A case of prenatally diagnosed fetal hypertrophic cardiomyopathy is reported. The mother was referred to our department at 37 weeks' gestation because of suspected congenital heart disease. Prenatal echocardiography showed biventricular hypertrophy and pericardial effusion, without additional abnormalities. Postnatal echocardiography confirmed prenatal diagnosis. Neonatal EKG showed biventricular hypertrophy and Wolff-Parkinson-White syndrome. Skeletal muscle biopsy was consistent with mitochondrial oxidative phosphorylation defect involving a combined defect of respiratory complexes I and IV. Echocardiographic followup during the first year of life showed progressive regression of hypertrophy and evolution to left ventricular myocardial noncompaction. Cardiomyopathies are among the clinical presentations associated with mitochondrial oxidative phosphorylation defects . CardiomNeonatal mitochondrial cardiomyopathies are often characterized by hypertrophy of one, generally left, or both ventricles. Ventricular dysfunction may be progressive in-utero and after birth. Neonatal cardiomyopathy often lead to fatal heart failure, although may eventually progress into a dilated form , into noWe present the case of a fetus diagnosed with hypertrophic cardiomyopathy at 37 weeks' gestation, which was finally found to have a mitochondrial oxidative phosphorylation defect.A 30-year-old woman, gravida 3, was referred to our Department at 37 weeks' gestation due to an abnormal obstetric ultrasound. Personal and pregnancy history were unremarkable. Familial history revealed a previous child died because of congenital cardiac anomaly, namely double outlet right ventricle. Fetal echocardiographic evaluation showed biventricular hypertrophy and pericardial effusion see , and lefSkeletal muscle histopathological and spectrophotometric studies were diagnostic of a mitochondrial oxidative phosphorylation defect involving respiratory complexes I and IV.Follow-up echocardiography showed progressive regression of hypertrophy, except at left posterior wall and interventricular septum, with no changes in ventricular function and no pericardial effusion. At the same time, left ventricular myocardium developed trabeculations accomplishing left ventricular noncompaction criteria. Parents echocardiographic study was normal. In addition, the patient presents a normal psychomotor development. Currently the patient has three years old and is treated with enalapril and vitamin complex.Cardiomyopathies are a very rare disease in fetuses with a very poor outcome. Only isolated case reports and small case series were reported. In series of neonates and infants the CM occur in about 2–7%, but probably during the fetal life the prevalence is higher: 6%–11% .Neonatal cardiomyopathies due to mitochondrial oxidative phosphorylation defects are severe conditions which can be either isolated or part of a multiorgan disease involving brain, skeletal muscle, liver, and kidney, in addition to heart .Incidence of neonatal mitochondrial cardiomyopathies can only be approached using the reports of referral diagnostic centers. Gibson et al., in a series of 32 newborns, reported 29% of mitochondrial diseases with a neonatal onset . García-Cardiomyopathy is more often hypertrophic than dilated. However, it may eventually progress into a dilated form or left ventricular noncompaction cardiomyopathy. Antenatal manifestations such as fetal hypertrophic cardiomyopathy, arrhythmia, and/or hydrops have been reported . In extrCardiomyopathy pathophysiological mechanisms are complex, and neonatal myocardium requires a normal mitochondrial functioning for its metabolic shift from prenatal anaerobic glycolysis to postnatal metabolism, relying on fatty acid oxidation, ketone body catabolism, and oxidative phosphorylation . ComplexIn neonatal cardiomyopathy, EKG monitoring is necessary for early detection of ventricular arrhythmias, which are sometimes precursors of episodes of sudden death . IntensiMitochondrial cardiomyopathies are more severe than mitochondrial diseases without heart involvement, being the survival rate at 16 years of age for cardiomyopathic patients 18% versus 95% survival at the same age in non-cardiomyopathic patients .Although heart dysfunction may be not progressive or even regress afterwards, neonatal mitochondrial cardiomyopathies often have a rapidly fatal outcome. Prenatal diagnosis and fetal echocardiography may improve perinatal care based on the expected natural history and postnatal course. In addition, detailed evaluation of fetal and maternal condition and standardized diagnostic procedures provide prognostic information for genetic counseling and further potential prenatal diagnosis.


ERMS, the LV synchronous contraction and the hemodynamics improved more with mechanical optimization strategy. Therefore, measures of mechanical dyssynchrony improve the sensitivity and specificity of predicting responders more. The model was subject to validation in future clinical studies.An optimal electrode position and interventricular (VV) delay in cardiac resynchronization therapy (CRT) improves its success. However, the precise quantification of cardiac dyssynchrony and magnitude of resynchronization achieved by biventricular (BiV) pacing therapy with mechanical optimization strategies based on computational models remain scant. The maximum circumferential uniformity ratio estimate (CURE) was used here as mechanical optimization index, which was automatically computed for 6 different electrode positions based on a three-dimensional electromechanical canine model of heart failure (HF) caused by complete left bundle branch block (CLBBB). VV delay timing was adjusted accordingly. The heart excitation propagation was simulated with a monodomain model. The quantification of mechanical intra- and interventricular asynchrony was then investigated with eight-node isoparametric element method. The results showed that (i) the optimal pacing location from maximal CURE of 0.8516 was found at the left ventricle (LV) lateral wall near the equator site with a VV delay of 60 ms, in accordance with current clinical studies, (ii) compared with electrical optimization strategy of  Congestive heart failure (CHF) is a common heart disease caused by dilated cardiomyopathy or damage to the excitation conduction system. Biventricular pacing (BiVP), or cardiac resynchronization therapy (CRT), was a major breakthrough in the treatment for patients with advanced CHF complicated by discoordinate contractions caused by inter- or intraventricular conduction delays . CRT hasOver the past decade, many studies have examined the pathophysiology of cardiac dyssynchrony and tested the effect of cardiac resynchronization on heart functions and the efficacy of symptoms enhancements. Most of these researches have focused on the ECG characteristic of distinct responders versus nonresponders to CRT. For example, left and right ventricular leads were placed in different locations to attain the shortest QRS duration during biventricular stimulation. Presently, the optimal electrode setups and timing delays are also determined by measuring the cardiac index using magnetic resonance tagging (MR tagging), nuclear imaging (NI) or Doppler flow imaging and so on –15, mostHowever, it may be not sufficient for clinicians to formulate a scientific and reasonable treatment scheme for CRT optimization with only physical examination of ECG or medical imaging. Quantitative information and precise programming of the optimal stimulation delays and lead positioning accordant with the physiological function are needed. For example, although it is generally accepted that the posterior-lateral wall is the preferred location for LV lead location in CRT, other LV pacing sites have also been shown to offer superior benefits for selected patient population. In other words, there is no universally accepted best LV pacing site, nor the best V-V interval. Therefore, patient-specific CRT optimization is needed. There are both intersubject variability and intrasubject variability . Modeling of heart can provide a useful supplementary tool to investigate the dynamical behaviour of heart quantitatively and thus enhance our understanding of the cardiac electrophysiological and mechanical properties under physical and pathological conditions. Consequently, the computer modeling of a patient-specific heart appears to be a reasonable solution for solving this problem, which can determine the optimal AV and VV timing pre- or postoperatively with respect to the lead positions in patients undergoing CRT. ERMS, was used as an optimization assessment index and automatically computed for 12 different electrode positions with different AV and VV intervals. Their results showed the importance of individually adjusting the electrode position, beside the timing delays, to the patient's anatomy and pathology in accordance with current clinical studies. Mohindra et al. recorded 120-electrode body-surface potential mapping (BSPM) data and calculated the epicardial potentials and isochrones of activation for different V-V intervals by means of an electrocardiographic inverse solution based on a ventricular computer model [Many scientists have concentrated on the study of individual optimization of lead position and pacing delays of CRT by means of heart modeling and simulation with the progress of mathematical modeling techniques. The electrical-based optimization approach, for example, minimizing the QRS duration, has been widely accepted due to its simplicity. Therefore, most of researches have concentrated on the electrical strategies of optimizing parameters in CRT. Reumann et al. simulated an atrio-ventricular (AV) and a left bundle branch block (LBBB) with different reductions in the interventricular conduction velocity based on computer models of the Visible Man and a patient's heart . They aser model . They user model , the simer model . Thus, wERMS) optimization strategy for CRT. The present study resolves this question through the simulation of the cardiac electrical activation spread and the mechanical strain maps based on our previous electromechanical canine model of HF combined with a complete LBBB (CLBBB) [Compared with previous electrophysiological models for CRT optimization, the present heart model in this paper is extended to include a mechanical contraction model for the optimization of the pacing lead locations and the interventricular delays (VVds) of CRT. Since the spatial distribution of local wall mechanics was very sensitive to the choice of myofiber orientations, specific data of real fiber orientations were used for true description of cardiac deformation in this study. The ventricular mechanical dyssynchrony is evaluated by the assessment of a circumferential uniformity ratio estimate (CURE) , 19. The (CLBBB) . The anatomical canine heart model used in this study was reconstructed from the MR scans of an intact dog heart derived at the Duke University Medical Center for In Vivo Microscopy, Durham, NC, USA Figures . The spaμA/cm2 and duration of 0.5 ms was added to the right bundle branch while blocking the conduction of the left bundle branch, leaving the rest of the conduction tree intact. Latest depolarization time in LBBB simulations occurred at 108 ms , , 7), we s before .Mechanical dyssynchrony is a potential indicator for predicting responses to CRT. For example, novel echocardiographic image speckle tracking applied to routine midventricular short-axis images can quantify dyssynchrony by calculating the radial strain from the multiple circumferential points averaged to several standard segments and thus predict the response to CRT . DyssyncAccording to the report , short-aεcc over the entire LV-midwall (y-axis) at 30 circumferentially-distributed locations around each short-axis section (x-axis), and plot εcc versus spatial position for each time-frame. The more oscillatory the plot, the greater was the dyssynchrony among the segments around the short axis. To explain this, we can plot circumferential strain versus spatial location of the segment as Compute circumferential strain A02 and A12 are the spatial and temporal sums of the zero- and first-order power terms, respectively. The ratio of mean to “mean plus first-order power” provides the CURE index, and the maximal value for CURE is 1 with all segments contracting synchronously; whereas symmetrically dyssynchronous contractions produce a CURE = 0 [Plots for the four mid-wall short-axis slices are then subjected to Fourier analysis with a function of fft in Matlab7.0.1, and the results are averaged over space and time to yieldCURE = 0 , 26, 27.A further description of calculating zero and first-order power terms of layer 6 to 9 around equator sites at a given time was given in Compute the CURE for each electrode pair and each VVD and choose maximum CURE as optimal result of CRT. Because the left ventricular dyssynchrony is an important determinant of CRT response, the CURE calculated from LV and septum is chosen alternatively as the criterion for predicting the response to CRT in the simulation.The optimization method was then applied to the electromechanical canine heart model of LBBB. The optimization parameter of the CURE was sequentially calculated for each combination of the pacing location and VVD. The optimal result of CRT can be determined by the combination that provided the maximum CURE. ERMS can be found in many published reports. Briefly, it is assumed that the optimal cardiac output is to be achieved through the sinus rhythm and the normal electrophysiological parameters [ERMS between the physiological excitation during the sinus rhythm and pathological excitation as below:N is the whole number of voxel elements, xi dedicates the activation time of voxel i under the sinus rhythm, and ei is the activation time of voxel i under the pathological condition. Thus, by minimizing the ERMS, the activation of the heart will be as close as possible to the healthy activation and will provide an optimal combination of the pacing site and timing delay in CRT. The description of the electrical optimization strategy with rameters . TherefoERMS) optimization strategy for CRT, two objective function are defined as below.In order to make a contrast analysis of cardiac function improvement between mechanical (CURE) and electrical , can help determine the cardiac hemodynamics effect. LVEF is defined asIn this study, BiVP was chosen for CRT simulations. In clinic, doctors often choose the branches of coronary sinus as the LV pacing lead site as shown in ERMS through adjustment of the pacing location and VVD.Generally, the activation of the sinus node serves as the reference time for the AV delay. Several studies have pointed out that the VVD should be optimized according to the changes in the AV delay to obtain the maximum hemodynamic benefit . HoweverSimulation of the cardiac excitation anisotropic propagation throughout the ventricular myocardium is computationally very expensive. Thus, high-performance computing techniques should be used. By using an operator-splitting scheme, adaptive time step, and backward differentiation formulation techniques in a parallel implement, we solved the monodomain equations of the cardiac excitation anisotropic propagation successfully . For a cThe maximal value of CURE was 0.8516, with pacing site at point LAT-E and a VVD of 60 ms see , which cERMS of 37.26 ms. The optimal stimulation site was also at point LAT-E, but with a VVD of 0 ms. With the electrical optimization strategy, an optimal pacing location and VVD were also found with a minimal error To find the potential relationship between CURE and VVD, a diagram of the CURE-VV delay time column map was plotted in Furthermore, CURE values of LV pacing sites near ventricular equator sites were all larger than those at base for VVD ≥ 12 ms. However, the CURE of LV pacing location near the lateral wall at equator site, that is, pacing location LAT-E, was always the largest. It can also be found that the CURE values were smaller when the pacing lead was at the anterior wall near base, that is, pacing location ANT-B and ANT-E. ERMS  was plotted as the optimal result of CRT from the electrical index , we have adopted the mechanical optimization strategy CURE as the synchrony assessment index in the research. As we know, the main function of heart is to pump blood and exchange the metabolites. Therefore, the mechanical function of heart and the cardiac hemodynamics were the most basic characteristics and essential criteria for evaluating the cardiac function.The clinical findings of CRT have demonstrated that the adjustment of pacing lead position and VVD were very important for an individual to get the best improvement in hemodynamics . HoweverThe implantation location of LV pacing lead was proven to be very important for the improvement of the ventricular systolic synchrony . From FiHowever, with the increasing of VVD, especially for VVD ≥ 48 ms, CURE varied little and the same thing happened when VVD ≤ −48 ms. For VVD ≥ 48 ms, LV was the first ventricle to be paced. However, when RV was paced, the intrinsic excitation or excitation from LV pacing lead had spread to the RV beforehand. Due to the influence of refractory period, the pacing lead of RV (point RVA) would not play a role. Therefore, CURE values make no variations when VVD was larger than a certain value.From ERMS) strategy, Maximum Strain-Time curves were plotted in ERMS) had a worse synchrony  for the optimal parameters of CRT. It also confirmed the fact that the CURE could better reflect the LV synchrony and hemodynamic result, although biventricles may not obtain the best electrical synchrony [ERMS as optimization strategy for CRT. The thickening of the cardiac walls also improved after CRT with the peak maximum principle strain (PMPS) increased from 0.70 in the LBBB model to 0.77 in CRT optimization model based on the CURE strategy as shown in ERMS strategy was larger, with a value of 0.98 as shown in To further observe the enhancement of LV synchronization after CRT optimization and to contrast the optimal result between mechanical (CURE) and electrical  to optimize the parameters of CRT, the problem could be solved. Alternatively, an improved mechanical coordination and function may be inducible in the LBBB-CHF hearts without generating electrical synchrony. The difference of optimal delays and pacing sites was due to the difference of heart geometry, electrical and mechanical properties, and also the time regional differences in the time between electrical excitation and mechanical contraction at one part of the model versus another part. Therefore, clinicians would not always choose the lateral wall for the pacing locations. With the help of a patient-specific computation heart model, quantitative information will be obtained to enhance our understanding of cardiac dyssynchrony and decrease the blindness of CRT. dPmax/dt ) that were usually used as the optimal parameters of CRT in clinic [In this study, however, there are still some defects in our optimization model of CRT. Because of the lack of the atria data, the construction of a whole heart model was not feasible and consequently, the adjustment of the AV delay has not been considered. Furthermore, the hemodynamics parameters should be taken into account in future modeling, such as the cardiac output and the n clinic , 36. In ERMS. We also demonstrated that the mechanical dyssynchrony measure was able to predicts well the effect of CRT, better than the electrical dyssynchrony measure.By using a coupled biventricular electromechanical models of the canine heart, the optimization of the electrode positions and VV delay timings for CRT with the BiVP have been investigated,  with both the mechanical criterion of CURE and electrical criterion of  In comparison with other computational optimization models of CRT, the mechanical contraction and deformation was included in our model, and the mechanical index CURE was calculated. The results indicated that the LV pacing lead positioning was a very important factor that affecting the consequence of CRT and the hemodynamic changes. Also, the changes of VVD will lead to a variation in the mechanical synchrony and should be considered in the optimization of CRT. Therefore, it was very important for an individual to adjust the electrode position as well as the timing delays to the patient's anatomy and pathology, in accordance with current clinical studies , 37, 38.


Pseudoaneurysms are rare complications of myocardial infarction with propensity for rupture. There is still a challenge with which diagnostic imaging we performed a final diagnosis of pseudoaneurysm and differentiate it from true aneurysm what is clinically important due to the different treatment.We presented the unusual case of a 56-year-old man with signs of decompensated heart failure which had worsened a few months before hospitalization. We believed that during worsening of symptoms the patient suffered a silent myocardial infarction complicated by subacute free wall rupture which resulted into left ventricular pseudoaneurysm formation without tamponade. Echocardiography showed dilatative cardiomyopathy which was already present years before and a very rare location of the left ventricular pseudoaneurysm on the anterolateral part of the left ventricle. Pseudoaneurysm was confirmed with CT scan. Due to the severity of contractile dysfunction and no response in treatment for congestive heart failure the directive for the resection was tempered and the patient died due to the progressive heart failure and embolic phenomena.This report shows the importance of non-invasive imaging diagnostic evaluation of acute decompensated heart failure where echocardiography and chest X-ray are the first diagnostic steps. Based on those findings further imaging diagnostic steps must be performed such as CT scan in our case which finally confirms left ventricular pseudoaneurysm with dilatative cardiomyopathy. Majority of patients with the acute free wall rupture after the myocardial infarction die suddenly, but only a few of them developed ventricular pseudoaneurysm mostly when the rupture is subacute and confined by epicardium, pericardial adhesions and thrombus formation.8Diagnosis of PSALV is mostly confirmed with ventriculography, echocardiography, pulse Doppler, computed tomography (CT), and recently with magnetic resonance imaging (MRI).16We present a pseudoaneurysm in the anterolateral part of the left ventricle in a patient with dilated alcoholic cardiomyopathy who suffered a heart failure a few months ago after a silent myocardial infarction. Our patient was a 56-year-old man who was an alcoholic and his general practitioner reported a repeated abuse of alcohol despite of the psychiatric treatment. We observed a dilated cardiomyopathy for 5 years before he was admitted to our hospital and it had also been confirmed that he had hepatic cirrhosis Child A 7 years before he was admitted to our hospital. He had been treated for heart failure with the ACE inhibitor and spironol-actone but he did not take his medication regularly. We conclude that dilatative cardiomyopathy and hepatic cirrhosis was due the alcohol abuse. Eight months prior the patient’s admittance in hospital, the main finding of the echocardiography was a dilated cardiomyopathy with a severely reduced ejection fraction, but without o segmental loss of contractility or aneurysm of the left ventricle. He was also a smoker.At admission to our hospital the patient complained about progressive dyspnoea, syncope, confusion and 10 kg weight loss during previous 2 months. At physical examination the patient was found to be confused, he had cachexia (56 kg) and jaundice, with blood pressure of 120/95, a regular pulse of 125 beats/min, respiratory rate 27 breaths/min. He had a jugular venous distension to the angle of the jaw at 30 degrees. The chest examination showed dullness on percussion in the basal part of the lungs. The cardiac examination was unremarkable. The liver was enlarged and there was peripheral oedema.On hospital day 1 we performed haematological tests which were normal except mild makrocytosis (MCV 97 fl). Liver function tests were pathological , he had hyperammoniemia (194 μmol/L) and INR were prolonged . The levels of cardiac enzymes and troponine were normal. N-terminal pro-B-type natriuretic peptide (NT-proBNP) was highly elevated (24357 ng/L). EKG showed sinus tachycardia 128 beats/min and QS from V1 to V6 with non-specific mild elevation of ST segment. Chest X-ray showed a large soft-tissue mass contiguous with the apical aspect of the heart . We concThe pathology report confirmed the presence of marked variations in myocyte size; some myocardial cells were hypertrophied and others were atrophied. There were areas of interstitial and perivascular fibrosis. The report was consistent with the dilated cardiomyopathy. Atherosclerosis was found particularly in the left anterior descending (LAD) coronary artery without thrombosis. Apical aneurysm included only fibrous tissue, pericardium and no myocardial cells consistent with a pseudoaneurysm. There were embolic masses in pulmonary circulation beside congestion of the lung.The PSALV is a rare complication of myocardial infarction in which a ventricular free wall rupture at necrosis site and escape of blood are locally contained by adherent pericardium shaping the aneurysmatic sac. The sac progressively enlarges and its internal surface is covered by thrombus. Less often PSALV has been reported in association with cardiac trauma, myocarditis, infective endocarditis, cardiac surgery, rheumatic fever, syphilis and tuberculosis.17PSALV is usually presented with non-specific symptoms as in our case where the patient complained of dyspnoea, syncope, confusion and weight loss. On admission the patient had clinical manifestation of heart failure and also plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) confirmed the diagnosis of heart failure. We also observed Q waves and ST segment changes which are common although non-specific signs of PSALV. Chest X-ray abnormalities are present with abnormal cardiac contour or cardiomegaly in more than 95% of patients. We also observed a large soft-tissue mass contiguous with the apical aspect of the heart . The enlThe most characteristic echocardiographic criteria of PSALV which were also confirmed in our patient include: the saccular space outside the left ventricle, break in the contour of the myocardium, an orifice diameter smaller than the cavity of the pseudoaneurysm and the presence of thrombus in the internal wall of the aneurysmatic sac. The communication between the ventricle and the cavity differentiates the pseudoaneurysm from localized pericardial effusion or haematoma, and a pericardial cyst.Although the diagnosis of PSALV is established by transthoracic echocardiography, further imaging with CT or MRI should be performed because pericardial mass can usually not be differentiated with echocardiography as a true or false aneurysm. The difference between true and false aneurysms is clinically important because false aneurysms have propensity for rupture.Most reports considered surgery as the appropriate treatment for PSALV since untreated pseudoaneurysms have an approximately 30% to 45% risk of rupture. Mortality rates are in patients who underwent surgery from 19% to 35% what was significantly lower than in those who were treated medically (48% to 55%). Operative mortality in most reports is related to the severity of the contractile dysfunction in the reminder of the ventricle.5In our patient physical findings and laboratory evidence of a liver failure  with a documented history of alcohol abuse were consistent with the diagnosis of the alcoholic liver disease. The liver disease was combined with dysfunction of heart due to dilated alcoholic cardiomyopathy and coronary artery disease which was complicated with PSALV.This report highlights the importance of basic non-invasive imaging diagnostic evaluation (echocardiography and chest X-ray) of the acute decompensated heart failure and afterwards the decision for further non-invasive imaging modalities or invasive cardiologic imaging. The case shows that we cannot presume the diversity or combination of the clinical picture based on the clinical ground. CT scan finally differentiates left ventricular pseudoaneurysm from true aneurysm as the complication of a silent myocardial infarction in our patient with alcoholic dilatative cardiomyopathy.


Ectopic accumulation of fat accompanies visceral obesity with detrimental effects. Lipid oversupply to cardiomyocytes leads to cardiac steatosis, and in animal studies lipotoxicity has been associated with impaired left ventricular (LV) function. In humans, studies have yielded inconclusive results. The aim of the study was to evaluate the role of epicardial, pericardial and myocardial fat depots on LV structure and function in male subjects with metabolic syndrome (MetS).A study population of 37 men with MetS and 38 men without MetS underwent cardiovascular magnetic resonance and proton magnetic spectroscopy at 1.5 T to assess LV function, epicardial and pericardial fat area and myocardial triglyceride (TG) content.-1 vs. 3.75 s-1, p = 0.02) LV early diastolic peak filling rate and the ratio of early diastole . The amount of epicardial and pericardial fat correlated inversely with LV diastolic function. However, myocardial TG content was not independently associated with LV diastolic dysfunction.All three fat deposits were greater in the MetS than in the control group (p <0.001). LV diastolic dysfunction was associated with MetS as measured by absolute  and normalized (3.37 sIn MetS, accumulation of epicardial and pericardial fat is linked to the severity of structural and functional alterations of the heart. The role of increased intramyocardial TG in MetS is more complex and merits further study. Cardiovascular diseases are a common co-morbidity of the worldwide obesity epidemic. Abdominal obesity in particular associates with metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM). Excess calorie intake and sedentary lifestyle combined with unfavorable genotype and several environmental factors result in lipid overflow, due to a failure of subcutaneous adipose tissue to expand and store the excess of circulating free fatty acids (FFA). Consequently, ectopic fat accumulates around the viscera and into sites regularly containing only minor amount of adipose tissue, such as the liver, pancreas, skeletal muscle, and heart ,2. Ectop1H-magnetic resonance spectroscopy (1H-MRS) has proved to be a reliable method to noninvasively quantify cardiomyocytic triglyceride (TG) content in vivox100 . An LV e1H-MRS was performed in a 1.5 T MR imager  using a standard flex-coil for signal reception. The spectroscopic volume of interest was placed within the interventricular septum using the end-systolic cardiac cine images in three planes. The localizer images and spectroscopic data acquisition were double-triggered to end-exhalation and end-systole, using Prospective Acquisition Correction navigator echoes  to control for respiratory movement and electrocardiograph-derived R wave to control for cardiac pulsation. Spectral localization and data collection were performed with the PRESS sequence with 35 ms echo time, while repetition time (TR > 3000 ms) did not fall below the respiratory cycle length. Navigator echoes were collected from the lung-diaphragm interface and the end-systole triggering was set at about 80% of the resting heart rate of the subject. The spectra were collected with and without water suppression, using 32 and 4 acquisitions, respectively, and analyzed with jMRUI v3.0 software [For measuring the myocardial TG content, cardiac software  using thsoftware  to deterThe 4-chamber oriented cine images were applied for measuring the epicardial and pericardial adipose tissue area as described previously . All phaU test, unpaired t-test, and the chi-square test, as appropriate. Analysis of covariance was applied to compare the means or medians of LV dimensions and function with adjustment for age. Levene’s test was used to assess homogeneity of variances. To detect determinants of myocardial TG content and epicardial and pericardial fat, univariate age-adjusted analyses were performed. The results of the correlation analyses are presented both with and without Bonferroni correction. Stepwise multivariable regression analyses were used to evaluate the impact of cardiac fat depots on LV diastolic parameters as dependent variables. In univariate analyses, epicardial fat showed a strong relationship with pericardial fat. Therefore, these variables were not forced into the same multivariate model. Differences were considered statistically significant at p < 0.05. Intra- and inter-observer variability was assessed via intra-class correlation coefficients (ICC). Absolute agreement ICCs were calculated via a two-way mixed model for single measures.All statistical analyses were performed with IBM SPSS Statistics for Windows, version 19.0 . Normality of continuous variables was analyzed by the Kolmogorov-Smirnov test. Logarithmic transformation of variables was performed, if necessary. Data are presented as frequencies or percentages for categorical variables, as means ± SD for normally distributed continuous variables, and as medians (range) for skewed variables. Between-group differences were assessed by the Mann–Whitney Clinical and biochemical characteristics and measurements of cardiac fat deposits are summarized in Table An overview of the CMR data adjusted for age is shown in Table Age-adjusted univariate correlation analysis Table  revealedFinally, we used a multivariate correlation analysis to further evaluate the interrelationship between the individual cardiac fat depots and LV diastolic dysfunction Table . We founIntra-observer reproducibility for epicardial fat assessment was high with a ICC of 0.97 and 0.99 for pericardial fat respectively. Inter-observer reproducibility showed ICC of 0.91 for epicardial and 0.96 for pericardial fat.1H-MRS with WIP-sequence, we repeated the sequence in five subjects with varying degrees of myocardial TG content. Shim values and measurement parameters were kept unchanged. The measurements correlated (R2 = 0.9975) with a coefficient of variation of 9.0%.In order to test the repeatability of the To the best of our knowledge, this is the first study utilizing CMR technology to combine the measurements of all three cardiac fat compartments with detailed analyses of LV function in a group of non-diabetic men free of cardiovascular disease. The main findings of the study are as follows: 1) MetS is associated with LV diastolic dysfunction; 2) MetS-linked changes in the structure of LV are rather concentric than eccentric by nature; 3) ectopic accumulation of epicardial and pericardial fat correlates with the degree of LV diastolic dysfunction, and 4) myocardial TG content is not independently associated with LV diastolic dysfunction.In our study, MetS was strongly associated with LV diastolic dysfunction, as demonstrated by lowered LV early diastolic PFR and ratio of early diastole. In earlier studies, reduced PFR in insulin-resistant obese women and in T2DM patients have been reported ,15. RideThe LV mass was similar in the two study groups, but LV concentric remodeling was present only in subjects with MetS. Concentric LV remodeling has been associated with abdominal obesity and is considered as an early sign of obesity-related cardiac remodeling before the development of LV hypertrophy . FurtherMetS is strongly associated with an increased amount of visceral adipose tissue, which in turn is the best predictor of pericardial and epicardial fat according to our previous study . An incrMost studies have focused on epicardial adipose tissue, and a lesser role has been left to pericardial or intra-thoracic fat. In our study, pericardial fat correlated with diastolic dysfunction even on a larger scale of parameters than epicardial fat. Similarly, as a marker of ectopic fat accumulation, pericardial fat has been reported to associate with insulin resistance and 10-year CAD risk more strongly than epicardial fat .Interestingly, unlike other cardiac fat deposits, myocardial TG content was not independently associated with LV diastolic dysfunction in multivariate analysis where other cardiac fat deposits are taken into account. In line with our results, two studies in insulin-resistant women, both without an assessment of epi/pericardial fat, reported the link between the myocardial TG content and diastolic dysfunction as of borderline significance  or negatHowever, in subjects with MetS, myocardial TG content was increased up to two-fold compared with the subjects without MetS. Notably, the range of myocardial TG content 0.14-2.33%) was relatively narrow. Rather than a stable fat deposit, myocardial TG is a highly dynamic lipid pool, where up to three or four-fold increase has been reported following 48–72 h fasting in lean subjects ,33. On t% was relIn conclusion, our study suggests that although myocardial TG is elevated in subjects with MetS, it cannot be used as a surrogate parameter for cardiac function. Further studies are needed to examine the dynamics of intramyocardial lipids, and elucidate the role of their excess in the myocardium.To exclude the effects of hormonal variability, our study population was limited to men. Recently, the association of myocardial TG content and obesity has been studied also in female subjects ,32. In oMetabolic syndrome associates with both structural and functional changes in the heart leading to LV diastolic dysfunction. The amount of epicardial and pericardial fat correlates with the severity of these changes. Myocardial TG increases as well, but it does not seem to act as a mere fat deposit in the same way as epicardial and pericardial fat. Instead, our study favors a more complex role for myocardial TG in obesity associated cardiovascular diseases.1H- magnetic resonance spectroscopy; ICC: Intra-class correlation coefficient; LV: Left ventricular; LVGFI: Left ventricular global function index; HOMA: Homeostasis model assessment; MetS: Metabolic syndrome; PFR: Peak filling rate; SV: Stroke volume; T2DM: Type 2 diabetes mellitus; TG: Triglyceride.BMI: Body mass index; BSA: Body surface area; CAD: Coronary artery disease; CMR: Cardiovascular magnetic resonance; EDV: End-diastolic volume; ESV: End-systolic volume; FFA: Free fatty acid; 1H-MRS: The authors declare that they have no competing interests.MRT conceived the study and all other authors assisted with the study design. KN and KL were responsible of CMR data and analyses, and JL and AH carried out MRS acquisition and analyses. MG, MP, and RS were involved in the subject recruitment and screening. MG performed statistical analyses and MG, MRT, KN, MP, and KL contributed to the data interpretation. KN and MG assembled the figures and tables. KN drafted the manuscript with the help of MG, MP, and KL, NL, MRT, KL, and MN provided supervision and expert advice, and revised the manuscript critically for important intellectual content. All authors read and approved the manuscript.


Due to time constraints, the T2 maps are commonly acquired as one or several two-dimensional slices, while the underlying pathology has a three-dimensional (3D) structure. The next logical step would therefore be to exploit recent hardware and software advances to directly acquire 3D T2 maps. To this end, we tested the feasibility of using a self-navigated 3D radial acquisition with a variable T2Prep for 3D T2 mapping at 3T.Cardiac T3, flip angle 70°) with a spiral phyllotaxis radial 3D trajectory  was implemented on a 3T clinical system . This self-navigated pulse sequence allows free breathing acquisitions with 100% scan efficiency, while ECG triggering every 2 heartbeats and TET2Prep=60/30/0ms allow for a total acquisition time of ~18min with an isotropic spatial resolution of (1.7mm)3. The datasets were registered using 3D affine registration . Through Bloch equation simulations, the heart-rate-dependent T1 -relaxation-related offset in the T2-fitting equation was ascertained. Subsequently, the validity and accuracy of the T2 fitting was tested in a phantom whose "true" T2 values were previously determined. The in vivo robustness of the T2 determination was then tested in 9 healthy adult subjects. Finally, the sequence was applied for the detection of edema in a 75-year-old male infarct patient after revascularization of his proximal left circumflex.Approval was obtained from the institutional review board. A 3D self-navigated undersampled balanced steady-state free precession (bSSFP) sequence . A region of significantly elevated T2 (60.4±9.1 vs. 41.0±4.5ms) was identified in the patient in the infero-lateral myocardium of the left ventricle (Fig.The Bloch equation simulations of the pulse sequence demonstrated that the input Tates Fig.. The phan 1% Fig.. The voln 1% Fig. suggesteicle Fig., consist2 maps of the whole heart. Accurate T2 values were obtained in the phantom, while those in volunteers are consistent with previously reported values. The preliminary patient study demonstrated elevated T2 in the infarcted region as expected.The proposed technique provides an easy and time-efficient way to obtain accurate isotropic TFoundation Emma Muschamp


A low resting heart rate (HR) is prognostically favourable in healthy individuals and in patients with left heart disease. In this study we investigated the impact of HR at diagnosis on long-term outcome in patients with differently classified precapillary pulmonary hypertension (pPH).pPH patients diagnosed as pulmonary arterial (PAH) or inoperable chronic thromboembolic pulmonary hypertension (CTEPH) were registered and regularly followed at our centre Baseline characteristics and events defined as either death or lung transplantation were noted. The prognostic value of HR was analysed using Kaplan Meier estimates, live tables and Cox regression.206 patients with PAH (148) and inoperable CTEPH (58) were included. The median HR was 82 bpm. pPH with a HR below 82 bpm had a significantly longer overall event-free survival . This advantage was similarly found if PAH and CTEPH were analysed separately. Although a lower HR was associated with a better hemodynamic and functional class, HR was a strong and independent prognostic marker for transplant free survival even if corrected for age, sex, hemodynamics and functional status.We show that resting HR at diagnosis is a strong and independent long-term prognostic marker in PAH and CTEPH. Whether reducing HR by pharmacological agents would improve outcome in pPH has to be assessed by future trials with high attention to safety. A lower resting heart rate (HR) is prognostically favourable in healthy individuals or in patients with cardiovascular disease -3. An inThe prognostic role of the HR in right sided heart failure due to precapillary pulmonary hypertension (pPH) is less clear. Studies have shown that an increased resting HR was a marker for disease burden and herewith associated with an unfavourable prognosis in patients with pulmonary arterial hypertension (PAH) ,6. CompaPatients who were diagnosed with pPH by right heart catheterisation (RHC) and classified in PAH or CTEPH by WHO  gave theThe study was performed according to the Declaration of Helsinki, ICH-GCP as well as all national legal and regulatory requirements. National and international guidelines did not require institutional review board approval because this study was retrieved from our prospective registry.All baseline data is summarized by mean ± standard deviation (SD) or medians (quartiles). Baseline variables by groups were compared using Mann-Witney-U-Test and Fisher-Test. Differential survival was assessed by Kaplan Meyer analysis and live tables, significance was tested by log-rank test and fishers test. Cox regression analysis was used for multivariate survival analysis. A p < 0.05 was considered significant. SPSS 19.0.0  and Excel were used.222 patients with pPH having had baseline evaluation with diagnostic RHC between January 1998 and June 2011 were included. 16 patients with subsequent pulmonary endarterectomy were excluded according to the protocol.-5. Conventional medical treatment at baseline consisted of diuretics and oral anticoagulation. After baseline evaluation HR assessment, the following treatments had been started: Endothelin-1 receptor antagonists (85), Phosphodiesterase inhibitors (34), inhaled (63) or parenteral Prostanoids (8) and calcium antagonists  are shown in Table During the median follow-up of 37  months, 24 patients died (18 PAH and 6 inoperable CTEPH), and 3 received lung transplantation (1 PAH and 2 CTEPH). Median overall survival was 4.8 years.2 61 ±11 vs. 57 ±10, p = 0.014). We found no other baseline differences and the overall event-free survival were similar in both classes .Patients with PAH were significant younger at baseline compared to CTEPH  and had a higher mixed venous oxygen saturation . Median survival were 2008 and 1766 vs. 4028 and 3170 days for cut offs of 70 and 75 bpm (p = 0.087 and p = 0.002), respectively. The cumulative Kaplan Meyer survival differences did not reach statistical significance for the cut off of 70 bpm (log rank p = 0.069) but highly significant for the cut off of 75 bpm. A relatively high HR cut off of 92 bpm still revealed an advantage for patients with a HR below this value (p = 0.001).If, in analogy to left heart failure studies ,3, lowerIn a multivariate Cox regression model including sex, age, PVR and HR, the resting HR was the strongest independent survival predictor (p < 0.0001). Baseline resting HR remained the strongest independent predictor of survival even when WHO functional class or the 6MWD were additionally included in the model (p < 0.0001 and p = 0.002). Resting HR persisted as strongest independent predictor even if the PVR was replaced by the cardiac index (p < 0.0001) or the right atrial pressure (p = .002) in the multivariate regression model.In this long-time follow up collective of well characterized patients with PAH and CTEPH we found that a low resting HR at diagnosis was a strong and independent predictor of a favourable long-term outcome overall and for both groups separately. pPH patients with a resting HR below thresholds of 75 to 82 bpm had a markedly and significantly prolonged median survival compared to patients with higher resting HR. A lower resting HR remained an independent predictor of favourable outcome even if corrected for demographics, pulmonary hemodynamic, exercise capacity and functional class.Many epidemiological studies in left heart failure have shown that a reduction of the HR improves cardiovascular outcome ,3, impliOne explanation might be that the decreased diastolic filling time due to a shortened heart cycle does not allow sufficient myocardial perfusion to supply adequate oxygen to the diseased heart. Another reason might be that the augmented sympathetic activity leading to an increased HR is overshooting and, in turn, has adverse effects itself. The fact that not only sympathetic blockade by beta receptor blockers, but also mere HR reduction by Ion channel modification, result in a better outcome in patients with left heart failure points against the hypothesis of a single sympathetic adverse effect responsible for higher HR along with unfavourable outcomes ,12.In this study we could demonstrate that a lower resting HR is not only a favourable prognostic factor in patients with left heart failure, but also in patients with right heart failure due to differently classified pPH. Although patients with a lower resting HR had a better hemodynamic profile, functional class and relatively preserved exercise capacity, the fact that the resting HR remained an independent prognostic factor even if corrected for age, sex, pulmonary vascular resistance, exercise and functional capacities underscores that resting HR not only reflects the degree of disease burden but represents an independent predictor by itself in patients with pPH.Although several studies linked a lower resting HR to longevity in healthy individuals and especially in patients with left heart disease ,2,13,14,Recent guidelines do not include HR as prognostic marker, as the prognostic significance of HR in right heart failure due to pulmonary vascular disease had not been sufficiently studied ,16. Our At physiological pressures, the thin-walled, highly compliant RV can accommodate with high volumes (preload-dependency) . HoweverOur study is relatively small, however, pPH is a rare disease and we can provide robust long-term flow-up data in a thoroughly investigated and well followed pPH collective. Resting HR was carefully obtain after at least 10 minutes of rest with stable continuous hemodynamic curves on the monitor over at least 10 minutes. In summary, our data show for the first time that baseline resting heart rate is a strong and independent long-term prognostic factor in a broad pPH collective including PAH and CTEPH. Whether reducing HR by pharmacological agents would improve outcome in pPH has to be assessed by future designed trials with high attention to safety.6MWD: 6 minute walk distance; CI: Cardiac Index; CTEPH: Chronic Thromboembolic Pulmonary Hypertension; HR: Heart Rate; LHF: Left Heart Failure; mAP: Mean Arterial Pressure; mPAP: Mean Pulmonary Arterial Pressure; NYHA: New York Heart Association; PAH: Pulmonary Arterial Hypertension; pPH: Precapillary Pulmonary Hypertension; PVR: Pulmonary Vascular Resistance; RHC: Right Heart Catheterisation; SVR: Systemic Vascular Resistance; WHO: World Health Organisation.The authors declare that they have no competing interests.FFH was involved in acquisition of data, analysis and interpretation of data, drafting the manuscript and revising it critically for important intellectual content and provided final approval of the version to be published. IF was involved in the interpretation of data and critical reading and revision of the draft manuscript, and final approval of the manuscript. LCH and SK made substantial contributions to the current study and publication, participating in the study process, analysis of data, development and revisions of the manuscript and has approved the final manuscript draft. RS was involved in the interpretation of data and critical reading and revision of the draft manuscript. SU developed the concept of this study, was involved in analysing the data, carried out the statistical analysis and participated in the interpretation, the critical revision of the study and final approval of the manuscript.All authors had full access to the data and read and approved the final manuscript.


The pericardium plays an important role in optimizing cardiac motion and chamber pressures and serves as a barrier to pathology. In addition to pericardial anatomy and function, this review article covers a variety of pericardial conditions, with mention of potential pitfalls encountered during interpretation of diagnostic imaging. Normal and abnormal appearance of pericardium on CT and MR imaging is emphasized, including dynamic imaging correlates of pericardial pathophysiology. More than just a tissue, the pericardium is an organ with specific functions and an embryologic origin distinct from the heart. Whereas the heart is derived from splanchnic mesoderm, the pericardium is derived from somatic mesoderm –3. Long-As with other organs, the pericardium is subject to various disease processes, include inflammatory, infectious, fibrotic, metabolic, and neoplastic. Imaging of these processes has advanced significantly in the past decade, with the refinement of multidetector CT and high-field-strength MRI. CT and MR permit visualization of the entire pericardium by virtue of three-dimensional acquisition and multiplanar imaging, respectively, and provide better assessment of surrounding structures than the prior standard of echocardiography . In addiAs with the other serosal surfaces of the body, the pericardium has parietal and visceral layers. The parietal layer of pericardium is several times thicker than the visceral pericardium . The norNormal pericardial recesses occur due to the closer apposition of the visceral layer than the parietal layer to the contours of the heart and great vessels. Also, portions of the left atrium are left uncovered by pericardium to a variable degree . These fOn a scale from 1 to 9, 1 being the least appropriate and 9 being most appropriate, both CT and MR are assigned a score of 8 for the evaluation of pericardial disease (per a multisociety consensus statement) , 15.ECG-gated multidetector row CT is useful for pericardial imaging, with a minimum of 16 detector rows, but preferably 64 or higher. If inflammatory, infectious, or neoplastic etiologies are considered, delayed imaging after intravenous contrast administration is preferred over first-pass cardiac imaging to permit the contrast bolus to clear the great vessels. This reduces blooming and streak artifacts and allows time for inflamed or neoplastic tissues to optimally enhance.Like echocardiography, MR can demonstrate morphology and function. MR affords advantages such as better tissue characterization, visualization of adjacent noncardiac structures, and lack of acoustic window constraints, allowing the entire pericardium to be imaged  16]. MR. MR16]. As pericardial fluid volume is not easily measured, pericardial effusion can be defined as separation of the parietal and visceral layers by a sufficient amount of fluid to be detected on imaging . The differential diagnosis of pericardial effusion is extensive  but can In the case of physiologically significant pericardial effusions, the absolute volume is less important than rate of fluid volume accumulation. Only 150–250 mL of pericardial sac fluid is needed to cause tamponade acutely, whereas slow accumulations, such as in thyroid myxedema, can reach 3 L without tamponade, as the pericardium will remodel over time , 20, 21.Normally, intrathoracic pressure changes are transmitted through the pericardium to the cardiac chambers, with respirophasic influence upon systemic venous return and right ventricular filling. In addition, the right and left ventricles are affected by pressure differences between them transmitted across the interventricular septum, normally higher on the left, with convex border of the septum relative to the right ventricle chamber. In the setting of tamponade, the cardiac chamber pressure differences are diminishingly influenced by intrathoracic pressure changes with respiration, leaving transseptal pressure differences to exert their effects upon the cardiac chambers, a phenomenon known as ventricular coupling or ventricular interdependence , 22.On dynamic imaging, ventricular interdependence is manifested by rocking motion of the interventricular septum during the cardiac cycle. Specifically, the septum moves toward the left ventricle in early diastole as the right ventricle fills with systemic blood resulting in a transient relative elevation of right heart pressure. The septum moves back toward the right ventricle only in late diastole as the pressure on the left eventually exceeds that of the right. With prolonged or severe tamponade, right ventricular filling becomes impaired as right ventricular end-diastolic pressure  approaches central venous pressure. On imaging, this can be suspected if the contrast bolus refluxes into dilated hepatic veins or collateral vessels  23]. Th. Th23]. Noncompliance of the pericardium that results in impaired cardiac function is called constriction . TamponaMR techniques have emerged which surpass both CT and echocardiography in the diagnosis of pericardial constriction. Morphology is assessed by measuring thickness of the entire pericardium in multiple planes. Function is evaluated by assessing pericardial motion in relation to myocardial motion, typically via steady-state free precession sequences, in combination with cine tagged imaging . In the The impact of pericardial function on myocardial motion can be inferred by observing motion of the interventricular septum during MR cine imaging . FlattenNonsuppurative pericarditis may be acute, chronic or recurrent. In otherwise healthy patients, pericarditis is often ascribed to an undiagnosed viral infection . In patiStaphylococcus, Streptococcus, Haemophilus, Propionibacterium, and Mycoplasma . Of these, primary neoplasm is the least common , 35. BenSymptoms related to neoplastic involvement of the pericardium are often mild, due to the long period of time typically required for pericardial masses and malignant effusions to enlarge . When acPericardial metastases are more common than suspected on clinical grounds, as they are found in 1.5 to 22% of autopsy specimens of patients who died from cancer . In otheThe pericardium can be affected by a variety of pathologies with important physiologic consequences. In acute pericardial dysfunction from rapid pericardial fluid accumulation , death may occur rapidly in the absence of intervention. In more chronic conditions, pericardial dysfunction from constriction can be treated surgically via resection or window placement. Echocardiography remains an important first-line imaging modality in the evaluation of pericardial disease, particularly in the acute setting at the bedside. The development of multidetector CT and cardiac MR pulse sequences has improved the ability of diagnostic imagers to evaluate pericardial disease and dysfunction on static and dynamic imaging, allowing more timely and appropriate treatment.


With TDI, we measured the standard deviation and the maximal difference in time from the QRS onset to the peak systolic velocity for 12 left ventricular myocardial segments, i.e. Ts-SD and Ts-Dif, respectively. The results showed that the Tmsv16-SD% and Ts-SD in the AAI mode were significantly lower than those in the DDD and VVI modes (P<0.05); however, there were no significant differences between the DDD and VVI modes (P>0.05). The LVEF in the AAI, DDD and VVI modes was 63.1±8.9, 58.6±11.2 and 57.9±7.6%, respectively (P>0.05). There were negative correlations between the LVEF and Tmsv16-SD%  and Ts-SD . A moderate correlation  was observed between Tmsv16-SD% and Ts-SD. The concordance rate between Tmsv16-SD% and Ts-SD for detecting LVMD was 76%. This study showed that DDD and VVI pacing modes induced significant LVMD and a reduction in LVEF, unlike the AAI pacing mode. RT3DE and TDI were capable of objectively evaluating LVMD; however, each method had certain faults. At present, there is a lack of a uniform standard for assessing LVMD; therefore, the use of a variety of techniques and indices is necessary in order to comprehensively evaluate LVMD in patients with different cardiac pacing modes.The aim of this study was to evaluate the left ventricular mechanical dyssynchrony (LVMD) and left ventricular dysfunction of patients in AAI, DDD and VVI pacing modes using real-time three-dimensional echocardiography (RT3DE) and tissue Doppler imaging (TDI). The results from the RT3DE and TDI were subsequently compared. Twenty patients with sick sinus syndrome (SSS) who had undergone the implantation of a dual-chamber pacemaker were enrolled in this study and the pacemakers were programmed to AAI, DDD and VVI modes, sequentially. The RT3DE and TDI parameters were obtained following pacing for 24 h in each mode. With RT3DE, we measured the systolic dyssynchrony indices, including Tmsv The use of an optimal pacing mode for the treatment of bradycardia is important. In patients with sick sinus syndrome (SSS), DDD and VVI pacing modes may increase the risk of congestive heart failure, atrial fibrillation and thromboembolism –3. The mEchocardiography is important in assessing LVMD and LV function. At present, real-time three-dimensional echocardiography (RT3DE) and tissue Doppler imaging (TDI) are the most sensitive and commonly used techniques for the quantification of LVMD. The aim of the present study was to: i) evaluate LVMD and LV function in different pacing modes using RT3DE and TDI; and ii) compare dyssynchrony indices derived from RT3DE with different TDI indices when acquired from the same patients. To the best of our knowledge, this is the first time a study of this nature has been performed. The study may provide objective data to act as a foundation for clinical physicians when choosing optimal pacing modes.Twenty patients, including 12 males and 8 females , with SSS and intact intrinsic atrioventricular (AV) conduction were enrolled during the period from August 2011 to December 2012. All patients received dual-chamber pacemaker implantation with the atrial leads placed in the right atrial appendage and the right ventricular leads positioned in the right ventricular apex. The patients had normal cardiac function , normal cardiac anatomy and no history of cardiovascular diseases. Any patients with atrial fibrillation, coronary heart disease, cardiomyopathy, AV conduction block and other rhythm disturbances were excluded. Pacemakers were provided by Medtronic , Biotronik SE & Co. KG  and St. Jude Medical, Inc.. . All the pacemakers were programmed with a basic rate of 70 bpm. The paced AV delay in the dual chamber pacing was programmed to 150±23 msec. All patients volunteered to participate in the study and were included once spoken and written informed consent had been received. The study protocol was approved by the Ethics Committee of the Affiliated Wuxi People’s Hospital of Nanjing Medical University .Dual-chamber pacemakers were programmed for AAI, DDD and VVI pacing modes, respectively, i.e. the AAI pacing mode was initially programmed in all patients, prior to the pacemakers being programmed from AAI to DDD modes and then from DDD to VVI modes. Subsequent to pacing being performed in each mode for 24 h, the RT3DE and TDI images were acquired, respectively.16-SD); as well as 12 segments, i.e. 6 basal and 6 middle segments (Tmsv12-SD), and the 6 basal segments (Tmsv6-SD) of the left ventricle in each patient. In addition to the Tmsv index, the maximal difference (Dif) in time from the QRS onset to the minimal regional systolic volume for the l6, 12 and 6 segments of the left ventricle  was automatically calculated. All the systolic dyssynchrony indices were normalized as percentages of the RR-interval   by employing an X3 matrix transducer. The individuals were asked to hold their breath and the images were coupled with an electrocardiographic record. The images were stored in the hard disk of the echocardiography system for further offline analysis with special software  for the same equipment. The parameters evaluated using RT3DE included LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LVEF and RT3DE volume-time curves (VTCs). The left ventricle was divided into 17 segments, from apex to base, according to the segmentation schema of the American Heart Association and the American Society of Echocardiography , and thev6-Dif%) . The cutTDI echocardiograms were acquired using the iE33 echocardiography system with a broadband transducer . The images were coupled with an electrocardiographic record. The TDI echocardiographic examinations were performed in accordance with the guidelines of the American Society of Echocardiography . The parThe RT3DE and TDI analysis of each patient was undertaken by three different observers and the data shown are the mean of three consecutive measurements.2 test was used to compare categorical variables. Data were processed with a statistical analysis software . P<0.05 was considered to indicate a statistically significant difference.Continuous variables are presented as the mean ± SD. A one-way analysis of variance (ANOVA) test was used to evaluate the differences among the three modes and a Student-Newman-Keuls test was performed to make a comparison between two modes. Non-parametric tests were used if the data were abnormally distributed or showed heterogeneous variance. To evaluate the correlation analysis, Pearson’s correlation method (r) was employed and the χ16-SD% (2.9±1.6) and Tmsv16-Dif% (5.8±2.6) in the AAI mode were significantly lower than those in the DDD mode  and the VVI mode . The same trends were also observed for Tmsv12-SD%, Tmsv12-Dif%, Tmsv6-SD% and Tmsv6-Dif%. These results showed that LV systolic synchronization in the AAI mode was superior to that in the DDD and VVI modes. However, no significant difference between the DDD and VVI modes was observed (P>0.05). The VTCs of the AAI, DDD and VVI pacing modes are shown in The descriptive analysis of RT3DE-derived LV dyssynchrony indices in patients with AAI, DDD and VVI pacing modes are shown in The descriptive analysis of TDI-derived LV dyssynchrony indices in patients with AAI, DDD and VVI pacing modes are shown in 16-SD% was −0.651 , while the correlation between Tmsv16-Dif% and Ts-SD was 0.636  pacing may lead to abnormal electrical activation and LV dyssynchrony –13. CardAt present, a number of different types of echocardiographic technologies are used as major methods for the evaluation of LVMD; however, there is no gold standard. In our prospective study, we attempted to quantify LV dyssynchrony and cardiac function in patients with AAI, DDD and VVI pacing modes using RT3DE, and compared the results from the RT3DE with the different dyssynchrony indices derived from TDI for the same patient. Previous studies have indicated that measuring the standard deviation and the maximal difference in time from the QRS onset to the peak systolic longitudinal velocity for 12 LV myocardial segments using TDI is useful for quantifying systolic dyssynchrony ,16–20. HIn the present study, the RT3DE and TDI-derived dyssynchrony indices in the AAI mode were significantly lower than those in the DDD and VVI modes (P<0.05); however, there was no significant difference between the DDD and VVI modes (P>0.05). These results showed that LV synchronization in the AAI mode was significantly superior to that in the DDD and VVI modes. In the AAI pacing mode, normal AV, left-right inter- and intraventricular conduction sequences were maintained, which was consistent with physiological ventricular activation; therefore, the synchronization of the AAI pacing mode was normal. In the DDD pacing mode, while the AV conduction sequence was maintained, the normal inter- and intraventricular conduction sequences were lost due to RVA pacing, which induced systolic and diastolic mechanical dyssynchrony. With regard to the VVI pacing mode, normal inter- and intraventricular conduction sequences, in addition to the AV conduction sequence, were lost. Therefore, the dyssynchrony in the VVI mode was worse than that in the DDD mode, although our study revealed no significant differences between the two modes (P>0.05).16-SD% and Ts-SD were inversely correlated with LVEF , which is consistent with previous studies . Previous studies have demonstrated an acute reduction in the LVEF of 6–13% following the initiation of DDD and VVI pacing ,22. In a studies ,24. Thes16-SD% and Ts-SD was 76% in the current study. A previous study showed that Ts-SD and Tmsv16-SD% had a concordance rate of 56.5% and when there was no agreement between the two indices, it was observed that Ts-SD was abnormal in 38% of patients and Tmsv16-SD% was abnormal in 8% . A possible explanation is that it is not possible to perform examinations in certain segments, such as the apex, with TDI whereas RT3DE enabled 16 segments of the whole left ventricle to be analyzed. Furthermore, TDI only studied longitudinal cardiac motion, while RT3DE was able to analyze the longitudinal, circumferential and radial cardiac mechanical motions. This result was controversial, taking previous studies into consideration. A number of studies have revealed contradictory results concerning RT3DE and TDI indices, ranging from poor  ,26 to goal in 8% . However16-SD% had a high concordance rate with the well-established TDI-derived dyssynchrony index Ts-SD. In the same patient, there was variability in the incidence of LVMD depending on the echocardiographic method used. Due to the lack of gold standard for the evaluation of LVMD, two different echocardiographic dyssynchrony indices appear to provide complementary, rather than opposing, information regarding the presence of LVMD. In clinical applications, if the conditions permit, it is preferable for all pacemakers to be programmed in the AAI mode, in order to reduce LV ventricular dyssynchrony, heart dysfunction and complications and to improve the survival rates.In conclusion, this study demonstrated that RT3DE and TDI were able to objectively and accurately evaluate LV function and LVMD in patients with various pacing modes and that LV systolic synchronicity in the AAI mode was superior to that in the DDD and VVI modes. The RT3DE and TDI-derived LV dyssynchrony indices increased with worsening LVEF. In addition, the RT3DE-derived dyssynchrony index TmsvThe present study had certain limitations. In particular, the study was a self-contrasted and was a single center study with a small sample size. A gold standard for the validation of the various dyssynchrony indices does not exist to date. It is necessary to note that the relatively low temporal and spatial resolution of RT3DE imaging may make the feasibility of this technique in the overall population limited. The current study only analyzed the changes in the different pacemaker modes in the acute phase; therefore, the acquisition of data from long-term follow-up studies is necessary. Furthermore, compared with the results from the RT3DE, only longitudinal cardiac motion was studied with TDI; it is possible that a stronger correlation may have been identified with other methods, such as circumferential or radial strain analysis using speckle tracking. In this study, the right ventricular leads were placed in the right ventricular apex; further discussion regarding the LVMD in patients with different pacing modes may be appropriate when the right ventricular leads are placed in the right ventricular outflow tract.


The aim of this study was to quantify the effects of right ventricular apical pacing (RVAP) on hemodynamics in left anterior descending coronary artery (LAD) and anterior interventricular vein (AIV) contrast to baseline condition in open chest beagles using Doppler ultrasound imaging.In 6 anesthetized open chest beagles, the spectral Doppler waveforms of the middle segmental LAD and the AIV were acquired with a 5 MHz linear array transducer at baseline condition and during RVAP. The aortic pressure-time curves were recorded synchronously. The Doppler hemodynamic parameters of the LAD and AIV at both states were derived and compared.P<0.001), and the acceleration of the Dp decreased . The spectral Doppler waveforms of the AIV only had a principal positive wave (Sp) at baseline condition, but an additional diastolic negative wave appeared during RVAP. The duration of the Sp shortened , and the acceleration of the Sp decreased .The spectral Doppler waveforms of the LAD had a principal diastolic positive wave (Dp), which heelled by a momentary negative wave and a positive wave during early systole at baseline condition. During RVAP, an additional negative wave appeared in the LAD at late systole. The duration of the Dp shortened (227.83±12.16 ms vs 188.50±8.97 ms, Obvious hemodynamic changes in the LAD and AIV during RVAP were observed, and these abnormal flow patterns in epicardial coronary arteries and vena coronaria may be sensitive and important hints of the disturbed cardiac electrical and mechanical activity sequences. Cardiac pacing is one of the most important medical innovations of the 20th century, which is poised to help millions of patients worldwide to live better Healthy heart has perfectly electromechanical synchrony, and the coronary artery and vena coronaria must have its homologous unique blood flow patterns. RVAP will definitely induce ventricular asynchrony, which has been confirmed as an unphysiologic pacing mode. We hypothesize that: 1) Hemodynamic characteristics of the left anterior descending coronary artery (LAD) and the anterior interventricular vein (AIV) in healthy hearts may be important reflections of physiological cardiac electrical and mechanical activity sequences. 2) Hemodynamics in the LAD and the AIV might be changed by RVAP, and such changes could be taken as a new window for insight the disturbed cardiac electrical and mechanical activity sequences.Blood stream in the LAD of open chest dogs can be imaged clearly by Color Doppler ultrasound with linear array transducer All animals involved received humane care in compliance with accredited facilities of Chinese Association for Accreditation of Laboratory Animal Care. The studies and animal care protocols were reviewed and approved by the Institutional Care and Animal Research Committee of Sichuan Provincial People's Hospital. This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the Ethics Committee of Sichuan Provincial People's Hospital. Each surgery was performed under general anesthesia, and all efforts were made to minimize suffering.2, ventilation frequency: 20 bpm, tidal volume: 10–15 ml/kg/min . Supplemental doses of anesthetics were given throughout the experiment to suppress the medial ocular reflex. Arterial blood gases and pH were kept stable by adjusting ventilation or bicarbonate infusion. All the sheaths and catheters were washed and filled using heparin sodium solution before insertion. The heart was exposed adequately by a lateral thoracotomy and suspended in a pericardial cradle. Under the monitoring of gray-scale echocardiography, a 7F Millar catheter tip was introduced into the aortic root via left carotid artery, with electrocardiography (ECG) and pressure monitoring . A bipolar pacing electrode lead was implanted directly into the subepicardium of right ventricular apical anterior wall after baseline data collection had been completed. RVAP was performed with fixed pacing rate at 160 bpm, and with fixed pulsed stimulating voltage at 2 volt .Six healthy beagles  were provided by Experimental Animal Institute of Sichuan Academy of Medical Sciences. Preoperative 12 hours fasting was applied to each animal. Intramuscular injection of atropine 0.5 mg and aminazine 50 mg were used for sedation. And thirty minutes later, ketamine 100 mg and fentanyl 100 mg were given intramuscularly for anesthesia. Anaesthetizd beagles were placed in a supine position. A polyvinyl cannula was inserted into the left femoral vein for drug and fluid administration. Slow intravenous infusion of saline maintained hydration throughout surgery, and anesthesia was maintained using continuous intravenous infusion of ketamine (500 mg/h) and fentanyl (500 mg/h). Mechanical ventilation was used via an orotracheal tube with 40–60% OCommercially available ultrasonic equipment  with a 1–5 MHz phased array cardiac transducer (UST-52101) and a 4–13 MHz linear phased array transducer (UST-5412) was utilized for all beagles ultrasonic imaging. The left ventricle (LV) real-time two-dimensional gray-scale images of standard apical 4-chamber view and standard apical 2-chamber view in 3 consecutive cardiac cycles were acquired with the phased array cardiac transducer and stored both at baseline conditions and during RVAP for measurement of the LV volumetric parameters. For assessment of global LV diastolic function, we acquired and measured LV isovolumetric relaxation time (IVRT), LV early peak filling velocity (E), and early diastolic velocity of mitral annulus (e′). The e′ was the average tissue Doppler velocity of the septal and lateral sides of mitral annulus during early diastole. The septal E/e′ ratio (E/e′) was calculated. The linear phased array transducer was applied to acquire the gray-scale images, the color Doppler flow images, and the spectral Doppler waveforms of the LAD and the AIV at both states. The preset for periphery arteries application was used, and the center frequency of the linear transducer was set at 5 MHz. The middle segments of the LAD and AIV, which just distal to the first diagonal branch, were interrogated in this study . To mainAll of the under-mentioned quantitative data were measured 3 times on 3 different cardiac cycles, and the average values were calculated and recorded. All the time parameters at baseline condition were normalized by making linear correction in light of the fixed heart rate of 160 bpm.LAD) or the maximal diameter of the AIV (ΦAIV) was measured on the static images respectively. When we measured the ΦLAD, the interval between the LAD and the AIV was recorded at the same time.LV end diastolic volume (LVEDV), end systolic volume (LVESV), stroke volume (LVSV), ejection fraction (LVEF) and cardiac output (CO) were derived via biplane Simpson rule. The real-time gray-scale images of the LAD and AIV at its minor axis cut plane were retrieved frame by frame until the maximal area of the LAD or the maximal area of the AIV appeared, then the maximal diameter of the LAD (ΦO) in the ECG to the measure point of AoDP on the synchronous aortic pressure-time curve (TAoDP) and the time from the QRSO in the ECG to the measure point of AoSP on the synchronous aortic pressure-time curve (TAoSP) (The aortic diastolic pressure (AoDP) and the aortic systolic pressure (AoSP), and the aortic pressure upstroke time (T) were measured through pressure-time curves stored in electrophysiologic equipment. And the aortic pulse pressure difference (△P) and the mean upstroke velocity of the aortic pressure (△P/T) were calculated: △P = AoSP−AoDP; △P/T = (AoSP−AoDP)/T. We also measured the time from the onset of the QRS (QRS (TAoSP) .Spectral Doppler waveform analysis was performed on the ultrasonic machine. Various Doppler hemodynamic parameters were acquired according to the different spectral Doppler waveforms of the LAD and the AIV at each state.Two double-blinded examiners repeatedly performed the spectral Doppler waveform analysis for intraobserver and interobserver analysis of the Doppler hemodynamic parameters of the LAD and the AIV. The second observer repeated the measurements 2 weeks after the first time.t test. Correlation analysis was performed between the aortic pressure parameters and the Doppler hemodynamic parameters of the LAD and the AIV. The bias tests for intraobserver and interobserver agreement were compared using paired t test. And intraobserver and interobserver variability was assessed by calculating the coefficient of variability. Statistical significance was defined as P<0.05. For P values <0.000, a value of <0.001 was chosen.Statistical tests were performed with SPSS 13.0 statistical software . Quantitative data are expressed as mean ± SD. We tested for data normality using the Shapiro-Wilk test. The cardiac volumetric parameters, the aortic pressure parameters, and the Doppler hemodynamic parameters of the LAD and the AIV were compared between each state respectively using the paired Student P<0.001). The LVEDV, the LVSV, the LVEF, the IVRT, the E, the e′, the E/e′, the AoSP, the AoDP, the △P, and the △P/T decreased during RVAP (P<0.01). The TAoDP and the TAoSP lengthened during RVAP (P<0.001).We found statistical significance existing in the LV function parameters and the aortic pressure parameters between each state except for the LVESV and the CO . The heaLAD and the ΦAIV at both states . And no statistical significance was found in the ΦLAD, the ΦAIV, and the ILAD-AIV between each state  The LAD at both states had a principal positive wave (Dp) during diastole, and heeled by a momentary negative wave (S1) and a positive wave (S2) during early systole. 2) Transitory cessation flow in the LAD during mid to late systole at the baseline condition. 3) During RVAP, an additional negative wave (S3) appeared at late systole that did not exist in the LAD at baseline condition.In all animals, the spectral Doppler waveform characteristics of the AIV were: 1) The AIV only had a principal positive wave (Sp) at baseline condition, and the Sp appeared at the middle systole and lasting almost the whole diastole. 2) A momentary cessation flow at the end of diastole in the AIV at baseline condition. 3) During RVAP, the Sp appeared at the early systole and heeled by an additional diastolic negative wave (D1) that did not exist in the AIV at baseline condition.P<0.001). 3) The accelerating time of the Dp lengthened, the acceleration of the Dp and the percentage of the duration of the Dp (D-Dp%) decreased during RVAP (P<0.001). The D-Dp% was calculated as the percentage of the duration of the Dp divided by the R-R interval. 4) The time from the QRSO to the onset of the Dp and the time from the QRSO to the peak of the Dp lengthened during RVAP (P<0.001). 5) The peak velocity of the S3 in the LAD during RVAP was 24.84±3.01 cm/s, and its duration was 25.06±1.69 ms.Compared between each state: 1) No statistical significance was found in the peak velocity of the Dp, the peak velocity of the S1, and the peak velocity of the S2 between each state. 2) The duration of the Dp shortened, but the duration of the S1 and the duration of the S2 lengthened during RVAP (P<0.001). The D-Sp% was calculated as the percentage of the duration of the Sp divided by the R-R interval. 2) The time from the QRSO to the onset of the Sp and the time from the QRSO to the peak of the Sp shortened during RVAP (P<0.001). 3) The accelerating time of the Sp lengthened, and the acceleration of the Sp decreased during RVAP (P<0.001). 4) The peak velocity of the D1 in the AIV during RVAP was 7.22±1.41 cm/s, and its duration was 32.47±2.28 ms.Compared between each state: 1) The peak velocity of the Sp in the AIV decreased, and the duration of the Sp shortened and the percentage of the duration of the Sp (D-Sp%) decreased during RVAP , and the acceleration of the Dp in the LAD correlated with the △P/T at baseline and RVAP . The acceleration of the Sp in the AIV correlated with the △P/T at baseline , and the peak velocity of the Sp in the AIV correlated with the AoSP at baseline and RVAP . We could not establish other statistical significant linear correlations between the aortic pressure parameters and the Doppler hemodynamic parameters of the LAD and the AIV successfully in this study.The duration of the Dp in the LAD correlated inversely with the TAoDP at baseline and RVAP (P>0.05). Intraobserver coefficient of variability was between 2.6% and 6.9%, with the smallest variation in measurements of the peak velocity of the Dp and the peak velocity of the Sp (2.6% and 2.9% respectively). The highest variation was found in D-Dp% and D-Sp% (6.9% and 6.5% respectively). Interobserver coefficient of variability was between 3.2% and 7.9%. The smallest variation was found in the peak velocity of the Dp and the peak velocity of the Sp (3.2% and 3.5% respectively). The highest variation was found in measurements of D-Sp% and D-Dp% (7.9% and 7.2% respectively).There was no statistically significant difference between the 2 observers or within an observer for the Doppler hemodynamic parameters of the LAD and the AIV  was detected in the peripheral coronary artery, such as the septal branch of normal subjects, and this reverse flow was caused by the milking effect produced by the contracting myocardium Furthermore, transitory cessation flow during mid to late systole in the LAD and a momentary cessation flow at the end of diastole in the AIV at the baseline condition were recorded in all cases. Although we did our best to retrieve related literatures of pioneers, the phenomenon that the transitory stopped-flow in the LAD of normal hearts, could not be reappeared in their results. This maybe because of the different observational techniques were used, or because of the complex phasic blood flow patterns in coronary artery have not been recognized adequately in the past. Using quantitative angiography and casts of epicardial coronary veins in dogs, Hodgson et al. found that the appearance of gaps in the column of contrast material within the epicardial veins could be consistently seen, and the flow in epicardial coronary veins occurred as a bolus during each cardiac cycle There were intimate correlations between ventricular asynchrony and coronary blood flow O to the onset of the Dp in the LAD lengthened and the time from the QRSO to the onset of the Sp in the AIV shortened during RVAP, these could be ascribed to the RVAP induced postponed mechanical relaxation and the early activated mechanical contraction in the LV wall Left bundle branch block and RVAP have similar LV mechanical activation sequence Why RVAP induced a systolic negative wave S3 in the LAD at late systole, and induced a diastolic negative wave D1 in the AIV? RVAP might cause a threefold difference in regional myofibers work within the LV wall, and this difference appeared large enough to regard as an important determinant for abnormalities in myocardial perfusion during asynchronous electrical activation Coronary flow velocity measurement by ultrasonic Doppler systems in laboratory and clinical research settings has provided information crucial to modern theories of coronary hemodynamics LAD and the ΦAIV. The average distance between the LAD and the AIV of human hearts was about 3.8 mm Quantification of the blood flow patterns in the AIV with Doppler ultrasound is valuable for improving recognition of the hemodynamics of coronary venous system under various physiological or pathophysiologic conditions. In addition, we found the average distance between the LAD and the AIV was about 2.1 mm, and found no statistical significance between the ΦClinical studies of coronary physiology will benefit greatly from combined measurements of coronary flow or velocity and pressure Obvious hemodynamic changes in the LAD and AIV during RVAP have been quantified by spectral Doppler ultrasound. Healthy hearts with normal sinus rhythm maintains its concordant myocardial contraction and relaxation, and the characteristics of the blood flow patterns in the coronary circulation may be taken as normal references. In contrast, the abnormal blood flow patterns in the epicardial coronary arteries and vena coronaria may be sensitive and important hints of the disturbed cardiac electrical and mechanical activity sequences. It will be of practical importance to elucidate the accurate relationships between the blood flow patterns of the coronary circulation and the myocardial mechanical activation sequence in further studies, so as to determine whether spectral Doppler waveform analysis of the epicardial coronary circulation could be incorporated effectively into clinical practice.


Heart failure (HF) affects nearly 5 million people in the US and 15 million people worldwide . HF has When HF is advanced, malfunction of multiple organs is involved and the degree of organ damage is correlated with the progress of HF. Treatment of HF patients depends on the stage of HF. This special issue on HF introduces a new HF evaluation “HLM” system and reviews the role of natriuretic peptide in HF diagnosis and management.At the end stage of HF, heart transplant often offers the best treatment option. Left ventricular assist devices (LVADs) are surgically implanted pumps that can be used as destination therapy and as a bridge to transplant. However, graft failure is a major cause of mortality among postheart transplant patients. Also, severe mitral regurgitation in HF patients has negative impact on left atrium, right heart, and lung function that ultimately impacts effectiveness of LVAD. The current issue reveals two new approaches, extracorporeal membrane oxygenation rescue and transapical concomitant mitral valve repair to improve the outcome of heart transplant and LVAD therapies. In addition, a review about interaction between renin and IGFII/M6P receptors in nonclassical renin effects and cardiac remodeling sheds light on manipulation of the IGFII/M6P receptor as a potential therapeutic approach to prevent cardiac remodeling in HF. We anticipate more progress in HF management in the near future.Yanggan WangYanggan WangYanzong YangYanzong YangXun AiXun Ai