreased approximately 12 fold (23.8% of beats to1.9%) while supraventricular ectopy decreased approximately 7 fold (5.3% of beats to 0.8%). The decrease in ectopy was associated with an improved sense of well being.Ranolazine had rapid onset, potent anti-arrhythmic properties in the absence of obstructive coronary artery disease in a patient with LVH and may be an ideal agent in patients where few anti-arrhythmic options exist. Malignant arrhythmias are a leading cause of morbidity and mortality in patients with, and without, ischemic heart disease -7. In pa+ current in ventricular cardiomyocytes [++ levels. This effect also improves membrane stability [Ranolazine is a novel anti-anginal agent, which inhibits the abnormal late inward Namyocytes . This prtability . Ranolaztability -14. As stability -14.In this case report, we describe the dramatic anti-arrhythmic effects of ranolazine in a patient with significant left ventricular hypertrophy and symptomatic ventricular ectopy and supraventricular ectopy.A 72-year-old male presented to our office for evaluation of a one- month history of increasing exertional dyspnea, palpitations and fatigue. The patient had past history of hypertension, ulcerative colitis with mild associated anemia, prostate cancer, and mild sinus bradycardia. His medications included furosemide 20mg/day and amlodipine 5mg/day. His physical exam was unremarkable except for mild bradycardia (55 beats/min.), frequent ectopic beats and a soft systolic ejection murmur.Initial workup included a normal chest x-ray, electrolytes, renal indices, and thyroid function studies. A hemogram confirmed his past history of mild anemia (hemoglobin 12.7 grams/dl) with a normal differential counts. The electrocardiogram revealed mild sinus bradycardia with frequent premature ventricular contractions (PVCs), non-specific ST-T wave changes and a corrected QT interval of 471 msec .Transthoracic echocardiogram revealed concentric left ventricular hypertrophy  without any out flow obstruction, left atrial enlargement, and grade II diastolic dysfunction. During the stress test, the patient was unable to tolerate exercise due to severe dyspnea and reached a heart rate of only 116 beats/min. Consequently the study was completed using an adenosine stress agent. Prior to terminating the exercise, moderate diffuse ST segment depression was observed in the inferior and anterior leads. His baseline electrocardiogram revealed frequent PVCs in a pattern of bigeminy. The PVCs decreased in frequency with exercise. The Thallium imaging was negative for ischemia and the ejection fraction was estimated at 66%.24-hour Holter monitoring revealed frequent PVCs . VentricBecause of his symptoms, frequent ectopy and concerns for "balanced ischemia" he underwent cardiac catheterization which revealed very mild non-obstructive coronary artery disease and a normal global left ventricular systolic function. The left ventricular end-diastolic pressure was elevated at 30 mm Hg. During the monitoring period prior to, and during the catheterization, the patient continued to demonstrate very frequent ventricular ectopy.On the basis of the information obtained, the patient was felt to have hypertensive heart disease with the frequent ectopic beats impairing cardiac performance. We felt it was highly likely that triggered activity was the mechanism of his ectopy. Thus, shortly after the catheterization he was given a 2000 mg dose of ranolazine  as he reThe patient noted marked improvement of his presenting symptoms and consequently requested that we continue ranolazine, though the dose was later lowered to 1000 mg in the morning and 500 mg in the evening because of constipation.In our patient with frequent symptomatic ectopy and significant left ventricular hypertrophy due to chronic hypertension, we observed a rapid and marked reduction in both ventricular and supraventricular ectopy with the anti-anginal agent ranolazine. Indeed within a couple of hours the ectopy went from being extremely frequent to very occasional. This occurred despite the absence of obstructive coronary artery disease indicating that this was a direct electrophysiologic effect of this medication. We have previously reported the ability of ranolazine to favorable effect ventricular ectopy in a case on non-ischemic cardiomyopathy in a rapid manner  as well In patients with significant left ventricular hypertrophy, there are limited anti-arrhythmic options due to the risk of pro-arrhythmia . Most anAlthough we feel that a reduction in triggered activity most likely explained the reduction in ectopy -14, we cOur patient also had relative bradycardia, likely reflecting sinus node dysfunction. This precluded us from initially trying a beta blocker for the ectopy.  Although we observed a slight decrease in the average heart rate with ranolazine between the two Holter monitors, no pauses or worsening of the minimum heart rate was observed.Ranolazine was remarkably effective in decreasing ventricular and supraventricular ectopy in a patient with significant hypertrophic heart disease secondary to chronic hypertension. More investigations into the anti-arrhythmic effects of this agent in man are warranted.


Although clinical diabetes mellitus is obviously a high risk factor for myocardial infarction (MI), in experimental studies disagreement exists about the sensitivity to ischemic injury of an infarcted myocardium. Recently, our group demonstrated that diabetic animals presented better cardiac function recovery and cellular resistance to ischemic injury than nondiabetics. In the present study, we evaluated the chronic effects of MI on left ventricular (LV) and autonomic functions in streptozotocin (STZ) diabetic rats.Male Wistar rats were divided into 4 groups: control , diabetes , MI , and diabetes + MI . MI was induced 15 days after diabetes (STZ) induction. Ninety days after MI, LV and autonomic functions were evaluated . Left ventricular homogenates were analyzed by Western blotting to evaluate the expression of calcium handling proteins.+-Ca2+ exchange and phospholamban expression (164%) and decreased phosphorylated phospholamban at serine16 (65%) and threonine17 (70%) expression. Nevertheless, diabetic groups had greater autonomic dysfunction, observed by baroreflex sensitivity and pulse interval variability reductions. Consequently, the mortality rate was increased in DI compared with I, D, and C groups.MI area was similar in infarcted groups (~43%). Ejection fraction and +dP/dt were reduced in I compared with DI. End-diastolic pressure was additionally increased in I compared with DI. Compared with DI, I had increased NaLV dysfunction in diabetic animals was attenuated after 90 days of myocardial infarction and was associated with a better profile of calcium handling proteins. However, this positive adaptation was not able to reduce the mortality rate of DI animals, suggesting that autonomic dysfunction is associated with increased mortality in this group. Therefore, it is possible that the better cardiac function has been transitory, and the autonomic dysfunction, more prominent in diabetic group, may lead, in the future, to the cardiovascular damage. Diabetes has been associated with an increased risk of cardiovascular abnormalities and microvascular complications. Although microvascular retinopathy and nephropathy are associated with a high degree of morbidity, the increased mortality in patients with diabetes is primarily a consequence of cardiovascular disease . In factIn this regard, experimental data have demonstrated that hyperglycemia in diabetic animals leads to changes in the heart that contribute to injury during and following an ischemic event; however, the response of an uncontrolled hyperglycemic diabetic heart to ischemic injury remains controversial -5. ExperHowever, most studies reported in the literature have been conducted using an ischemia/reperfusion model, thus it has not been possible to verify whether chronic hyperglycemia can protect the diabetic heart against permanent coronary ligation. Recently, our group demonstrated that after 15 days of MI, diabetic animals had reduced heart fibrosis, improved systolic function, and reduced infarct size. In accordance with this study, it is possible that these data may have indicated the final pathway promoted by a positive balance in regulatory genes related to programmed cell survival, reduced inflammatory cytokines, and increased utilization of glucose as an energy substrate . HoweverChanges in critical processes that regulate intracellular calcium concentration and signaling have been a hallmark of cardiomyopathy and heart failure. Alterations in the expression and activity of cardiac proteins that participate in the calcium handling, , dephosphorylated phospholamban (PLN), which respectively decreases the affinity of SERCA2 for calcium, and sarcolemmal sodium calcium exchanger (NCX), which mediates calcium efflux from the cell  have beead libitum. The animals were housed in collective polycarbonate cages in a temperature-controlled room (22°C) with a 12-hour dark-light cycle (light 07:00-19:00 h). The experimental protocol was approved by the institutional animal care and use committee of the Medical School of the University of São Paulo, and this investigation was conducted in accordance with the previously described [Experiments were performed in adult male Wistar rats (~240 g) from the Animal House of the University of São Paulo, São Paulo, Brazil. Rats were fed standard laboratory chow and water escribed . Rats weExperimental diabetes was induced by intravenous injection of 50 mg/kg STZ  dissolved in citrate buffer (pH 4.2). Rats were fasted overnight before STZ injection. Control rats were injected with buffer only . Forty-eight hours after STZ injection, diabetes was confirmed by blood glucose levels above 200 mg/dL.Fifteen days after diabetes induction or buffer injection, anesthetized rats  underwent surgical occlusion of the left coronary artery, which resulted in myocardial infarction, as previously described elsewhere ,13. BrieThe animals were maintained in the ventilator until recovery. All rats received antibiotics  and Tramadol . Eight animals from each group were evaluated 90 days after myocardial infarction induction (105 days after diabetes induction) to perform the following experimental protocols. The whole sample (n = 75) was evaluated for mortality, an assessment that started after myocardial infarction surgery, excluding the influence of anesthesia or surgical procedure stress.Echocardiography was performed by a double-blinded observer, under the guidelines of the American Society of Echocardiography, 2 days  and 90 days  after myocardial infarction. Rats were anesthetized (80 mg/kg Ketamine and 12 mg/kg Xylazine), and images were obtained with a 10-14 mHz linear transducer in a SEQUOIA 512  for measurements of morphometric parameters: left ventricular (LV) mass (corrected by body weight) and LV end-diastolic diameter (LVEDD); systolic function parameters: ejection fraction (EF) and velocity of circumferential fiber shortening (VCF); diastolic function parameters: LV isovolumetric relaxation time (IVRT) and peak E deceleration time (EDT) corrected by the square root of R-R interval, because EDT and IVRT are HR dependent; and global function: myocardial performance index (MPI). Echocardiographic parameters were measured as described in detail elsewhere .The infarction area was delimited, which led us to analyze the movement of the LV walls. Regions with systolic shortening classified as absent or with paradoxical movement were considered infarcted. The infarcted area (in %) was thus measured as the ratio of these regions by the total area of LV walls ,13,15.One day after the final echocardiographic evaluation, 2 catheters filled with 0.06 mL of saline were implanted into the femoral artery and femoral vein of the anesthetized rats . Twenty-four hours later, the arterial cannula was connected to a strain-gauge transducer , and arterial pressure (AP) signals were recorded over a 30-minute period in conscious animals by a microcomputer equipped with an analog-to-digital converter board . The recorded data were analyzed on a beat-to-beat basis to quantify changes in mean AP (MAP) and heart rate (HR) ,15.Sequential bolus injections (0.1 mL) of increasing doses of phenylephrine (0.25 to 32 μg/kg) and sodium nitroprusside (0.05 to 1.6 μg/kg) were given to induce increases or decreases in MAP pressure responses (for each drug), ranging from 5 to 40 mm Hg. Baroreflex sensitivity expressed as bradycardic (BR) and tachycardic (TR) responses in beats per minute per millimeter of mercury, as described elsewhere. The overall variability of the pulse interval (PI) in the time domain was assessed by the standard deviation (SD) of the time series ,15.© Scientific, USA) and digitally recorded (5 min) with a data acquisition system . The recorded data were analyzed on a beat-to-beat basis to quantify changes in LV pressure. The following indices were obtained: heart rate (HR), LV systolic pressure (LVSP), LV end-diastolic pressure (LVEDP), and maximum rate of LV pressure rise and fall (+dP/dt and -dP/dt), as previously described [One day after the final autonomic evaluation, LV function was also measured invasively in anesthetized rats . One catheter of PE-50 was inserted into the right carotid artery and advanced into the LV. Ventricular pressure signals were measured with a transducer and conditioner , phosphorylated - PLN at threonine 17 (phospho-thr17-PLN), phosphatase protein 1 (PP1), and sodium calcium exchanger (NCX), as described elsewhere [16-PLN (1:5000) and phospho-thr17-PLN (1:5000) were obtained from Badrilla . Glyceraldehyde-3-phosphate dehydrogenase  was obtained from Advanced Immunochemical . Targeted bands were normalized to cardiac GAPDH.Left ventricular homogenates were analyzed by Western blotting to evaluate the expression of sarcoplasmic reticulum calcium ATPase pump (SERCA2), phospholamban (PLN), phosphorylated - PLN at serine 16 . After 90 days of MI, STZ-diabetic rats had a reduced body weight (D: 213 ± 10 and DI: 211 ± 10 g) compared with normoglycemic rats (C: 508 ± 3 and I: 471 ± 9 g). Glycemia was increased in STZ-diabetic rats (D: 400 ± 27 and DI: 371 ± 37 mg/dL) in comparison with normoglycemics (C: 90 ± 3 and I: 96 ± 3 mg/dL).The myocardial infarction akinetic area (MI area) measured by echocardiography was similar between infarcted groups at the initial  and final  evaluations. There was a correlation between the MI area evaluated by echocardiography and Masson's trichrome stain histological method .The noninvasive left ventricular function parameters are shown in Table Final echocardiographic evaluation  showed that LV mass was not different in D rats in relation to the C; however, the I group had an increase compared with the initial evaluation. Moreover, diastolic dysfunction was present in D, I, and DI compared with C rats and in the diabetic groups (D and DI) compared with that at the initial evaluation. The D group had reduced systolic function evaluated by EF and VCF in relation to the initial evaluation and C group (VCF). Myocardial infarction groups (I and DI) demonstrated systolic dysfunction compared with the C group. However, DI animals showed attenuation of systolic dysfunction, as demonstrated by an increase in EF and VCF compared with I rats at the final evaluation. MPI was increased in the final evaluations of the D, I, and DI groups in comparison with the C group. Parallel with these results, DI had reduced MPI compared with the I group, indicating lower global ventricular dysfunction in these animals.Invasive LV function data, performed after the final echocardiographic evaluation, demonstrated that the LVSP was reduced in D, I, and DI groups compared with that in the C group . Furthermore, STZ-diabetic animals (D and DI) had additional impairment in LVSP compared with I animals. As expected, LVEDP was markedly increased in both I (20 ± 2 mmHg) and DI (12 ± 3 mmHg) rats compared with D and C rats . However, the DI group had attenuated LVEDP compared with the I group. Ventricular function was also estimated by +dP/dt (inotropic index) and -dP/dt (lusitropic index). Experimental groups  exhibited diastolic dysfunction evaluated by -dP/dt compared with the C group . Similarly, D, I, and DI animals displayed a reduction in +dP/dt inotropic index  compared with C animals (9445 ± 420 mmHg/sec). However, it is important to point out that the DI group had attenuated systolic dysfunction, also evidenced by invasive measurements (+dP/dt), compared with I rats.Invasive LV function data paralleled echocardiography findings, as observed by the positive correlation obtained between LVEDD and LVEDP , suggesting that increased diastolic diameter was associated with higher LVEDP values. In addition, a positive correlation was also obtained between EF and +dP/dt .Hemodynamic and autonomic evaluations are presented in Table Pulse interval variability, evaluated in time domain by standard deviation of pulse interval (SD), was reduced in all experimental animals compared with C, with additional impairment in the DI group compared with that in D and I Table .GAPDH protein levels remained unchanged among all groups studied and were used to normalize regulatory protein expression involved in calcium homeostasis. SERCA2 expression levels were reduced in both infarcted groups (I and DI) compared with C and D Figures  and 2B. 16 and Thr17 residues. PLN expression levels were increased in group I compared with that in D, and reduced in DI compared with that in C, D, and I groups  showed that groups I  and DI  had a higher mortality rate compared with C (no deaths) and D groups . However, the DI group had an increased mortality rate compared with I group.The key finding of the present study was that the ventricular dysfunction determined by myocardial infarction was attenuated in diabetic rats, an attenuation that was associated with improved net balance of regulatory proteins that participate in the cardiac calcium handling. In opposition, autonomic dysfunction was more prominent in DI compared with I. This alteration may have induced an increase in the mortality rate, as observed in DI compared with normoglycemic MI animals.Epidemiological studies have shown that the incidence of microvascular, macrovascular, and autonomic complications in diabetic patients is directly associated with the degree of hyperglycemia . AlthougIn addition to the clinical studies and trials, experimental designs also have reported controversial data about the role of hyperglycemia in the mechanisms involved in cardioprotection in animals. Several studies have shown that hearts from diabetic rats are equally  or more In fact, some studies have demonstrated that the reduction in myocardial infarction size  is deterMyocardial remodeling after MI is usually characterized by compensatory hypertrophy of myocytes, ventricular dilatation and increased interstitial collagen deposition and fibrosis . In our To further investigate the mechanisms underlying the improved tolerance to ischemia of diabetic rats, we evaluated the cardiac function of the experimental groups. Our data indicate that diabetes partially attenuated the ventricular dysfunction caused by myocardial ischemia . In fact, DI animals had improved systolic and diastolic function indexes, paralleled by reduced MPI, an index that represents global myocardial stress . These d16-PLN, phospho-thr17-PLN, PP1, and NCX. It was previously reported that in heart failure cardiac dysfunction is in part a consequence of changes in intracellular calcium homeostasis, which may be related to an altered expression, function, or regulation of SERCA2 [16 and threonine17 in DI rats reinforces the possibility that SERCA2 function is better preserved in these experimental animals. Indeed, the phosphorylation of PLN in both residues is involved in an increased calcium reuptake by sarcoplasmic reticulum, although the increase in PLN phosphorylation at Thr17 may be interpreted, in some cases, as one of the latest compensatory mechanisms activated when cardiac function is deteriorated, as observed in acidosis and reperfusion periods [Because cardiac dysfunction observed in cardiomyopathy and heart failure is strongly associated with the expression profile of the cardiac proteins related to intracellular calcium handling , we evalf SERCA2 ,28. In t periods .In the present study, because the molecular analyses were performed in all LV homogenates to quantify the expression of proteins by Western blot, it is possible that the compensatory mechanisms involving calcium regulation in the noninfarcted area might have influenced the results. However, it is necessary to consider that not only the myocardial infarction area, but also LV mass were similar between the infarcted groups (I and DI). These findings suggest that experimental diabetes is associated with the activation of endogenous cardioprotective mechanisms, which successfully remain after 90 days of myocardial ischemia attenuating the remaining LV dysfunction in the DI group.Independently of the mechanism involved in the preserved left ventricular function observed in DI rats, it was expected that the mortality rate would be reduced in this group compared with the I group. However, DI animals evidenced an increase in mortality rate 90 days after myocardial infarction compared with the I group, suggesting that other mechanisms and dysfunctions might be influencing the survival rate of the diabetic animals. Possible mechanisms, all involving the metabolic characteristic of the diabetic state, have been previously suggested: long duration of the diabetes, severity of hyperglycemia , high leCardiovascular autonomic neuropathy has been considered an important determinant of mortality in diabetic patients independently of other known risk factors . In the Some possible limitations of the present investigation deserve comment. First, because the MI animals (I and DI) started the protocol with similar values for MI area and LF function and necropsy evaluations were not performed in the animals that died during the 90 days of the protocol, the prediction of survival  based on these parameters becomes difficult and is limited to methods used in this study. Second, the hemodynamic and autonomic parameters were evaluated at the end of the protocol, and comparisons were made by including a control group in the experimental design. Indeed, the direct method for recording blood pressure depends on the catheterization of arterial vessels that are functional during a small time period. Consequently, the biological signals were recorded only at the end of the experimental period, leading to the lack of baseline values in the same animals at the start of the study.We have demonstrated that the left ventricular dysfunction in diabetic animals was attenuated after 90 days of myocardial infarction. This is probably a compensatory mechanism associated with metabolic and molecular adjustments of the cardiac tissue, where the end point was a better profile of calcium handling proteins. However, this positive adaptation was not able to reduce the mortality rate of DI animals. These data suggest that other mechanisms, as well as cardiovascular autonomic dysfunction identified in this study, is associated with mortality rate in these animals. It is important to emphasize that in the present investigation, the time course of diabetes and MI was determined and well knows, in contrast with that observed in clinical situations. Therefore, it is possible that the better cardiac function has been transitory in DI rats, and the autonomic dysfunction, more prominent in diabetics, may lead, in the future, to cardiovascular damage, as observed in diabetic patients after an ischemic event.BR: bradycardic response; DAP: diastolic arterial pressure; +dP/dt: maximum rate of left ventricular pressure rise; -dP/dt: maximum rate of left ventricular pressure fall; EDT: peak E wave deceleration time; EF: ejection fraction; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HR: heart rate; IVRT: left ventricular isovolumetric relaxation time; LV: left ventricle; LV mass: left ventricular mass corrected by body weight; LVEDD: left ventricular end-diastolic diameter; LVEDP: left ventricular end-diastolic pressure; LVSP: left ventricular systolic pressure; MAP: mean arterial pressure; MI: myocardial infarction; MPI: myocardial performance index; NCX: sodium calcium exchanger; phospho-ser16-PLN: phosphorylated phospholamban at serine 16; phospho-thr17-PLN: phosphorylated phospholamban at threonine 17; PI: pulse interval; PLN: dephosphorylated phospholamban; PP1: phosphatase protein 1; SAP: systolic arterial pressure; SD: standard deviation; SEM: standard error of mean; SERCA2: calcium pump ATPase of sarcoplasmic reticulum; STZ: streptozotocin; TR: tachycardic response; VCF: velocity of circumferential fiber shortening.The authors declare that they have no competing interests.BR designed, performed, and coordinated the experiments, as well as prepared the manuscript. KTR carried out the echocardiographic measurements. AM participated in the Western blot analysis. BDS helped to draft the manuscript. PCB participated in the data discussion and helped to draft the manuscript. KDA participated in the design, data discussion and helped to draft the manuscript. MCI conceived the study and participated in its design and coordination. All authors have read and approved the final manuscript.


Heart failure is a significant and growing health problem. To enable a preventative health care system in heart failure, a move is required from the current, intermittent episodical treatment to continuous and ubiquitous access to medical excellence. Home telemonitoring systems that monitor vital body signs and symptoms with wearable technology, have been proposed to enhance treatment and anticipation of adverse events in heart failure patients (decompensation).We investigated whether the data recorded in a home telemonitoring system using innovative sensors had predictive value in detecting heart failure related events.In the MyHeart observational clinical trial, 148 heart failure patients were followed daily for up to one year using an innovative telemonitoring system recording symptoms questionnaires, basic parameters such as body weight and blood pressure, as well as advanced information provided by a bed sensor monitoring night heart rate and activity and a thorax bioimpedance (BIM) device, designed to monitor fluid accumulation in the lungs. The area under the receiver operator characteristic curve (AUC) was used to evaluate the predictive value for heart failure related events of single and combined telemonitoring measurements.The telemonitoring system including innovative sensors was rated positively by the patients, which is further supported by the reasonable compliance rates (>65%) measured. The most predictive variables 14 days preceding an event were thoracic bioimpedance (area under the curve of 0.70), night breathing rate and some symptoms. The initial multiparametric analysis achieved a mean accuracy of 80.6% but would require more data to confirm its generalisation ability.The measurements performed during the MyHeart trial with 148 patients and 12 months’ follow-up provided evidence supporting the development of predictive algorithms of decompensation to support heart failure management at home. An innovative wearable monitor of thoracic congestion by means of bioimpedance was tested and showed the highest predictive value for heart failure decompensation among a large set of monitored vital signs and symptoms.


In severe mitral regurgitation, a subset of patients who are asymptomatic may develop left ventricular decompensation before changes in echocardiographic parameters become evident. Since N-terminal brain natriuretic peptide (NT-proBNP) is used to detect early heart failure, we hypothesised that NT-proBNP would be activated in patients with mitral regurgitation.Patients submitted to surgery were prospectively evaluated over eight months in the Department of Cardiology at Inkosi Albert Luthuli Central Hospital. Control patients with severe mitral regurgitation were obtained from the outpatient clinic. In order to define their value in identifying left ventricular decompensation, NT-proBNP levels and tissue Doppler imaging (TDI) indices were simultaneously measured and compared with conventional echocardiographic indices at baseline and this was repeated at one week and at six weeks after valve replacement.p = 0.0001). The diastolic E-mitral/E-annulus ratio, measured using TDI, was higher in the study group, indicating higher left ventricular filling pressure present in the study group. NT-proBNP levels increased further at one week after surgery and subsided at the six-week follow-up visit to levels similar to the control group. The TDI diastolic ratio also decreased at one week, and increased slightly again at the six-week follow up. These changes were accompanied by significant reduction in left atrium and left ventricular chamber dimensions with an increase in the ejection fraction from one to six weeks.Mean NT-proBNP levels were markedly elevated pre-operatively in all surgical cases compared to controls (Marked differences in mean NT-proBNP levels and TDI ratios between the study and control groups suggest that using TDI and NT-proBNP assays may detect covert left ventricular decompensation. Chronic organic mitral regurgitation (MR) has a variable course and requires careful monitoring by the clinician. Symptoms often occur late due to the compliance properties of the left atrium that allow it to accommodate large volumes of blood without a significant rise in pressure. As the regurgitation becomes more severe, contractile dysfunction may precede the onset of symptoms associated with disease progression as the ejection fraction (EF) declines but it may still remain in the normal range. An EF less than 60% has been shown to be associated with poorer survival rates after corrective surgery and is likely to indicate covert contractile dysfunction in MR patients.1Although numerous qualitative and quantitative echocardiographic modes have been developed, previous studies have demonstrated that existing measures of severity of MR correlate poorly with clinical signs and symptoms.The development of contractile dysfunction and its relation to the severity of volume overload in MR is not clearly understood. Prolonged contractile dysfunction eventually becomes irreversible even after the MR is corrected and is predictive of both congestive heart failure and death.In this study we evaluated tissue Doppler imaging and NT-proBNP levels in patients with severe chronic MR and determined their time-course patterns following mitral valve replacement.The study population was selected from Inkosi Albert Luthuli Central Hospital, Durban. Informed consent was obtained from each patient, and in the case of minors, from the parent or legal guardian. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki. Ethics approval was given by the Biomedical Research Ethics Committee at the University of KwaZulu-Natal, Nelson R Mandela School of Medicine (Ref No. H112/06).2.The study enrolled patients prospectively from February to September 2007. Patients with severe, chronic isolated MR underwent comprehensive quantitative Doppler echocardiography performed by one trained echocardiographer (RP). Patients were excluded if they had acute MR, MR due to ischaemic heart disease or cardiomyopathy, previous valve surgery and associated aortic or congenital valve disease. Patients with associated mitral stenosis were excluded if the valve area was less than 2.0 cmClinical evaluation and management of the patients were conducted by their independent clinicians. Assessment of symptoms was determined clinically by the New York Heart Association (NYHA) classification, and atrial fibrillation was evaluated by electrocardiography. Doppler echocardiographic recordings and blood samples were collected simultaneously and estimation of the NT-proBNP levels were processed independently.Control subjects with severe MR were selected from the cardiology outpatient follow-up clinic where they were assessed as not requiring surgery in the short term and were receiving medical therapy. Controls were selected as severe MR, but without evidence of ischaemic heart disease, as it is known that NT-proBNP is activated in the presence of ischaemia.3et al.Colour Doppler echocardiography was performed on all patients using a Siemens Sequoia machine . Dimensions and wall thickness were measured according to the American Society of Echocardiography guidelines using the leading-edge method,TDI was performed in the apical four-chamber view. The myocardial systolic wave (Sm) velocity, the diastolic indices, namely early myocardial (Em) and atrial contraction (Am) peak velocities, Em/Am ratio, and early diastolic filling ratios  (Em/Ea ratio) were measured. The ratio of the E wave across the mitral valve to the annulus E wave on tissue Doppler (E/Ea) was used as an estimate of the LV filling pressure. All echocardiographic measurements were performed by a single echocardiographer (RP) blinded to all other measurements. The images and measurements were reviewed off-line by a trained cardiologist (DPN). The intra-observer variability for the measurements of proximal isovelocity surface area (PISA) and TDI was < 5%.For measurement of NT-proBNP, venous blood samples were taken in gel-filled tubes with the patient resting quietly at the time of echocardiography. Additional samples were taken from subjects undergoing mitral valve replacement at one and six weeks post surgery.t-test or chi-square tests. Associations of baseline NT-proBNP were tested with linear and non-parametric regression . The time course of NT-proBNP within the cases was evaluated using paired t-tests. The discriminating capacity of the NT-proBNP for separating surgical cases from controls was assessed by the construction of ROC curves. Bivariate analysis was performed to assess the ability of the different parameters in predicting a favourable outcome using an NT-proBNP level of 50 pmol/l.SPSS for Windows version 15.0 was used for the statistical analysis. Clinical variables were normally distributed and expressed as mean ± SD. NT-proBNP levels were log-transformed for statistical analysis. Group comparisons were performed with ANOVA, A total of 54 patients with severe rheumatic mitral regurgitation were enrolled in the study and surgical cases were followed up for six weeks. Their baseline characteristics are shown in Only one patient in the control group had markedly elevated systolic pressure (63 mmHg) together with NYHA class III symptoms. This patient subsequently had a valve replacement seven months after the echocardiographic and NT-proBNP assessment.p = 0.04). A similar pattern was observed with NT-proBNP level, which was elevated in both groups, but was markedly higher (p < 0.001) in the study group The orifice area was markedly increased in 12 patients in the study group The immediate post-operative period showed a rise in NT-proBNP levels from pre-operative levels (262 ± 224 pmol/l) to a mean of 395 pmol/l at one week, and subsiding thereafter to 94 pmol/l at six weeks Four patients exhibited persistently elevated NT-proBNP levels at six weeks compared to the other study cases. The ejection fraction fell in three of these patients post-operatively, and was accompanied by little change in the end-systolic dimension (ESD) and NT-proBNP values compared to pre-operative levels. There was an increase in the diastolic filling ratios (Em/Ea) and a decrease in the TDI systolic wave. The fourth patient had a large drop in the NT-proBNP level, as well as an increase in the TDI systolic wave, in keeping with the preserved LV contractility. There was a small decrease in the ESD post-operatively A ROC curve was constructed for each variable to assess its discriminating capacity to distinguish between surgical cases and controls. The area under the curve was highest for NT-proBNP; this was the only parameter that approached 90% p = 0.014), tissue Doppler S wave (p = 0.049) and left atrium (LA) size (p = 0.027), all pointing to the interrelationship between severe regurgitation, systolic function and NT-proBNP levels.A second ROC curve This is one of the first studies to use new modalities of measuring left ventricular function with TDI and NT-proBNP assays. NT-proBNP level has been shown to be a marker of left ventricular dysfunction and has been used to predict diastolic abnormalities in patients with normal systolic function,et al.In a study similar to ours, Pillai Two other studies have examined patients with varying degrees of MR, and showed that changes in ventricular function occur early in the disease process, even before they could be detected echocardiographically.The six-week correlation between NT-proBNP levels and chamber dimensions suggests that in MR, changes in volume load may be paralleled by changes in the NT-proBNP level and that the fall in NT-proBNP was related to corrections in volume and removal of the diastolic run-off into the left atrium. These results are also in keeping with those found by the Mayo Clinic,Increased Em/Ea (> 12) ratios and elevated NT-proBNP (> 170 pg/ml) have been shown to be useful parameters to identify patients at increased risk of developing paroxysmal atrial fibrillation (AF) as well as to reflect early left ventricular dysfunction.The challenge in evaluating mitral regurgitation is a determination of what really constitutes normal ventricular function in these patients. The limitations of using the ejection fraction in the timing of surgery become clear in subjects with apparently normal ejection fraction and minimal symptoms.et al.In a study of 84 asymptomatic patients who underwent surgical correction for MR, Agricola Left ventricular contractile dysfunction is present in many patients with severe MR despite a normal ejection fraction and returns to normal after corrective mitral valve surgery in most but not all patients.19In our study, 15 (15/27) of the patients referred for surgery had ejection fractions above 60% and ESD values below 45 mm, indicating that the reason for surgery in these patients was the presence of significant symptoms while on medical treatment. There is an inherent subjectivity in defining significant valve-related symptoms. Indeed, when the second ROC curve was constructed using NYHA class as the determinant, NT-proBNP again emerged as the strongest discriminator of advanced NYHA class.The low specificity of 45% for NT-proBNP indicates a high number of false positive cases, i.e. patients selected by NT-proBNP level as requiring surgery when in fact they were still being followed up in the clinic on medical therapy. We believe that what is considered the high false-positive rate with NT-proBNP actually indicates that many of these control subjects with or without minimal symptoms actually required surgery, rendering them true positives. Waiting for more advanced symptoms or change in dimensions increases the risk of left ventricular dysfunction postoperatively. Two studies, both from the Mayo Clinic, have highlighted the poor outcomes in patients with severe MR who were managed conservatively rather than surgically.21et al.In another study, Pizzaro Most of the subjects in our control group had values above this level, indicating that all our patients were at risk while being followed up at the clinic. We attributed this to the subtle nature of symptoms, or particularly in our study, lack of awareness (on the part of patients or patients’ caregivers) of worsening symptoms and poor referral guidelines from peripheral healthcare centres. This low rate of intervention has also been reported in other centres as well.24In our study, no parameter could discriminate pre-operatively between the four patients who exhibited persistently elevated NT-proBNP levels at six weeks and the rest of the sample. All four of these patients had atrial fibrillation pre-operatively, which persisted at six weeks and at six months. There was no indication of difficulties with myocardial preservation to suggest this as the cause for the decline in postoperative EF by almost 30% from normal pre-operative levels.One of the limitations of this study was that it was performed only in patients with severe MR. The study needs to be repeated in different subgroups with varying degrees of MR in order to determine the time course of NT-proBNP levels in the different stages of MR as well as in patients with ischaemic MR. Finally, we need to determine the association of NT-pro BNP levels in a longer follow-up study with hard end-points such as heart failure and death.et al.We have shown that decision making regarding the timing of surgery in this cohort of rheumatic heart disease patients was determined largely by advanced symptomatology, so that patients are referred to surgery late in the course of severe MR, with a risk of permanent LV decompensation. We propose that NT-proBNP level be an additional marker, particularly in less symptomatic patients, even if the EF is normal. In time, it may prove to be the composite marker for the assessment of LV decompensation. These findings support those of Detaint


Early detection and accurate estimation of aortic stenosis (AS) severity are the most important predictors of successful long-term outcomes in patients. Current clinical parameters used for evaluation of the AS severity have several limitations including flow dependency. Estimation of AS severity is specifically challenging in patients with low-flow and low transvalvular pressure gradient conditions. A proper diagnosis in these patients needs a comprehensive evaluation of the left ventricle (LV) hemodynamic loads. This study has two objectives: (1) developing a lumped-parameter model to describe the ventricular-valvular-arterial interaction and to estimate the LV stroke work (SW); (2) introducing and validating a new index, the normalized stroke work (N-SW), to assess the global hemodynamic load imposed on the LV. N-SW represents the global hemodynamic load that the LV faces for each unit volume of blood ejected. The model uses a limited number of parameters which all can be measured non-invasively using current clinical imaging modalities. The model was first validated by comparing its calculated flow waveforms with the ones measured using Cardiovascular Magnetic Resonance (CMR) in 49 patients and 8 controls. A very good correlation and concordance were found throughout the cycle (median root mean square: 12.21 mL/s) and between the peak values . The model was then used to determine SW using the parameters measured with transthoracic Doppler-echocardiography (TTE) and CMR. N-SW showed very good correlations with a previously-validated index of global hemodynamic load, the valvular arterial impedance ( Aortic stenosis (AS) is a complex “systemic” disease. There are compelling epidemiological and histopathological data suggesting that “degenerative” calcified AS is, in fact, an active and multifaceted disease that involves atherosclerotic-like and elastocalcinosis-like processes The degenerative process is not limited to the aortic valve; it involves the vascular system distal to the valve as well, which in turn can further contribute to deteriorating of left ventricle (LV) function 2) and consequently low transvalvular pressure gradients (<40 mmHg) despite the presence of preserved LV ejection fractions (>50%), is a challenging clinical entity Moreover, in patients with severe AS, “paradoxical” low flow (stroke volume index (SVi) <35 mL/mRecently, Briand et al. (2005) proposed the valvulo-arterial impedance   which reThe LV stroke work has been shown to be effective in characterizing the LV loads and consequently in characterizing patient’s outcome and in assessing the inotropic state in patients with AS i.e., the normalized LV stroke work (N-SW). This index in J/mL, representing the energy required to eject 1 mL of blood through the valvulo-arterial system, is calculated by dividing the estimated LV stroke work by the stroke volume (SV).The first objective of this study was therefore to develop and to introduce a simple lumped parameter model, solely based on non-invasive parameters, to describe the ventricular-valvular-arterial coupling and to investigate the impact of AS and vascular diseases on LV workload. The second objective was to introduce and validate a new index easily measurable in the clinical setting, A schematic diagram of the lumped parameter model is presented in LV(t), V(t) and V0 are the left ventricular pressure, the left ventricular volume and the unloaded volume max, i.e., the slope of the end-systolic pressure-volume relation, giving EN(tN) = E(t)/Emax. Time then was normalized with respect to the time to attain peak elastance, TEmax (tN = t/TEmax). Normalized time-varying elastance curves EN(tN) have similar shapes in the normal human hearts with various inotropic situations or for diseased human hearts despite the existence of differences with regard to etiology of cardiovascular diseases Heart function was described by time varying elastance as followingAortic stenosis was modeled using the semi-analytical formulation for the net pressure gradient −5 and initial voltages and currents of capacitors and inductors set to zero.The lumped model illustrated in The total systemic resistance was computed as the average brachial pressure over the cardiac output  compared to aortic pressure (mean ∼100 mmHg)). This total systemic resistance represents the electrical equivalent resistance for all resistances in the current model. Because what the left ventricle faces is the total systemic resistance and not the individual resistances, for the sake of simplicity, we elected then to consider the aortic resistance, SAC). Therefore, CSAC adjustment was done by a simple trial and error for each degree of hypertension Physiologically, arterial hypertension is determined by two factors This study was approved by the Ethics Committee of Research of Laval Hospital affiliated to Laval University. Informed consents were obtained from all patients.2), diabetes (16%) and metabolic syndrome (35%). The summary of performed measurements is presented in 2), mild (1.5<EOA≤2 cm2), moderate (1.0 cm2<EOA≤1.5 cm2) and severe (EOA≤1.0 cm2).Forty-nine patients with mild to severe AS  and eight healthy subjects  diameter, LVOT flow velocity measured by pulsed-wave Doppler, the aortic transvalvular jet velocity measured by continuous-wave Doppler and valve effective orifice area (EOA) using the continuity equation as follow,Valve hemodynamic parameters: the left ventricle outflow track (LVEF), Sa wave and left ventricle geometry Parameters of LV systolic function: the left ventricle ejection fraction  Parameters of LV diastolic function: Ea wave, SAC) and the systemic vascular resistance (SVR) Vascular hemodynamic parameters: the systemic arterial compliance  Global  LV load, estimated by the valvulo-arterial impedance . CMR image acquisitions and analyses were performed by investigators blinded to clinical and TTE results, as previously described EOA from CMR  to process and analyze CMR images A). We have introduced a lumped-parameter method for clinical practice that accurately investigates the impact of AS and concomitant vascular diseases on the LV function. This method only needs few non-invasively measured quantities described as follows. TTE and CMR can both provide the effective orifice area .in vivo CMR flow waveforms with an average root mean square error of 12.21 mL/s. There was a very good correlation between the peak values of flow waveforms obtained from simulations and CMR measurements . Using the above mentioned protocol, data obtained non-invasively in forty-nine patients with mild to severe AS and eight healthy subjects  were incVAZ .2. Patients with AS often have concomitant arterial diseases. This should alert clinicians that the degenerative process is not only limited to the aortic valve, but also involves the arterial system distal to the valve. The latter can further contribute to deteriorating LV function N-SW represents the global hemodynamic load that the LV faces for ejecting a unit volume of the blood. It has a very good correlation with This study demonstrates a very good correlation between the N-SWs computed based on the data from TTE and CMR methods. Similarly Since the management of patients with AS remains a source of debate 2), low transvalvular pressure gradients (<40 mmHg) and preserved LV ejection fractions (>50%). Clinically, this highly insidious situation represents a challenging clinical entity because the AS may appear less severe on the basis of low transvalvular pressure gradients. This situation may lead clinicians to erroneously conclude that no surgery is required because the stenosis is not considered to be severe. Indeed, these patients are at a more advanced stage of the disease. When compared with patients with severe AS but normal LV output, thus high pressure gradients, these patients are characterized by higher degrees of LV concentric remodeling, lower LVEFs and reduced mid-wall shortenings. It was found that these patients have poor prognoses and outcomes More specifically, as already reported in pendency  [8]. In pendency .in vivo CMR measurements.Patients with AS often have concomitant arterial diseases. Under this condition, the LV faces a double load: a valvular load imposed by the AS plus an arterial load. The double load results in increasing of the LV stroke work. We, therefore, introduced a lumped parameter method, capable of accurately assessing the impact of AS and concomitant vascular diseases on the LV workload using the data obtained non-invasively by TTE or CMR. The proposed method was then validated by comparing its estimated flow rates with We introduced a new index of LV hemodynamic load, the N-SW, representing the energy required to eject 1 mL of blood through the valvulo-arterial load. N-SW is less flow dependent than


Diffuse myocardial fibrosis is frequently observed in histologies of dilated cardiomyopathy (DCM). T1-mapping techniques have the potential to measure fibrosis quantitatively and therefore provide novel cardiac magnetic resonance (CMR) insights into myocardial tissue characterization beyond the presently employed late gadolinium enhanced (LGE) techniques. Fibrosis results in expansion of the myocardial extracellular volume fraction (ECV). Recent reports indicate that T1-mapping calibrated by the blood hematocrit is a promising tool to non-invasively quantify ECV. We explored the clinical utility of this technique in a DCM cohort with different disease stages.All CMR examinations were performed using 1.5 T CMR scanner (Philips Achieva). Short axis slices covering the LV were acquired using SSFP-sequences to measure volumes and ejection fraction. T1-relaxation times were measured from 62 patients  with DCMP and 56 healthy volunteers  before and 15 minutes after gadolinium DTPA contrast injection  whereas focal myocardial fibrosis was assessed in LGE images 10 minutes after i.v. injection. T1-maps were created out of 11 mid-ventricular short axis views with increasing inversion times  using a single breath-hold modified Look-Locker inversion- recovery sequence  in late diastole. The formula for calculating extracellular volume fractions is given in Figure Mean LVEF was 43±12% in DCM and 62±3% in controls. Compared to controls, ECV fraction was significantly higher in DCM patients (28±8% vs 0.23±2%;p<0.0001, Figure Extracellular volume fraction as quantified by T1 mapping CMR is enlarged in DCM reflecting diffuse myocardial fibrosis, which is present even in milder disease forms. In contrast to conventional T1 mapping , ECV fraction measurement quantifies diffuse fibrosis in absolute, easy to understand units making it easier to follow up patients or to compare the amount of fibrosis in different patients' groups.None.


The fundamental abnormality of restrictive right ventricle (RV) physiology is reduced RV compliance as a result of chronic increase in pressure overload.In this study, we test the hypothesis that the persistence of Restrictive RV physiology after balloon pulmonary valvoplasty (BPV) is related to RV fibrosis assessed by Gadolinium-DTPA delayed-enhancement magnetic resonance imaging (de-MRI).A total of 10 selected patients (17± 5) years with severe Pulmonary Valve Stenosis (PVS) referred for BPV were studied. All patients were cyanotic. 5 out of 10 patients presented with frank right sided failure. Restrictive RV physiology was assessed by Doppler echocardiography defined by the presence of antegrade diastolic pulmonary flow.All patients had undergone successful BPV with a recorded hemodynamics. Their RV function  long-axis movement was measured by M-mode and Pulsed Wave (PW) Tissue Doppler imaging (TDI) during the follow up period range from (1-5) years. Also their RV function was compared with 10 normal controls. The RV fibrosis for these patients was assessed using de-MRI.Before BPV, RV Angiogram demonstrate severe RV hypertrophy in all patients. RV hypertrophy and dilatation with impaired systolic function in 5 out of 10 patients. RV end diastolic pressure mean 20±8 was significantly higher than pulmonary end diastolic pressure mean 12±8mmHg P≤0.001.After BPV, the RV systolic pressure decreased from mean (179±40mmHg) to (60±20mmHg) with significant P<0.001. RV end diastolic pressure decreased from mean (20±8 mmHg) to (14±6mmHg) with significant P<0.001 after BPV.Compared with control group patients with restrictive physiology, patients had a lower tricuspid annular systolic and diastolic velocities and lower RV long-axis function.During follow up, delayed enhancement MRI revealed the presence of varying degrees of myocardial fibroses and scarring which ranged from mild patchy areas of enhancement seen at the insertion points, to full enhancement of anterior right ventricular free wall, explaining the presence of restrictive RV physiology in those patients.persistence of restrictive RV physiology after relief of pressure overload in severe pulmonary valve stenosis in adolescents reflects RV diastolic dysfunction associated with RV fibrosis.Egyptian Medical Insurance.