It is not known whether abnormalities of left ventricular diastolic function are influenced by the various cardiac geometric patterns in Nigerians with newly diagnosed systemic hypertension.To evaluate the relationship between the parameters of left ventricular diastolic function and the geometric patterns in this group of patients.Two-dimensional, guided M-mode echocardiography including Doppler was performed in 150 consecutive, newly diagnosed hypertensive individuals and normotensive controls aged between 35 and 74 years. Left ventricular mass index and relative wall thickness were used to classify the hypertensive individuals into four geometric patterns, and the pulsed-wave Doppler parameters obtained were used to categorise the abnormalities of diastolic function.p < 0.001).Four left ventricular geometric patterns were identified: 23 (15.3%) had normal left ventricle geometry, 33 (22%) had concentric remodelling, 37 (24.7%) were found to have eccentric hypertrophy, and concentric hypertrophy occurred in 57 (38%) of the hypertensive individuals. Left ventricular diastolic dysfunction occurred more in hypertensives with concentric left ventricular geometric pattern. Increased left ventricular mass index and relative wall thickness were found to be associated with the mitral E-wave, E/A ratio and pulmonary venous flow S-wave in the hypertensives (In newly diagnosed Nigerian hypertensives, the abnormalities in left ventricular diastolic function varied between the different left ventricular geometric patterns, being worst in those with concentric geometry. Left ventricular hypertrophy (LVH) is a known complication of systemic hypertension (SH) and has long been recognised as an independent risk factor for adverse outcomes in individuals with systemic hypertension.Left ventricular diastolic function has been well documented in Caucasians with SH complicated with LVH.The study involved 150 consecutive, newly diagnosed adult Nigerians with SH aged between 35 and 74 years . They were seen at the cardiology clinic of the University of Ilorin Teaching Hospital. Their blood pressure (BP) was measured with a mercury (Accoson’s) sphygmomanometer in the sitting position in the consulting room after 10 minutes of rest, according to standard guidelines.One hundred and fifty age- and gender-matched healthy normotensive (BP < 140/90 mmHg) controls were recruited from individuals on routine medical check-up, patients’ relatives and the hospital staff. Excluded from this group were individuals with a history of diabetes mellitus, congestive cardiac failure, chronic renal failure, coronary artery disease, thyrotoxicosis, moderate to severe obesity and chronic alcohol abuse. Pregnant women and patients with atrial fibrillation were also excluded. The study protocol was approved by the ethical review committee and written informed consent was obtained from all those who participated in the study.All the 300 subjects  underwent transthoracic two-dimensional guided Mmode and Doppler echocardiography. The echocardiograms were obtained with a commercially available cardiac ultrasound machine  equipped with a 2.5-MHz transducer in the parasternal and apical views with the subjects in the left lateral decubitus position. LV measurements were obtained at end-diastole and end-systole, according to the American society of echocardiography (ASE) recommendations.LV mass was achieved using the modified Devereux formula:83 – LVDd3] + 0.6.LV mass (ASE) = 0.8 [1.04 (IVSd + PWd + LVDd)2 in men and more than 110 g/m2 in women.8LV mass was indexed to body surface area to obtain LVMI.Accordingly, the combinations of LVMI and RWT values were used to define four LV geometric patterns as follows; normal geometry, composed of both normal LVMI and RWT; concentric remodelling: increased RWT but normal LVMI; eccentric hypertrophy: increased LVMI and normal RWT; and the increase in both variables in identified hypertensive individuals with concentric LVH.11LV diastolic function was evaluated by pulsed-wave Doppler recordings of both the transmitral inflow and pulmonary venous flow velocities in the apical four-chamber view.The variables measured include the early filling (E-wave) and late (A-wave) diastolic peak filling velocities. From these, the E-wave to A-wave (E/A ratio) velocity was calculated. The Valsalva manoeuvre was performed where applicable. The mitral deceleration time (DT) was measured as the time interval from the peak to the end of the E-wave. Isovolumic relaxation time (IVRT) was measured as the interval between the aortic valve closure click to the beginning of the transmitral inflow with the simultaneous visualisation of the aortic and mitral flows.13The pulmonary venous velocity was recorded by placing the cursor 1 to 2 cm into the right upper pulmonary vein, close to the interatrial septum. In difficult cases this was achieved with the guidance of colour Doppler. The peak systolic (S-wave) and diastolic (D-wave) forward velocities and the peak atrial reversal (Ar) wave velocity were recorded, and the ratio of S/D was calculated. Where the pulmonary S-wave was biphasic, the higher peak velocity was used. LV diastolic dysfunction was categorised according to its clinical severity into normal, impaired relaxation, pseudonormal and the restrictive pattern.14t-test and comparisons between the different LV geometric patterns were done with analysis of variance (ANOVA). Scheffé’s test was used for post hoc analyses. The Pearson correlation was used to evaluate the relationship between two parameters. Linear regression analysis using an enter method was applied to determine the effects of cardiac parameters  as determinants of parameters of LV diastolic function. A two-tailed value of p < 0.05 was considered significant.Data analysis was performed with SPSS software . Continuous variables were expressed as mean ± SD and categorical variables as percentages. Comparison between the means of independent samples was performed with the Student’s p > 0.896) p < 0.001). The two groups were, however, comparable in the mean values for age, body mass index and heart rate. The demographic and echocardiographic characteristics of the different geometric patterns in patients are shown in A total of 300 subjects were involved in the study; 150 were patients with SH and 150 were age- and gender-matched normotensive controls. They were aged between 35 and 74 years, with a mean age of 52.74 ± 9.8 for the patients, compared to 52.59 ± 9.6 for the control group (p < 0.001). It varied within the subgroups, being higher in patients with concentric geometry than in those with eccentric geometry. The RWT also increased significantly (p < 0.001) in subjects with concentric geometry and concentric remodelling compared with the controls. Patients with the four geometric patterns and the normotensive controls were similar regarding the fractional shortening (p = 0.445) and ejection fraction (p = 0.365).LVMI was increased in the patient subgroups with concentric and eccentric geometry compared to the controls (p < 0.001). The mean S-wave (p < 0.009) and S/D ratio (p < 0.003) also differed significantly between the study groups. No statistically significant difference was observed between the subgroups with regard to the mean A-wave (p = 0.852) and the mean Ar wave (p = 0.483). In a subgroup analysis, the E-wave, E/A ratio and IVRT differed significantly between those with concentric geometry and the controls (p < 0.001).In the patients with SH, 85% showed an altered geometry pattern: 22% with concentric remodelling, 25% with eccentric hypertrophy and 38% with concentric hypertrophy. None of the controls showed severe forms of altered geometry or abnormal LV diastolic function. The patients with concentric LVH had the highest incidence of diastolic dysfunction, with 56.1% of them having impaired relaxation, the pseudonomal pattern occurred in 3.5%, and only 1.8% had the restrictive pattern. None of the patients with a normal geometry pattern demonstrated the restrictive pattern.p < 0.001), LVMI (p < 0.001) and relative wall thickness (p < 0.01). There was no significant correlation between the A-wave and the above independent variables (p > 0.05). Also, IVRT did not relate to LVMI (p = 0.331), PWd (p = 0.639) and RWT (p = 0.547). The S-wave and the S/D ratio correlated negatively with LVMI . Multiple regression analysis 2 = 0.134; p < 0.001 between the E-wave, pulmonary venous S-wave and E/A ratio and the LVMI and RWT.Correlation coefficients were calculated between some of the LV diastolic function parameters as dependent variables and LVMI, RWT and posterior wall thickness as independent variables after accounting for the confounding factors age, gender, blood pressure and heart rate The purpose of this study was to evaluate LV diastolic function with a view to highlighting its association with the different geometric patterns in Nigerians with newly diagnosed SH. Our results showed that the LV diastolic function, as reflected by the combinations of transmitral and pulmonary venous flow velocities, was common in newly diagnosed and untreated SH patients compared with normotensive controls. Secondly, concentric hypertrophy was the commonest pattern of LVH and also demonstrated the greatest proportion of LV diastolic dysfunction. Thirdly, the LVDF abnormalities were related to cardiac structural changes.et al.et al.et al.2The combined use of LVMI and RWT enabled the distinction of four geometric patterns. Ganau It has been suggested that the increase in LVMI in Caucasians is related to the presence of coronary artery disease and tends to compensate for the loss of contractile elements. In SH patients, concentric LVH predominates to compensate for the pressure overload, thereby preserving systolic function. In addition to environmental and genetic factors, it appears that eccentric LVH, being a powerful coronary artery disease risk factor, may have been present even before the ischaemic event.et al.,Previous studies in Caucasians have reported the relationship between LV geometric patterns and LV diastolic function.et al. found the E/A ratio to be lower in patients with concentric LV geometry. This was attributed to a higher late transmitral gradient, the hallmark of greater left atrial ejection force.et al.In an echocardiographic study of a large sample of patients with SH, Cloffi The study enrolled only hypertensive individuals with mild obesity to minimise the contribution of more severe forms of obesity to LVH. This would have eliminated hypertensive individuals with greater LVM and consequent LVDD. Although CAD is not very common in patients in our environment and was excluded using only clinical examination and electrocardiography, the use of treadmill exercise electrocardiography and coronary angiography would have helped to conclusively exclude CAD. It is also possible that the so-called newly diagnosed hypertensive individuals might have been previously diagnosed but were not compliant with taking their medication.This study has shown that LV diastolic dysfunction, which is an important cause of morbidity in SH patients, differed between the four LV geometric patterns. Concentric LVH was the predominant pattern in Nigerians with SH. Also, LVMI and RWT were associated with low E/A ratios and the Ar velocity of pulmonary venous flow.


Objective: Cardiac failure due to iron overload remains the most common cause of death in patients with beta-thalassemia major. This study aimed to evaluate myocardial function in children with beta-thalassemia major using standard echocardiography technique and strain rate imaging.Materials and Methods: Conventional echocardiographic analysis, tissue velocity imaging, and strain/strain rate imaging of the left ventricle were evaluated in 48 children with beta-thalassemia major  and 22 healthy children . Results: Conventional echocardiographic examinations revealed that beta-thalassemia patients had larger left ventricular end-systolic diameter, end-diastolic and end-systolic volume, left ventricular mass index, and mitral early/late diastolic flow velocity ratio (p<0.05). Strain and strain rate imaging study of the basal lateral wall of the left ventricle was higher in patients than in controls, at p=0.035 and p=0.008, respectively. Conclusion: We found that superior systolic strain and strain rate imaging of the left ventricle indicated the presence of regional systolic function in the left ventricular wall. We suggest that left ventricle volume and mass index parameters might be more sensitive than the other conventional and strain/strain rate imaging parameters during childhood. However, the adulthood strain and strain rate imaging values may be lower than controls, exceeding the critical level of iron overload.Conflict of interest:None declared. Cardiac failure due to iron overload remains the most common cause of death in patients with beta-thalassemia major, accounting for up to 71% of all deaths from this disease . CardiacA number of cardiological parameters of left ventricular (LV) function have therefore been assessed to determine their efficacy in identifying early myocardial iron overload in order to prevent heart failure and avert its poor prognosis through increased chelation therapy. The stored iron in the heart is heterogeneous. Regional myocardial asynchrony characterizes diastolic abnormalities even in the absence of changes in systolic functions reported in thalassemia patients and, thus, LV diastolic function may be more sensitive as an early marker of myocardial iron overload. A number of techniques used in clinical practice have been utilized to assess diastolic function in thalassemia major ,4,5.Strain rate imaging (SRI) is a new noninvasive echocardiographic method for the analysis of local myocardial stress. SRI is potentially superior to tissue Doppler imaging (TDI) in regional myocardial function assessment ,7,8. ThiPatient Population Two distinct groups were studied. The patient group comprised 48 beta-thalassemia major patients . Thalassemia major patients were selected from cases in follow-up in the Gaziantep University Pediatric Hematology Department and Gaziantep Children’s Hospital. The diagnosis of thalassemia was based on hemogram, blood smear, hemoglobin electrophoresis, and clinical evaluation. All patients were under chelation therapy with an oral iron chelator  or a parenteral iron chelator . Serum ferritin levels were noted as ng/mL. Inclusion criteria were diagnosis of beta-thalassemia major, normal renal function, normal left ventricular functions, normal estimated pulmonary pressures by echocardiographic Doppler evaluation, and absence of congenital or acquired structural heart or lung diseases. All thalassemia patients had asymptomatic heart failure and were in New York Heart Association functional class I. They had been receiving blood transfusions since the age of 6 months to 2 years. Twenty-three (47.9%) of the patients had been splenectomized. Severity of iron overload was defined by serum ferritin level. Twenty-two healthy children  without history of cardiac disease were included in the study as a control group. All children were in normal sinus rhythm and had normal resting 12-lead electrocardiographs. All studies were performed in accordance with the rules of the local ethics committee. Informed consent was obtained from all participants prior to the study.EchocardiographyConventional echocardiography  and strain and strain rate imaging were performed by the same experienced pediatric cardiologist. Echocardiographic images were obtained in the parasternal long-axis and short-axis, and apical 2-chamber and 4-chamber views were obtained with standard transducer positions. Conventional echocardiographic measurements were done according to the American Society of Echocardiography guidelines . Left veDigital data of color TDI were transferred for off-line analysis with EchoPAC-PC software (GE Vingmed Ultrasound). Scanning was performed longitudinally from the apex to acquire apical 2-chamber and 4-chamber views with a 3-MHz transducer and a frame rate of 100 ± 20 frames/s, depending on the heart rate, to minimize the noise level. Myocardial velocities were measured for the local motion of a tissue by TVI and S, and the local rates of deformations were measured by SRI. Longitudinal strain and strain rate in the basal septal, basal lateral, mid-septal, and mid-lateral wall were estimated by measuring the spatial velocity gradient over a computational area of 3 mm × 5 mm. Tissue velocity, strain, and strain rate were obtained at each site from 3 consecutive b eats and average values were calculated. End-diastole was defined as the R peak in echocardiography, and end-systole was defined as the end of the T wave in echocardiography. Peak positive systolic values were calculated from the extracted curve. From the 4-chamber view, the TVI sample volume was located sequentially at septal and lateral sites of the valvular ring. Mean values of early diastolic, late diastolic, and systolic myocardial velocities were calculated as cm/s.Statistical AnalysisStatistical analysis was performed using SPSS 11.0 . All data were expressed as mean ± standard derivation. Comparison of measurements between 2 groups was analyzed with the unpaired Student t-test. Correlation coefficients between various measurements were determined by the linear regression analysis. A p value of less than 0.05 was considered significantly different. The demographic characteristics of the patients with beta-thalassemia major and the control group are presented in In the TVI technique, left ventricle lateral late diastolic myocardial velocity was lower in beta-thalassemia patients compared to the control group, and the lateral early-to-late diastolic myocardial velocity ratio was higher in beta-thalassemia patients compared to the control group . Strain Pearson’s correlation coefficient showed significant correlations between the serum ferritin levels and the following echocardiographic variables: LV end-diastolic volumes , LV end-systolic volumes , EDV , EF , FS , E , septal early TVI , and lateral systolic TVI . The most common cause of morbidity and mortality in thalassemia major patients is cardiomyopathy due to iron overload. Heart disease is mainly expressed by a particular cardiomyopathy that progressively leads to heart failure and death ,2,11. IrSince cardiac function remains normal until late stages in the spectrum of iron cardiomyopathy, other tools are necessary to anticipate and prevent iron cardiomyopathy. Cardiac magnetic resonance imaging, tissue Doppler echocardiography, radionuclide angiography, and stress echocardiography are useful imaging studies for the detection of early cardiac dysfunction. Recently, tissue Doppler echocardiography and radionuclide angiography (with exercise or low-dose dobutamine stimulation) have been shown to detect regional wall motion abnormality, even in early-stage thalassemic patients . This fiFitchett et al. demonstrated the deposition of iron within the myocytes rather than the interstitium, and this cardiac iron deposition was patchy . LattanzThe novel contribution of our study is the demonstration of the superiority of SI over the conventional echocardiographic parameters, LVEF and LVFS, in the detection of regional myocardial function. Our patients had superior systolic S and SRI of the LV lateral wall, indicating the presence of regional systolic function in the left ventricular wall. We suggest that LV volume and mass index parameters might be more sensitive than the other conventional and S/SRI echocardiographic parameters. However, adulthood S/SRI sensitivity may be lower than in the controls.Regular clinical follow-up is strongly recommended for precocious detection of symptoms and signs of myocardial dysfunction . On the Previous studies have shown that beta-thalassemia major is frequently associated with progressive LV dysfunction, leading to congestive heart failure. LV diastolic function, measured by traditional measurements such as transmitral flow recordings, is preserved until the final stages of diseases ,17,18. CIn our patients, chronic iron overload resulted in significant increase in serum ferritin and significantly increased LVMI. However, EF and FS were not altered significantly in patients compared with controls, suggesting preserved systolic functioning until late stages of the disease. This finding is consistent with those of Parale et al. and Seliem et al. ,19.Magri et al. suggested TDI and strain imaging as a potential method for detecting early stages of abnormal iron deposition . OlivierS/SRI offers a new way of measuring regional tissue deformation noninvasively with both good spatial and temporal resolution. Authors have demonstrated it to be a tool that would appear to offer reproducible and reliable data . Our finThis study demonstrates the ability of S/SRI to accurately depict regional myocardial function in asymptomatic beta-thalassemia patients with normal systolic and diastolic function. LV dilatation or increased LVMI was balanced with increased basal segment S/SRI measurements. During this period, increased LV dilatation may progress to lower S/SRI values and to LV diastolic and systolic function disorders. Until the critical level of iron overload, peak systolic strain and SRI may accurately reflect local systolic function, and we may say that iron overload is not related to a specific area of LV myocardium and that cardiac changes are possibly related to a threshold level of iron overload. While serum ferritin levels remain above 2500 µg/L, echocardiographic measurements such as basal TVI, S, and SRI parameters might show compensatory increase although LV dilatation starts with normal systolic function. This compensation would probably be inadequate at greater ferritin levels and systolic and diastolic functions would globally decrease eventually. Therefore, clinical manifestations usually occur in adulthood rather than childhood. According to the Frank-Starling law, if heart volume increases, this compensation might be inadequate, and these parameters worsen through adulthood. Accurate assessments of cardiac dysfunction and cardiac iron status are currently based on imaging techniques. The T2-star magnetic resonance is currently the best noninvasive modality to estimate iron in the heart and other organs . In addiOne of the limitations of our study is that we could not compare the patients within every ferritin level. In asymptomatic patients, normal systolic and diastolic functions might be related to good LV compensation. Strengthening the chelation treatment in this period may normalize these measurements. Even when LVEF and LVFS are normal, increased LV mass and volume may be seen. In this study we found compensatory increase in S and SRI measurements, and these parameters would probably worsen first to be followed by cardiac failure appearing due to decreased LVEF and LVFS.The authors of this paper have no conflicts of interest, including specific financial interests, relationships, and/ or affiliations relevant to the subject matter or materials included.


Endothelial progenitor cells (EPCs) are responsible for angiogenesis and maintenance of microvascular integrity, the number of EPCs is correlated with oxidative stress. Their relation to myocardial dysfunction in patients with type 2 diabetes mellitus (T2DM) is nonetheless unknown.Eighty-seven patients with T2DM and no history of coronary artery disease were recruited. Transthoracic echocardiography and detailed evaluation of left ventricular (LV) systolic function by 2-dimensional (2D) speckle tracking derived strain analysis in 3 orthogonal directions was performed. Four subpopulations of EPCs, including CD34+, CD133+, CD34+/kinase insert domain-containing receptor (KDR) + and CD133+/KDR + EPCs, were measured by flow cytometry. Oxidative stress was assessed by superoxide dismutase (SOD).The mean age of the patients was 62 ± 9 years and 39.6% were male. Those with an impaired longitudinal strain had a lower number of CD34+ EPCs  than those with preserved longitudinal strain. When compared with those with preserved circumferential strain, patients with an impaired circumferential strain had a lower number of CD34+ EPCs  and SOD level . Patients with an impaired radial strain nonetheless had a lower number of CD34+ EPCs . Multivariate analysis demonstrated that only impaired global circumferential strain remained significantly associated with CD34 + EPCs and SOD.LV global circumferential strain was independently associated with number of CD34+ EPCs and SOD. These findings suggest that myocardial dysfunction in patients with T2DM is related to depletion of EPCs and increased oxidative stress. Type 2 diabetes mellitus (T2DM) is associated with myocardial dysfunction, independent of underlying coronary artery disease. Patients with T2DM have a 2–5 fold higher risk of developing heart failure than those without,2. AlthoIncreasing evidence is emerging to support the role of endothelial progenitor cells(EPCs), a subpopA total of 110 consecutive patients with T2DM as defined by World Health Organization criteria and no coronary artery disease were recruited at Queen Mary Hospital from January 2008 to January 2010. Patients were excluded if they had a documented history or clinical symptoms and signs of macrovascular disease including myocardial infarction, coronary artery disease, stroke or peripheral vascular disease. Patients with dilated cardiomyopathy, New York Heart Association class III/IV heart failure, significant renal dysfunction with creatinine level > 220 umol/L, liver failure or clinical/biochemical evidence of concomitant inflammatory disease or patients who declined to participate were also excluded. As a result, 87 subjects were eligible for this study. The current study is in compliance with the Helsinki Declaration and has been approved by the Hong Kong West Cluster Ethics Committee. All patients had a written informed consent.2. Fasting blood samples were obtained to measure serum total cholesterol, triglyceride, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), glucose, HbA1c, creatinine, and high sensitivity C-reactive protein (hs-CRP).Baseline demographic data and cardiovascular medications were recorded in all subjects. Hypertension was defined as resting systolic or diastolic blood pressure ≥140 /90 mmHg on two occasions or the prescription of anti-hypertensive medication. Hypercholesterolemia was defined as fasting total plasma cholesterol level ≥4.9 mmol/L or the prescription of lipid-lowering medication. SmokingAfter mixing, samples were centrifuged at 3000 rpm for 20 minutes and the supernatants frozen at −80°C until assay. Oxidative stress was measured as superoxide dismutase (SOD), a potent antioxidant enzyme.Four subpopulations of EPCs, including CD34+, CD133+, CD34+/kinase insert domain-containing receptor (KDR) + and CD133+/KDR + EPCs, were measured by flow cytometry. Fluorescence-activated cell analysis was performed to determine the number of EPCs as described previously. BrieflyTransthoracic echocardiography was performed in all patients using a commercially available system . A 3.5-MHz transducer was used to obtain images that were digitally stored in cine-loop format (5 cardiac cycles). Measurements were performed offline using EchoPAC version 108.1.5 . The inter-ventricular septum thickness, posterior wall thickness, and LV dimensions were measured in M-modal according to the current recommendation. LV volume and ejection fraction was determined from apical four and two-chamber views using the modified Simpson’s biplane method of discs. Evaluation of LV diastolic function was based on the pulsed-wave Doppler of mitral valve inflow. Peak velocity in early diastole (E-wave) and late diastole (A-wave) was measured and the E/A ratio calculated. Pulsed wave tissue Doppler imaging was used to measure the early diastolic velocity (E’) with the sample volume placed at lateral annulus. In addition, E/E’ ratio was calculated as an estimation of LV filling pressure. LV diasTwo-dimensional speckle tracking strain analysis allows detailed assessment of LV myocardial deformation by tracking natural acoustic markers (speckles) in a frame-to-frame basis within the cardiac cycle. LV deformation can be evaluated in three orthogonal directions as longitudinal, circumferential and radial strains.Longitudinal strain, assessing the shortening/lengthening of the myocardial wall, was measured from the 3 apical views: 2-chamber view , 4-chamber view  and long axis view . Each wall was subsequently divided into 3 levels  and a total of 18 segmental strain curves were obtained. Global longitudinal strain was calculated as the mean of the peak systolic strain value of the 18 segments.From LV mid-ventricular short-axis view, both circumferential strain  and radial strain  were measured. The global value of circumferential and radial strains were derived from the average peak systolic strain value of 6 segments. Global longitudinal and circumferential strains are expressed as negative values, and a lower strain is represented by less negative values. Global radial strain is expressed as a positive value: a lower value indicates lower strain.Impairment of the 3-orthogonal directional global strains was defined as mean ± 2 standard deviations according to the results of a recent study that assessed global strains in healthy Asian subjects using the same vendor machine as the current study. Thus inThe interobserver and intraobserver variability for longitudinal, radial, and circumferential strains were 6.5% and 2.6%, 10.4% and 7.6%, 4.9% and 2.4%, respectively.U test and categorical demographic variables were compared using Pearson Chi-square test or the Fisher’s exact test if at least one cell had an expected cell count below five. Correlation coefficients were performed in order to assess the association of circulating EPCs and oxidative stress with myocardial function in T2DM patients. Multivariate analyses were performed to detect the predictors for abnormal myocardial function. To avoid multi-collinearity, multi-directional strains were entered individually into the model. All statistical analyses were performed using the statistical package SPSS for windows . All P values reported are 2-sided for consistency. A P value <0.05 was considered statistically significant.All continuous variables and categorical variables are expressed as mean ± standard deviation and frequencies or proportions, respectively. Continuous demographic variables were compared using the Mann–Whitney The baseline characteristics of all patients are shown in TableThe clinical demographics of patients with and without impaired LV strain are shown in TableP < 0.01). Nonetheless CD133+ , CD34+/KDR +  and CD133+/KDR + EPCs  showed no such correlation.The correlation between the 3 orthogonal directional strains and clinical demographics is shown in TableUnivariate analysis revealed that impaired circumferential and radial strains were associated with CD34+ EPC level and impaired global longitudinal, circumferential and radial strains were related to SOD (TableThe present study demonstrated that at least 30% of T2DM patients, with apparently normal LV dimensions and ejection fraction, have impaired myocardial function as measured by 2D speckle tracking derived strain. Importantly, LV global circumferential strain was independently associated with depletion of CD34+ EPCs and increased oxidative stress measured by SOD.The pathogenesis of myocardial dysfunction is multifaceted, but includes activation of renin-angiotensin aldosterone system, myocardiDiI labelled bone marrow derived EPCs contributed to myocardial microvasculature and function in rats with diabetic heart disease[The presence of diabetes induces thickening of the capillary basement membrane and endothelial swelling of the myocardium,27. Thes disease. No studThe present results indicate that CD34+ EPCs were most strongly correlated with myocardial dysfunction, compared with other subtypes of EPCs. Although the reason is uncertain, this could be partly explained by the ability of CD34+ EPCs to differentiate not only into hematopoietic stem cells, but also cardiomyocytes, smooth muscle and endothelial cells. PreviouOxidative stress, represented by an overproduction of reactive oxygen species, plays a role in all stages of diabetic heart disease, ranging from cardiac hypertrophy to myocardial fibrosis and dysfunction. Animal The present study is the first to demonstrate that impaired myocardial function in patients with T2DM is independently associated with depletion of EPCs and increased oxidative stress. In animal studies, therapeutic interventions aimed at increasing EPCs and reducing oxidative stress improved myocardial function. Future A causal relationship between CD34+ EPCs, SOD and impaired myocardial strain could not be established because of the cross-sectional nature of the study. Further, although patients with T2DM were all clinically free of cardiovascular complications, the presence of asymptomatic coronary artery disease could not be excluded. The small study population did not allow additional analysis of other mechanisms that could potentially contribute to myocardial dysfunction. In addition, the reason for the correlation of CD34+ EPCs and SOD with only global circumferential strain, not longitudinal and radial strains, is uncertain. The LV myocardial fibre architecture has a typical orientation of myocardial strands that change from being oblique in the subepicardium, to circumferential in the middle, and longitudinal in the subendocardium. Thus, wPatients with T2DM and no clinical evidence of macrovascular disease showed impaired myocardial strain detected by 2D speckle tracking derived strain analysis. Importantly, LV global circumferential strain was independently associated with both CD34+ EPCs and SOD. These findings suggest that myocardial dysfunction in patients with T2DM is related to depletion of EPCs and increased oxidative stress.2D: 2-dimensional; BMI: Body-mass index; EPCs: Endothelial progenitor cells; HDL-C: High-density lipoprotein-cholesterol; hs-CRP: High sensitivity C-reactive protein; LDL-C: Low-density lipoprotein-cholesterol; LV: Left ventricular; SOD: Superoxide dismutase; T2DM: Type 2 diabetes mellitus.The authors declare that there is no competing interest associated with this manuscript.CTZ coordinated analyses, interpreted results and wrote the manuscript. MW performed statistical analyses and revised the manuscript. CWS advised and supervised statistical analyses and revised the manuscript. YLH and TW were involved in the conception and design of the study, interpretation of the data, ongoing support and advice to the first author. KHY contributed to study design, data interpretation and manuscript revision. HFT designed and led the project and revised the manuscript. All authors have approved the final version of the manuscript.


Increased xanthine oxidase (XO) activity may contribute to heart failure pathophysiology. This study evaluated whether a XO inhibitor, allopurinol produces clinical and functional benefits in patients with New York Heart Association functional class III to IV heart failure due to systolic dysfunction receiving optimal medical therapy as estimated by global left myocardial function.Fifty-nine patients with a diagnosis of chronic heart failure due to coronary heart disease or idiopathic dilated cardiomyopathy and 20 healthy controls who attended the outpatient clinic of cardiology were subjected to full echocardiographic study including left ventricular diastolic and systolic function, and the combined index of myocardial performance [Tei index: isovolumetric relaxation time (IRT) + isovolumetric contraction time (ICT)/ejection time (ET)]. Patients were randomized to allopurinol (300 mg/day) or placebo. Improvement at 36 weeks was assessed using a composite end point comprising global left cardiac function as well as heart failure morbidity and mortality.P = 0.001). In a subgroup analysis, patients with elevated SUA (more than 7mg/ dL) responded favorably to allopurinol whereas those with SUA less than 7mg/dL exhibited a trend toward no change. In addition, SUA reduction to allopurinol correlated with favorable clinical and functional response. Within the entire allopurinol patient cohort, those characterized as either improved or unchanged had significantly greater reductions in SUA compared with patients who did not change (P = 0.0007). In placebo patients, lower baseline SUA, but not change in SUA, correlated with improved clinical outcome.The percentage of patients characterized as improved, unchanged, or worsened did not differ between those receiving allopurinol or placebo. Allopurinol reduced serum uric acid (SUA) by 1.5 mg/dL (Allopurinol did not produce significant clinical and functional improvement in unselected patients with moderate-to-severe heart failure. However, it is suggested that it is useful in patients with elevated SUA in a manner according to degree of SUA reduction. SUA may serve as a valuable biomarker to target heart failure therapy. Most epidemiological studies associate increasing serum uric acid (SUA) with increased cardiovascular event rate and mortality in those with known or elevated risk of vascular disease and among healthy volunteers. These data have been thoroughly reviewed in many studies. There iset al.[Mellinet al. report tEchocardiography has introduced the possibility to evaluate not only systolic, but also diastolic function. LV systolic dysfunction reduces ejection fraction and ejection time, and prolongs isovolumetric contraction time. On the other hand, LV diastolic dysfunction increases isovolumetric relaxation time (IRT) and modifies the timing of diastolic filling. A relatively new Doppler index of combined systolic and diastolic myocardial performance of the left ventricle, defined as the sum of the isovolumetric contraction time and IRT divided by ejection time, has been reported.5This index is easily obtained, reproducible, has a narrow range in normal subjects, does not depend on LV geometry, and correlates with invasive obtained measures of systolic and diastolic cardiac function. This indThis study not only raises an interesting suggestion regarding the role of oxidative stress in heart failure, but also offers a new pharmacological tool for a novel class of heart failure therapeutics: the XO inhibitors. This is by the use of a relatively new sensitive Doppler index of combined systolic and diastolic myocardial performance of the left ventricle.Fifty-nine patients with a diagnosis of CHF due to coronary heart disease or idiopathic dilated cardiomyopathy and 20 healthy controls who attended the outpatient clinic of cardiology were subjected to full echocardiographic study including LV diastolic and systolic function, and the combined index of myocardial performance (Tei index = IRT + ICT/ET). PatientsE/A ratio , by analysis of trans-mitral (L) flow for the assessment of diastolic function.Patients were subjected to M-mode and two-dimensional (2D) echocardiography with spectral and color flow Doppler analysis using a Hewlett-Packard  ultrasound machine with a 2.5/3.5-MHz transducer. Patients were examined in left lateral decubitus position. In this study, the following parameters were considered: left ventricular end-diastolic (LVDD) and end-systolic (LVSD) left ventricular diameters; end-diastolic (RVDD) and end-systolic (RVSD) right ventricular diameters, interventricular-septal wall (SWT) and posterior left ventricular wall (PWT) thickness (mm). The systolic function was assessed by the ejection fraction of the left ventricle (EF) in percentage calculated using the area–length method. Diastolic function was evaluated by LVM = 1.04 × LVEDD + LVEDSEP + LVEDPW−LVEDD3−13.6.Left ventricular mass (LVM) was calculated with the application of Devereux’s formula: LVM = 1.The IRT was measured with the pulsed wave sample volume placed between the mitral inflow and the LV outflow tract. The total isovolumic ejection index (Tei index) was obtaForty control subjects were studied. They were healthy volunteers. The same procedures for the echocardiographic examinations were applied.t-test for independent means. Two-tailed values of P < 0.05 were considered significant.Data are expressed as mean ± SE. The statistical significance of the differences between the groups was calculated using Student’s Informed consent was obtained from all the adults. The aim and the value of the work were explained in a simplified manner for them. There was no harm inflicted on them. On the contrary, all had benefits of the follow-up and the final results of the study.P = 0.001). In a subgroup analysis, patients with elevated SUA (more than 7mg/dL) responded favorably to allopurinol whereas those with SUA less than 7 mg/dL exhibited a trend toward no change. Within the entire allopurinol patient cohort, those characterized as either improved or unchanged had significantly greater reductions in SUA compared with patients who did not change. In placebo patients, lower baseline SUA, but not change in SUA, correlated with improved clinical outcome.The percentage of patients characterized as improved, unchanged, or worsened did not differ between those receiving allopurinol or placebo. Allopurinol reduced SUA by 1.5 mg/dL  are shown in Chronic heart failure is characterized by a progressive LV remodeling11 and deOxygen free radical generation has been proposed to be an important mechanism of cellular injury in ischemic and reperfused tissues. Studies in a variety of tissues, including heart, lung, kidney, and brain, have demonstrated that intravascular administration of antioxidant enzymes or free radical-scavenging drugs can prevent reperfusion damage and improve postischemic function.Although several mechanisms have been demonstrated to be involved in the generation of oxygen free radicals, XO has been proposed to be a central mechanism in a variety of postischemic cells and tissues. AlthoughIn patients with idiopathic dilated cardiomyopathy, intracoronary administration of allopurinol resulted in an acute, significant improvement in myocardial efficiency by diminishing oxygen consumption in the presence of standard supportive therapy. CHF alsoSome studies have shown that short-term administration of allopurinol improves myocardial efficiency in patients with idiopathic dilated cardiomyopathy by decreasing the oxygen cost of LV contraction. However,In agreement with this, a recent study who demonstrated that oxypurinol did not improve a clinical composite score in patients with systolic, symptomatic heart failure, and could potentially cause harm to some patients. Subgroup analysis supports the concept that patients with these clinical characteristics and a high SUA may benefit from XO inhibition. Moreover, the degree of SUA reduction correlated with clinical outcome, such that patients who worsened despite oxypurinol therapy had relatively less reduction in uric acid. Measurements of uric acid may aid in individualizing therapy with XO inhibitors.There are several reasons why oxypurinol may not have led to clinical benefits in the broad population of symptomatic, treated patients. First, it is possible that sources of oxidative stress are already inhibited by other medications such as inhibitors of the rennin–angiotensin–aldosterone pathway or carvedilol. In this regard, angiotensin II can activate XO directly and indiHowever, more larger studies are needed as XO inhibitor therapy in myocardial infarction and CHF appear appealing possibility for various reasons. First, there is evidence that increased levels of uric acid strongly correlate with mortality rates in congestive heart failure, and XO i


As recently shown, non-invasive late gadolinium contrast enhanced MRI (LGE-CMR) is able to detect myocardial infarction (MI) typical patterns in patients after heart transplant (HTX). Patho-physiologically, the underlying reason is an accelerated vascular immuno-atherosclerosis, the so-called transplant coronary artery disease (TCAD) which limits long-term survival of HTX pts. To date, there is only scarce data on the detection of early infarctions after HTX, the time course and the effects on myocardial function.We hypothesized that LGE-CMR could detect TCAD-related MI in pts already early after the HTX procedure.123 patients (pts) were divided into group I  and group II . LGE-CMR (Gadolinium:0.2mmol/kg bw) was performed on a 1.5T Whole Body MRI scanner  and analysed blindly by two experienced observers. For anatomic LGE description, hearts were divided according to the 17-segment model. Areas of infarct-typical LGE patterns were defined as sub-endocardial LGE patterns of various transmurality and were quantified by delineation of hyper-enhanced areas related to the myocardial mass on LGE images (relative infarct size). Groups were compared using ANOVA. P-values ≤ 0.05 were considered statistically significant.In group I, already 21% of patients and 18 of 1054 segments (1.7%) showed infarct-typical LGE patterns. In contrast, significantly more patients (33%) of group II and 34 of 1037  segments were affected . These findings could have potential impact on a modified HTX patient risk stratification including LGE-CMR for tissue characterisation and detection of unknown MI.None.


Non ST-segment acute coronary syndromes (NSTE-ACS) comprise 70% of all ACS. Difficulty in recognizing which patients have myocardium at risk contributes to heterogeneity in NSTE-ACS management, leading to poor outcomes compared to ST-elevation myocardial infarction (STEMI). To date, lack of suitable animal models has impeded progress in optimizing care. We developed a novel canine model to mimic NSTE-ACS, and evaluated ex vivo myocardial characteristics in the context of in vivo T2-CMR that may identify at-risk and salvageable regions.Five mongrel dogs underwent thoracotomy to create a left circumflex coronary artery stenosis without complete occlusion and to place epicardial pacing electrodes, and two dogs underwent sham thoracotomy. Pacing the animals with circumflex stenosis produced ST depression that resolved upon termination of pacing. Pre- and post-pacing CMR was performed in anesthetized, intubated animals on a 1.5 Tesla scanner with T2 mapping and late gadolinium enhancement (LGE) scans.T2 increased significantly  in the circumflex-supplied lateral wall post-pacing in animals with stenosis compared to their remote myocardium  without producing evident LGE-positivity; no such T2 increase occurred in sham-operated animals. Ex vivo measurements of cellular respiration revealed decreased respiration in ischemic vs. remote regions . Electron microscopy showed mitochondrial swelling in the ischemic region, but no membrane breaks or other signs of cellular necrosis.in vivo T2-CMR can identify regions of that heart with potentially reversible myocardial and mitochondrial injury in a novel canine model of NSTE-ACS.These preliminary studies suggest that DHLRI, AHA


Acute pulmonary embolism (APE) and septic shock (SS) are highly prevalent dysfunctions in the ICU due to the immunocompromised and immobile state of ICU patients. This research retrospectively tests the ability of a computer-based method to monitor acute hemodynamic changes in pigs. If proven, this method could assist ICU staff by providing a clear physiological, patient-specific picture of cardiovascular status for decision support.n = 5) and SS (n = 4) were induced using autologous blood clots and endotoxin infusions. Hemodynamic measurements were recorded every 30 minutes for 4 hours (n = 80). Subject-specific cardiovascular models were identified from typical ICU measurements obtained from each of these datasets, including aortic and pulmonary artery pressure, stroke volume, heart rate, global end-diastolic volume, and mitral and tricuspid valve closure times. Model outputs and identified parameters were compared to experimentally derived indices, measurements not used in the identification process, and known trends to validate the accuracy of the models.In two porcine studies, APE (R2 = 0.81 for APE and R2 = 0.95 for SS) to experimentally derived values. Importantly, in the APE study a 91% rise from baseline in the mean PVR was identified with an 89% increase seen in the SS pigs. Contrasting behaviour between the two studies was observed for systemic vascular resistance (SVR) with a maximum drop of 40% from baseline recorded at T120 for SS, indicating a loss of vascular tone as expected, where at the same time in the APE study the average SVR had increased by 13%. An increase in the ratio of right to left ventricle end volume was identified in all nine pigs, indicating right ventricular distension and a leftward shift in the intraventricular septum.The models accurately predicted maximum ventricular pressures and volumes, not used in the identification process, to mean percentage errors of 7.1% and 6.7% (less than measurement error ~10%). Mean modelled pulmonary vascular resistances (PVR) compared well (These results indicate that subject-specific cardiovascular models are capable of tracking well-known global hemodynamic trends of two common forms of shock in the ICU. The method shows potential and could provide a means for continuous cardiovascular monitoring at little extra cost as no extra measurements or expensive devices are required.


Context. Heart failure (HF) is a common condition causing much morbidity and mortality despite major advances in pharmacological and device therapies. Preclinical data suggest a cardioprotective role of Angiotensin-(1-7) in animal models of HF. Objective. Perform a systematic review on the effects of Angiotensin-(1-7) on humans, focusing on HF. Results. 39 studies were included in the review (4 in human HF and (35) in non-HF patients). There is only one intervention study on 8 patients with human HF, using Angiotensin-(1-7), with forearm blood flow (FBF) as the endpoint. Angiotensin-(1-7) caused no significant effect on FBF in this HF study but caused vasodilation in 3 out of 4 non-HF studies. In one other non-HF study, Angiotensin-(1-7) infusion led to a significant increase in blood pressure in normal men; however, effects were <0.03% that of angiotensin II. Cardioprotective effects seen in non-HF studies include for instance beneficial actions against atherosclerosis and myocardial fibrosis. Conclusions. The main finding of our systematic review is that Angiotensin-(1-7) plays an important cardioprotective role in HF in animals and in patients without heart failure. More research is required to test the hypothesis that Angiotensin-(1-7) benefits patients with heart failure. Heart failure (HF) is a major health problem for many developed world populations and has a relatively poor prognosis. Within the US population, the incidence approaches 1%, with a lifetime risk of 1 in 5 for both men and women at the age of 40 years . This suThis bioactive endogenous heptapeptide is taking increasing amounts of interest from investigators because of its potential as a therapeutic agent. Angiotensin-(1-7) (Ang-(1-7)) is becoming recognised as an increasingly important player of the RAAS where accumulating evidence suggests that it may have a key role in the regulation and homeostasis of the RAAS, exerting cardiovascular protection. Ang-(1-7) is different from angiotensin II due to the absence of an amino acid at position 8, described as the most pleiotropic metabolite of angiotensin I (Ang I), and is known to have actions which on most occasions are opposite  of those known for angiotensin II (Ang II) , 10. Manin vivo and prostaglandins may participate in the mechanism of potentiation by Ang-(1-7).There has been an abundance of animal studies investigating the effects of Ang-(1-7) in a variety of environments. Increased activation of the RAAS in heart failure is a compensatory mechanism. However, this increased afterload can have adverse effects on cardiac function. Angiotensin converting enzyme inhibitors are commonly seen in the management plan of HF; one reason is to reduce arterial pressure and to reduce the levels of Ang II. Vasodilatation is a property of Ang-(1-7) . It doesThere are other potentially cardioprotective effects of Ang-(1-7) shown in animal studies.The objective of this systematic review will be to discuss human studies on the beneficial effects of angiotensin-(1-7) focusing on patients with heart failure.Highly sensitive search strategies were developed using appropriate subject headings and text word terms. The following electronic databases were searched: Pubmed, Embase, and Cochrane. In addition, conference proceedings and reference lists of all included studies were scanned to identify additionally potentially relevant studies. There were no start year restrictions, but the studies examined were restricted to English language reports.Two reviewers screened the titles (and abstracts if available) of all reports identified by the search strategy. Full copies of potentially relevant reports were obtained, studied, and assessed for inclusion. Data was discussed with the senior author, and disagreements were resolved by consensus.See See The main finding of this systematic review is that Ang-(1-7) plays an important cardioprotective role in heart failure in animals and in patients without heart failure. However, to date, the evidence for the role of Ang-(1-7) in human heart failure is limited , whilst The only study which evaluated the effects of Ang-(1-7) on patients with heart failure examined only 8 patients. These patients were all treated with an ACE inhibitor. The interaction of Ang-(1-7) with bradykinin was elegantly studied . Ang- on coronary arteries and others looked at mesenteric arteries). It seems that Ang-(1-7) is biologically inactive, in keeping with a study by Kono et al.  who alsoOn the other hand, Ang-(1-7) attenuates vasoconstriction and increases blood flow in some studies, involving a larger number of patients, across different vascular beds, including the forearm and internal mammary artery , 34, 44.Other studies about Ang-(1-7) in human heart failure have provided important insight into its role and suggested mechanisms, whereby it might be further exploited as a peptide with cardioprotective therapeutic benefits. Zisman et al.  validateFurthermore, few animal studies have shown that AT2 mediates antiproliferative and apoptotic signaling . This haCampbell et al.  have impin vitro. The common theme from these two studies along with Zisman et al. [As discussed, Ang-(1-7) attenuates vasoconstriction and increases FBF in some studies , 44, 63.n et al.  is an inn et al.  was relan et al. .Additionally, in 33 patients with end-stage HF undergoing heart transplant, as well as 11 controls, MAS17, MMP3, and collagen I mRNA expression were analysed in myocardial biopsies . The patHeart failure (HF) is a common condition associated with significant morbidity and mortality despite major advances in medical, revascularization, and modern cardiac resynchronisation therapy (CRT)/implantable defibrillator (ICD) devices . In 2006Stem cell therapy is the subject of many substantial research programmes. An alternative approach is to stimulate progenitor cells and vascular proliferation. Angiotensin (Ang)-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas , which hin vitro and in vivo [Importantly, Professor Walther's team has also found that infusion of Ang-(1-7) after MI in an animal model increased the number of c-Kit- and vascular endothelial growth factor-positive cells in infarcted hearts, inhibited cardiac hypertrophy, and improved cardiac function . Further in vivo . Ang- selectively prevents cardiac fibrosis in the DOCA-salt model of hypertension, without any effect on blood pressure or cardiac hypertrophy . FurtherTo follow on from Davie and McMurray , it woulOther cardioprotective effects that were demonstrated in animal studies might be translated into humans. We are planning to conduct a randomised controlled trial to test the hypotheses that Ang-(1-7) might improve cardiac hypertrophy and function.Investigating the expression of Mas-gene mRNA or Mas-receptor distribution throughout the human failing heart will provide good insight into activity of Ang-(1-7). Furthermore, the study can also check if there is a correlation between expression and stage of HF and the remodelling process, ventricular size, and ejection fraction.The nonpeptidic Ang (1-7) receptor agonist AVE0991 has already been shown to improve cardiac contractility in diabetic rats. Development of an oral nonpeptidic Ang (1-7) receptor agonist will enable us to perform a well-designed randomised controlled trial to study the cardioprotective effects of Ang-(1-7) in patients on ACE inhibitors or ARBs .The main finding of this systematic review is that Ang-(1-7) plays an important cardioprotective role in heart failure in animals and in patients without heart failure. However, to date, the evidence for the role of Ang-(1-7) in human heart failure is limited. Nevertheless, accumulating evidence from a few studies demonstrated the importance of Ang-(1-7) as a potential therapeutic agent in heart failure.


Editor,Fabry disease is an X-linked lysosomal storage disorder with deficiency of alpha-galactosidase activity leading to impaired organ function due to glycosphingolipids accumulation . We pres9/L), CRP (251 mg/L), procalcitonin (4.62 ng/mL), eGFR 15 mL/min and creatinine 3.7 mg/dL.On admission, he was in a serious condition with systolic murmur at the heart apex, radiating to the left armpit, and a grossly fluctuant subcutaneous collection with redness and warmth at the side of the generator pocket. An ECG showed atrial fibrillation and effective ventricular pacing at 70 beats per minute. Laboratory tests revealed elevated inflammatory parameters—leukocytosis  revealed left ventricular hypertrophy, ejection fraction 55 %, significant mitral regurgitation and a mobile mass of approximately 16 × 16 mm on the septal tricuspid leaflet. No presence of an abscess was recorded. A transesophageal echocardiography (TEE) revealed a mass of maximum size 12 × 22 mm in the right atrium, above the tricuspid valve, attached to the device lead . In our patient, Fabry disease was suggested by the pathologist evaluating kidney biopsy. It took several years to establish the diagnosis at the Department of Rare Diseases in Cracow. In some patients with Fabry disease, a pacemaker is needed due to symptomatic bradycardia. Recent retrospective studies have shown that 1–8 % of Fabry patients require pacemakers implantation . Unfortu


Isolated anomalous pulmonary venous return of one pulmonary vein is relatively rare (~1/1000) and has an unclear natural history. Patients with Turner syndrome (TS) have a relatively high incidence of partial anomalous pulmonary venous return (PAPVR). Our aim is to describe the natural history of unrepaired isolated anomalous pulmonary venous return and its hemodynamic consequences through analysis of cardiac volumetric data and Qp:Qs ratios in asymptomatic volunteers with TS.249 subjects underwent cardiac magnetic resonance imaging in an IRB-approved natural history study of TS at the National Institutes of Health. Cardiac anatomy was characterized with steady-state free precession cine imaging, phase contrast imaging, as well as contrast enhanced magnetic resonance angiograms in adults. Fifteen patients with partial anomalous pulmonary venous return and 42 age-matched controls with TS and normal pulmonary venous return were identified. Ventricular functional analysis was performed by a pediatric cardiologist. Phase offsets on velocity encoded phase contrast images were corrected using 3-dimensional fits to static pixels.Subjects ranged in age from 9-62, with a mean age of 36.3 years. One of fifteen patients with PAPVR was found to have two anomalous pulmonary veins, an RVEDVi of 83 mL/m2 and a Qp:Qs ratio of 1.8. She underwent surgical correction. The remaining fourteen patients all had isolated PAPVR. The median right ventricular end diastolic volume (RVEDV) indexed to body surface area (BSA) of the PAPVR group was 78 (IQR 57-94) ml/m2 and the normal TS group was 64 (49-72) ml/m2 (p = 0.023). Amongst the group of patients with PAPVR, the median Qp:Qs ratio was 1.56 (1.3-1.8). Based on cine MRI volumetric analysis, the median ratio of RV:LV stroke volume was 23% higher in the TS with PAPVR group compared with the normal TS group (p = 0.001)Women and girls with TS and isolated anomalous pulmonary venous return have larger right ventricles than age matched controls that are, however, within the normal range for indexed RV volumes. The median Qp:Qs estimates by velocity-encoded phase contrast are slightly greater than the usual threshold for consideration of surgical intervention. These observations demonstrate cardiovascular changes in patients with isolated PAPVR that should be monitored.National Institutes of Health National Heart, Lung and Blood Institute Intramural Funding


This observational study documented heart rate over the entire course of electrically induced seizures and aimed to evaluate the effects of stimulus electrode placement, patients' age, stimulus dose, and additional predictors.In 119 consecutive patients with 64 right unilateral (RUL) and 55 bifrontal (BF) electroconvulsive treatments, heart rate graphs based on beat-to-beat measurements were plotted up to durations of 130 s.In RUL stimulation, the initial drop in heart rate lasted for 12.5 ± 2.6 s (mean ± standard deviation). This depended on stimulus train duration, age, and baseline heart rate. In seizures induced with BF electrode placement, a sympathetic response was observed within the first few seconds of the stimulation phase (median 3.5 s). This was also the case with subconvulsive stimulations. The mean peak heart rate in all 119 treatments amounted to 135 ± 20 bpm and depended on baseline heart rate and seizure duration; electrode placement, charge dose, and age were insignificant in regression analysis. A marked decline in heart rate in connection with seizure cessation occurred in 71% of treatments.A significant independent effect of stimulus electrode positioning on cardiac action was evident only in the initial phase of the seizures. Electrical stimulation rather than the seizure causes the initial heart rate increase in BF treatments. The data reveal no rationale for setting the stimulus doses as a function of intraictal peak heart rates (‘benchmark method’). The marked decline in heart rate at the end of most seizures is probably mediated by a baroreceptor reflex. Cardiac action in electrically induced seizures follows a characteristic phase-dependent course with rapid changes . In caseThe measurement of pulse rate and blood pressure once a minute appears to be inadequate for investigating such rapidly changing cardiac action. Besides, automated non-invasive blood pressure monitoring takes some time, often more than 30 s, and cardiac action may not remain constant during this period. In view of the rapid changes that take place, precise statements regarding intraictal blood pressure values require arterial catheterization . The accHuang et al.  investigt test after removal of these subjects resulted in p = 0.044, so an ordinary two-tailed t test would have shown no impact of the stimulus dose on the peak heart rates in regular seizures.In another paper , Swartz The following observational study describes the cardiac action in the course of 119 seizures induced by right unilateral (RUL) or bifrontal (BF) stimulation. In the same patient sample, a previous analysis of vagal activation during the stimulation period [n = 64) or BF (n = 55) stimulation. Both clinics made use of a Thymatron II device  which provided a maximum charge of 1,008 mC with current held constant at 0.9 A. For RUL stimulation, an adhesive electrode was affixed to the right temple, and the second electrode (mounted on a handle) was placed adjacent to the vertex. For BF stimulation, two adhesive electrodes were applied above the lateral halves of the eyebrows, the alignment commonly being vertical. The distance between their midpoints varied from 8.4 to 12 cm and averaged 10.3 ± 0.7 cm. The selection of the electrode placement and the setting of the stimulus dose were at the discretion of the attending psychiatrists. Concomitant medications remained unchanged with the exception of the dose before anesthesia. Further details on treatment procedures and patient characteristics have been described previously [Data were collected prospectively from all patients undergoing electroconvulsive therapy in two hospitals between October 2008 and June 2010. A total of 119 patients received treatment series with either RUL  and the time to peak heart rate (Tmax). Tachycardia duration was assessed in two ways: (1) the time period from the end of stimulation until the heart rate fell to its baseline level again (Tbase) and (2) the time to the center of the sharpest heart rate decline within a 5-s period (Tdec) if a pronounced decline was present. With the exception of Trise, time (s) was always measured from the end of stimulation. The speed of decline in heart rate at the end of the seizure was calculated by HR at the end of the seizure minus HR 20 s later. Final HR denoted the heart rate before transfer to the post-anesthesia care unit. Motor seizure duration was determined in the right foot, which had been cuffed prior to the injection of succinylcholine. Electroencephalogram (EEG) seizure duration was taken into account only if a flatline was visible within 2 s after unequivocal seizure signs, in accordance with a suppression index >90%. The term seizure duration refers to motor seizure duration unless otherwise stated.To characterize the heart rate graph, a total of ten outcome variables were defined. The maximum heart rate in the course of the seizure (peak HR) was calculated from the shortest R-R interval in the ECG record; ectopic beats were excluded. Further outcomes were the time from the onset of stimulation until the heart rate rose above baseline level  on outcomes of interest were assessed in multiple regression analysis. If clinical experience or previous investigations suggested further predictors, they were added in the process of model building. SPSS 16.0 was used for the calculations, and all significance tests were two-sided. A total of eight regression analyses were carried out. To compensate for multiple testing, the level of significance for the regression coefficients was adjusted to Upon arrival in the ECT unit, the patients, still aware and oriented, had a mean heart rate of 82 ± 14 bpm and a mean blood pressure of 136 ± 21 / 74 ± 11 mmHg. The mean heart rate in anesthetized patients immediately before administration of the electrical stimuli was 90 ± 18 bpm. Automated blood pressure was monitored once a minute; however, owing to divergent measuring times, no clear assignments to seizure time points could be established. The diastolic level in definite intraictal measurements regularly exceeded 100 mmHg. When the patients were transferred to the post-anesthesia care unit, their mean heart rate was again 81 ± 15 bpm, and the average blood pressure was 130 ± 22 / 72 ± 15 mmHg.Table r = 0.358, p = 0.000) and another one with the patients' age . Charge dose had no effect on the peak HR . The same applied to the positioning of the stimulus electrodes (Table p = 0.296). The time taken to reach the peak HR (Tmax) overlapped the seizure durations . The multiple regression analysis confirmed the baseline HR  and seizure duration  as independent predictors. A higher baseline HR of 10 bpm was associated with a higher peak HR of 5 bpm and reducing seizure durations by 10 s brought down peak HRs by 4 bpm on average.The mean peak HR in all treatments was 135 ± 20 bpm. Bivariate analyses showed a moderate correlation with baseline HR (Trise) was considerably longer in RUL ECT than in BF stimulation and showed a bimodal distribution with a median of 3.5 s in BF electrode placement and 12.5 s in RUL positioning. As evident from Table The time until the HR started rising above baseline  was removed.The onset of tachycardia was traceable in half of the BF treatments as early as 3.5 s after initiation of the electrical pulses. At the end of the stimulation period, which lasted for 7.2 s on average, a higher heart rate was present in 43 of the 55 patients. None of the predictors listed in Table Trise with age , stimulus duration , and baseline HR . The predictors remained significant in regression analysis. It took longer for older patients to exceed their baseline level, and it took more time to exceed a higher baseline. Clinical relevance can be attributed to the high coefficient of the stimulus duration . Extending the duration by 1 s prolonged the corresponding parasympathetic phase by 1.27 s.In RUL treatments, bivariate analyses revealed correlations of Tmax) did not differ in RUL and BF ECT. Regression analysis established an effect of age  and frequency . The calculation, however, was flawed by heteroscedasticity and its predictive value was only 12%.The time interval between stimulation and peak HR (Tbase) was often associated with the termination of motor convulsions . There were additional correlations with baseline HR  and peak HR , but they were trivial if Tbase was chosen as the outcome variable.At the end of the seizures, the cardiac rate dropped below baseline in 93 patients (78%). Short self-limiting asystole events could be seen in RUL as well as in BF treatments. The longest pause in the 119 ECGs of this sample lasted for 4.1 s. In 26 patients, the heart rate remained above baseline or could not be determined because of frequent extrasystoles. The time at which the heart rate fell to its baseline level (Tdec) as the end point of tachycardia resulted in a similarly high correlation with the convulsive period . As shown in Table r = 0.774, p = 0.000). In most cases, however, Tdec preceded the EEG end point, so the latter variable did not seem to be a suitable predictor for the former. An abrupt EEG end point was only recorded in 25 RUL and 8 BF treatments.Taking the point of greatest heart rate deceleration ; it was attenuated in lengthy seizures  and in older patients .The speed of decline in heart rate at the end of the seizure could be assessed in 94 patients. In the 20 s following the termination of seizure activity, the heart rate fell by 30 ± 20 bpm with a median of 25 and a range of −3 to 89 bpm. The decline was faster in the case of higher peak HRs .We could not reproduce the ‘general absence of correlation between peak and baseline HRs,’ as stated by Swartz in 1999 . In our B = −0.015, p = 0.250). There was no evidence that the administration of higher stimulus doses in the first treatment of a series caused higher heart rates.This small sample size also formed the statistical basis for the ‘Benchmark Method’ , in whicn RUL = 16, n BF = 16). Subconvulsive stimuli were not taken into account. Although the mean charge dose in these 32 patients had been doubled from 253 ± 106 mC to 507 ± 211 mC, there was no corresponding increase in the peak HRs. On the contrary, their mean fell from 130 ± 19 bpm to 123 ± 20 bpm . This decrease is not surprising given that the baseline HRs fell from 90 ± 18 bpm in the first treatments to 83 ± 16 bpm in the subsequent treatments. Likewise, seizure durations fell from 45 ± 12 to 34 ± 11 seconds. Doubling the stimulus dose in the course of a treatment series seems to be a futile attempt to achieve higher peak HRs  served as an outcome variable. In a previous analysis of the same patient sample [Trise’ as an outcome variable instead of the ‘stimulation interval’ yielded markedly better results. Age, baseline HR, and stimulus duration turned out to be significant predictors in the RUL group, explaining more than 50% of the variation, as shown in Table In the present study, the time from the onset of stimulation until the heart rate started rising above baseline  can often be determined more simply. This point, however, is reached more rapidly in the case of a high baseline or a low peak HR. Tdec is not affected and seems to be more appropriate for marking the onset of the post-ictal period of vagal dominance.Incidents of temporary asystole concomitant with the end of seizure signs have been described repeatedly -17. In 1The parasympathetic surge during stimulation depended on the positioning of the stimulus electrodes; it appeared with the first cardiac action starting in the stimulation period, and it was strongly linked to stimulus train duration. Bradycardia was also visible during irregular RUL stimulations. In the case of an interrupted treatment, we recorded a prompt heartbeat slowdown induced by no more than 14 pulses of 0.5 ms each . All these observations are explicable by assuming direct stimulation of the vagus nerve if the electrical field is placed in its proximity.The quick activation of the sympathetic nervous system in the first half of the stimulation period was only traceable in the ECG records of BF treatments. As evident from its rapid onset, this tachycardia is neurally mediated. Epinephrine from the adrenal glands might contribute to cardiovascular action later on but cannot play a part at an early stage. A valuable insight into the physiological mechanisms was provided by subconvulsive stimulations, i.e., stimulations followed by neither motor nor EEG seizure signs. There were no such cases within the RUL sample and six (11%) in the BF group; all were successfully re-stimulated at higher doses. Cardiac action was similar in subconvulsive and convulsive stimulations, with five of the patients showing cardioacceleration during application of the electrical pulses. Subsequently, the heart rate fell below baseline level in three patients within 4.2–17.8 s following completion of the subconvulsive stimuli. The onset of tachycardia during BF stimulation can hence be attributed to the application of electrical pulses rather than to the seizure itself Figure . BifrontAt the end of the seizures, some heart rate graphs gradually drifted towards baseline. In 78% of cases, however, they fell below that level and a steep, non-steady decline was recorded in 71%. These time curves are indicative of additional activation of the vagus nerve. Unlike the vagal surge during stimulation, it did not depend on electrode positioning. A potential mechanism is reflex bradycardia. Neurally mediated sympathetic activity is mainly based on norepinephrine. The IV infusion of this neurotransmitter rapidly leads to vasoconstriction and blood pressure elevation and is consistently followed by bradycardia. In keeping with neural mediation, arterial line recordings in ECT showed maximum systolic and diastolic blood pressure levels within 7 s of the first post-stimulus heartbeat . The barIn this study, stimulus electrode positioning had a marked effect on cardiac action during electroconvulsive therapy in the stimulation phase. We did not find an effect on heart rate during the subsequent convulsive period. The influence of the patients' age on cardiac action in ECT seemed to be only of minor importance: bradycardia lasted longer during RUL stimulation; the heart rate reached its maximum a little later and had a tendency to decrease more gradually at the end of the seizure. The common decline of autonomic nervous system function in old age offers a simple explanation for this blunted heart rate response. The stimulus dose had no independent effect on heart rate, particularly peak heart rate, in fully developed seizures. In consequence, peak heart rate is an unsuitable parameter for adjusting the stimulus dose.BF: Bifrontal; ECT: Electroconvulsive therapy; HR: Heart rate; RUL: Right unilateral; Tbase: Time until the heart rate falls to baseline level; Tdec: Time to the steepest heart rate decline during and after the seizure; Tmax: Time to peak heart rate; Trise: Time from the onset of stimulation until the heart rate rises above baseline level.The author declares that there are no competing interests.


Whether β1R-AABs and M2R-AABs participate in the pathogenesis of PPCM is still unknown.Peripartum cardiomyopathy (PPCM) is characterized by left ventricular systolic dysfunction and heart failure. However, its pathogenesis is not clear. Our preliminary study revealed that autoantibodies against β1R-AABs or M2R-AABs by enzyme linked immunosorbent assay (ELISA) were performed.Totally 37 diagnosed PPCM patients and 36 normal pregnant women were enrolled in this study. Clinical assessment and 2-dimensional echocardiographic studies as well as the measurement of β1R-AABs and M2R-AABs were 59.5% (22/37) and 45.9% (17/37) in PPCM patients, and 19.4% (7/36) (P<0.001) and 16.67% (6/36) (P<0.001) in normal pregnant women, respectively. Both β1R-AABs and M2R-AABs had a positive correlation with serum expression level of NT-proBNP, left ventricular dimension and NYHA FC . In addition, a negative correlation between the activity of β1R-AABs and M2R-AABs and LVEF, LVFS was observed . Moreover, autoantibodies against cardiovascular receptors increased the risk of the onset of PPCM .The positive rates for β1R-AABs and M2R-AABs reveal a significant elevation and are correlated with the increased left ventricular dimension and worse cardiac contraction function. The autoantibodies of cardiovascular receptors are independent risk factors for the onset of PPCM.The β Peripartum cardiomyopathy (PPCM) is a serious disease with unknown etiology, which occurs between the last month of pregnancy and 5-month puerperium with significant morbidity and mortality. The diagnostic criteria include: (1) The disease occurs between the last month of pregnancy and 5-month puerperium; (2) There has no definite reason for heart failure; (3) LVEF <45%, LVFS <30%. The reported incidence fluctuates among geographic regions, but it is higher in Africa. It has been estimated to be 1∶3000–4000 in USA, 1∶400 in Haiti, and 1∶1000 in South Africa 1-adrenergic and M2-muscarinic receptors belong to the family of cardiac G-protein-coupled receptors. Circulating autoantibodies against the second extracellular loop of β1-adrenergic receptors and M2-muscarinic receptors have been detected in a number of cardiovascular diseases characterized by heart failure including idiopathic dilated cardiomyopathy (IDCM) 1R-AABs 1R-AABs and M2R-AABs are highly prevalent and participated in the pathogenesis of dilated cardiomyopathy. In addition, the density of β1R-AABs and M2R-AABs is significantly higher in patients with heart failure regardless of the primary heart disease 1R-AABs and M2R-AABs.The role of autoimmunity in cardiovascular diseases has become one of the focal points in the field of cardiomyopathy and heart failure. The βP<0.05). Left ventricular dimension was significantly enlarged and left ventricular ejection fraction coincided with left ventricular fractional shortening was significantly decreased (P<0.001).The characteristics of the study population at the first presence in cardiac clinic (baseline) are shown in 1R-AABs were observed in 59.5% (22/37) of PPCM patients, while 19.4% (7/36) (P<0.001) in normal pregnant women. The positive sera for M2R-AABs were 45.9% (17/37) in PPCM patients, while 16.67% (6/36) (P<0.001) in normal pregnant women. Moreover, in positive cases, autoantibody titer (geometric mean) was higher in patients with PPCM when compared with normal pregnant women both for β1R-AABs and M2R-AABs. The geometric mean titers for β1R-AABs and M2R-AABs were 1∶129 and 1∶143, while they were 1∶80 (P = 0.003) and 1∶53 (P<0.001) in normal pregnant women. Totally 17 of 37 (46%) PPCM patients were positive for both β1R-AABs and M2R-AABs. Among other 19 patients, 15 (40%) patients were negative for β1R-AABs and M2R-AABs, and 5 (14%) patients were positive for β1R-AABs.The positive sera for βOne patient (3%) died during the study period. The death was due to the progression of heart failure. Since the death was due to the progression of heart failure, patients who died were classified in FC IV at the latest follow-up examination. All patients received standard therapy for heart failure, which included daily 0.125 mg of digitalis, furosemide [median daily dose 40 mg (20–40 mg)], perindopril [median daily dose 4 mg (2–4 mg)], and betaloc [median daily dose 25 mg (6.25–50 mg)].P≤0.001) and NYHA FC (P<0.001). Normalization of LVEF (≥50%) was observed in 31 (86.1%) patients. Clinical data and NYHA FC were compared at the first presence in the cardiac clinic at baseline and after 12 months of standard therapy as described in Patients who completed 12 months of standard therapy showed a significant reduction in heart rate, LV dimension, and significant improvement in echocardiographic LVEF and LVFS (1R-AABs declined from 59.5% to 22.2% (P<0.001), as well as M2R-AABs declined from 45.9% to 19.4% (P<0.001). The geometric means of autoantibodies were also decreased significantly (P<0.001). The geometric mean titers for β1R-AABs and M2R-AABs were declined from 1∶129 to 1∶71 and 1∶143 to 1∶50, respectively ; left ventricular end systolic dimension (LVESD): 51.2±7.5 vs. 45.8±2.1 vs. 42.2±4.3, ; left ventricular ejection fraction (LVEF): 33.7±7.9 vs. 38.6±1.7 vs. 41.9±2.9, ; left ventricular fractional shortening (LVFS): 16.8±4.0 vs. 19.4±1.4 vs. 21.2±2.8, . After standard treatment for 1 year, three groups had obvious improvement on echocardiography, however, the degree of improvement was different: LVEDD: 52.3±4.4 vs. 46.4±1.1 vs. 44.5±1.2, ; LVESD: 38.4±5.1 vs. 32.4±1.1 vs. 28.4±2.9, ; LVEF: 57.2±7.0 vs. 61.6±2.9 vs. 68.5±5.0, ; LVFS: 28.5±3.4 vs. 30.4±2.1 vs. 33.9±2.4,  (There were 17 (46%) patients with double positive (DP) autoantibodies, 5 (14%) patients with single positive (SP) autoantibodies and 15 (40%) patients with double negative (DN) autoantibodies. Echocardiographic data among three groups had significant difference: left ventricular end diastolic dimension (LVEDD): 62.5±7.1 vs. 56.9±1.0 vs. 54.8±4.3, (χ= 0.002) .1R-AABs and M2R-AABs (both frequency and titer of autoantibody) were positively correlated with left ventricular dimension, NT-proBNP and NYHA FC . Besides the levels of serum β1R-AABs and M2R-AABs (both frequency and titer of autoantibody) were negatively correlated with LVEF and LVSF . A significant correlation was observed between β1R-AABs and M2R-AABs . The results were described in The levels of serum βP = 0.012; pregnancy-induced hypertension: OR = 17.305, 95% confidence interval 1.061–282.299, P = 0.045). The result was shown in Univariate analysis showed that several factors increased the risk for the onset of PPCM, including autoantibodies against cardiovascular receptors, advanced maternal age, multiple pregnancies, pregnancy-induced hypertension, and poor socioeconomic status. Multiple logistic analysis showed that the level of autoantibodies against cardiovascular receptors and pregnancy-induced hypertension were an independent predictor of the PPCM attack  and M2 receptor (amino acid sequence number: 169–193) were used. We detected the autoantibodies against β1 and M2 receptors in patients’ sera with ELISA and demonstrated that the frequency and titer of serum β1R-AABs and M2R-AABs in patients with PPCM were higher than those of normal pregnant women. The comparison between β1R-AABs and M2R-AABs double positive group, single positive group and double negative group revealed that the expansion of left ventricular and decrease of heart function: double positive group> single positive group> double negative group. After treatment for 1 year, recovery of left ventricular dimension and heart function: double positive group< single positive group< double negative group. The test of β1R-AABs and M2R-AABs may have predicted value for the prognosis of PPCM. The levels (both frequency and titer) of serum β1R-AABs and M2R-AABs were positively associated with New York Heart Association functional class, left ventricular dimension and plasma NT-proBNP levels, and were negatively associated with left ventricular ejection fraction, left ventricular fractional shortening. Autoantibodies against cardiovascular receptors were independent predictors of the onset of PPCM. This study suggested that β1R-AABs and M2R-AABs play an important role in the pathogenesis of PPCM.In this study, synthetic peptides corresponding to the sequences of the second extracellular loop of human β1R and M2R are the major adrenergic and muscarinic receptors present in myocardial tissue, respectively 1R-AABs and M2R-AABs were first detected in the idiopathic dilated cardiomyopathy (IDCM) 1R or M2R could induce cardiac morphological changes including significantly enlarged ventricles and thinner walls, resembling the changes of IDCM in humans 1AR or M2R proteins, which can lead to contractile dysfunction and cardiac remodeling During the past few years, autoimmune mechanisms in heart disease have gained extensive attentions. Autoimmunity has been observed in several cardiovascular diseases such as dilated cardiomyopathy (DCM) and heart failure, rheumatic fever, myocarditis, atherosclerosis, and others 1R-AABs and M2R-AABs not only existed in IDCM patients, but also in heart failure caused by different cardiac diseases. Moreover, the serum level of autoantibody has no significant difference among different heart diseases, which suggested that the generation of β1R-AABs and M2R-AABs had no relationship with primary heart disease, but was correlated with the damage of cardiac function.Our preliminary study revealed that β1R-AABs existed in the serum of PPCM patients, and was correlated with plasma NT-proBNP PPCM is characterized as systolic dysfunction and heart failure as well as IDCM. Its pathogenesis was still unclear. The autoimmune mechanism was believed to participate in the pathogenesis of PPCM. High titers of auto-antibodies against selected cardiac tissue proteins have been found in the majority of women with PPCM 1R-AABs and M2R-AABs might lead to cardiac remodeling in cardiomyopathy. In the present study, significantly higher levels of β1R-AABs and M2R-AABs in the serum of PPCM than normal pregnant women were observed. For PPCM patients, the enlarged left ventricular chamber may return to normal level, which seems to improve better than IDCM. In our study, the titer of autoantibodies revealed a decline, which is coincided with the decrease of left ventricular and the improvement of heart function after treatments. Therefore, β1R-AABs and M2R-AABs may participate in the pathological change of cardiomyocytes. What’s more, these two autoantibodies were the independent risk factors for the attack of PPCM and may influence the prognosis of PPCM patients. All of these investigations suggested that β1R-AABs and M2R-AABs might participate in the pathogenesis of PPCM.Previous studies revealed that β1 is increased in patients with preeclampsia It’s interesting to notice that, a hypothesis currently being widely entertained is that PPCM may be a vascular disease PPCM is a diagnosis by exclusion. As the objects of this study are pregnant women, the coronary angiography, and right and left catheterization are not allowed for application to exclude other kinds of cardiac diseases. Because the morbidity of PPCM is not very high in China, especially in Beijing, the case number is insufficient. As all these patients enrolled in our study were Chinese Han and body mass index (BMI) was not mentioned in this article, the assessment of autoantibodies as an independent risk factor for PPCM were incomplete, which could result in the continuous improvement in the future. What’s more, the predictive value of autoantibodies against cardiovascular receptors for the prognosis of PPCM needs further studies.1R-AABs and M2R-AABs were prevalent in a cohort of PPCM patients. The positive rates and the serum titers of β1R-AABs and M2R-AABs were positively correlated with left ventricular dimension, and negatively correlated with the cardiac contraction function of PPCM patients. The autoantibodies of cardiovascular receptors were independent risk factors for the onset of PPCM.This study has demonstrated that the presence of βWe propose that autoantibodies against cardiovascular receptors may be involved in the pathogenesis of PPCM. Further studies are needed to confirm these findings and dissect the underlying mechanisms for this novel observation.The protocol as well as the consent form was approved by the Ethics Committee of Capital Medical University Beijing Chao-Yang Hospital and the study protocol complied with the Declaration of Helsinki. All participants provided written informed consent prior to admission into the study.Since 1998, 37 Chinese Hanpatients with newly diagnosed PPCM were enrolled in Beijing Chao-Yang Hospital. The enrolled patients should meet following inclusion criteria: (1) age ≥16 or ≤40 years old, (2) New York Heart Association functional classes (NYHA FCs) II–IV, (3) symptoms of congestive heart failure developed in the last month of pregnancy or during the first 5 months post-partum, (4) no other identifiable causes for heart failure, (5) left ventricular ejection fraction (LVEF) <45%, left ventricular fractional shortening <30% by transthoracic echocardiography, (6) sinus rhythm and (7) eligible patients with high quality echocardiographic images. Exclusion criteria: (1) significant organic valvular heart disease, (2) systolic blood pressure (SBP) >160 mmHg and/or diastolic blood pressure >100 mmHg, (3) clinical conditions other than cardiomyopathy with increased autoantibody by screening the serum for rheumatoid arthritis and HIV and the evidence of sepsis, (4) severe anaemia (haemoglobin concentration <9 g/dL), (5) metabolic disorders affecting lipoprotein metabolism such as thyroid disease and (6) Clinical data are not complete. Clinical assessment, echocardiography and blood analysis were conducted at baseline and after 12 months of standard therapy. All patients received standard therapy for PPCM . Patients with an ejection fraction ≤25% or LV thrombus additionally received anticoagulation therapy. The follow-up examination at Beijing Chao-Yang Hospital was provided for all patients.1-adrenergic and M2-muscarinic receptors were measured in patient sera through an enzyme-linked immunosorbent assay (ELISA) using a synthetic peptide corresponding to the sequence of the second extracellular loop of human β1 and M2 receptor . The peptide was synthesized by Biological Institute of the Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC) using a solid-phase method of Merrifield, and the purity was evaluated by high-pressure liquid chromatography (HPLC) on an automatic amino acid analyzer . The procedures of ELISA were as follows: 50 µL of peptide (5 mg/L) in 100 mmol/L Na2CO3 solution (pH = 11.0) was incubated overnight at 4°C on NUNC  microtiter plates. The wells were saturated with phosphate-buffered saline  supplemented with 0.01% (w/v) Thimerosal , 0.1% (v/v) Tween-20  (PBS-T) and 10% (v/v) fetal bovine serum (PMT). A total of 50 µL of patient serum with gradient dilutions from 1∶20 to 1∶160 was added to saturated microtiter plates and incubated for 1 h at 37°C. After the wells were washed with PBS-T for 3 times, an affinity-purified biotinylated rabbit anti-human IgG (H+L) antibody  (1∶500 dilution in PMT) was added and allowed to react for 1 h. After washing the wells for 3 times with PBS-T, the bound biotinylated antibody was detected by incubating the plates for 1 h with streptavidin-peroxidase (2 ml/L)  solution in PMT, which was followed by washing for 3 times with PBS and the addition of substrate for peroxidase 2.5 mmol/L H2O2-2 mmol/L ABTS . Optical density (OD) was recorded after 30 min at 405 nm in a micro plate reader . Positive rate was defined as positive/negative [P/N = (sample OD-blank OD)/blank OD)] ≥2.1 The autoantibodies against βAll studies were performed and interpreted by the same operator who was blinded to the protocol. Two-dimensional targeted M-mode echocardiography with Doppler color flow mapping was performed for every patient. Left ventricular dimension was measured according to the American Society of Echocardiography guidelines 1-AABs or anti-M2R-AABs and the echocardiographic and clinical indices were assessed by Spearman’s correlation. Risk factor analysis was performed by univariate and multivariate logistic analysis. All tests were 2-tailed, and statistically significant difference was considered at P < 0.05. Statistical analysis was performed using SPSS Base 16.0 statistical software package .The measured data were expressed as mean ± SD or median  and categorical data were expressed as percentage. Antibody titer was reported as geometric mean. Positive rate of autoantibody was described as the frequency of autoantibody. For two-group comparison, we used the Student’s t test or Mann-Whitney U test for continuous variables and the chi-square test or Fisher’s exact test for categorical variables. For three-group comparison, Kruskal-Wallis test was used. Correlation between the levels of serum anti-β