This was more pronounced in T1DM patients with a longer disease duration (p = 0.038). T1DM patients with serum HbA1c > 9% showed impaired longitudinal (p = 0.008) and circumferential strain (p = 0.005) and a reduced E/A-ratio (p = 0.018). In conclusion, asymptomatic T1DM patients have signs of hyperdynamic LV contractility early in the course of the disease. Moreover, poor glycemic control is associated with early subclinical LV systolic and diastolic impairment.Diabetic cardiomyopathy substantially accounts for mortality in diabetes mellitus. The pathophysiological mechanism underlying diabetes-associated nonischemic heart failure is poorly understood and clinical data on myocardial mechanics in early stages of diabetes are lacking. In this study we utilize speckle tracking echocardiography combined with physical stress testing in order to evaluate whether left ventricular (LV) myocardial performance is altered early in the course of uncomplicated type 1 diabetes mellitus (T1DM). 40 consecutive asymptomatic normotensive children and adolescents with T1DM (mean age 11.5 ± 3.1 years and mean disease duration 4.3 ± 3.5 years) and 44 age- and gender-matched healthy controls were assessed using conventional and quantitative echocardiography (strain and strain rate) during bicycle ergometer stress testing. Strikingly, T1DM patients had increased LV longitudinal ( Type 1 diabetes mellitus (T1DM) is ranging among the most common chronic disorders of childhood and adolescence , 3. CardMyocardial deformation is a complex three-dimensional process influenced by heterogeneously organized heart muscle fibers. Measurements of left ventricular (LV) function are important for the evaluation, management, and estimation of prognosis in patients with various forms of cardiovascular disease . HoweverThe aim of this study was to investigate whether STE can be used to detect subclinical alterations of LV myocardial deformation in asymptomatic pediatric patients with uncomplicated T1DM. Furthermore, we combined STE with physical stress testing in order to unmask subtle changes of cardiac contractility that might potentially be occult at rest.2, submaximal effort during exercise testing, short leg length, or pathologic EKG-changes at rest or during exercise. None of the included patients suffered from sings of end-organ damage such as evidence of renal failure or retinal changes. Healthy control subjects had an entirely negative medical history with regard to the cardiovascular as well as to any other organ system. A written informed consent was obtained from each participant as well as from their legal guardian prior to inclusion in the study. Subsequently, a thorough history and physical examination as well as both resting and exercise echocardiography and EKG were obtained. The sample size was achieved by including all patients from the hospital's diabetes clinic that were willing to participate in the study. A priori study design was established dividing the diabetes population into subgroups of patients with a disease duration of less than 4 years  and more than 4 years  as well as a three-column stratification according to glycemic control with serum HbA1c < 7.5% , HbA1c 7.5–9% , and HbA1c > 9% . The study was approved by the Witten/Herdecke University ethics committee and carried out in accordance with declaration of Helsinki's ethical principles for medical research involving human subjects. The study was registered to the Witten/Herdecke University Ethics and Clinical Trials Committee and assigned the trial number 113/2013.For this prospective diagnostic study we enrolled 40 consecutive children and adolescents with T1DM aged 6 to 17 years  and 44 age- and sex-matched healthy controls . Mandatory inclusion criteria in the study group were the diagnosis of insulin-dependent T1DM and a good general health state. Exclusion criteria were other past or present medical conditions that may affect the cardiovascular system such as congenital heart disease, systemic inflammatory disease, for example, history of Kawasaki disease, proteinuria, the use of any type of systemically acting medication (other than insulin for the study group), developmental delay, body mass index > 30 kg/mZ-scores [All examinations were performed with the commercially available ultrasound device iE33 by Phillips Ultrasound Inc., USA, using a S5-1 Sector Array transducer (Sector 1–5 MHz). All images were digitally recorded and transferred to an offline workstation for analysis, using XCelera Version 3.1.1.422 by Phillips Ultrasound Inc., USA. According to echocardiography guidelines a complete standard 2D study, as well as a spectral and color flow Doppler examination, was carried out . Image aZ-scores . During Myocardial deformation parameters (strain and strain rate) were measured acquiring standard 2D grayscale LV images. Circumferential strain (CS) was assessed in the standard parasternal short axis at the mitral valve plane (SAXB) and the papillary muscle plane (SAXM). Longitudinal strain (LS) was measured with standard apical 4-chamber (AP4), 3-chamber (AP3), and 2-chamber (AP2) apical views using conventional B-Mode imaging as previously described . Five coBoth resting and exercise echocardiographic images were additionally analyzed by a second, independent reader who was blinded to the results of the first examiner and the study group status of the respective echocardiographic image in order to determine interobserver reliability.After the general echocardiographic studies, participants pedaled in a supine position utilizing a standard cycle ergometer at approximately 60 rounds per minute against a ramp protocol with increasing resistance. Image acquisition for speckle tracking deformation analyses was carried out in the resting state and at the maximum level of physical exhaustion (≈2 Watt per kilogram body weight). A standardized pattern of consecutive images was acquired at each time point in the following order: SAXB, SAXM, AP4, AP2, and AP3. A 12-channel EKG was continuously monitored and blood pressure measurements were collected at 2-minute intervals.All echocardiographic analyses were performed by the same investigators, who were blinded to the study group status at the time of the assessment of strain and strain rate. The results were reproducible and interobserver variability was below 5.8% in our study.In order to reduce the risk of exercise induced hypoglycemia in diabetic patients, serum glucose levels should exceed 100 mg/dL to 150 mg/dL. Patients with blood sugar levels below 100 mg/dL were provided with extra carbohydrate exchange such as candy bars or orange juice prior to physical exercise testing.U test. Wilcoxon signed-rank test was used for the measurement of the effect of exercise within one group. p values <0.05 constituted statistical significance. Box-Whisker-Plots were used for the graphic representation of the data distribution. SPSS Statistics for Macintosh, Version 22.0. , was used for all statistical analyses.Baseline demographics, clinical data, hemodynamic parameters, and echocardiographic characteristics of the two groups were described by mean and standard deviation. Clinical parameters, hemodynamic data, and echocardiographic characteristics of the two study groups were compared using the Mann-Whitney p = 0.001). However, all baseline and hemodynamic parameters in both groups were within normal limits [1c) was 8.3 ± 1.2%. One patient was excluded from the study due to detection of a previously unknown valvular aortic stenosis.Baseline demographic and hemodynamic data of the study population are summarized in l limits . Mean diZ-scores [p = 0.031). E/E′-ratio, IVRT, and mitral deceleration time as well as all other assessed parameters of diastolic function showed no significant differences between the two groups.Conventional echocardiographic characteristics are outlined in Z-scores . Analysi strain rate are displayed in p = 0.016) and during stress (p = 0.021). While statistical significance was reached in 4 out of 14 comparisons, T1DM patients had higher circumferential and longitudinal strain rate than healthy controls in 13 out of 14 comparisons. The significance of the difference of AP2 derived longitudinal strain rate in the diabetic and control group at rest (−1.94 ± 1.14 versus −1.54 ± 0.25 s−1) is limited by the nonnormal distribution of the parameters.Myocardial deformation was quantitatively measured using speckle tracking echocardiography at rest and during physical stress testing on a bicycle ergometer. Results for peak LV myocardial strain rates at rest when compared to healthy controls, patients with a disease duration of >4 years had significantly increased LV strain rate at rest (p = 0.038) and during exercise (p = 0.05).  strain rate in a patient with T1DM and a healthy sex- and age-matched control subject.The effect of disease duration on LV myocardial contractility is demonstrated in  strain was not shown to be statistically different between the two groups, neither at rest, nor during physical exercise (see 1c > 9% had significantly depressed peak LV CS (p = 0.005) and LS (p = 0.008) when compared to diabetic patients with better glycemic control and healthy controls, respectively.Overall, peak LV myocardialcise see . Howeverp = 0.031) and more pronounced in patients with poor glycemic control represented by serum HbA1c levels > 9% (p = 0.018) as visualized in T1DM patients showed beginning impairment of LV diastolic function (E/A-ratio) when compared to healthy controls see . This ef strain rate both at rest and during exercise (see −1) should not be overinterpreted as a single finding with direct clinical implication but rather regarded as the tip of the iceberg of the overall tendency for T1DM patients to exhibit increased peak systolic LV strain rate. At first, this may seem surprising given the fact that diabetic cardiomyopathy potentially results in a gradual decline of myocardial function with the ultimate end-point of diabetic heart failure. However, we hypothesize that diabetic cardiomyopathy may in fact feature an early subclinical phase of paradoxical LV hyperdynamics as a sign of impaired mechanical efficiency long before long-term deterioration of myocardial function becomes evident. While most studies focus on intermediate or late stage disease reporting of depressed LV systolic function, there are a number of human and animal model studies in favor of our hypothesis.In order to assess the effect of type 1 diabetes mellitus on LV myocardial contractility in the absence of ischemic events early in the course of the disease we performed speckle tracking echocardiography in combination with ergometer stress testing in asymptomatic normotensive pediatric patients with uncomplicated T1DM and healthy controls. Interestingly and somewhat counterintuitively, we found diabetic children to exhibit LV systolic hypercontractility represented by overall increased peak circumferential and longitudinalcise see . The obsγ-ATP ratio as a sign of altered myocardial energetics in young adults with uncomplicated T1DM, independent of coronary microvascular function [Chung et al. found increased LV torsion despite preserved EF, circumferential strain, and longitudinal shortening using tagged MRI in young adult patients with tightly controlled T1DM . Similarfunction . In anotfunction . Moreovefunction , 36. Furfunction . Additiofunction . Therefo−1). While most studies assessing myocardial deformation in diabetic patients mainly focus on strain, strain rate is in fact a more robust index of LV myocardial contractility as it is less dependent on confounding factors such as pre- and afterload [Strain and strain rate are quantitative measures for the echocardiographic assessment of myocardial deformation . Strain fterload –43 and ifterload . The preIn contrast, Di Cori and colleagues used tissue-Doppler imaging to analyze myocardial deformation in adult T1DM patients (mean age 30 ± 4.1 years and mean disease duration 8.9 ± 3.7 years) and found depressed LV myocardial strain and equivocal strain rate . There aIn this study there was no significant difference in overall peak LV longitudinal or circumferential strain between T1DM patients and healthy controls neither at rest nor during stress testing. This is in accordance with a Korean study of a very similar  T1DM population that also failed to demonstrate overall impairment of systolic strain . Strain Recently, a blinded speckle tracking study in 1065 normotensive T1DM patients (mean age 49.5 ± 14.5 years and mean disease duration 26.1 ± 15.7 years) convincingly demonstrated that the impairment of myocardial strain in T1DM is solely driven by the presence of albuminuria . There w1c became evident (see 1c on LV myocardial strain in adult patients with diabetes mellitus [Subdividing our T1DM population according to the degree of glycemic control, an association of both longitudinal and circumferential strains with serum levels of HbAdent see . This ismellitus , 65, 66.mellitus . In addimellitus , 69. Accmellitus , formatimellitus , alteredmellitus , and sevmellitus , 72. Themellitus .The present study provides further evidence for the presence of diastolic dysfunction in diabetes mellitus. We found a statistically significant decrease of E/A-ratio in poorly controlled T1DM patients when compared to healthy controls see . This isIn a recent study on premature infants Sanchez and colleagues demonstrated a link of the reliability of two-dimensional speckle tracking derived deformation parameters and adjusted frame rate during image acquisition . A frameThe present study provides further evidence for diabetes-associated nonischemic cardiomyopathy. A paradoxical increase of LV myocardial performance may occur very early in T1DM as a sign of impaired mechanical efficiency. T1DM patients with poor glycemic control have early signs of subclinical LV systolic and diastolic dysfunction. Consequently, tight glycemic control must be a high priority therapeutic aim for diabetic patients in order to minimize the ultimate risk of heart failure. Further experimental and clinical studies are needed in order to illuminate the spatiotemporal complexity of diabetes-associated heart failure.


To determine whether 3.0-T magnetic resonance imaging (MRI) could assess right ventricular (RV) function in patients with hypertrophic cardiomyopathy (HCM), and if this assessment is correlated with the New York Heart Function Assessment (NYHA) classification.Forty-six patients with HCM and 23 normal individuals were recruited. Left and right ventricular function parameters including end-diastolic and end-systolic volumes , stroke volume (SV) and ejection fraction (EF) and dimensions were measured and compared using 3.0-T MRI. RV function parameters between HCM patients and controls were compared using independent sample t tests. A one way ANOVA test with Bonferroni correction was used to determine significant differences among different NYHA groups. Receiver operating characteristic analyses calculated the sensitivity and specificity of RV dysfunction on MRI for the prediction of HCM severity.Statistical analysis revealed significant differences of left ventricular (LV) and RV volumetric values and masses between the HCM patients and controls . Within the HCM group, the simultaneously decreased maximum RVEDD correlated well with the LVEDD . The function and dimension parameters among Class I to III were not determined to be significantly different . However, significant differences between the Class IV and I-III groups  indicated that the diastolic and systolic function in both the RV and LV were impaired in Class IV patients. ROC analyses identified the EDV, ESV and EDD of both the LV and RV with a high sensitivity cutoff value to predict the HCM patients with severe heart failure (Class IV) with high sensitivity and specificity.RV involvements were comparable to those of LV global function impairments in patients with HCM. The presence of RV dysfunction and decreased dimension on the MRI helped to predict the severe symptomatic HCM with high sensitivity and specificity. Hypertrophic cardiomyopathy (HCM) is the most prevalent, heritable cardiovascular disease with a prevalence rate of 1 in 500 Currently, echocardiography is the most common imaging modality used to assess cardiac function. However, two-dimensional echocardiography has several limitations including operator dependence, inadequate endocardial border discrimination and geometric assumptions. Because the RV has complex geometry, it is difficult to accurately measure RV function parameters using conventional imaging modalities For its retrospective characteristic of this study, a application for exemption of patients' informed consents was approved by the Institutional Review Board (IRB), and we pledged to abide by the declaration of Helsinki (2000 EDITION) in accordance with the relevant medical research rules of China in the study. In addition, no intervention were given in participations with strict secrecy for personal information and privacy. IRB at West China Hospital of Sichuan University approved this study.Patients with HCM that underwent MRI at our hospital from February 2011 to October 2012 were initially enrolled in the study. After 2-dimentional echocardiography examination and clinical assessment, diagnosis of HCM was established based on the practice guidelines of the American College of Cardiology/European Society of Cardiology Prior to MRI examination, a clinical evaluation and assessment of symptoms using the NYHA classification were conducted by the patient's referring cardiologist. All patients and normal controls were examined using a 3.0-T whole-body scanner  in the supine position with a dedicated two-element cardiac phased array coil to assess cardiac function. Electrocardiographic gating and breath holding in expiration were used when feasible. The transverse, coronal and sagittal plane localizing images were acquired using TrueFISP sequence . Double-angulated long-axis two- and four-chamber images were acquired with a segmented ECG-gated FLASH 2D cine sequence . For functional measurement, the short axis images from the base to the apex were acquired via 8–12 images with turboflash sequences . Forty-three patients in this study had underwent first-pass perfusion CMR imaging to evaluate the regional myocardial microvascular dysfunction differences in hypertrophic cardiomyopathy (HCM) patients with or without left ventricular outflow tract obstruction Cine MRI data were analyzed offline with commercial software  by an experienced observer without access to any patient information. In each short-axis slice, the myocardial contours were delineated on images of the end-diastolic phases, which were visually identified as the largest chamber areas, and the end-systolic phases, which were visually identified as the smallest chamber areas, to obtain the function parameters . Papillary muscles and moderator bands were carefully assigned to the lumen of the ventricle Fig. 1. To determine the intra-observer variability of MRI assessment of RV function, one experienced radiologist first measured all RV function values, and the same investigator repeated the measurement in 30 randomly selected patients one month later. Furthermore, to determine the inter-observer variability, a second experienced investigator re-analyzed the measurements of those 30 patients without knowledge of the results of the first investigator. Variability values in each patient were averaged over the entire patient group, and these values are presented as the mean ± standard deviation.. Receiver operating characteristic (ROC) analysis was used to predict the NYHA class. For all statistical testing, a two-tailed P value of <0.05 was considered statistically significant.Statistical analysis was performed with commercially available software . Continuous variables were presented as the mean ± standard deviation (SD). All the function parameters were standardized with body surface area (BSA). The differences in function and size parameters between the HCM and control groups were evaluated using an independent t test. The Kruskal–Wallis and Wilcoxon tests for unpaired samples were used to examine the differences in functional parameters among the NYHA classification groups. Bonferroni correction was performed for multiple pairwise comparisons by adjusting the significance level (α).The Spearman correlation test was used to examine the relationship between the functional parameters and the NYHA classificationp>0.05). According to NYHA classifications, 14 patients (30.43%) had no symptoms (NYHA class I), 15 patients (32.61%) were mildly symptomatic (NYHA class II), 11 (23.91%) were moderately symptomatic (class III) and 6 (13.04%) were severely symptomatic (class IV). The condition of the patients was stable during the examination period. All imaging examinations were performed successfully in all patients without any complications. Good quality images from each imaging technique were obtained for function analyses. Overall MRI time was 20–30 min, and it took approximately 20 min to obtain all the measurements.A total of 46 HCM patients and 23 healthy controls were eligible for the study Table 1.The mean values of function and size parameters on the MRI in 46 patients with HCM and 23 normal controls are summarized in P<0.0167) indicated that thediastolic and systolic function in both the RV and LV were impaired in Class IV patients. Although no significant differences of EF values of both ventricles were found between the HCM patients and healthy subjects, the EFs between the class IV and class I–III patients were significant difference (p<0.05), and similar results were found between the class IV patients and the controls (p<0.05). Similarly, dimensional limitations (LVEDD and RVEDD) were revealed in those Class IV patients (p<0.001), but for IVS thickness (p>0.05). ROC analyses identified the EDV, ESV and EDD of both the LV and RV with a high sensitivity cutoff value, as predictors of the HCM patients with severe heart failure (Class IV) with high sensitivity and specificity  in HCM, as well as the corresponding LV parameters.Based on previous reports, RV dysfunction plays a vital role in determining the clinical outcomes of patients with heart failure In the present study, we found that the RV involvements were comparable to those of LV global function impairments in patients with HCM. Similarly, previous studies demonstrated that the magnitude of maximum RV wall thickness and mass correlated significantly with LV wall Additionally, the current study underlines the importance of the RV diastolic dysfunction in HCM patients. Mörner et al Unlike previous reports We acknowledge the following limitations of our study. Until now, right ventricular hypertrophy and scarring in HCM patients is not widely documented In summary, this study demonstrated that RV involvement is comparable to the LV global function impairments in patients with HCM. When HCM patients were severely symptomatic , the presence of RV dysfunction and decreased dimensions on the MR imaging helped predict the severity of HCM with high sensitivity and specificity.


There are several evidences that right ventricular (RV) volume is important for the patients underwent surgery for tetralogy-of -Fallot, However, there is lack of evidence of RV volume after tricuspid valve surgery. Our aim was to evaluate right ventricular (RV) function using cardiac magnetic resonance imaging (CMRI) in patients who underwent tricuspid valve surgery for identifying predictors of poor postoperative prognosis.From 2008 to 2014, 842 patients underwent tricuspid valve operation at a single tertiary institution. All patients underwent preoperative echocardiography. Among them, 124 patients underwent preoperative CMRI to evaluate heart function including many parameters of volumetric measurement. Short-axis cine MRI images were analyzed using dedicated software. Ejection fraction, end-diastolic volume, end-systolic volume, and myocardial mass of both ventricles were evaluated. The primary composite endpoints or poor outcomes were defined as any cause of death, re-hospitalization due to aggravated heart failure, and redo-valve surgery. Using electronic medical record, baseline characteristics, past medical history, and patient outcome data were reviewed. We compared the CMRI and clinical variables between poor outcome and no poor outcome groups.2; RV mass index, AUC 0.763, cut-off 27 g/m2). RV ejection fraction was significantly decreased and RV end-systolic volume index was enlarged . Unadjusted Kaplan-Meier survival curves showed significantly lower survival rate in patients with large RV systolic volume and large ventricular mass index of both RV and LV.During follow-up , 34 patients (30.6%) had at least one poor outcome, including 9 patients of all cause of death. In poor outcome group, left ventricular (LV) mass index and RV mass index were significantly greater (LV mass index, AUC 0.747, cut-off 61 g/mRV function measured by CMRI may provide prognostic information in patients who underwent tricuspid valve surgery. Measurement of both ventricular mass index and right ventricular end-systolic volume may help to identify patients with poor prognosis.N/A.


A new non-linear approach was applied to calculate the left ventricular ejection fraction (LVEF) using multigated acquisition (MUGA) images.In this study, 50 patients originally for the estimation of the percentage of LVEF to monitor the effects of various cardiotoxic drugs in chemotherapy were retrospectively selected. All patients had both MUGA and echocardiography examinations (ECHO LVEF) at the same time. Mutual information (MI) theory was utilized to calculate the LVEF using MUGA imaging (MUGA MI).MUGA MI estimation was significantly different from MUGA LVEF and ECHO LVEF, respectively (p < 0.005). The higher repeatability for MUGA MI can be observed in the figure by the higher correlation coefficient for MUGA MI (r = 0.95) compared with that of MUGA LVEF (r = 0.80). Again, the reproducibility was better for MUGA MI  than MUGA LVEF . The higher correlation coefficients were obtained between proposed MUGA MI and ECHO LVEF compared to that between the conventional MUGA LVEF and ECHO LVEF.MUGA image with the aid of MI is promising to be more interchangeable LVEF to ECHO LVEF measurement as compared with the conventional approach on MUGA image. Left ventricular ejection fraction (LVEF) is an important indicator in left ventricular dysfunction diagnosis. Electrocardiographically (ECG) gated myocardial perfusion on single-photon emission tomography (SPECT) and multigated acquisition (MUGA) is an effective method for measuring left ventricular function in patients over a wide range of left ventricle (LV) volumes and LVEF values . MagnetiCardiotoxicity could be induced by the drugs of chemotherapy (i.e. Anthracyclines). It may give rise to serious heart failure. Therefore, the oncology patient who receives chemotherapy will have exams before and after the course to detect a possible subclinical decline in left ventricular function. When such a decline occurs, the chemotherapy course is adjusted to limit cardiotoxicity. Currently, MUGA imaging is one of the most widely used methods to assess left ventricular function in patients who receive chemotherapy with risk of the cardiotoxicity associated with the drugs , 3. HoweMutual information (MI) has been used to quantify the similarity with images, and the MI value represents entropy-based image similarity invariant to the overlapped region of two images –10. In tThe study group included all patients who underwent both gated planar left ventriculography (MUGA) and echocardiography examinations for LVEF measurements in our hospital from August 2012 through July 2013. Fifty patients  were retrospectively selected in this study for the estimation of the percentage of LVEF (MUGA LVEF %) monitoring the effects of various cardiotoxic drugs in chemotherapy. Written informed consent was obtained from all patients, and the collection of clinical patient data in this study was approved by the institutional review board of China Medical University Hospital (DMR99-IRB-010-2).2. The scan time of MUGA scan was about 15 min.A Tc-99m MUGA scan was taken with Tc-99m pertechnetate- labeled autologous red blood cells (RBCs). Approximately 740 MBq of Tc-99m was used for the labeling of RBCs in each case. Planar acquisition was done by using a γ-camera  equipped with a high-resolution collimator. A Tc-99 m MUGA scan was acquired over 600 cardiac cycles with 24 frames per R–R interval , and the %LVEF was automatically calculated by drawing a region of interest over LV end diastolic volume (EDV) and LV end systolic volume (ESV). The count parameter of our study was 200,000 per frame (minimum). The spatial resolution of MUGA images was 64 × 64 and FOV was 282.85 × 282.85 mmLVIDs and the LVIDd using ECHO is shown in Fig. Two dimensional echocardiography with M-mode was performed by one experienced operator. A standardized imaging protocol was adopted with cross-sectional imaging of the left ventricle immediately distal to the mitral valve tips and apical two-dimensional imaging based on orthogonal four- and two-chamber views. M-mode left ventricular ejection fraction (ECHO LVEF) based on the cubed method was calculated as mentclass2pt{minimMutual information (MI) is an important concept in information theory , 9, whicMI computes the joint probability histogram of the EDV and ESV, and MI is the maximum MI value in MUGA images. LVEF MI % is expressed as a percentage of heart pumps between EDV and ESV using maximum MI value as the reference. In fact, LVEF MI % is a measure of how much blood is being pumped out of the left ventricle of the heart with contraction.In this study, an in-house MI based software was applied on MUGA image intensity statistics (MUGA MI) to estimate the LVEF which is defined asThe comparison of intra- and inter-operator observability are based on the results measured from different region of interest (ROI) delineated by physicians. Following the routine clinical practice, all the ROIs for MUGA LVEF and MUGA MI measurement was manually delineated by two independent experienced physicians  for assessments of the inter-operator variability. Physician A performed the ROI delineation twice at different times for assessments of the intra-operator variability, from which A1 and A2 represent the ROI of 1st and 2nd times, respectively. Examples of ROIs for MUGA LVEF and MUGA MI measurements calculated from EDV, ESV and background are showing in Fig. Taking ECHO as the reference, the aim of the evaluations was to pick the one, either MUGA LVEF or MUGA MI, that better correlates with ECHO. To do this, correlation coefficient (r) between ECHO and MUGA LVEF or MUGA MI was calculated using least-square fit. Statistical analysis was conducted using the two tailed t test and the results were considered significant at p < 0.05. The variability of the results generated by the two operators was assessed using the standard deviation of the differences between the two results. All of the statistical analysis was performed using SPSS 16.0 .The mean LVEF was 53 ± 16 % by the MUGA LVEF method and 54 ± 13 % by the ECHO method respectively, while it was 45 ± 6 % by the MUGA MI method for all operations. MUGA MI estimation difference was statistically significant compared to the conventional MUGA LVEF and ECHO LVEF estimations (p < 0.005). ESV, EDV, and mean differences for the comparisons of MUGA MI and MUGA LVEF versus ECHO LVEF with the ROIs drawn by physician A (A1), the repeated drawing A2) and physician B are listed in Table  and physTo the best of our knowledge, the presented MUGA MI method is the first non-linear approach for LVEF estimation using MUGA images. The major finding in this study was that LVEF MI value using MUGA image was correlated well with assessment of ECHO LVEF (r > 0.80) in comparison of low correlation from MUGA LVEF r = 0.60). In previous studies, LVEF measurements by various techniques are not interchangeable 0. In pre. It is iThe inter- and intra-observer variations have been observed in previous studies, which is the clinical challenge when using the MUGA for LVEF measurement , 12, 13.There are very wide variances ejection fraction between technologies, which are most marked in comparisons using MUGA and ECHO . Our resA few limitations in this study are summarized here. Although the non-linear method introduced in this study can avoid dependence on the ROI delineation and noise background, very high noise in ROI can still add variations on both sides of the histogram, which may cause errors in LVEF estimation. Additionally, as gated MUGA images were acquired, if with image registration applied before data analysis, the motion blur problem due to respiration and heartbeat will improve. Finally, the major limitation in this study was the absence of comparison of MUGA MI with a ground truth. In this study, MUGA MI and MUGA LVEF were only compared with ECHO but the estimation of ECHO was highly operator dependent. Although our results show a closer correlation between ECHO and MUGA MI than ECHO and MUGA LVEF, it does not mean that MUGA MI is necessarily more accurate or reliable than MUGA LVEF. Therefore, an alternative method such as cardiac magnetic resonance imaging or Simpson method of ECHO, as the gold standard could be used to provide more confidence in the estimation. However, MUGA MI could be used to improve confidence when ECHO and MUGA are both performed for the LEVF estimation.In this study, our results demonstrated lower inter-observer variation and better repeatability by using MI for LVEF estimation on MUGA image compared to the conventional approaches on MUGA image. MUGA image with the aid of MI is promising to be more interchangeable LVEF to ECHO LVEF measurement.


In patients with pulmonary artery hypertension (PAH), right ventricular pressure overload eventually causes right heart failure (RHF), leading to a poor prognosis. Right atrial (RA) overload and RA dysfunction occur in patients with PAH-complicated RHF.We evaluated RA function using right atrial longitudinal strain (RALS) by two-dimensional speckle tracking echocardiography (2D-STE) and investigated the association between RALS and the severity of RHF in patients with pulmonary artery hypertension (PAH) noninvasively.We performed 2D-STE in 56 PAH patients and 20 normal control subjects. The peak global RALS and peak global RA longitudinal strain rate (RALSR) were analyzed by 2D-STE. Simultaneous right heart catheterization was performed to determine the right atrial pressure (RAP) and cardiac index (CI).p < 0.0001) and peak global RALSR  were significantly lower in PAH patients compared with normal controls. There was a significant negative correlation between peak global RALS and RAP . There was a significant positive correlation between peak global RALS and CI . Peak global RALSR was also correlated with RAP  and CI .Peak global RALS (34.6 ± 14.1 vs. 58.3 ± 9.9 %, RALS and RALSR by 2D-STE were useful for noninvasive evaluation of RA dysfunction and the severity of RHF in patients with PAH. In patients with pulmonary artery hypertension (PAH), the pulmonary vascular resistance (PVR), pulmonary artery pressure (PAP), and right ventricular (RV) afterload are all increased. The increase of RV afterload causes RV dilatation and hypertrophy, and impaired compliance of the hypertrophied and dilated RV contributes to a further increase of RV end-diastolic pressure and right atrial pressure (RAP), eventually leading to right heart failure (RHF) and a poor prognosis. In fact, RHF is the main cause of death in patients with PAH. RAP and the cardiac index (CI) are parameters with established usefulness for assessing the severity of RHF and prognosis of PAH patients . AssessmTwo-dimensional speckle tracking echocardiography (2D-STE) is a reliable technique for angle-independent tracking of myocardial deformation that allows noninvasive and quantitative assessment of global or regional myocardial function , 9. ThisWe investigated 56 patients with PAH  and 20 healthy control subjects . According to current recommendations, PAH was defined as a resting mean pulmonary artery pressure >25 mmHg and with a normal pulmonary capillary wedge pressure (≤15 mmHg) . PatientEchocardiography was performed with an Artida ultrasound system . Transthoracic two-dimensional echocardiography was done using a 3-MHz/PST-30SBT transducer. Images of the RV and RA were obtained in the apical four-chamber view during breath-holding and with a stable ECG recording. These images were obtained while taking care to capture the entire RA, allowing for more reliable delineation of the atrial endocardial border. The frame rate was set at between 60 and 80/s. Three cardiac cycles recorded at each plane were stored in cine loop format in order to subsequently select the images with the best quality for off-line speckle tracking analysis. The same transducer (1.7–3.6 MHz) was used with both systems, and special care was taken to employ a similar sector width, focus position, and frame rate range during image acquisition. The RV end-diastolic area index (RVEDAI: RVEDA/body surface area) and RV end-systolic area index (RVESAI: RVESA/body surface area) were measured in the apical four-chamber view to calculate the RV fractional area change [(%RVFAC) = (RVEDA – RVESA)/RVEDA × 100 %] , 15. TheThe IVC diameter was measured on 2DE images at a site approximately 2 cm from its junction with the right atrium. Maximal and minimal IVC diameters during the respiratory cycle (with a sniff test) were measured to calculate the extent of IVC collapse during respiration.Speckle tracking analysis was performed by a single experienced and independent investigator, who was blinded to the invasive hemodynamic data, using commercially available semiautomated 2D-STE software for a Toshiba system . The RA endocardial border was manually traced in the four-chamber view, followed by manual tracing of the epicardial border, thus delineating a region of interest composed of six segments. After analysis of segmental tracking quality and manual adjustment of the region of interest, longitudinal strain curves were generated for each atrial segment by the software. RA longitudinal strain (RALS) was measured in six segments of the RA. As previously described, peak RALS at the end of the RA reservoir phase was calculated by averaging the values for all RA segments to yield the global RALS. The RA longitudinal strain rate (RALSR) was also measured in each of the six segments, and the average for all six segments was calculated  Fig.  8, 10, , 18.Fig.Invasive measurement of cardiac pressures was performed by an investigator who was blinded to the echocardiographic data. The median time difference between echocardiography and right heart catheterization was 4 h (interquartile range 2–5 h). The pressure transducers were balanced before data acquisition with the zero level being set at the mid-axillary line. Right heart catheterization was done to measure the mean PAP, mean RAP, and mean PCWP. The position of the wedge was verified by fluoroscopy, phasic changes of pressure waveforms, and measurement of oxygen saturation. Cardiac output (CO) and the cardiac index (CI) were derived by the direct Fick method as the average of five cardiac cycles with <10 % variation. PVR was calculated by the following formula: PVR = (mean PAP – PCWP)/CO.The serum BNP concentration was also measured. Natural log (Ln) transformation of BNP values was performed because of their skewed distribution.t test and the chi-square test were used for comparison of data as appropriate. The relations between echocardiographic parameters acquired by speckle tracking analysis and invasive data were assessed by calculation of Pearson correlation coefficients. A two-tailed p value <0.05 was considered to indicate statistical significance in all analyses. Intraclass correlation coefficients were calculated to examine intra- and interobserver variability. Analysis was performed with SPSS software for Macintosh .Continuous variables are expressed as the mean ± SD, and categorical variables are expressed as percentages. Student’s The major clinical and hemodynamic parameters for the study population are listed in Table 2 (range 1.0–6.3 l/min/m2), and PCWP was 8.6 ± 3.6 mmHg. Serum BNP was median 79 pg/ml (interquartile range 30–250 pg/ml). LVEF was 70.2 ± 6.6 %, and all patients had normal left ventricular function.Right heart catheterization showed that the systolic PAP was 72.2 ± 19.6 mmHg (range 33–115 mmHg), mean PAP (MPAP) was 43.0 ± 11.5 mmHg (range 25–76 mmHg), mean RAP was 7.8 ± 6.0 mmHg (range 2–30 mmHg), CI was 2.8 ± 1.2 l/min/mOf the 56 patients, 27 (48 %) were on a prostacyclin analog at the time of echocardiography. There were 40 patients (71 %) on an endothelin receptor antagonist, 46 patients (92 %) on a phosphodiesterase-5 inhibitor, and 30 patients (54 %) on a diuretic. We offered optimal combinations of targeted therapies.2/m2, p < 0.0001) and right ventricular end-systolic area index (RVESAI)  were significantly larger in the PAH patients compared with the normal controls, while the right ventricular fractional area change (%RVFAC)  was significantly smaller. Evaluation of RA size and function by 2DE revealed that maximal RAVI  was significantly larger in the PAH patients compared with the normal controls. Maximal RAVI showed significant correlations with RAP  and BNP , but not with CI , PVR , and systolic PAP .RV and RA dimensions and function were evaluated by 2DE (Table p < 0.0001) was significantly lower in the PAH patients compared with the normal control subjects. There were also significant differences of peak global RALSR  between the PAH patients and normal controls , a positive correlation with CI , a negative correlation with PVR , and a negative correlation with BNP . There was a significant correlation between peak global RALS and maximal RAVI  .Peak global RALS showed a negative correlation with RAP , %RVFAC , and TAPSE . There was a significant difference in peak global RALS between mild TR patients and moderate or severe TR patients . There was no significant correlation between TR severity and peak global RALS.There were significant correlations between peak global RALS and RVEDAI  and significant negative correlations with RAP , PVR , and BNP . Peak global RALSR also showed a significant correlation with maximal RAVI  . In patients with PAH, RV remodeling (dilatation and hypertrophy) is a complex set of functional and structural adaptations that occur in response to chronic pressure overload. The ability of the right ventricle to sustain its stroke volume and cardiac output despite an increased pressure load determines the severity of a patient’s symptoms and is also one of the most important factors impacting the survival of patients with PAH –21. In tRV systolic function is initially preserved in the face of RV pressure overload, but diastolic dysfunction occurs as a consequence of myocardial hypertrophy and dilatation. With time, the ventricle also thickens and its filling becomes more dependent on RA performance, which means that RHF can occur if atrial function is sufficiently impaired. It is likely that RA dysfunction contributes heavily to the occurrence of RHF in PAH patients.As RV dysfunction progresses because of RV pressure overload, the preload reserve responds by the Frank-Starling mechanism, and the atrium compensates for ventricular dysfunction to maintain cardiac output by augmentation of RA ejection through the increase of both RA pressure and RA volume. However, when RV pressure overload progresses further and the preload reserve reaches its limit, atrial compensation for the increased RV afterload is lost, leading to a decrease of cardiac output with the onset of severe RHF and rapid deterioration until death occurs , 23. DueMeasurement of RA dimensions by 2D and 3D echocardiography is used for the evaluation of RA function , 25. It Speckle tracking imaging (STI) is a reliable method for angle-independent and objective quantification of myocardial deformation during each phase of the cardiac cycle using 2DE. Strain is defined as the percent change of myocardial deformation, while its derivative (the strain rate) represents the rate of deformation of the myocardium over time. The strain rate has been shown to be closely correlated with myocardial contractility by both in vitro and in vivo experimental studies .The right atrium has multiple roles during the cardiac cycle, since it (1) provides a reservoir for systemic venous return when the tricuspid valve is closed, (2) provides a passive conduit for bleed during early diastole when the tricuspid valve opens, and (3) actively expels blood during late diastole with atrial contraction . Gaynon We demonstrated that peak global RALS and peak global RALSR showed significant inverse correlations with RAP and maximal RAVI, as well as PVR. In previous reports, peak global RALS and peak global RALSR were also inversely correlated with PVR. In addition, the peak global RALS and peak global RALSR both decreased progressively with the increment of RAP and RA dilatation. Moreover, peak global RALS and peak global RALSR were closely correlated with the CI. Therefore, peak global RALS and peak global RALSR can be used as parameters for the evaluation of RA overload and RA dysfunction in PAH. Peak global RALS may even be a factor affecting the prognosis of PAH since it showed strong correlations with all of RAP, CI, and BNP, which are known prognostic indicators for pulmonary hypertension.The present study demonstrates little correlation between PAP and peak global RALS. It was previously reported that RALS showed a significant correlation with systolic PAP in patients who had chronic systolic heart failure complicated by left ventricular dysfunction . This diPadeletti et al.  divided RALS and RALSR measured by 2D-STE were useful for noninvasive evaluation of RA dysfunction and the severity of RHF in patients with PAH.


Tetralogy of Fallot (ToF) is associated with late right ventricular (RV) dilatation and dysfunction. However the relative contribution of the various haemodynamic lesions on RV growth have not been precisely defined, due to small sample sizes in prior studies. In this study, we investigated the independent determinants of RV size and function in a large single centre population.417 patients  with repaired ToF who underwent cardiovascular magnetic resonance (CMR) imaging between 2003 and 2012 were included. Median age at CMR was 18yrs (IQR 12-29yrs). Data from these patients were used create multivariate linear regression models of RV end diastolic volume (EDV), end systolic volume (ESV), and ejection fraction (EF).-6), tricuspid regurgitant (TR) volume , body surface area , and age . Significant residual outflow tract stenosis , branch pulmonary artery stenosis  and RV EF  were negatively associated with RV EDV . Initial palliation with a Blalock-Taussig Shunt  was associated with lower RV EF. TR volume was associated with higher RV EF , ; residual outflow tract obstruction was not associated with RV EF. RV ESV had similar associations to RV EDV, except residual outflow tract obstruction and branch PA stenosis were not associated, and RVEF was the most influential covariate .RV EDV was positively associated with pulmonary regurgitant (PR) volume (β 0.59, p < 1eIn this large, adequately powered study, we report a comprehensive model of RV size and function in patients with repaired ToF. Unsurprisingly PR, TR and EF, are the most important covariates associated with RV EDV. However, we have also demonstrated the contribution of novel independent covariates, such as residual outflow tract and branch pulmonary artery stenosis on reduced RV EDV, which could only be identified due to sufficient statistical power. We also report for the first time an association of prior BT shunt with reduced RV function. These data provide important clinical insights, suggesting that strategies which avoid complete abolition of pulmonary stenosis could produce long-term clinical benefit.British Heart Foundation.


Dilated cardiomyopathy occurring in HIV-infected patients raises both diagnostic and therapeutic challenging problems. Indeed myocardial involvement in HIV infection has been variously attributed to several causes, including viral, toxic, nutritional and autoimmune, but no specific treatment capable to substantially improve patients’ prognosis has been recognized so far.Hereby we describe the case of an autoimmune myocarditis manifesting with heart failure in a3 9-year-old man with HIV infection.Left ventricular endomyocardial biopsy showed a lymphocytic myocarditis characterized by over-expression of HLA-DR and negative polymerase chain reaction for cardiotropic viruses. Steroid treatment was followed by recovery of cardiac dimension and function.Presence of auto-reactive myocarditis should be considered in patients with HIV-associated dilated cardiomyopathy. Its recognition by endomyocardial biopsy followed by steroid administration may result in a complete resolution of cardiac disease.The online version of this article (doi:10.1186/s12879-014-0729-3) contains supplementary material, which is available to authorized users. Occurrence of dilated cardiomyopathy (DCM) in patients with HIV infection raises particular challenging and investigational problems; indeed it is believed that the intrinsic as well as the contamination risks of invasive procedures like endomyocardial biopsy, outweigh the clinical benefit it may derive from the knowledge of the histological and molecular cardiac substrate. However, although myocardial involvement in HIV infection has been variously attributed to HIV itself ,2], opp, opp2], 6 copies/ml) at the time of HIV infection recognition at the age of 29 years. He experienced several infectious events including gastroenteritis, pneumonia and toxoplasma encephalitis before the introduction of anti- retroviral therapy seven years before. Since then he was under antiretroviral treatment  registering a recovery of lymphocyte count (CD4+ up to 500/cmm) and an undetectable viral load in the peripheral blood. The time course of heart failure symptoms and laboratory/instrumental changes from antiretroviral therapy was about seven years. His heart failure was characterized by progressive dyspnea, absence of fever and chest pain but mild and constant increase of troponin T . The electrocardiogram documented a sinus tachycardia (125 bts/min) with low QRS voltages while 2D-echocardiogram showed normal valvular pattern but a progressive bi-ventricular dilatation (right and left ventricular end diastolic diameter was 36 and 68 mm respectively) and dysfunction (RV and LV ejection fraction 35 and 25%) despite an optimized dose of carvedilol (50 mg bid), digoxin (0.125 mg/daily), enalapril (20 mg bid) and furosemide (up to 250 mg/daily). Cardiac magnetic resonance showed a left ventricular (LV) end-diastolic volume of 231.6 ml  and high blood viral load , drug-resistant heart failure the patient underwent an invasive cardiac study including coronary with LV angiography and a LV endomyocardial biopsy with histology and polymerase chain reaction for a large panel  of cardiotropic viruses on 6 samples. Coronary network was normal while at histology a severe active lymphocytic myocarditis was observed characterized by intense cell necrosis (Figure Control histology showed a resolution of the inflammatory process Figure M with inThe underlying myocardial damage in DCM has been attributed to various causes and mechanisms -6], and, and6], Finally HIV itself is supposed to modify lymphocyte gene expression , leadingWritten informed was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.


The aims of this study were to demonstrate ventricular function changes in patients with congenital hypothyroidism and to investigate whether there is an association between any such changes and thyroid-stimulating hormone (TSH) levels using M-mode and Doppler electrocardiography (ECG) and tissue Doppler imaging (TDI).Twenty-seven patients 5-30 days of age with congenital hypothyroidism who were scheduled to receive L-thyroxine treatment and 20 healthy newborns were included in this study. Twelve-lead ECG and M-mode TDI recordings of the patient and healthy groups were obtained. The patient group was divided into two subgroups according to TSH level (>100 uIU/mL or <100 uIU/mL), which were then compared on all parameters.Decreases were observed in the ejection fraction (EF), shortening fraction (SF), and mitral lateral annulus, mitral septal annulus, and tricuspid lateral annulus systolic velocity (Sa) on TDI, whereas left ventricular end-systolic diameter (LVESd) and corrected QT interval (QTc) dispersion were significantly increased in the patient group compared with the control group. No significant differences between the groups were found in left ventricular end-diastolic diameter (LVEDd) or heart rate. When the two patient subgroups (TSH >100 uIU/mL and <100 uIU/mL) were compared, TDI septal annulus Sa wave length and heart rate were significantly lower in the TSH >100 group.Impairment in left ventricular systolic function and increased risk of arrhythmia were observed in newborn infants with congenital hypothyroidism. TSH level was associated with heart rate and interventricular septum velocity. Impaired left ventricular contraction and relaxation are observed in adults with hypothyroidism.Our results showed that congenital hypothyroidism can reduce the left ventricular systolic function and increase the risk of arrhythmia in newborn. Thyroid-stimulating hormone level is associated with heart rate and interventricular septum velocity.The incidence of congenital hypothyroidism in newborns varies between 1/3,500 and 1/4,000. As a result of the recent introduction of screening programs for congenital hypothyroidism also in Turkey, early diagnosis is now possible, and the number of children with cognitive delay due to hypothyroidism has decreased. Primary hypothyroidism is characterized by an increased level of blood thyroid-stimulating hormone (TSH) and decrease in free triiodothyronine (fT3) and free thyroxine (fT4) levels =QT/√R-R] and were expressed as QTc .Transthoracic two-dimensional Doppler ECG was performed using GE Vivid 3 equipment  and a 7S transducer. M-mode echocardiography measurements were obtained at the level of the posterior mitral valve, per the recommendations of the American Echocardiography Society (Pulsed wave (PW) Doppler sampling volume and Nyquist limit in the TDI program using a 7 MHz probe were adjusted to 2-4 mm and 15-20 cm/s, respectively, and the gain was adjusted to receive minimal noise and thus provide clear tissue signals. In the apical four-chamber image, the sample volume was placed at the junction of the left ventricular (LV) free wall, the mitral valve annulus, the mitral septal wall, the right ventricular (RV) free wall, and the tricuspid annulus. The recording was performed over at least five cardiac cycles, during calm periods, so that the flow was not affected by respiration. Systolic velocity (Sa) waves were recorded from the mitral lateral, mitral septal, and tricuspid lateral walls .Statistical analysis was performed using the SPSS for Windows software package . The Kolmogorov-Smirnov test was used to investigate the normality of distribution of the variables. Student’s t-test and the Mann-Whitney U-test were used for variables with and without normal distribution, respectively, to detect any differences between the control and patient groups. A value of p<0.05 was taken to indicate statistical significance.Decreases were observed in the ejection fraction (EF), shortening fraction (SF), and mitral lateral annulus, mitral septal annulus, and tricuspid lateral annulus Sa on TDI , whereas left ventricular end-systolic diameter (LVESd) and QTc dispersion were significantly increased in the patient group compared with the control group . No significant differences were detected in left ventricular end-diastolic diameter (LVEDd) or heart rate between the two groups .When the two patient subgroups (TSH <100 uIU/mL and >100 uIU/mL) were compared, the TDI septal annulus Sa wave velocity and heart rate were significantly decreased in the TSH >100 compared with the TSH <100 group  .Impaired LV contraction and relaxation are observed in adults with hypothyroidism, commensurate with their decreased thyroid hormone levels; this condition is reversible with treatment ,11,12,13Despite recent developments resulting from improved understanding of myocardial mechanics, clinical measurement of EF, LV systolic volume change, SF, and the percentage change in systolic diameter represent the most commonly used methods of assessing ventricular function . In a stIncreased QT interval dispersion (QTd) is an electrocardiographic parameter that has been shown to be associated with malignant ventricular arrhythmias and sudden death, and QTc for heart rate has emerged as a potentially important predictor of cardiac death. Increased QTd is directly related to TSH levels in overt hypothyroidism and mean QTc was reported to be significantly increased in subclinical hypothyroidism compared with controls in several studies . SimilarSympatho-vagal regulation of heart rate is diminished in hypothyroidism. QTc dispersion is decreased significantly following treatment; however, PR and RR intervals and the duration of QRS remain unchanged . In a stWe are aware that our study had some limitations. In this context, difficulties in recording tissue Doppler flow rates due to tachycardia in newborn patients need to be mentioned. The study would have benefited from a larger number of subjects, and follow-up information on the patients would also have improved the study.In conclusion, congenital hypothyroidism during the neonatal period causes impairment in the systolic functions of the heart and increases QT dispersion. Heart rate and the interventricular septal wall are affected by increased TSH levels.


Ischemic heart disease is a common condition and a leading cause of mortality and morbidity. Macrophages, besides their role in host defense and tissue homeostasis, are critical players in the pathophysiological processes induced by myocardial infarction. In this article we will summarize the current understanding of the role of monocytes and macrophages in myocardial damage and cardiac remodeling in relation to their origin and developmental paths. Furthermore, we describe their potential implications in therapeutic strategies to modulate myocardial healing and regeneration. Cardiac diseases, especially acute myocardial infarction and congestive heart failure, are among the most frequent causes of death in the western world and are on the uprise in developing countries. Even though the survival after myocardial infarction has significantly improved by early revascularization therapy and drug treatment, a significant number of patients develop heart failure. A broad spectrum of local and systemic mechanisms are initiated in myocardial infarction and contribute to cardiac remodeling. If uncontrolled, they may lead to negative changes in the geometry, structure and function of the ventricle and thus may have deleterious effects on cardiac function in the long term. Therefore, great interest lies in the discovery of new therapeutic strategies to treat the conditions, which precede heart failure.In myocardial infarction, occlusion of a coronary vessel  results in acutely diminished oxygen supply to the myocardium, which leads to myocyte necrosis and acute inflammation. As the human heart has only limited regeneration capacity  and a less frequent subset of Ly6Clo CCR2− CX3CR1hi monocytes (CD14dim CD16+ in humans). Ly6Clo monocyte “patrol” the luminal side of the endothelium of small blood vessels under homeostatic and inflammatory conditions  monocytes  monocytes correlate negatively with the recovery of left ventricular function after acute myocardial infarction  reduced adverse cardiac remodeling  and a late (7–10 days) phase. The kinetics are dependent on the pathological conditions and respective disease models . Within 30 min after induction of infarction through ligation of the left anterior descending artery (LAD), monocytes are recruited to the site of injury as shown by Future studies are needed to clearly define the role and impact of monocyte subsets in the course of infarction. In any case, preclinical , the monocyte/macrophage population could be divided into 4 subsets. The CCR2− population had a diversified phenotype with MHC IIlo and MHC IIhi macrophage subsets and a mixed developmental origin. In contrast, the CCR2+ population derived exclusively from definitive hematopoiesis and could be subdivided into MHC IIhi and MHC IIlo populations , which facilitates monocyte chemotaxis. This marker helps to identity macrophages, which recently derived from circulating monocytes , the ischemic myocardium has been shown to completely regenerate by proliferation of preexisting cardiomyocytes. This regeneration capacity is already lost during the first week after birth. Induction of myocardial infarction 14 days postpartum (P14) showed left ventricular scarring and cardiomyocyte hypertrophy comparable to the pathophysiological changes seen in adult animals after myocardial infarction  with an expansion of the MHC IIlo macrophage subpopulation. It could be shown that these macrophages possess proangiogenic and reparative properties which, at least partially, contribute to the regenerative capacity of the neonatal heart. Fate mapping analysis revealed that this macrophage subset is of yolk sac origin. In contrast, adult mice respond to myocardial injury with the recruitment of inflammatory MHC IIhi CCR2+ macrophages from the blood circulation and loss of potentially beneficial CCR2− (resident) macrophages. These mice developed pathological left ventricular remodeling including cardiomyocyte hypertrophy, fibrosis, and LV dilation resulting in a decreased LV function. Blocking the recruitment of CCR2+ monocytes into the injured myocardium preserved cardiac MHC IIlo macrophages in the adult heart and showed beneficial effects on coronary angiogenesis and attenuated inflammation , or by inhibition of their recruitment into the ischemic myocardium , macrophage migration inhibitory factor MIF). Reduction of inflammatory CCR2Another approach to modulate macrophage function is to modify their environment. As shown only recently, macrophage phenotypes and functions are shaped by the microenvironment of the organ of residence  are performed, as macrophage populations in the heart are –at least in mice– replaced over time (Molawi et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Systemic lupus erythematosus (SLE) is a disease of autoinmune origin that may involve numerous internal organs of the body. It is associated with high cardiovascular morbility and mortality. The cardiovascular magnetic resonance (CMR) provides us with a global evaluation of patients with active SLE and clinical suspicion of acute myocarditis. OBJETIVES The aim of study was the identification of cardiac alterations in patients with active SLE and clinical suspicion of acute myocarditis.A total of twenty - eight patients were included in the study, with an average age of 30.7 years ( SD 12.7 yrs), 96% female, diagnosed by criteria of American College or Rheumatology (ACR). Cardiovascular magnetic resonance (CMR) was performed on a 1.5 T scanner and include the following sequences: steady- state free precession, STIR T2 weighted (Ts-2W), T1- Weighted spin - echo before and after gadolinium injection and late enhancement.The ejection fraction of left ventricle < 50% was found in 54%, 83.4 % with contractility alterations, 87.5% with valvulitis and affection of the subvalvular apparatus in 50%, pericardial effusion was observed in 62.5% and tissue characterization suggestive of myocarditis for the Lake Louise criteria were found to have global and relative enhancement in 37.7 and 50 % respectively and late gadolinium enhancement (LGE) in 66.7%.In our study group we found that patients with acute myocarditis asoociated with SLE have a high incidence of valvulitis and affection of the subvalvar apparatus.


Studies have demonstrated that phosphodiesterase 5 (PDE5) inhibition is associated with right ventricle (RV) functional improvement in patients with primary pulmonary hypertension. This study aims to demonstrate the immediate impact of Sildenafil, a PDE5 inhibitor, on RV function, measured by cardiovascular magnetic resonance (CMR), in patients with heart failure (HF).We conducted a randomized double-blind controlled trial. Inclusion criteria: diagnosis of HF functional class I-III; left ventricle ejection fraction < 35%. Patients underwent CMR evaluation and were then equally randomly assigned to either 50 mg of Sildenafil or Placebo groups. One hour following drug administration, they were submitted to a second scan examination.26 patients were recruited from a tertiary reference center in Brazil and 13 were allocated to each study group. The median age was 61.5 years (50–66.5 years). Except for the increase in RV fractional area change following the administration of sildenafil , there was no statistically significant change in parameters. There was no improvement in left ventricular parameters or in the fractional area change of the pulmonary artery.This study demonstrated that a single dose of Sildenafil did not significantly improve RV function as measured by the CMR.NCT01936350ClinicalTrials.gov  Heart failure (HF) is a complex syndrome, involving morphologic and functional alterations in both the right and left ventricular apparatus. Although most of the HF burden is associated with left ventricular dysfunction, right ventricular (RV) impairment is also an independent predictor of morbidity and mortality in systolic HF . HoweverAmong the causes of RV impairment in HF, pulmonary hypertension secondary to left sided dysfunction represents the main pathophysiological mechanism . Thus, tex vivo human [As well as the indirect effects on RV, PDE5 inhibition may improve the RV function of HF patients through direct mechanisms. It has been suggested that there is an up-regulation of myocardium PDE5 expression in the RV of patients with HF , 10 and vo human  experimePrevious studies have demonstrated that PDE5 inhibition is associated with RV functional and geometrical improvement in patients with primary pulmonary hypertension , 12. NevThe protocol for this trial and supporting CONSORT checklist are available as supporting information; see Patients were recruited from a tertiary reference center  in Salvador, Northeast Brazil during September 2013. Inclusion criteria were: diagnosis of HF functional class I-III (New York Heart Association); left ventricle ejection fraction <35% (measured by echocardiography); and stable pharmacologic treatment for HF, prescribed by the referring physician for at least one week.Exclusion criteria included newly diagnosed lesions during CMR evaluation ; significant claustrophobia; low blood pressure (systolic blood pressure <90 mmHg or diastolic blood pressure <60 mmHg); nitrate or nebivolol use during the previous 24 hours; and the presence of non-magnetic resonance imaging-compatible implantable devices.All patients provided written consent to participate in the study after receiving detailed information about procedures, possible clinical benefits, and risks. The study was approved by the local research ethics committee—Comitê de Ética em Pesquisa / HAN / UFBA under protocol number 118.327-2 and is registered at Clinical Trials, number NCT01936350.Initially, patients from a HF outpatient service in a tertiary health care institution were screened for eligibility and a CMR exam was scheduled. Clinical data was then collected for all recruited patients, who underwent CMR evaluation without any intervention. Subsequently, the patients were equally randomly assigned to either the Sildenafil (50 mg of Sildenafil citrate) or Placebo groups and one hour following administration of the drug they were submitted to a second scan examination. This time lapse was selected because the median peak plasma serum concentration of sildenafil is 60 minutes. The simple randomization process was based on a computer-generated list of random numbers. Except for interventionists, nurses and technicians were kept blind to drug assignment .All subjects were scanned in the supine position. CMR was performed on an Avanto 1.5 T whole-body scanner , using an 8 channel cardiac coil. Scout images were performed to program the four-chamber, three-chamber and two-chamber, as well as short axis cine images acquisition. The cine images were all acquired using a cardiac gated multi-slice balanced steady-state free precession sequence with breath hold . A stack of images, using a minimum of eight and a maximum of twelve slices, in short-axis plane with 8-mm-thick slices and a 2 mm inter-slice gap were acquired covering the entire left and right ventricles. Every effort was made to obtain adequate images with a satisfactory RV depiction.Ventricular volume, mass, and systolic function, including RV ejection fraction (RVEF), were calculated using the cine magnetic resonance images and ARGUS 4D VF software. End-systolic frames were identified by the smallest cavity area and diastolic frames were identified by the largest cavity area. Endocardial contours were manually traced in both the systolic and diastolic frames, for at least eight slices from base to apex.For a better depiction of RV systolic function, we measured seven septum to free wall transverse lines in the four-chamber view (for both systolic and diastolic frames). Line one was the nearest to the apex, line four was at mid-level and line seven was the baseline. These lines accurately describe regional and global RV function as described by Kind and colleagues (2010) . FurtherPulmonary artery relative area change was calculated through diastolic-systolic change in the pulmonary artery area. This image was based on the RV outflow tract, where a transverse image was traced perpendicular to the artery long-axis in plane and a cine image was acquired at both the diastole and systole.All these measurements were taken both before and after drug use.Based on a previous study , we projAll variables were tested for normality using the Shapiro-Wilk test. Normal continuous variables were presented as mean and standard deviation, and compared with either the unpaired Student’s t test or the paired Student’s t test, as appropriate. Variables with a non-normal distribution were described through the median and 25th-75th percentiles, and compared with the Mann-Whitney test or the paired Wilcoxon signed-rank test, as appropriate. Categorical variables were expressed as absolute values and proportions and compared with the chi-square test. Statistical analyses were performed using SPSS version 9.A two-sided p value of 0.05 was considered the cutoff for statistical significance. The main intervention outcome was change in RVEF.Twenty six patients were recruited and 13 were allocated to each study group. Two patients from the Placebo group were excluded, due to the impossibility of repeating their CMR exam, following technical issues with the magnetic resonance which compromised their original imaging evaluation. The Sildenafil group was therefore composed of 13 subjects, while the Placebo group contained 11 subjects . Fig. 1.th–75th percentile: 50–66.5 years; minimum = 33 years, maximum = 88 years). Seventeen patients (70.8%) had a systemic arterial hypertension diagnosis, 10 (41.7%) had been subject to heart catheterization, 9 (37.5%) had heart rhythm disorders, 7 (29.2%) had had myocardial infarction, and 3 (12%) had Chagas disease. Both study groups presented similar clinical characteristics  were male and median age was 61.5 years , left ventricle end-diastolic volume (LVEDV) and left ventricle end-systolic volume (LVESV) altered only minimally .There were no adverse effects related to the administration of either Sildenafil or placebo pills.The study demonstrated that a single dose of 50 mg of Sildenafil citrate causes minimal, if any, change in RV function as measured by CMR in patients with HF. The main outcome of the investigation, change in RVEF, did not demonstrate any effect due to the studied intervention. This result was confirmed by the evaluation of other RV function parameters, such as fractional TAAD and septum to free wall RV dimensions. Although the increase in RV fractional area change following Sildenafil administration suggests an improvement in RV function associated with the intervention, this is a less reliable parameter for RV function and may reflect minor changes in RV function or geometrical RV changes unrelated to its function. In general, RV fractional area change underestimates MRI derived volume and is inferior to using 3D echo to estimate RV volume, since it does not evaluate right ventricle out flow.There is an intrinsic problem in determining RV function. RV myocardial fibers have a longitudinal orientation giving them a distinctive longitudinal contraction and this complex, three dimensional shape cannot be compared to any geometrical form. This means that, due to a range of geometric assumptions, any two dimensional measurement, such as RV fractional area change and TAPSE, may be misleading .Previous studies have confirmed the effect of sildenafil on right ventricular function in patients with pulmonary hypertension, especially in relation to long-term use ,12. NeveControversially, a small number of previous studies have demonstrated that Sildenafil was able to improve the RV function of patients with HF. These demonstrated that both a single dose of Sildenafil (50 mg) and continued use of this medication (60–225 mg per day) improved the functional parameters of the RV, such as RVEF (measured by right heart catheterization), TAPSE, and right ventricle end-diastolic diameter (measured by echocardiography) –16.There is no clear explanation for the contradiction in findings regarding the efficacy of Sildenafil to improve the RV function of HF patients. One possibility may be related to the HF etiology in the patients enrolled in these studies. Evidence has been found of an etiology-dependent PDE5 expression in the RV myocytes of patients with HF  and thisThe absence of improvement in left ventricular parameters and in the fractional area change of the pulmonary artery in this study probably reflect the same rationale that applies to the minimal changes in the parameter for RV function. Thus, these findings reinforce the minimal impact of a single dose of Sildenafil on cardiac function.Certain study limitations should be addressed. Despite the accuracy of CMR in evaluating heart function, the effect of Sildenafil on systolic function may be so small as to fall within the normal variation that may result from two points of evaluation. The study used a 50mg dose of Sildenafil citrate and it is possible that a 100mg dose could have had an impact on RV function. Furthermore, this was not a prospective study and did not evaluate the impact of the long-term use of Sildenafil.This study demonstrated that a single dose of Sildenafil did not significantly improve RV function as measured by the CMR of patients with HF. Since controversies persist regarding the effect of Sildenafil on cardiac function in the setting of HF, more studies are required to elucidate this issue, particularly in certain groups of patients with heart failure.S1 CONSORT Checklist(DOC)Click here for additional data file.S1 Protocol(DOC)Click here for additional data file.S2 Protocol(DOC)Click here for additional data file.S1 Sildenafil Data Bank(XLSX)Click here for additional data file.S1 IRB Approval(PDF)Click here for additional data file.


Peripartum cardiomyopathy (PPCM) is a systolic heart failure that occurs during the last month of pregnancy or within 5 months after delivery. It is an uncommon disease of unknown etiopathogenesis and has a very high rate of maternal mortality. Because of similarity between symptoms of PPCM and physiological discomforts during pregnancy, the early diagnosis of PPCM presents a major challenge. Since hemodynamic changes during PPCM can vitally jeopardize the mother and the fetus, patients with severe forms of PPCM require a multidisciplinary approach in intensive care units. This review summarizes the current state of knowledge about the diagnosis, monitoring, and the treatment of PPCM. Having reviewed the recent researches, it gives insight into the new treatment strategies of this rare disease. Even at the beginning of the twenty-first century, heart diseases continue to be the leading cause of maternal deaths in many countries . One of Peripartum cardiomyopathy is a rare and very serious type of idiopathic cardiomyopathy, presenting with a left ventricular systolic dysfunction and heart failure during the last month of pregnancy or up to 5 months after delivery, in previously healthy women .This time limit is very important as an exclusion factor for other previously undiagnosed or preexisting types of cardiomyopathies, which can be unmasked by hemodynamic changes during pregnancy. Therefore, it is very important to have in mind the fact that a woman without a history of a heart disease can develop heart failure in the peripartum period.2 body surface area, have been included in the diagnosis of PPCM  is reported in Haiti , while i9 is repoPregnancy is a physiological state accompanied by maternal hemodynamic changes, during which time, signs and symptoms could mimic signs of heart failure. Awareness of these changes is of great importance for early recognition and timely management of PPCM, which correlate with better prognosis of these patients. Symptoms of PPCM, such as dyspnea, cough, fatigue, leg edema, malaise, are very often misinterpreted as physiological symptoms due to pregnancy. This is the reason of delayed recognition of PPCM, so at the moment of diagnosis patients are presented with NYHA III or IV functional class .The clinical course of PPCM can vary from mild to extremely severe heart failure and even cardiogenic shock, which can vitally jeopardize both the mother and the fetus. Progression to heart failure can be rapid, very often within few days from the first presentation of symptoms. Paroxysmal nocturnal dyspnea, nocturnal cough, hemoptysis, chest pain, and hepatomegaly should raise suspicion of heart failure . TachycaDespite numerous researches, the etiopathogenesis of PPCM is still unknown. There are many hypothesis including myocarditis , 20, genSince the cause of PPCM is unknown, there is still no specific treatment of this serious disease. Understanding of etiopathogenesis could represent a breakthrough in the treatment of PPCM. From that aspect, studies that investigated inflammation, prolactin, and oxidative stress as a possible cause of PPCM reported promising results.In a large prospective study, Sliwa et al. reported significantly higher levels of inflammatory markers – CRP, IL6, TNFα, and plasma marker of apoptosis (Fas/Apo-1) in patients with PPCM than in healthy controls , 24. TheIn contrast to these researches, other studies suggest that PPCM is a consequence of vascular disorders due to cleavage of PRL and increased oxidative stress.Hilfiker-Kleiner et al. have found that decreased levels of signal transducer and activator of transcription 3 (STAT3) in mice induce decreased activity of manganese superoxide dismutase (MnSOD) leading to increased oxidative stress. Reactive oxygen species (ROS) accumulation induces cathepsin D activation, which further cleaves nursing-hormone prolactin of 23 kDa (23 kDa PRL) into 16 kDa prolactin (16 kDa PRL), which was proved to have antiangiogenic and proapoptotic effects on cardiomyocytes . HalkeinFrom the clinical point of view, data from these studies may have an impact on the new treatment strategies of PPCM in the future.When considering PPCM, it is very important to have in mind the fact that a woman without a history of a heart disease can develop heart failure in the peripartum period. Thus, rising awareness of PPCM is very important for early diagnosis. Delayed diagnosis is followed by higher incidence of complications. When the diagnosis is made before LVEF decline below 0.35, the mortality rate approaches 0, and the chance of full recovery is much greater. Because of similarity in clinical presentation between PPCM and other types of systolic heart failure, the diagnosis of PPCM presents a major challenge. It is based on exclusion of other conditions that could cause heart failure: idiopathic dilated cardiomyopathy, myocardial infarction, severe preeclampsia, pulmonary embolism, sepsis, and valvular heart disease. Diagnostic criteria proposed by Demakis  and N-terminal portion of pro BNP (pro-NT BNP) are biomarkers sensitive for heart failure, but are not specific for PPCM. However, these markers in combination with echocardiography can be very useful for risk stratification and accuracy of diagnosis in patients with asymptomatic PPCM in cases when levels of BNP and pro-NT BNP are intermediate . SeveralBecause of the complexity of this disease, which can be fatal for both mother and the fetus, PPCM should be managed by multidisciplinary team. Patients admitted in the ICU require intensive treatment and hemodynamic monitoring.Monitoring before and 24 h after delivery is very important because it is the period of the most prominent hemodynamic changes. Understanding of physiological hemodynamic changes during pregnancy is of great importance for interpretation of hemodynamic parameters of PPCM. Auto transfusion due to uterine contractions and fluid shifts after delivery could alter the condition of patients with PPCM, augment the fluid load, and cause acute heart decomposition. PPCM presents with decreased cardiac output and increased right and left heart filling .The choice of monitoring devices depends on the severity of clinical presentation. Intra-arterial blood pressure should be measured in severe forms of PPCM followed by intense hypotension. Because of the risk of potential complications, central venous catheter and pulmonary artery catheter are not routinely used, except in cases of severe PPCM. However, in a patient with dyspnea at rest, severe chest pain, ECG evidence of myocardial ischemia, severe impairment of myocardial contractility, invasive monitoring with a Swan Gang catheter is justified . The useTran esophageal echocardiography (TEE) is rarely used in obstetrics, because it very often requires tracheal intubation and can be performed only by an experienced practitioner. However, some authors suggest it as a guide in management of refractory hypotension and cardiac arrest in obstetric patients , thus TTTran thoracic echocardiography (TTE) is crucial not only for diagnosis of PPCM but also for evaluation and monitoring of the effects of the therapy. It enables the intensives to get non-invasive serial evaluations of the heart function and structure at the bedside, without risk of complications. PPCM presents with decreased EF, systolic dysfunction, decreased LVFS, decreased cardiac output . TTE is The treatment of PPCM does not differ from that of other types of dilated cardiomyopathy, but the choice of medications depends on fetal safety during ante partum heart failure and on excretion of the drug during breastfeeding.In the cases of acute decompensate heart failure, the initial management is based on ABCs  . PatientAttention should be paid to the clinical assessment of decreased cardiac output and hypoperfusion rather than on the exact value of blood pressure, which must not always indicate hypotension . The treAngiotensin converting enzyme inhibitors (ACEI) efficiently reduce afterload, but due to their proven teratogenic effects they are contraindicated during pregnancy. In antenatal heart failure, vasodilatators such as hidralazine and nitroglycerin can be safely used instead of ACEI and ARB, but should be carefully titrated if systolic blood pressure is between 90 and 110 mm Hg . ACEI caSodium nitroprusside should be avoided because of thiocyanate toxicity. Loop diuretics reduce preload and fluid overload and relieve symptoms of PPCM, but should be used with caution because they can cause hypotension, uterine hypoperfusion and, consequently, fetal distress.Digoxin has positive inotropic effects and improves ejection fraction in combination with vasodilatators. It can be safely used during pregnancy and breastfeeding . In caseThe use of levosimendan in PPCM is still controversial. There are case reports about the successful use of levosimendan , 50, butBeta blockers are indicated in PPCM, and some authors suggest that they should be continued for at least 1 year . Beta-1 Uterotonics should be very carefully used in PPCM. Oxytocin decreases systemic vascular resistance, compensatory increases heart rate, and can cause coronary vasoconstriction, so is poorly tolerated in state of LV dysfunction. Therefore, it should be slowly titrated. Ergometrine causes coronary and pulmonary vasoconstriction, and should be avoided in PPCM . PostparArrhythmias are not rare in PPCM. Refractory life-threatening arrhythmias in patients with poor left ventricular function are indications for implantable cardioverter defibrilator . PatientData from researches related to the pathogenesis of PPCM were the basis for further investigations in the field of the treatment of PPCM.Pentoxifylline, an inhibitor of TNFα, was evaluated in patients with PPCM. Significantly higher levels of CRP, IL6, TNFα were reported in patients with PPCM than in healthy controls having suggested that inflammation could be a cause of PPCM ( of PPCM .Sliwa et al. have studied the effects of pentoxifylline on outcome in patients with PPCM  and founNew researches by Hilfiker-Kleiner et al. suggested that oxidative stress and the cleavage of PRL may play a central role in the pathogenesis of PPCM . Based oPeripartum cardiomyopathy is a rare and very severe disease. Symptoms of PPCM can mimic symptoms of a normal pregnancy, which is the most common reason of delayed diagnosis. Delayed diagnosis almost always leads to severe forms of PPCM. Thus, attention should be paid on early diagnosis and treatment, which are crucial for better outcome. We should always have in mind the fact that the woman without previous heart disease can develop heart failure. Therefore, increased awareness of PPCM as well as high level of suspicion are the most important steps in establishing the early diagnosis. Early symptoms such as dyspnea, fatigue, leg edema, and malaise, which are often misinterpreted as physiological, should not be underestimated. Paroxysmal nocturnal dyspnea, nocturnal cough, and chest pain should raise suspicion of heart failure. PPCM is the diagnosis of exclusion. TTE is crucial not only as a diagnostic tool but also as a bedside non-invasive hemodynamic monitoring device. Treatment of PPCM is basically the same as for other non-ischemic cardiomyopathy, with the limitation concerning fetal development and wellbeing. The task for future studies is to find the cause of PPCM, and the specific biomarker of this disease, which would significantly contribute to early diagnosis and specific treatment of PPCM. In that context, studies that investigate inflammation, prolactin, and oxidative stress give promising results.All aforementioned authors contributed significantly to the final design of manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


We present a patient with a congenital left ventricular aneurysm who visited our outpatient clinic for a routine check-up and, during this visit, lost consciousness due to sustained ventricular tachycardia. In our patient, endocardial mapping revealed extensive conduction abnormalities, and successful ablation was accomplished at the endocardial surface. A 19-year-old male individual with a surgically corrected congenital left ventricular aneurysm (LVA) in the basal posterior wall visited our outpatient clinic for a routine check-up. Surgical resection of the aneurysm was performed 10 years ago. LVA recurrence was discovered only 1 year after surgery. The left ventricle was dilated (end-diastolic diameter 70 mm), and the ejection fraction was decreased (36 %). During this visit, the patient lost consciousness due to sustained ventricular tachycardia (VT; left upper part of Fig. Congenital LVA is a rare congenital defect. It is defined as the presence of an akinetic or dyskinetic structure with a wide connection to the left ventricle, which is normal in size and function . ReportsIn a group of 108 patients with either LVA or diverticulum, who were followed during a median period of 50 months, VTs occurred in only ten patients  describeVentricular tachycardia after cardiac surgery for LVAs can be treated by endocardial catheter ablation at the endocardial surface of the left ventricle. Extensive local conduction abnormalities are recorded within the endocardial surface of the aneurysm which may form the substrate of the ventricular tachycardia.None.None declared.